- 1 Introduction
- 2 Preparation of phosphines
- 2.1 From halogenophosphines and organometallic reagents
- 2.2 From metallated phosphines
- 2.3 By the addition of P–H to unsaturated compounds
- 2.4 By reactions at phosphorus
- 2.5 Modification of functional substituents in phosphines
- 2.6 Miscellaneous methods of preparing phosphines
- 3 Reactivity of phosphines
- 3.1 The formation of phosphonium and related compounds by nucleophilic attack at carbon and other atoms
- 3.2 Oxidation of phosphorus atoms
- 3.3 Miscellaneous reactivity of phosphines
Tertiary phosphines: preparation and reactivity
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Published:14 Apr 2020
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Special Collection: 2020 ebook collection
E. I. Musina, A. V. Shamsieva, A. S. Balueva, and A. A. Karasik, in Organophosphorus Chemistry: Volume 49, ed. D. W. Allen, D. Loakes, L. J. Higham, and J. C. Tebby, The Royal Society of Chemistry, 2020, vol. 49, pp. 1-63.
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The annual survey of the literature relating to the chemistry of traditional tertiary phosphines containing only P–C bonds published during 2018 is presented. It includes the synthesis of new phosphines classified according to the used synthetic approaches and data concerning the reactivity of phosphines excluding metal complexation (mainly the attack of phosphorus at carbon or other atoms and the formation of P(v) derivatives of phosphines).
1 Introduction
This chapter covers the literature published during 2018 relating to the synthesis and the reactivity of tertiary phosphines excluding the chemistry of their metal complexes. Although it has been necessary to continue to be selective in the choice of publications cited, it is hoped that the most significant developments have been noted. A considerable number of review articles have been published in 2018 and many of these reviews are cited in the various sections of this report. The use of a wide range of tervalent phosphorus ligands in transition metal catalysis and in organocatalysis continues to be a major driver in the chemistry of traditional P–C-bonded phosphines which inspires the design of new phosphines of various structures and the tuning of their properties. As in recent years, a noteworthy feature of the literature reviewed here is the large number of papers reporting studies of the reactivity of phosphines, in particular those involving nucleophilic attack at a carbon atom of an electrophilic substrate. Recent general reviews represent the current state of knowledge in the fields of the chemistry of Xantphos-like bisphosphine ligands and their catalytic applications,1 the chemistry of π-extended molecules based on six-membered phosphorus heterocycles, including corresponding phosphines and their derivatives,2 the chemistry of ambiphilic intramolecular frustrated Lewis pairs containing amine or phosphine Lewis basic centers,3 carbeniophosphines and phosphoniocarbenes,4 PCP, PCS, PCN and SiPSi pincer phosphines5 and ferrocene-based N-heterocyclic carbenes, including their numerous representatives bearing phosphino groups.6
In 2018 two very large reviews have been published which have summarized the recent data concerning the application of phosphorus compounds, in particular phosphines, in organocatalysis7 and asymmetric organocatalysis.8 Organocatalysis is the main field of tertiary phosphine application after metal-complex catalysis, so the application of phosphines will not be specially considered in this chapter.
2 Preparation of phosphines
2.1 From halogenophosphines and organometallic reagents
This synthetic approach continues to be the most widely-used and universal one. The interaction of Grignard organomagnesium reagents with corresponding chlorophosphines has been applied in the synthesis of new representatives of diphosphines containing combined sterically hindered and amphoteric heterocyclic moieties on the P atoms and ortho-xylylene (1)9,10 or 1,n-alkylene linkers (2),11 furyl- and pyridyl-(tert-butyl)benzylphosphines,9 the vinyl-functionalized dppm-type diphosphine (3)12 and (4-vinylphenyl)dimesitylphosphine13 as monomers for the preparation of phosphorus-containing polymers, benzyl-, bromobenzyl- and phenethyl-substituted diphosphines (4),14 a series of bis(diarylphosphino)ferrocenes (5) with substituents of variable electronic properties,15 highly electron-deficient 1,3,5-triazinylphosphine ligands (6)16 and new long-chain tris(ω-alkenyl) phosphines with C12–C16 substituents as starting reagents for the synthesis of gyroscope-like complexes of dibridgehead diphosphine cryptands.17
Organolithium compounds are the most common reagents for the synthesis of phosphines. The organolithium-halogenophosphine synthetic routes include mainly the in situ lithiation of a pre-designed organic precursor by the halogen-lithium exchange. New tertiary monophosphines reported include (bromopyridyl)diarylphosphines (7) as starting reagents for the transformation to various functionalized phosphinopyridine ligands,18,19 (methylthiophenyl)phosphines (8)20 and (9),21 bis(m-anisyl)-, bis(p-anisyl)phenylphosphines and tris(m-anisyl)phosphine,22 various (o-anisyl)dialkylphosphines (10),23 [o-(dioxolanyl)phenyl]diarylphosphines (11) as protected phosphinobenzaldehydes,24 tert-butyldi(1-naphthyl)phosphine,25 dimethyl(1-pyrenyl)phosphine (12),26 tris(o-n-butylphenyl)phosphine,27 quinoline- and phenanthridine-based phosphine ligands (13) for the preparation of copper(i) complexes showing an orange-red phosphorescence,28 new rigidly planar 8-phosphino-2-(pyridine-2′-yl)quinoline P,N,N-ligands (14)29 and various carbazolyl-substituted phenylphosphines (15) as the basis for the design of copper- or boron-containing luminophores.30,31 New oxazolyl- or thiazolyl-containing phosphine ligands (16),32 (17)33 and (18)34 for the creation of enantioselective transition metal catalysts, cyclic monophosphadiynes (19),35 peri-substituted (1-bromobiphenylen-8-yl)diphenylphosphine (20),36 a wide range of new phosphine-sulfonate ligands (21) with varied electron-donating and electron-withdrawing substituents at different positions37 and enantiopure strained phospha[1]ferrocenophanes (22)38 were also obtained by the use of this approach. In the case of the synthesis of phosphine ligands (23)39 and (24)40 with crowded biaryl- or triaryl-substituents, respectively, the initial lithiation of the corresponding iodo- or bromoarene was followed by a successive treatment with copper(i) chloride and chlorodiorganylphosphine.39,40
Various new di- and poly-phosphines have been also synthesized by organolithium-halogenophosphine routes, in particular 5-bromo-1-(di-o-methoxyphenylphosphino)-2-di-R-phosphinobenzenes (25),41 PNP pincer diphosphine ligand (26) containing 9,10-dihydroacridine backbone,42 a new pincer ligand (27) with pentafluoroethyl substituents on phosphorus atoms,43 bis(diphenylphosphino)azobenzene (28) as a ligand for photoswitchable gold-containing catalysts,44 a pincer diphosphine (29) possessing hemilabile alkoxyl side arms45 and new air-stable tripodal triphosphine ligands (30)46 based on triptycene scaffolds, tridentate 1,3,5-tris[(4-phospholano-2,6-diethyl)styryl]benzene (31) with a semi-rigid backbone as the basis of a two-dimensional coordination gold-containing polymer47 and a tetraphosphine ligand (32) for the design of boat-shaped complexes of group 11 metals.48
A direct lithiation of the corresponding precursor through lithium/H exchange, (usually with n-, sec- or tert-butyllithium in the presence of TMEDA or KOBut, more rarely with LDA or lithium 2,2,6,6-tetramethylpiperidide (TMPLi)), followed by the treatment with chlorophosphines to give the desirable tertiary phosphine is widely used for the synthesis of phosphines with heterocyclic substituents. A wide range of 5-phosphino-1,2,3-triazoles (33) was synthesized and tested as ligands in Pd-catalyzed cross-coupling reactions.49 Several easily tunable alkylimidazole-based phosphine ligands (34),50 a series of polyethylene glycol-containing imidazolium-functionalized phosphine ligands (35),51 new bulky imidazolyl- and pyrazolyldialkylphosphines (36) and (37)52 were also obtained and tested in catalytic systems for various coupling and hydrosilylation processes.50–52 This synthetic approach was also applicable for the synthesis of the first representatives of (5-methyl-1,3-dithiazinan-2-yl)phosphines (38).53 The direct lithiation of aryl moieties was used for the synthesis of various 2-alkoxyphenylphosphines (39) as the precursors of new phosphine-phenolate ligands,54,55 new biarylphosphine ligands (EvanPhos) (40) for Pd-catalyzed Suzuki–Miyaura cross-coupling56 and a new DPPE-type phosphine (41) as an intermediate for the corresponding bis-phosphine oxide host of hyperfluorescent OLEDs.57 The highly polarized PO bond in arylphosphonic or diarylphosphinic amides functioned as an ortho-directing group in the aryl metalation which provided a one-pot synthesis of P(iii)–P(v) chelating phosphonic (or phosphinic) amide – phosphine ligands (42) for transition-metal-catalyzed polymerisations or oligomerisations of alkenes.58,59 The similar directing role of sulfonate groups allowed synthesis of one of the representatives of phosphines (21, Ar=Ph, R=5-CF3),37 the betaine forms of new ortho-sulfophenyl substituted phosphines (43)60 and of the phosphine-phosphonate-sulfonate proligand (44) as a building block for multinuclear Zn- and Pd-complexes.61 The study of metalation/electrophilic substitution reactions of phenylsulfonamides with chiral substituents on nitrogen provided an effective synthetic route to a variety of chiral (o-diphenylphosphinophenyl)sulfonamides (45) based on the use of n-BuLi in THF as the metallating reagent.62 The metalation of 2-naphthylsulfonamides with TMPLi, followed by the treatment with chlorodiphenylphosphine, smoothly gave (3-(diphenylphosphino)naphth-2-yl)sulfonamides (46) as the preferred products, whereas the use of n-BuLi led mainly to the products of C-1 phosphinylation which were isolated only as the corresponding phosphine oxides due to their instability towards oxidation during purification. New chiral P,O-ligands (45) and (46) were evaluated in Pd-catalyzed asymmetric allylic substitution.62 The lithiation through lithium/H exchange was also used for the synthesis of the first phosphines (47) appended with anionic 10-vertex perchlorinated closo-carboranes63 and 1-diphenylphosphino-2-fluoroferrocene (48).64
The easy lithium/H exchange on a carbon atom at the α-position relative to the aryl (heteroaryl) fragment or electron-withdrawing group was used in the preparation of pincer phosphine-sulfonate ligands (49) for Pd-containing olefin polymerization catalysts,65 (phosphinomethyl)pyridines (50),23,66 a naphthyridine-based phosphine ligand (51) as the multidentate platform for heterobimetallic complexes,67 methylene-bridged bisphosphine monoxide ligands (52) for Ni-catalyzed polymerization of alkenes68 and air-stable bisphosphine (53), stabilized by neighbouring phosphine sulphide groups which were also the additional binding sites for the transition metals.69
Combined procedures including both lithium/halogen and lithium/H exchange allowed synthesis of the triazole-based ambidentate bisphosphine ligand (54) with switchable coordination modes70 and W- or Mo-containing alkynylbis(alkylidynyl)phosphines (55) as new linkages for the preparation of polymetallic assemblies.71 The simultaneous transmetalation and ortho-lithiation of a tetrachlorodigallium derivative of 1,3-bis[2-(dimethylphenylsilyl)vinyl]benzene led to a trilithium compound which reacted with phosphorus trichloride to form the sterically-constrained tricyclic phosphine (56).72 The mono- or di-lithiation of the corresponding dibromobiaryl, followed by the successive treatment with MgBr2 and fluorinated diarylbromophosphine, led to a fluorinated monophosphine (57) and a new SEGPHOS-type diphosphine (58).73
There are a few examples of phosphine synthesis based on the interaction of organosilicon or organozirconium reagents with halogenophosphines.
(Halodifluoromethyl)diphenylphosphines XCF2–PPh2 (X=Cl, Br) were obtained by the interaction of chlorodiphenylphosphine with Me3Si–CF2X (X=Cl, Br).74 The reaction of a carborane-fused zirconacyclopentane with dichlorophenylphosphine produced a diastereomeric pair of carborane-fused phosphacyclopentanes (59).75
In some cases other phosphorus-containing starting reagents were applied. A trifluoromethyl-substituted analogue of bisphosphine (27) was prepared by the interaction of the corresponding diphosphinite 1,3-[(PhO)PButCH2)]2C6H4 with (trifluoromethyl)trimethylsilane.43 The lithiation of borane-protected O-(2-bromoaryl)diphenylphosphinites resulted in the formation of a P–C bond to give borane-protected 2-phosphinophenols (60) as intermediates for the synthesis of chiral phosphine–phosphite ligands.76 A mixed phosphine sulphide – phosphine ligand (61) was prepared in a single step from lithiated trimethylphosphine sulphide and triphenylphosphite.69
The interaction of halogenophosphines with sufficiently strong C–H acids (as a rule heterocycles) may proceed in the presence of weaker bases. 2,4-Dimethylpyrrole reacted with chlorobis[3,5-di(trifluoromethyl)phenyl]phosphine in the presence of trimethylamine with an unexpected formation of the corresponding (1H-pyrrol-2-yl)phosphine (62).77 A tandem deprotonation of a triazolium salt with potassium tert-butoxide and the reaction with chlorodiphenylphosphine afforded 4-phosphino-1,2,3-triazolium salt (63). Further deprotonation of the salt (63) with potassium tert-butoxide led to a thermally stable 4-phosphino-1,2,3-triazol-5-ylidene (64) which showed a strong σ-donation ability towards coinage metals.78 The interaction of a benzoyl-functionalized N-heterocyclic carbene with chlorodiphenylphosphine in the absence of any base led to the 2-phosphinoimidazolium salt (65).79
2.2 From metallated phosphines
Reactions between organophosphide anions, prepared or generated in situ, and halogenated alkanes or their analogues is an alternative to the above routes to the various, usually functionalized, phosphines. The suitability of these approaches depends on the availability and stability of the corresponding metal phosphide and organometallic reagents. Lithium-, sodium- and potassium-organophosphide reagents, sometimes as borane-protected systems, remain the most commonly used in the synthesis of new phosphines, the borane group also providing protection against oxidation of the new phosphine during purification steps.
Traditional lithium phosphide reagents are available via a simple deprotonation of primary or secondary phosphines by commercially available butyl lithium or similar organolithium reagents. It has been shown that 4-methylenehex-5-enol and its saturated analogue were activated with mesyl chloride and reacted with lithium diphenylphosphide to give phosphines (66) and (67), whose ruthenium(ii)- and gold(i)-complexes demonstrated strong antiproliferative properties for several types of cancer.80 Unexpectedly, the interaction of a mixture of lithium diphenyl- and di(p-tolyl)-phosphides with 1,1-dichloroethene led to isolation of the unsymmetric diphosphine (68).81 Interaction of diphenylphosphine with butyllithium followed by reaction with the corresponding dimesylate gave 2,2-disubstituted 1,3-bis-(diphenylphosphino)propanes (69), used for the preparation of Ni-catalysts for branch-selective alkylation of unactivated aryl fluorides.82
Bis-[(trimethylsilylmethyl)phenylphosphino]ethane (70), which is a precursor of new tetraphosphines via the interaction with chlorodiphenylphosphine, was obtained by the treatment of the lithium salt of 1,2-bis(phenylphosphino)ethane with trimethylsilyl(chloro)methane.83 Bis(diphenylphosphinomethyl)dimethylsilane (71), used for palladium-catalyzed ethylene oligomerization, was obtained analogously.84
The procedure is tolerant for a number of functional groups, for instance corresponding phosphines with ether (72)23 or iminophosphorane (73)85 fragments have been synthesized.
Borane-protected diphosphine (74, R=Br) was prepared by the deprotonation of the chiral secondary phosphinoborane precursor with MeLi, followed by treatment with a bis(benzyl bromide), although it was only isolated in low yield, in contrast to diphosphine (74, X=H), synthesized by a known procedure via deprotonation of the corresponding precursor with KOH followed by P–C bond formation under biphasic conditions. The deprotection of (74, R=H) with DABCO gave the bis(phospholane) as a colorless oil.86
A deprotonation of enantiopure alkylmethylphosphine-boranes with butyllithium, followed by alkylation with bis(2-chloroethyl)-N-trimethylsilylamine, gave the protected PN(H)P pincer ligands (75) with high stereoretention at phosphorus.87 The same procedure was used to prepare borane-protected P-stereogenic phosphinopyridines (76) and (77).88 The above approach is ideally suited for dialkylphosphine-boranes, whose corresponding lithium phosphide-boranes are configurationally stable during the course of the reaction. Interaction of chiral epoxides with LiPHMes* (Mes*=2,4,6-(t-Bu)3C6H2), followed by addition of tosyl chloride, yielded a roughly 1 : 1 mixture of diastereomeric tosylates, which cyclized under mild conditions to form selectively P-stereogenic syn-phosphiranes (78) in a dynamic kinetic asymmetric transformation.89
Lithium phosphides could be prepared via the reaction of metal lithium with corresponding chlorophosphines. The representative of a class of novel diphosphine ligands (79) bearing pyridine substituents was synthesized from 2-(tert-butylchlorophosphanyl)pyridine, converted to the corresponding phosphide by the interaction with metal lithium, and 1,3-dichloropropane.11 Lithium diarylphosphide obtained from diarylchlorophosphine and metallic lithium has been applied for a phosphination of polymers containing chloromethyl groups to give the polymers (80). A series of novel heterogeneous gold(i) catalysts was synthesized by immobilizing gold(i) complexes on these mesoporous polymers.90
Sodium- and potassium-diphenylphosphides are commercially available. Using these reagents, a number of functionalized phosphines have been obtained. A compound (81), with the phosphine group tethered on the cyclopentadiene ring of an iron-containing functional group, was designed and synthesized via direct substitution of chlorine in a corresponding chloroalkane by sodium diphenylphosphide for the effective synthesis of macrocycles in bulk.91 Bis(diphenylphosphino)trispyridylamine (82) was synthesised by the nucleophilic substitution of bis-bromo-trispyridylamine with potassium diphenylphosphide in 84% isolated yield.92
P,O-iminosugar-based ligands were prepared from easily available carbohydrates (d-mannose, d-ribose and d-arabinose). Tosylation or mesylation of corresponding hydroxy groups, followed by the displacement with potassium diphenylphosphide, afforded amino-phosphines (83)–(85) based on d-mannose and d-arabinose respectively.93 Nucleophilic ring opening of cyclic carbamates derived from d-ribose with commercial potassium diphenylphosphide in THF gave the corresponding pyrrolidine-phosphines (86) and (87) (R=BOC, H). Phosphine (87, R=H), after the treatment with methoxycarbonyl chloride and reduction with LiAlH4, gave aminophosphine ligand (86, R=Me).94
The stereochemical and polyfunctional diversity of carbohydrates allowed the modulation of the ligands, both from their electronic properties and the rigidity of their backbone. High enantioselectivities (ee's up to 99%) could be reached in the hydrogenation of selected tri- and di-substituted substrates with the use of such ligands.93
The metal phosphides can be generated from corresponding P–H phosphines in the presence of other strong bases. An improved method for the synthesis of tris(1-naphthyl)phosphine (88) from phosphine gas and 1-bromonaphthalene in the superbasic system ButONa/DMSO, allows the target phosphine (88) to be obtained in 34% yield.95
In order to improve the efficiency of corresponding cobalt catalysts for reductive alkylation of anilines with carboxylic acids, a series of tailor-made Triphos ligands (89) has been obtained via interaction of 1,1,1-tris(chloromethyl)ethane or (1,3-dichloro-2-(chloromethyl)propan-2-yl)benzene with a corresponding secondary phosphine in the presence of the strong bases (NaOH, KOBut).96
The stereoselective synthesis of phospholyl l-α-amino esters was achieved by substitution of β- or γ-iodo amino esters with phospholide salts, obtained from corresponding phosphole with a strong base (potassium hexamethyldisilazane (KHMDS) is the best one). The desired phosphines were isolated as P-borane complexes (90).97
Interaction of substituted benzoyl chlorides with diphenylphosphine in the presence of less basic triethylamine gave corresponding acylphosphines (91) and (92) in excellent yields.98
A new synthetic route to modify the cubane nucleus has been reported. Methyl-4-iodocubane-1-carboxylate and 1,4-diiodocubane reacted with the diphenylphosphanide ion, generated under irradiation in liquid ammonia, with dimethylsulphoxide to afford diphenylphosphinocubane derivatives (93) and (94) in moderate to good yields.99 Organophosphines showed a very high reactivity towards cyameluric chloride C6N7Cl3 without any additional base. For example, 2,4,6-trisdiphenylphosphino-tri-s-triazine (95) (R=Ph) was formed quantitatively within a few seconds.100
Trimethylsilylphosphines could also be regarded as useful reagents to create P–C bonds via the interaction with corresponding organohalogenide compounds. α,α′-Dibromo-m-xylene had been phosphinated with (But)(TMS)PH in the presence of BuLi to give diphosphine (96) with P–Si bonds. The trimethylsilyl groups of (96) were substituted by perfluorinated iodoalkanes, forming a new class of hybrid donor/acceptor pincer ligands (97).43.
4-(Diphenylphosphino)-5-chlorophthalonitrile (98), 4,5-bis(diphenylphosphino)phthalonitrile (99), and 4-(diphenylphosphino)-5-(diphenylphosphoryl)-phthalonitrile (100) were prepared by the reaction of 4,5-dichlorophthalonitrile and diphenyltrimethylsilylphosphine, as starting materials for the synthesis of several phthalocyanines in which four or eight phosphino groups were directly linked to their periphery.101
The cleavage of P–C bonds of tertiary phosphines by lithium and potassium is also a convenient method for preparing of phosphide precursors. Lithium diphenylphosphide prepared by the cleavage of P–C bond of triphenylphosphine by metallic lithium was used for the nucleophilic substitution of 3-(4-chlorobutyl)-1-methyl-1H-imidazol-3-ium chloride to give diphenylphosphino- tethered imidazolium (101), the precursor of the related phosphine-functionalized N-heterocyclic carbene (NHC) ligand.102
3,4-Dimethyl- and naphthyl-phospholide anions, obtained by P–C bond cleavage of the corresponding phospholes with potassium, readily reacted with β- or γ-iodo amino esters to give novel phospholyl l-α-amino esters, isolated as P-borane complexes (102) and (103).97
2.3 By the addition of P–H to unsaturated compounds
Hydrophosphination of unsaturated compounds with reagents containing P(iii)–H bonds is a most straightforward and atom-economical strategy for the preparation of various phosphines, so investigations directed to the elaboration of efficient catalysts and optimal conditions providing the control of its regio-, chemo- and stereo-selectivity are continuing. Catalytic hydrophosphination of activated and inactivated alkenes with phenylphosphine using [κ5-N,N,N,N,C-(Me3SiNCH2CH2)2NCH2CH2SiMe2CH2]Zr under photolysis led to the quantitative formation of secondary phosphines. This zirconium complex catalyzed previously unknown tandem inter/intramolecular hydrophosphination of 1,4-pentadiene to give the corresponding phosphorinane.103 Zirconium complexes stabilized by amine-bridged bis(phenolato) ligands showed good activity and chemoselectivity in catalysis of the intermolecular hydrophosphination of alkenes and alkynes with primary phosphines under mild conditions.104 Neutral zirconium complexes supported by multidentate aminophenolate ligands exhibited a high activity in the hydrophosphination of arylalkenes with diphenylphosphine to form anti-Markovnikov adducts, whereas relative cationic complexes were found to be more active for the hydrophosphination of heterocumulenes (carbodiimides and isocyanates) to give phosphaguanidines and phosphaureas.105 A series of calcium(ii) and ytterbium(ii) complexes, coordinated by amidine-amidopyridinate ligands, were studied as precatalysts for the hydrophosphination of alkenes and dienes with primary and secondary phosphines and provided high chemo- and regio-selectivities in some reactions.106 Tetranuclear barium- and strontium-sulfoxide/amide clusters were found to be active catalysts for the hydrophosphination of terminal alkenes with diphenylphosphine.107 The well-defined cobalt catalyst Co(PMe3)4 provided E-selective hydrophosphination of terminal and internal alkynes under mild conditions in good-to excellent yields. The reactions provided a wide scope and a good functional tolerance.108 A commercially available iron derivative [CpFe(CO)2]2 was found to be an efficient catalyst for the double hydrophosphination of terminal alkynes with diphenylphosphine under visible light irradiation or thermal conditions (110 °C) which led to 1-aryl-1,2-bisphosphinoethanes.109
KHMDS-catalyzed double hydrophosphination of functionalized alkynes with diphenylphosphine was a convenient route to 1,1-diphosphines (104). Some of them were obtained on a preparative scale and their structures were established by an X-ray diffraction analysis. The use of phenylphosphine and arylalkynes led to the formation of Z,Z-di(2-arylvinyl)phosphines (105).110
A diastereoselective catalytic hydrophosphination of dienones containing a pyridinylene backbone with diphenylphosphine was catalyzed by a chiral palladacycle and led to the chiral PCP pincer diphosphine (106).111 Chiral PC-palladacycle-catalyzed asymmetric hydrophosphination of functionalized 1-[2′,2′-di(methylcarboxy)-ethen-1′-yl]naphthalenes and 9-[2′,2′-di(methylcarboxy)-ethen-1′-yl]phenanthrene gave phosphines (107), containing a malonate moiety at the chiral carbon atom, in high yields and ee.112
AIBN-catalyzed hydrophosphination of hexene-1 with primary 3-alkoxypropylphosphines bearing peracylated mannosyl or glucosyl substituents led to the corresponding tertiary phosphines (108).113 Based-catalyzed hydrophosphination of diphenyl(vinyl)phosphine with primary 1-(phosphinomethyl)-1-aza-15-crown-5 or AIBN-catalyzed addition of N-(2-phosphinoethyl)-substituted aza-crown ethers to various di-R-vinylphoshines (R-phenyl, alkyl) led to a family of tris-phosphine ligands (109) containing tethered aza-crown fragments of various sizes.114
Phosphine-polymer network (110) was prepared by the photoinitiated hydrophosphination of 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione with iso-butylphosphine in the presence of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (IRGACURE 819). This polymer was used as a basis for stibino-phosphonium- and stibino-bis(phosphonium)-functionalized polymers.115
P–H functionalized Al/P frustrated Lewis pair (FLP) (Me3Si)2CH–P(H)–C(CHBut)–Al(CH(SiMe3)2)2 reacted with heteroatom-substituted nitriles (PhOCN, BnSCN, C4H8NCN) to form heterocyclic hydrophosphination products (111) where the imine nitrogen atom coordinated to the aluminium center.116
2.4 By reactions at phosphorus
2.4.1 Reduction of phosphine oxides and related compounds
For the moment a reduction of phosphoryl compounds using a wide range of reducing agents still remains the most effective pathway to tertiary phosphines. As in recent years, a wide range of reagents has been employed for the reduction of phosphine oxides. Silane-based reagents continue to be widely employed and trichlorosilane, usually in the presence of an amine base (commonly amines TEA, DIPEA etc.), has continued to be the most commonly used in the final or intermediate step of a multistage synthesis.
A variety of phosphines, namely compounds (112), (113),117 both diastereoisomers of (114),118 (2,2-diphenylvinyl)phosphine (115),119 ferrocenylphosphine (116),120 amine-phosphine ligand (117),121 phosphines (118) on the spiroketal-based C2-symmetric chiral scaffold,122 planar chiral [2.2]paracyclophane-based phosphine–phenol catalyst (119),123 planar-chiral pillar[5]arene-based monophosphine (120)124 and a series of (R)-BICMAP-ligands (121)125 were synthesized by the reduction of corresponding phosphine oxides with trichlorosilane in presence of triethylamine or diisopropylethylenamine. A series of new monophosphine ligands (122) containing a naphthofuran skeleton have been prepared by the easy reduction of corresponding phosphoryl compounds with HSiCl3 in presence of DIPEA.126 A new representative of SEGPHOS-ligands, phosphine (123), was obtained by HSiCl3/Et3N-reduction of the corresponding phosphine oxide in mesitylene at 130 °C.73 Reduction of the phosphine oxide with HSiCl3/Et3N, followed by the reaction with borane gave borane-protected phosphine (124) with only slightly reduced chirality.127
Some approaches allow reduction of phosphine oxides with HSiCl3 without base addition. In this manner, bidentate NHC/phosphine ligand (125) was obtained from the corresponding phosphine oxide.128 Chiral phosphines derived from trans-hydroxy-l-proline (Hyp), namely “HypPhos” ligands (126), were successfully synthesized in decagram scales by base-free HSiCl3-reduction under very mild conditions (dichloromethane/toluene mixture, room temperature, 2 hours).129 Reduction of a series of [2.2]paracyclophane phosphines oxides with HSiCl3 or neat PhSiH3 at 145 °C gave the corresponding phosphines (127); however, the authors noted an extreme instability of the products.130
The use of HSiCl3/Et3N, poly(methylhydrosiloxane)/Ti(Oi-Pr)4 or 1,3,3-tetramethyldisiloxane/Ti(Oi-Pr)4 as reduction systems in the final stage of a multistep synthesis of dihydrobenzooxaphospholes (BOP) and dihydrobenzoazophospholes (BAP) (128)–(130) opened up a series of tunable chiral phosphines, because the 3,5-positions of the lower aryl ring of (128) might be functionalized.131,132 Several approaches were used to reduce (R)-[2-(tert-butoxy)phenyl](methyl)(phenyl)phosphine oxide with HSiCl3/Et3N, poly(methylhydrosiloxane)(PMHS)/Ti(Oi-Pr)4 or 1,3,3-tetramethyldisiloxane (TMDS)/Ti(Oi-Pr)4 to the corresponding borane-protected phosphine (131) with the retention of chirality, because (131) is a key intermediate compound in scalable, chromatography-free synthesis of tBu-SMS-Phos. Retention of chirality was observed in the case of reduction with TMDS and PMHS, whereas in the case of HSiCl3, the opposite enantiomer of (131) was obtained.133
A simple and efficient access to new P-chiral racemic ligands (132) featuring ortho-trityl and ortho-biaryl motifs was achieved, through efficient three- to four-step modular syntheses. The last step, namely the phosphine oxide reduction, was performed with TMDS as the hydride source and Ti(OiPr)4 as the Lewis acid at 120 °C in toluene to give the desired phosphines (132) which were converted in situ to the stable phosphine-borane complexes for the prevention of oxidation.134
A family of bidentate benzooxaphosphole oxides were designed by Pd-catalyzed C–C coupling reactions; their subsequent reduction with TMDS/Ti(Oi-Pr)4 in THF or with HSiEt3/Et3N in toluene gave a series of bidentate ligands (133), namely O-BABIPhos135,136 and N-BABIPhos.135
Triethoxysilane in the presence of catalytic amounts of Ti(OiPr)4 was used for the reduction of phosphorylated 2-indolylmethanols to give corresponding phosphines (134) and (135) in good or high yields.137
Phenylsilane was used as the reducing agent in the enantiospecific synthesis of aryl- and pyridyl-(tert-butyl)(phenyl)phosphines (136) and (137),138 O,N,O–P multidentate ligand (138)139 and 1,1′-spirobiindane-based amino-substituted phosphine (139).140
A series of triarylphosphines bearing one to three hexa-peri-hexabenzocoronene (HBC) groups (140) was obtained by the reduction of corresponding phosphine oxides by LiAlH4/CeCl3 or with diphenylsilane. The LiAlH4–CeCl3 method was complicated by the apparent reduction of the P–HBC bond, whereas the milder reducing agent SiH2Ph2 showed no evidence of P–C bond cleavage. The reduction was performed at 170 °C in o-xylene or o-C6H4Cl2.141
Relatively mild reaction conditions (benzene, 70–80 °C or CHCl3, room temperature) were reached in the reduction of phosphine oxides by Si2Cl6 to give C and P-chirogenic phosphines (141) in good yields and of high enantiomeric purity, with no need to protect the hydroxyl group.142
Metal hydride reduction of phosphine oxides or aminophosphonium salts (with LiAlH4143 or NaAlH4144 ) was used for the synthesis of phosphine (142),143 diphosphine (143) and 1,2-bis(dimethylphosphino)ethane.144 Phosphine (142) was an intermediate compound for new chiral HMSI-PHOX ligands (see Section 2.5.3).143
The reduction of optically active phosphine oxides by LiAlH4 leads predominantly to the racemized phosphines, owing to pseudorotation of the pentacoordinate intermediates. A convenient method for the stereospecific reduction of phosphine oxides suggested by Imamoto in 2001 involves using of LiAlH4 and methylation reagents (MeI, MeOTf, MeOTs, MeOMs) as activators. The reduction of P- and axially chiral-phosphine oxides by Imamoto's method provided chiral phosphines (144) and (145) with complete enantiospecificity.145 Phosphine (146) was obtained by the reduction of the corresponding phosphine oxide under classical conditions with trichlorosilane, without erosion of enantiopurity.145
A comparable study of reducing the reactivity of the aluminium hydrides LiAlH4>AlH3>(Bui)2AlH towards tertiary phosphine oxides (P(O)Ph3, P(O)Et3) was presented by Tyler et al.146 It has been shown, that (Bui)2AlH is somewhat less reactive than AlH3, the latter possibly reacting faster because there are more available hydrides for the reduction. However, these reactions were all run with an excess of aluminum hydrides, so the effect of multiple hydrides on the Al center should be minimized. Notably, AlH3 was the only reducing agent capable of reducing P(O)Cy3 to PCy3, albeit with incomplete conversion. This result shows that AlH3 is a superior reducing agent compared to LiAlH4 and (Bui)2AlH for chemically difficult phosphine oxide reductions. The mechanism of electrophilic aluminum hydride reduction of tertiary phosphine oxide to a phosphine was studied.146
The metal-free reduction of phosphine oxides with molecular hydrogen (H2) using oxalyl chloride as activating agent was suggested by Paradies et al.147 The reaction could also be catalyzed by the frustrated Lewis pair (FLP) consisting of B(C6H3F2-2,6)3 and 2,6-lutidine or the phosphine oxide itself as Lewis base. The mechanistic investigation supported the heterolytic splitting of H2 by the in situ formed electrophilic phosphonium cation (EPC) and phosphine oxide and subsequent barrierless conversion to the phosphine and HCl. This novel reduction was demonstrated for a wide variety of triaryl- and diaryl(alkyl)-phosphine oxides, providing access to phosphines in good to excellent yields (51–93%).147
The electrochemical reduction of triphenylphosphine oxide to PPh3 facilitated by boronic acids (B(OC6H4OMe)3 or B(OPh)3) was performed at glassy carbon- electrodes with Faradaic efficiencies of 37% by Nocera et al.148
An efficient method for the reduction of the mercapto- or aminoalkyl-phosphineoxides by commercially available BH3 complexes to corresponding phosphine-boranes was described (Scheme 1).149 The reduction of the strong PO bond by BH3, a mild reducing agent, has been achieved through an intramolecular PO–B complexation directed by proximal SH or NH activating groups located at the α- or β-position to the phosphoryl moiety.149
2.4.2 Desulfurization
The thioanalogues of phosphine oxides can also be used as precursors of phosphines. Tertiary bis-phosphine disulfides have been reduced by the Schwartz reagent Cp2Zr(H)Cl to give the corresponding bis-phosphines (147)150 and (148)151 with high efficiency and under mild conditions. Dithieno[3,4-b:3′,4′-d]phosphole sulfide has been quantitatively converted into the corresponding trivalent phosphine (149) by treatment with tris(dimethylamino)phosphine in toluene at 90 °C.152 The sequential treatment of phosphine sulfides with MeOTf and P(NMe2)3 allowed desulfurization at relatively lower temperatures, which prevents a thermal decomposition, and also in a more polar, halogenated solvent that could better dissolve the sulfonate salt. In this manner functionalized ferrocenylphosphine (150) was obtained in dichloromethane at room temperature.153
A precursor bis(phosphinesulfide)imidazolium salt was reduced by RANEY®-Ni to give the corresponding phosphine (151).154 Various (heteroaryl)diorganylphosphines (152)–(155) were prepared in excellent yields via desulfurization of corresponding phosphine sulfides with Bun3P in o-dichlorobenzene.155
2.5 Modification of functional substituents in phosphines
2.5.1 Addition reactions
Hydroboration and hydroamination reactions of unsaturated phosphines continue to be perspective methods for the synthesis of novel phosphines. A copper-catalyzed hydroamination of borane-protected vinylphosphine with hydrosilanes and O-benzoylhydroxylamines proceeded regioselectively to form the corresponding α-aminophosphine boranes (156).156 It provides a new electrophilic amination approach to α-aminophosphine derivatives. Additionally, asymmetric induction is also possible by using a chiral bisphosphine-ligated copper catalyst.156
Rhodium-catalysed hydroboration of vinylphosphine by pinacolborane in the presence of AgOTf as a catalytic additive with excellent selectivity led to the formation of the branched 1-phosphino-1-boranylethane (157) regioisomer. The regioselectivity could be inverted to favour the linear product (158) by lowering the reaction temperature and by the use of an excess of diphenylvinylphosphine.157
Cu-catalyzed regiospecific and stereoselective hydroboration of alkynylphosphines gave (E)- and (Z)-2-phosphino-1-alkenyl boronates (159).158
The addition of aryllithium reagents to unsaturated sulfinamides resulted in novel representatives of chiral Xiang-Phos ligands (160) which were effective in gold-catalyzed intramolecular enantioselective cyclopropanation of indenes and trisubstituted alkenes.159
2.5.2 C–H- and C–Si-activation
An effective method for the synthesis of 8-substituted (naphthalen-1-yl)phosphines (161) by rhodium(i)-catalyzed C-8 arylation of the readily available (naphthalen-1-yl)phosphines has been developed. The reaction is applicable to the coupling of various aryl- and heteroaryl-halides with precursors bearing dialkyl- and diaryl- phosphine groups.160
Two (phosphinobiphenyl)sulfonic acids (162) were obtained by the reaction of 2-hydroxy-2′-dicyclohexylphosphinobiphenyl or its methyl ether with concentrated H2SO4.161
The 2′-(di-tert-butylphosphino)-2,6-dimethoxy-[1,1′-biphenyl]-3-sulfonate (162, X=Na) was prepared analogously and isolated as the sodium or tetrabutylammonium salt after treatment of the sulfonic acid with NaOH or NBu4HSO4.162
The subsequent reaction of the phosphine (50) (see Section 2.1) with BuLi and C6F6 led to a diastereomeric mixture of fluorinated (α-pyridylalkyl)(biphenylyl)phenylphosphines (163) which were successfully separated by column chromatography.66
The treatment of C4-diphenylphosphinoimidazolylidenes with equimolar amounts of benzoyl chloride gave C2,C4-functionalized imidazolium salt (164) as the basis for the the first examples of highly functionalized abnormal carbenegold(i) complexes.79
Phosphinine (165) was obtained by a desilylation of the corresponding 2-diphenylphosphino-6-trimethylsilyl-phosphinine with and without BH3 protection, using 1 equivalent of HCl in a mixture of Et2O and CH2Cl2.163
The treatment of (trimethylsilylethynyl)phosphinocarbynes (55) (see Section 2.1) with tetrabutylammonium fluoride cleaved the protecting group and furnished the ethynylphosphinocarbynes (166, R2=H). Its lithiation with BuLi followed by the interaction with BrAsPh2 gave an unusual derivative (166, R′=AsPh2) containing a PCCAs unit.71
Cyclic diboranes (167) based on a chelating monoanionic benzylphosphine linker were prepared through boron–silicon exchange between arylsilanes and B2Br4. Coordination of Lewis bases to the remaining sp2 boron atom yielded unsymmetrical sp2-sp3 diboranes, which were reduced with KC8 to their corresponding trans-diborenes (168).164
A series of dialkylphenylphosphines have been metallated with the synergistic mixed-metal base [(TMEDA)Na(TMP)(CH2SiMe3)-Mg(TMP)] and two heterobimetallic complexes (169) and (170) with non-coordinating phosphino groups were obtained and crystallographically characterised. Lateral product (169) was formed in the case of the dimethylphenylphosphine while predominately meta-metallation was observed for the diethyl- and diisopropyl-phenylphosphines.165
2.5.3 Functionalization of peripheral halogen groups
Various phosphines bearing peripheral halogen groups serve as convenient precursors for the insertion of different functional groups and fragments into the molecules of ligands. Phosphine-imidazolium ligands (171) were synthesised by the interaction of (2-(chloromethyl)phenyl)diphenylphosphine with different imidazoles.128,166 The twofold phosphine-functionalized imidazolium salt (171, R=2-Ph2PC6H4) was accessible in approximately 60% yield by the reaction of sodium imidazolide or trimethylsilyl imidazole with two equivalents of the phosphine.166
Reactions of 1-chloro-2-diphenylphosphinoethane with 1-[(4-methylthio)phenyl]-1,2,2-triphenylethene or 1-(4-thiophenyl)-pyrene in the presence of KOBut or Cs2CO3, respectively, gave hemilabile ligand (172) which possesses an electron-donating methylene spacer between the tetraphenylethene and sulfur atom and ligand (173) with an electron-withdrawing phenylene spacer between the pyrene and sulphur.167
Novel hydrophilic and recyclable ethylene glycol-modulated s-triazine-based multifunctional Schiff base/N,P-ligands (174) were prepared from corresponding chloro-derivative by subsequent reactions with ButOLi and ethylene glycol or methoxypolyethylene glycol 2000.168 Functionalized phosphinopyridines (175) were obtained by the reaction of 6-bromo-derivatives (7, X=OCH2OMe) (see Section 2.1) with KOBut, followed by treatment with HCOOH to give bis-hydroxyl-derivatives.19 A Pd-catalyzed bromo-cyanide substitution in phosphine (142) (see Section 2.4.1) with zinc cyanide gave the spirocyclic phosphine (176) bearing a cyano group in 65% yield.143 Iododifluoromethylsubstituted phosphine Ph2PCF2I is easily prepared by halogen-substitution reaction of Ph2CF2Br with excess of NaI in DME.74 (Di-(R)-phosphino)phenyllithium, generated from di-(R)(bromophenyl)phosphine and BuLi, is commonly employed as the phosphine forming part of various phosphine ligands. Trapping of 2-(di-isopropylphosphino)phenyllithium with FB(Fxyl)2 (Fxyl – 3,5-(CF3)C6H3) cleanly afforded the phosphine-borane (177). The 31P, 11B NMR and X-Ray data indicate the presence of a strong P→B interaction in solution and in the solid state.169
Similar reaction of two equivalents of dicyclohexyl-2-lithiobenzylphosphine with B2Br4 gave a diphosphine-diborane which transformed after reduction with KC8 into diborene (178).170 Lithium salts of triarylborate (179), containing two diorganylphosphino groups, were obtained by subsequent lithiation and treatment with tris(3,4-difluorophenyl)borane of the corresponding (5-bromo-2-diarylphosphinophenyl)diorganyl phosphine.41
Treatment of [1-(lithio)biphenylen-8-yl]diphenylphosphine36 or the carbazole-substituted (4-lithiophenyl)di-R-phosphine31 with Mes2BF resulted in compounds (180) and (181) correspondingly. A series of new saturated and unsaturated ortho-phenylene bridged N,P-bisphosphines (182) was obtained by the reaction of 2-(di-organylphosphino)phenyllithium and 2-chloro-1,3-dimesityl-1,3,2-diazaphospholidine or 2-bromo-1,3-dimesityl-1,3,2-diazaphospholene respectively.171 Lithiation of (2-bromophenyl)diarylphosphine, followed by treatment with methyldiglycol chlorophosphate, provided ligands (183) in moderate yields.172 Diphosphine ligand (184) was obtained from (2-bromophenyl)-1,3,5,7-tetramethyl-2,4,6-trioxa-8-phosphaadamantane, BuLi and Mes2PCl.173
Substitution of bromine in the corresponding Br-precursor by a diphenylstibyl group was successfully achieved through a similar lithium-halogen exchange/Ph2SbCl reaction sequence to give the new diarylamino-based pincer ligand (185) with one phosphino and one stibino side donor.174 Di-(phosphinophenyl)ketone ligand (186) was obtained by the reaction of two equivalents of 2-(di(p-tolyl)phosphino)phenyllithium with N,N-dimethylcarbamoyl chloride.175
The reaction of borane-protected 2-(dicyclohexylphosphino)phenyllithium with various sulfinyl imines or sulfonamides, after work up, resulted in the corresponding XuPhos and N-Me-XuPhos ligands (187).176 Similar sequential reactions of (5-iodo-9,9-dimethyl-9H-xanthen-4-yl)diphenylphosphine with BuLi and sulfinyl imines gave new representatives of PC-Phos ligands (188).177
Bromine-lithium exchange of 1-bromo-6-diarylphosphinopyridine (7, X=H) (see Section 2.1) and subsequent quenching with CO2 provided a range of phosphinopyridine-carboxylic acids (189).18
A lithiation/functionalization approach was used to prepare free or borane-protected ferrocene-phosphines (190) containing a sulfo-group,153 additional diorganylphosphino-groups,178 and a carbonyl-group.178
The route to the synthesis of 9-phosphatriptycene-10-phenylborate anion (191) was based on the treatment of tris(o-bromophenyl)phosphine with ButLi followed by a slow addition of PhBCl2179 or PhBF3K.180 Treatment of the reaction mixture180 with 1 M of aqueous HCl and purification by silica gel column chromatography gave a P-protonated borate-phosphine hybrid, which transformed into sodium phosphine-borate after an addition of Na2CO3. The countercations [Li(THF)4]179 or Na180 were straightforwardly replaced by the treatment of a methanolic solution of the initial salt with NEt4Br or ASNBr (where ASN is 5-azoniaspiro[4.4]nonane)179 or with Bun4NBr in MeCN/CH2Cl2180 respectively.
A Cu-promoted homocoupling of (R)-2-lithiophenyl(tert-butyl)(methyl)phosphine-borane and the subsequent removal of the borane protecting group with DABCO results in the BipheP* ligand (192).181
2.5.4 Functionalization of carbonyl groups
The condensation of 2-di(organyl)phosphinobenzaldehyde with various amines and diamines gave a wide range of iminophosphines, which could be reduced to aminophosphines. Iminophosphines (193) were prepared from methyl-, phenyl- and tert-butyl amines,182 3-phenylpropyl-1-amine,183 (S)-α-4-dimethylbenzylamine or (R)-α-methyl-4-nitrobenzylamine hydrochloride,184 o-amino-substituted anilines,168 3-(heptadecafluorooctyl)aniline,24 2-thiophenecarboxylic acid hydrazide and 4-phenyl-3-thiosemicarbazide,185 3-(2-aminoethyl)-1-methyl-1H-imidazol-3-ium chloride,186 p-aminobenzoic acid,187 3-aminoquinazolinones,188 d-gluco- and d-galactosamine.189 Employing a bifunctional o-phosphinoaniline in similar reactions resulted in bis-phosphine-imine ligand (193, R=2-R12PC6H4, R1=Ph, Tolo).190 Bis-phosphine bis-imine ligand (194) was obtained from two equivalents of 2-diphenylphosphinobenzaldehyde with a triazine-bonded bis-aniline.168
The following reduction of some ligands (193) with NaBH4 gave corresponding phosphine-containing amines (195).182,189 A series of chiral phosphine-amine-oxazoline ligands (195) was synthesized by the condensation of 2-di(organyl)phosphinobenzaldehyde with chiral aminooxazolines bearing various substituents in the oxazoline ring followed by in situ reduction with NaBH4.191 Reductive amination of a ferrocene-phosphinoaldehyde with methylamine in the presence of Ti(OiPr)4 as a Lewis acid and NaBH4 as a reducing agent formed aminomethylated ferrocenylphosphines (196, R2=NHMe).192
A reduction of borane-protected ferrocenyl-phosphino-aldehydes with borane BH3-SMe2 afforded the corresponding alcohols (196, R2=OH).178
Ferrocenylphosphine–oxazoline ligand (197, R=H) was obtained by the reaction of a lithiated ferrocenyloxazoline with 2-diphenylphosphinobenzaldehyde.193
A one-step polycondensation of tris(4-formylphenyl)phosphine and 2,5-dihydroxy-1,4-benzoquinone at 220 °C gave a hydroxyl- and phosphorus-rich porous phenolic resin (198) with Brunauer–Emmett–Teller (BET) surface area of 775 m2 g−1.194
2.5.5 Functionalization of carboxyl groups
The condensation reactions between alcohols or amines and phosphines bearing carboxylic groups in the presence of reagents DIC, DCC, EDC, BOP etc. and organic base (DMAP, DIPEA) or inorganic base (Cs2CO3) are commonly used for the synthesis of various ester- or amide-derivatives.
Condensation of 2-(diphenylphosphino)benzoic acid with 5-(dimethylamino)-N-(2-hydroxyethyl)-N-methylnaphthalene-1-sulfonamide in the presence of EDC and DMAP gives the dansyl dye-conjugated triaryl phosphine (199).195 Under the same or similar conditions the compounds (200),196 phosphinated polyester (201),195 2-(methacryloyloxy)ethyl 4-(diphenylphosphino)benzoate (202) (DIC, DMAP),197 the fluorescent phosphine (203) called “probe N”,198 bis-phosphine (204),199 chiral proline-phosphine (205) (DCC, DMAP),200 phosphine-amide (206),168 amidophosphines derived from chiral 1,2-diphenylethylenediamines and natural α-amino acids (207),201 and the chiral phosphine-amide (208), having a phosphafluorene fragment (HATU, Cs2CO3),97 were obtained. Coupling reactions between phosphines (189) (see Section 2.5.3) and a mono-Boc-protected guanidine in the presence of BOP and N-methyl morpholine gave ligands (209).18
Modification of different surfaces can be achieved through condensation reactions between phosphines bearing carboxylic groups and surfaces bearing amino groups.
1-{[3-(Diphenylphosphino)propanoyl]oxy}pyrrolidine-2,5-dione, generated from the corresponding 3-(diphenylphosphino)propionic acid and N-hydroxysuccinimide, was used in a reaction with MNPs@NH2 in DMF, catalysed by DMAP under sonication conditions and at room temperature to furnish nanoparticles (210).202
A silica-polyamine composite, in which poly(allylamine) (or poly(ethyleneimine)) chains were anchored on an amorphous silica gel surface, were modified with 4-diphenylphosphinobenzoic acid by covalent and ionic coupling to form hybrid materials (211) and (212) respectively.203
2.5.6 Functionalization of peripheral amino- or amido-groups
The aminophosphines are valuable platform precursors for the synthesis of other types of functionalized phosphine catalysts.
The approach based on the condensation reactions between phosphines containing peripheral amino groups and various carbon acids or their derivatives in the presence of reagents for peptide synthesis (DCC, EDC, BOP, HBTU etc.) and organic base (DMAP, DIPEA), is also commonly used for the synthesis of various amido-derivatives.
This methodology was used for the synthesis of phosphine-phosphonium ligands (213) (DIPEA and HBTU)204 and chiral β-amide-phosphines (214) and (215) (DIPEA and HOBt, EDCI).205 Ligands (215), bearing two diphenylphosphine groups (R1=PPh2) were obtained by sequential reactions including the hydrolysis of chiral sulfonamides to amines and their condensation with RCOCl in the presence of NEt3.206
Chiral phosphine–amide (216), having a phosphafluorene fragment, was obtained in moderate yield by the peptide coupling of the corresponding phosphine amine hydrochloride with an alanine derivative in the presence of HATU and inorganic base Cs2CO3 instead of DIPEA.97 Borane-protected chiral phosphine-amides (217) were prepared in high yields from corresponding phosphine-amine and 4-isocyanobenzoate in THF at room temperature.207 Subsequent reactions of an N-Boc-protected chiral phosphine-amine with TFA and 3,5-bis(trifluoromethyl)phenyl isothiocyanate gave the ligand (218).208 Carbamate-phosphine ligands (219) were prepared from (1R,2R)-2-amino-1-(diphenylphosphino)-cyclohexane and Boc2O or chloroformate in the presence of NEt3.209
The terminal hydrazide NH2 group of 1′-(diphenylphosphino)-1-(hydrazinylcarbonyl)ferrocene was functionalized with HNCO, EtNCO, PhNCO, Me2NC(O)Cl/pyridine, and Ac2O/NEt3 to give the corresponding N-functionalized derivatives (220).210
Lysozyme samples functionalized with cyclopropenethione or cyclopropenone (Lys-CpS or Lys-CpO, respectively) were treated with a phosphine-amine-biotin probe to give the stable amide or thioamide Lys-Phos products (221).211
Thiourea–phosphine and carbamate-phosphine ligands (222) were available through the reaction of pyrrolidine-phosphines with 3,5-di(trifluoromethylisothiocyanate) groups and Boc2O/Py.93 Methylation of the amino group was achieved (222, R=Me) through the treatment of the parent pyrrolidine-phosphine with methoxycarbonyl chloride and reduction of the corresponding carbamate with LiAlH4.94
The analogous reductive amination is a common approach to novel phosphine-amines. Reaction of 2-diphenylphosphino-1-aminoethane with 2-picolylaldehyde, followed by the reduction with DIBAL or NaBH4, resulted in ligands (223).212 A new tridentate phosphorus-aminopyridine ligand (224), with the cyclohexyl-fused spirobiindane backbone was prepared from compound (139) (see Section 2.4.1) via reductive amination using 3-methylpicolinaldehyde and NaBH(OAc)3.140
Functionalization of the amino-group in indole-phosphines (134) (see Section 2.4.1) was performed by metallation-halogen exchange reactions with BuLi and PPh2Cl or with NaH and MeI and afforded corresponding derivatives (225).137 The same approach was used for the synthesis of novel hybrid phosphorus ligands (226), from N-benzyl-2′-(diarylphosphino)-[1,1′-binaphthalen]-2-amine, BuLi and 4-chlorodinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine,213 and ligand (227) from tris-2-(3-methylindolyl)phosphine.214 Another tripodal, tetradentate tetraphosphine ligand (228) was obtained from the reaction of 2-(diisopropylphosphino)imidazole with PCl3 and an excess of triethylamine.215
Schiff-base condensation of 2,3-butanedione with the respective (3-aminopropyl)phosphine provided the bis(phosphine-imines) (229).216
Endo-1,2,3,4-tetrahydroquinolinylphosphanes (230) were regioselectively obtained by a multicomponent Povarov type [4+2]-cycloaddition reaction between 2-(diphenylphosphino)aniline, aldehydes and styrenes in the presence of two equivalents of BF3·Et2O in refluxing chloroform.217
The reaction of 1,2-bis(diphenylphosphinomethyl-amino)benzene with arylborates in the presence of triethyl- or trimethyl-amine results in bis-phosphine 1-aryl-2,1,3-diazaboroles (231).218 Two phosphine-functionalized pincer-type N-heterocyclic carbene analogues (232) were synthesized by the treatment of a bis(phosphine-amine) pro-ligand with two equivalents of KHMDS and the corresponding divalent metal salts [GeCl2(dioxane)] and anhydrous SnCl2.219
Boron-bridged trisimidazolylphosphines (233) were obtained by the condensation of tris(1H-imidazolyl)phosphine with different boranes, including chiral ones.220
Alkylation of PTA with a chloromethyl-substituted phosphahydrazone dendrimer results in a corresponding dendrimeric salt which is soluble in aqueous media, in particular in water/isopropanol mixtures.221
2.5.7 Functionalization of OH-, OR-, SH-groups
The ferrocenylphosphine alcohols (196, R2=OH) (see Section 2.5.4) reacted with diphenylphosphine in the presence of Me3SiCl and NaI (in excess) in dry acetonitrile to provide the respective diphosphines, which were isolated as the corresponding borane adducts (196, R2=PPh2) by BH3*SMe2 addition and column chromatography. Deprotection of phosphine groups in neat morpholine gave the free diphosphine.178
A ferrocenylphosphine – oxazoline ligand (197, R=H) (see Section 2.5.4) reacted with iodomethane and iodoethane in the presence of KH to give the corresponding ethers (197, R=Me, Et).193
A series of novel and easily accessed ferrocene-based amino-phosphine-sulfonamide ligands (234) was obtained from ferrocene-based acetate and different amino sulfonamides.222,223 Nucleophilic substitution of an N-(p-hydroxyphenyl)-substituted pyrrole with a ferrocenylphosphine containing a peripheral acetoxy-group, in the presence of an equimolar quantity of In(OTf)3, afforded bis-ferrocenylphosphine (235).224 Deprotection of a tetrahydro-2H-pyranoxy group in a phosphinoether by hydrochloric acid gave phosphinophenols (236), bearing substituents with different steric bulk.55
A cyclophosphazene-based diphenylphosphine ligand (237) was obtained from (4-hydroxyphenyl)diphenylphosphine and a dichlorocyclophosphazene [N3P3Cl2(O2C12H8)2] in the presence of Cs2CO3.225
Subsequent reactions of borane-protected phosphinophenols (60) (see Section 2.1) with DABCO, PCl3 and (R,R)-Taddol resulted in chiral phosphine–phosphite ligands (238).76
6-(Diphenylphosphino)pyridine-2,5-diol (175, RR′H) was involved in esterification reactions with R- and S-phenylpropionic acid, S-Naproxen, and S-Ibuprofen to give the ligands (239).19 Cyclopropenethiones (CpS) reacted readily with 2-diphenylphosphinophenol or 1-hydroxy-2-diphenylphosphinocyclohexane to provide thiocarbonyl adducts (240). It should be mentioned that the reaction proceeded ∼300-fold faster than the analogous cyclopropenone phosphine ligation. Analogous thiol-substitiuted phosphines reacted with CpS sluggishly to give a mixture of products.211
Reaction of 1,1-dimethyl-2-(di-tert-butylphosphino)ethanol with scandium-mixed alkyl/diaryloxide complex Sc[CH2SiMe3][O-2,6-tBu2C6H3]2[THF] gave a frustrated Lewis pair (241) as a colorless solid in 72% yield.226 Spiro-phosphine-phosphinoxide (242) (S,S,S-SPIRAP(O)) was obtained by Pd-catalysed substitution of triflate group in the parent spiro-phosphine by diphenylphosphine oxide in the presence of DPPB and DIPEA. Reduction of the diphenylphosphine oxide group with HSiCl3 led to bis-phosphine (118, X=PPh2) (see Section 2.4.1).122
Cyclophanes (243) and (244) were isolated from the base-promoted macrocyclization of tris(2-mercaptophenyl)phosphine and tris(3-bromopropyl)methane as in,in- and in,out-isomers of (243), and a dimeric in,out,in,out-isomer of (244).227
2.5.8 Miscellaneous methods of modification of phosphines
The novel diphosphine-phosphine oxide ligand (245) was easily prepared by hydrolysis of the corresponding chlorophosphine.228 The phosphine-tethered NHC (246), generated in situ from the corresponding N-(diorganylphosphinoalkyl)imidazolium tetraphenylborates, reacted with the triphosphenium cation [dppeP]+ to form compound (247).229 The tetramerization reactions of 4-(diphenylphosphino)-5-chlorophthalonitrile or 4,5-bis(diphenylphosphino)phthalonitrile in the presence of DBU in ethoxyethanol led to the formation of phthalocyanine ligands (248). Compounds (248) were slightly unstable, and slowly oxidized in air to produce the corresponding phosphine oxide derivatives. The tetramerization of 4,5-bis(diphenylphosphino)-3,6-difluorophthalonitrile proceeded only with magnesium butoxide in butan-1-ol at 120 °C for 5 h.101
Treatment of bis(o-diisopropylphosphinophenyl)chlorosilane with (2-(isopropylthio)-[1,1′-biphenyl]-3-yl)lithium afforded the ligand (249).230 (Diphenylphosphinomethyl)(amino)dimethylsilanes (250) were obtained analogously from ((chlorodimethylsilyl)methyl)diphenylphosphine and lithium (diphenylphosphanyl)(R)amide or primary alkyl amine in the presence of NEt3.231
The addition of 1-diphenylphosphino-3-trimethoxysilyl-propane to Ti- and Zr-SBA-15 metalated materials dispersed in anhydrous toluene under inert atmosphere resulted in the formation of Ti-PPh2-SBA-15 and Zr-PPh2-SBA-15, solid ambiphilic systems (251).232
The material ABIL-HT-A (252) was obtained by the grafting of iminophosphine ligand [o-Ph2PC6H4CHN(CH2)3Si(OMe)3] onto the surface of a calcinated hydrotalcite material.233 The condensation of [N,N-bis((diphenylphosphino)methyl)-3-(triethoxysilyl)prop-1-yl]amine with MCM-41, followed by the silylation with Me3SiCl, gave a bidentate phosphino-functionalized material MCM-41-2P (253).234
2-(Diphenylphosphino)-benzoate was converted into axially chiral phosphinobiarylsilane (254) with excellent atroposelectivity, by using a chiral 1,5-bifunctional organomagnesium alkoxide reagent, in 63% yield with an e.r. value of 95 : 5 (Scheme 2).235
2.6 Miscellaneous methods of preparing phosphines
Transition metal-catalyzed C–P(iii) bond formation has become an effective and widely-used synthetic approach to various aryl- and heteroaryl-phosphines. In 2018 several new synthetic protocols based on C–P(iii) cross-coupling reactions have been developed.236–239 Most of the catalysts are based on Pd(ii)41,122,236,240,241 and Pd(0)190,242–244 complexes and salts, which may be used both in the presence and sometimes in the absence of additional ligands and basic reagents. As a rule, the phosphorus sources are secondary phosphines.41,122,190,236,238,240–245 Pd-catalysed C–P(iii) cross-coupling was successfully used for the synthesis of a wide variety of phosphines including bis(2-methoxyphenyl)(2,4-dibromophenyl)phosphine (255) as the precursor for diphosphines (25) (see Section 2.1),41 new functionalized cage 2,4,6-trioxa-8-phosphaadamantanes (256) as ligands for Pd-catalyzed aza-Heck cyclization reactions,242 a new mechanoluminescent benzophenone (257) bearing diphenylamino and diphenylphosphino groups which displayed tunable emission colours,243 a new phosphine precursor (258) for the corresponding aggregation-induced emission (AIE)-active photochromic phosphine oxide.244 New diphosphine ligand (118, X=PPh2) (see Section 2.4.1) on the spiroketal-based C2-symmetric chiral scaffold,122 2-(diphenylphosphino)[6]helicene isolated as the corresponding borane complex (259),241 2-(di-o-tolylphosphino)aniline and 2-(di-o-tolylphosphino)benzaldehyde as starting reagents for the synthesis of diphosphine-tethered imine ligands (193, R=2-R22PC6H3)190 have also been prepared by Pd-catalyzed phosphination of the corresponding aryl precursors. Pd-catalyzed coupling of dicyclohexyl- or diphenyl-phosphine with carbazole aryl halides led to new phosphine ligands (260) containing carbazole motifs which were used for the efficient Pd-catalyzed alkoxycarbonylation of alkynes.240 A specially designed chiral palladium catalyst [Pd-{(S,S)-Me-FerroLANE}(m-phenylurea)I] was successfully used in a highly efficient and accelerated asymmetric synthesis of P-stereogenic urea-containing phosphines (261) via C–P coupling reactions between asymmetric secondary phosphines and various iodophenylureas. A small library of 18 chiral phosphines (261) was obtained with moderate to very good ee's.236
Rh(i)-catalyzed C–P cross-coupling reactions between aryl iodides and acyldiarylphosphines were disclosed for a straightforward synthesis of various triarylphosphines. The starting acylphosphines were employed as both the phosphorus source and the ligand to the Rh(i) catalyst.237
A phenanthroline-functionalized MCM-41-supported copper(i) iodide complex in the presence of Cs2CO3 appeared to be an effective catalyst of the heterogeneous cross-coupling of various aryl- and heteroaryl-iodides with diphenyl phosphine. This protocol could tolerate a wide range of functional groups.238 Another novel protocol of copper-catalyzed C–P(iii) cross-coupling between different secondary phosphines and (hetero)aryl bromides included the use of a CuI/2,6-(N-methylaminomethyl)pyridine/KOBut catalytic system and led to a variety of tertiary phosphines.239 Tandem alkylation/arylation of primary phosphines with 5-bromo-6-chloromethylacenaphthene in the presence of the base NaOSiMe3 and a commercially available catalyst Cu(IPr)Cl (IPr – N,N-bis(2,6-diisopropylphenyl)imidazolidene) led to a series of new PyraPhos phosphines (262) which were isolated as the corresponding borane adducts. The mechanism and intermediates of these reactions have been studied.246 Copper iodide – catalyzed coupling of phosphorus trichloride and 4-methylcarboxyphenylacetylene led to phosphine (263, R=Me) which was hydrolyzed to tris[(4-carboxyphenyl)ethynyl]phosphine (263, R=H). This new ligand was used for the synthesis of a permanently porous Mn(ii)-based MOF which showed a highly selective acetylene sorption.247
A new example of metal-free C–P coupling was the substitution of electron-rich 1,3-dimethoxybenzene with in situ-generated diphenylphosphinotriflate under inert conditions to give (2,4-dimethoxyphenyl)diphenylphosphine.248
Mannich-like condensation between hydroxyalkylphosphines and amines is an effective approach for the synthesis of various α-aminoalkylphosphines. Hydroxyalkylphosphines are usually generated in situ from P–H phosphines and aldehydes (mainly formaldehyde249–254 ) or from the corresponding hydroxymethylphosphonium salts with bases,192,255,256 so the condensations are usually performed as one-pot processes or even directly in three-component phosphine–aldehyde–amine mixtures. The phosphines synthesized on the basis of this approach include new representatives of nitrogen-centered triphosphine ligands (264) which were studied in Rh-based catalytic systems for the hydroformylation of inactivated alkenes,255 ferrocene-based diphosphine (265) which acted as unusual trans-spanning ligand towards Pd(ii) ions,192 phosphine-peptide conjugate Ph2P-CH2-Sar-Gly-OH256 and several new 1,5-diaza-3,7-diphosphacyclooctanes (266).249–251 Heterocycles (266, R1=C6H4CF3-4) containing electron-withdrawing substituents on phosphorus atoms were studied as new ligands for electrocatalytic H2 production,251 and diphosphine (266, R1=Ph, R2=Mes) showed a moderate activity in Ru-catalyzed cyclization of alkynyl amines to indoles.249 Mannich-type condensation was successfully used for the synthesis of phosphine-peptide conjugates as the basis of cytotoxic copper(i) complexes.256 One-pot Mannich type condensations of 1,3-bis(arylphosphino)propanes, formaldehyde and various primary amines proceeded as stereoselective covalent self-assembly processes and led to a series of new representatives of RPSPSpRP-isomers of 1,9-diaza-3,7,11,15-tetraphosphacyclohexadecanes (267) with alkyl, arylalkyl, heteroarylalkyl and chiral substituents on nitrogen atoms,252,254 including the first 16-membered aminomethylphosphine corand (267, R1=Py-2, R2=Pri) with pyridyl groups on phosphorus atoms.253 Corands (267) with chiral substituents on nitrogen atoms appeared to be convenient objects for the investigation of their transformations in solutions caused by the lability of P–CH2–N fragments, namely the unprecendented intermolecular exchange of endocyclic amino fragments observed for these macrocycles and the mechanism of this process was studied and discussed.254
The use of covalent self-assembly for the synthesis of P(iii)-containing macrocycles, including various macrocyclic phosphines, has been summarized.257
The substitution of a dimethylamino group of dimethyl(1-ferrocenylethyl)amines bearing dicyclohexylphosphino- or various phosphinoyl substituents in 2-position of the ferrocene fragment with secondary phosphines in acetic acid medium, led to new optically active Josiphos-type diphosphine ligands (268)258 and JosPOphos-type ligands (269) respectively.259 Both types of new ligands have been employed in the asymmetric catalysis of different reactions.258,259 The similar phosphination of the 1,3-bis(hydroxymethyl)(trifluoromethyl)tetramethylruthenocene gave a ruthenocene-based pincer ligand (270).260 The substitution of chloropyridinium salts with secondary phosphines under microwave irradiation and the subsequent treatment with NaSbF6 led to a family of new N-arylpyridiniophosphines (271). Their Au(i) complexes demonstrated high catalytic activity in two mechanistically differentiated cycloisomerizations.261
A diphosphination of arynes generated in situ from stable precursors, namely 2-(trimethylsilyl)aryl triflates, with tetraaryldiphosphines in the presence of fluoride-(Bu4NSiPh3F2) or carbonate-based (Cs2CO3/18-crown-6) activators led to various 1,2-bis(diarylphosphino)benzene derivatives, but most of them were sulfurized and isolated as corresponding bis(phosphine) disulfides. Only 1,2-bis(diphenylphosphino)benzene was isolated directly after diphosphination.150 A new bulky lithium diadamantylamide base-promoted insertion of arynes into Si–P(iii) bonds led to a series of 2-silylarylphosphines (272).262
Experimental and quantum-chemical studies of the triple nucleophilic substitution of halogen atoms in 2-chloro- and 2-bromopyridines with P-centered nucleophiles generated in the system red phosphorus (Pn)/KOH/DMSO to afford tri(2-pyridyl)phosphine have been carried out.263 Tris(4-methylpyridin-2-yl)phosphine was also obtained by this simple and straightforward one-pot method,264 whereas tris(m-tolyl)phosphine was synthesized from red phosphorus and 3-fluorotoluene in the superbasic medium KOH/hexamethylphosphoramide.265 Reactions of white phosphorus (P4) with fluorinated alkyl iodides I(CH2)mRfn (Rfn=CF3(CF2)n−1) and SmI2, or with fluorinated aryl iodides and SmBr2 or SmCl2, afforded the corresponding trialkylphosphines P((CH2)mRfn)3 (m,n=2,8; 2,10; 3,6; 3,8; 4,8) or the triarylphosphines P(C6H4(C6F13)-3)3, P(C6H4(C6F13)-4)3 and P(C6H4(C6F13)2-3,5)3. These transformations involve non-chain radical additions to P4.266
A novel 1,3,5-diazaphosphorinane (273), which could be used as both a co-curing agent and a flame-retarding agent for epoxy resins (EPs), was synthesized by the decomposition of di[tetrakis(N-(4-hydroxyphenyl)aminomethyl)phosphonium] sulfate with trimethylamine.267
An improved synthetic protocol for the optically active P–NH–NH–P ligand (274) included the basic deprotonation of a phosphonium dimer, namely 1,1,4,4-tetraphenyl-2,6-dihydroxy-1,4-diphosphoniacyclohexane dibromide, to release diphenylphosphinoacetaldehyde, which underwent an iron-templated condensation reaction with (S,S)-1,2-diphenylethylenediamine to produce the iron(ii) complex of the correponding bis(phosphine)-diimine ligand. The final reduction of this complex with LiAlH4 released diphosphine (274) which was used in Mn-based catalytic systems for the asymmetric transfer hydrogenation.268
A reaction of phenylphosphine with 2-butyne in the presence of CpFe(CO)2Me as a phosphinidene-generating catalyst gave 2,3,4,5-tetramethyl-1-phenylphosphole (275).269
AlCl3-promoted 1,2-migration of the diphenylphosphino group of 1-diphenylphosphinopyrene led to 2-diphenylphosphinopyrene (276) in low yield (5%).270
The interaction of 4,6-di(tert-butyl)-1,3,2-diazaphosphinine with two equivalents of diphenyl(propyn-1-yl)phosphine led to the formation of two isomeric bis(diphenylphosphino)-dimethylphosphinines (277) and (278), which were successfully separated.271
Steady-state photolysis of triarylphosphines under an argon atmosphere in a solvent of the structure CH3X (X=CN, C(O)OEt, C(O)Me) was acknowledged as a convenient method to prepare functionalized phosphines Ar2PCH2X (Ar=Tolo, Tolp, Mes; X=C(O)OEt, C(O)Me) in significant amount.272,273
Several new polymers containing phosphine centers have been described. RAFT copolymerization of diphenylphosphinostyrene and 1,1,2,2-tetrahydroperfluorodecyl acrylate led to gradient copolymers which were successfully used to extract palladium from commercial Pd/Al2O3-supported catalysts in supercritical CO2.274 A sequential RAFT polymerization of dimesitylphosphinostyrene and styrene gave a new Lewis basic block copolymer. This polymer was used in the combination with a boron-containing Lewis acidic block-copolymer for the design of macromolecular FLPs as a basis of CO2-responsive systems.13 AIBN-catalyzed copolymerization of phosphino-substituted monomer (202) (see Section 2.5.5) and methyl methacrylate led to a polymer bearing surface diphenylphosphino groups which was employed for metal post-loading and for surface photoligation chemistry.197 The polymerization of the borane-protected phosphino-substituted isocyanide (217) (see Section 2.5.6) in the presence of alkyne-palladium catalysts gave helical poly(phenylisocyanides) bearing phosphine pendants which were used as organocatalysts of asymmetric cross-Rauhut-Currier reactions.207 AIBN-catalyzed polymerizations of vinyl-functionalized Xantphos-type diphosphine and dppm-type diphosphine (3) (see Section 2.1) led to new porous organic ligands which acted as both ligands and supports to prepare efficient heterogeneous Ni- and Pd-based catalysts for the hydrosilylation of alkynes and for the synthesis of thiazoles, respectively.12,275 New threefold phosphine cross-linked polymer-immobilized ionic liquids (PIILs) (279) were prepared by AIBN-initiated radical copolymerization of tris(4-vinylphenyl)phosphine, styrene and the corresponding N-(4-vinylbenzyl)imidazolium monomers. These PIILs were able to stabilize palladium nanoparticles for the preparation of various effective catalytic systems including ones for reactions in aqueous media.276
3 Reactivity of phosphines
3.1 The formation of phosphonium and related compounds by nucleophilic attack at carbon and other atoms
The classical formation of phosphonium compounds by the nucleophilic attack of phosphorus at a carbon atom of organic electrophiles (as a rule organyl halides, triflates, sulfonates or related compounds with labile leaving groups) has continued to attract attention. Sometimes these reactions are followed by the anion exchange step. This approach was used for the synthesis of tris(4-methylthiophenyl)methylphosphonium iodide,277 polymerisable phosphonium salts [R3P–CH2–C6H4–CHCH2–p]+Cl− (R=Ph, Bun, (CH2)3OH),278 [Ph3P–CH2–C6H4–CHCH2–p]+ [B(C6H3(CF3)2-3,5)4]− 279 containing 4-vinylbenzyl substituents and 4-vinylbenzylated phosphonium derivatives of phosphines (108) (see Section 2.3)113 as monomers for the synthesis of various phosphonium-containing copolymers,113,278,279 air/water-stable P-trifluoromethyl-substituted salts [MeP(CF3)Ph2]+ An− (An=OTf, BArF)280 and water/base-tolerant P3-trimethylated tricationic salts (280) and (281)281 as new convenient Lewis acid catalysts,280,281 phosphonium salts (282) with (benzo)thiazolyl-thienyl fragment where weak hypervalent bonding interactions between nitrogen and phosphorus centers were observed.282 The quaternization of tertiary phosphines with appropriate reagents (and the subsequent anion exchange if it was necessary) led to alkyne-terminated phosphonium salts [HCC–(CH2)n-PAr3]+ Hal− (Ar=C6H2(OMe)3-2,4,6; n=1, 4; Hal=Cl, Br) used for the preparation of anion-conductive copolymers,283 (2-methoxyethyl)trialkylphosphonium bis(trifluoromethylsulfonyl)imides as the precursors of the glycol-grafted ionic liquids,284 4-(bromomethyl)benzylated phosphonium salts [BrCH2–C6H4–CH2PAr3]+Br− used as intermediate reagents for the synthesis of phosphonium-functionalized aza-crown-based chelators,285 phosphonium salts (283) and (284), derived from 4-diphenylphosphinobenzoic acid, as the precursors of amphiphilic phosphine oxides,286 antifungal inulin derivatives (285) with quaternary phosphonium pendant groups,287 a series of new substituted (anthracenylmethyl)diphenylphosphoniomethyl thioesters (286) used as reagents for a visible-light-triggered traceless Staudinger ligation,288 ferrocene derivatives (287) with a peripheral phosphonium group as the precursors of 99mTc-labeled phosphonium salts and similar rhenium-containing phosphonium salts (288).289 The reactions of tertiary phosphines with but-3-en-1-yl- and n-octyl organylsulfonates gave a series of new flame-retardant phosphonium sulfonates [R13PR2]+ R3SO3− (R1=Ph, Bun; R2=–(CH2)2CHCH2, C8H37; R3=Et, Tolp).290 The interaction of triphenylphosphine with 1,3-propane sultone, followed by treatment with trinitromethane, led to the unique nanosized molten salt [Ph3P(CH2)3SO3H]+ [C(NO2)3]−,291 whereas the treatment of Xantphos with one equivalent of this sultone gave a new phosphino-substituted zwitter-ionic ligand (289), which was applied in Au-catalyzed hydration of alkynes.292
Phenyl- and anthracenyl-(ferrocenyl)methanol reacted with triphenylphosphine in the presence of triflic acid to give corresponding [aryl(ferrocenyl)methyl]triphenylphosphonium triflates.293 Several new 1-(N-acylamino)alkyltriarylphosphonium salts derived from tris(m-chlorophenyl)- or tris[p-(trifluoromethyl)phenyl]phosphine were obtained by the treatment of N-(1-methoxyalkyl)amides with triaryl phosphines in the presence of HBF4·Et2O.294 A series of novel polythiophene-based cationic conjugated polyelectrolytes with phosphonium and ammonium pendants were prepared by a simple quaternization of poly[3-(6-bromohexyl)thiophene] with tributylphosphine or an amine, including polyelectrolytes containing both types of ionic pendant groups.295 The treatment of poly(sulfone-methylene) polymers with pendant chloromethyl groups with tris(2,4,6-trimethoxyphenyl)phosphine gave phosphonium-functionalized polymers which were combined with graphite nanoplatelets for the creation of composite chemically modified electrodes.296 The same phosphine was used for the introduction of pendant phosphonium groups into multiblock copoly(arylene ether) polymers with long bromoalkyl side chains. Bromide counter ions were exchanged to hydroxide ions by soaking of the polymers in a NaOH solution and the resulted polymers were tested in the preparation of anion conducting membranes.297 The interaction of polymeric sulfonic acids with trialkylphosphines led to poly(ionic liquids) with tertiary phosphonium counter ions [HPR3]+ (R=Bun, C8H17, Cy) for the construction of proton conducting membranes.298
Copper(i) tetrafluoroborate-mediated C–H functionalization of 1-diphenylphosphinopyrene and 2-diphenylphosphinopyrene (276) (see Section 2.6) with diphenylacetylene led to pyrene-fused cyclic phosphonium salts (290) and (291).270
The interaction of 6-bromo-1,2-naphthoquinone with tertiary phosphines led to new tetraarylphosphonium zwitter-ions (292), which were converted to the corresponding phosphonium salts by the treatment with trifluoroacetic acid.299 A similar betaine was a minor product of the reaction between 3-bromo-1,2-naphthoquinone and tributylphosphine, whereas the major product was a complex of 3,3′,4,4′-tetrahydroxy-1,1′-binaphthyl with tributylphosphine oxide.300
An unusual C3-symmetric zwitter-ion (293, R=H, X=Cl) was obtained by the interaction of tris(2-hydroxy-3,5-di(tert-butyl)phenyl)phosphine with AlCl3. The treatment of this compound with MeLi led to the lithium salt of Al-methylated deprotonated anionic form of (293), and the subsequent reaction with methyl iodide or triflate gave Al,P-dimethylated zwitter-ion (293, R=Me, X=Me).301
Several new triarylphosphonium salts [Ph3PC6H4X-4]+ Hal− (X=NH2, OH, Cl, CH3, CH2OH; Hal=Cl, Br) were synthesized by the interaction of triphenylphosphine and the corresponding aryl halide in the presence of Ni(PPh3)3 and tested as iron corrosion inhibitors.302 A Pd(0)-catalyzed reaction of diphenyl(trifluoromethyl)phosphine with phenyl triflate led to triphenyl(trifluoromethyl)phosphonium triflate.280 The peri-iodo naphthyl phosphine reacted with CuI to give the unusual peri-bridged phosphonio-naphthalene (294).303
The interaction of substituted N-heteroaryl triflates, generated in situ from the corresponding heterocycle and Tf2O, with triphenylphosphine in the presence of trimethylamine or DBU led to a wide variety of pyridyl-, quinolyl-, pyrimidinyl- and quinoxalinyltriphenylphosphonium triflates which could serve as coupling partners with seven classes of aromatic heteronucleophiles due to the replication of the behavior of corresponding organometallic intermediates.304 Inherent factors that control a site-selectivity of these reactions with the participation of substrates containing several N-heteroaryl fragments have been studied along with mechanistically driven approaches for the switching of the selectivity (in particular by the creation of acylation-blocking conditions in the presence of AcCl and AgOTf) so that the C–+PPh3 group can be predictably installed at other positions in the polyazine system.305
The reactions of dibromonaphthalenediimides with tertiary phosphines were performed in a solvent-free manner by heating of the reaction mixture up to the melting point of the phosphines in the presence of a triethylamine base to give a wide series of ambient-stable diphosphonium substituted naphthalenediimide radical ions (295) with excellent yields.306
Reaction of the Ruppert–Prakash reagent Me3SiCF3 with aromatic aldehydes and methyl(aryl)ketones, in the presence of triphenylphosphine, lithium iodide and lithium tetrafluoroborate, selectively furnished gem-difluorinated phosphonium salts (296) along with 2,2-difluorovinylarenes; a simple alkaline hydrolysis of these compound mixtures resulted in various 2,2-difluoro-1-arylethanols and could be regarded as method for the difluoromethylation of aromatic aldehydes.307
A labile α-ferrocenylvinyl cation generated in situ by the protonation of ethynylferrocene with Nafion in supercritical CO2 reacted with triphenylphosphine or 1,2-diphenylphosphinoethane with the formation of (1-ferrocenylethenyl)triphenylphosphonium tetrafluoroborate or bis-phosphonium salt (297) respectively.308
Highly electrophilic 1,1-bis(trifluoromethylsulfonyl)ethylene, generated in situ from zwitter-ionic 1,1-bis(trifluoromethylsulfonyl)-2-(2′-fluoropyridinio)ethane, reacted with a range of tertiary phosphines to form phosphorus 1,3-carbabetaines (298) in which the carbanion moiety was significantly stabilized by two trifluoromethylsulfonyl groups.309
4-Dimethylaminophenyltropilium tetrafluoroborate formed relatively unstable phosphonium adduct (299) with triphenylphosphine.310 1-tert-Butyl-3,3-diphenyl-3H-indazolium tetrafluoroborate also formed Lewis acid/base adducts (300) with trialkylphosphines.311 A unique set of arylazophosphonium salts [Ar-NN-PR3]+ BF4− (Ar=C6H4X-4; X=H, NO2, Br, Cl, OMe, NMe2; R=Ph, Mes, But), of tunable colours, was obtained by the interaction of aryldiazonium salts with tertiary phosphines.312,313 The analogous reactions with two equivalents of triphenylphosphine or with 1,2-bis(diphenylphosphino)ethane led to acyclic or cyclic bis-phosphonium salts (301) and (302) respectively.313
Ferrocenium salts [(C5H5)2Fe]X (X=BF4, PF6) reacted with tertiary phosphines in dichloromethane at room temperature to form a mixture of the corresponding ferrocenylphosphonium salts (303), ferrocene and phosphonium salts [HPR3]+ X− (R=Alk, Ph; X=BF4, PF6). The same reaction was also carried out in an electrochemical cell.314
Triarylphosphines reacted with elemental bromine to give triarylbromophosphonium bromides and larger polybromides, with an excess of bromine. The influence of the stepwise fluorination of the cation on the formed polybromide anions was investigated.315
Polymeric phosphine-containing network (110) (see Section 2.3) was swelled in CH2Cl2 solutions of SbClPh2 and TMSOTf in different stoichiometric ratios to give new stibinophosphonium and stibino-bis(phosphonium) functionalized polynuclear networks.115
The chemistry of P/E (E=B, Al, Sc) ‘Frustrated Lewis Pair’ (FLP) systems has continued to generate interest. The treatment of P/B FLPs tBu2PCH2BPh2 and o-Ph2P(C6H4)BCat (Cat=catechol) with oxiranes resulted in epoxide ring-opening to yield the six- and seven-membered zwitter-ionic heterocycles (304) and (305), respectively.316 A dimethylxanthene-based phosphine/borane FLP reacted with (4-methoxyphenyl)acetylene with the formation of the 1,2-addition product (306), whereas in the case of phenylacetylene this FLP was shown to effect reversible C-H activation, cleaving phenylacetylene to give an equilibrium mixture of the free FLP and phosphonium acetylide in CD2Cl2 solution at room temperature. The last compound underwent a slow transformation due to the presence of the free alkyne in solution with the formation of a multiinsertion zwitter-ionic product (307), in which three molecules of phenylacetylene have been assimilated by one molecule of the starting FLP.317
The reaction of a borane-appended analogue of 1,1′-bis(phosphino)ferrocene, namely 1-(diphenylphosphino)-1′-[(2″-diphenylborylphenyl)(tert-butyl)phosphino]-ferrocene, with two equivalents of BF3(OEt2) afforded compound (308) as a single diastereomer, presumably with release of PhBF2. Formation of (308) likely proceeds through initial exchange of a B-phenyl substituent for fluoride followed by abstraction of the newly installed fluoro substituent by a second equivalent of BF3. Compound (308) may be described either as a boronium cation stabilized by intramolecular bisphosphine coordination or as a phosphine-coordinated borylphosphonium cation.318
The Sc/P FLP (241) (see Section 2.5.7) and its previously described P-phenyl substituted analogue (241, R=Ph) displayed diverse FLP reactivity toward a variety of small molecules. Reactions with organic carbonyl compounds through selective 1,2- (with phenylisocyanate) or 1,4-addition reactions (with enones and ynones) formed various zwitter-ionic metallacycles. The addition of dimethyl acetylenedicarboxylate unexpectedly resulted in the formation of unique Sc/P double 1,4-addition product (309). Notably, the reaction with phenyl(cyclo-propyl) ketone afforded a unique 10-membered zwitter-ionic metallacycle (310) as a result of a formal Sc/P 1,5-addition. 1,1-Addition of trimethylsilyldiazomethane to (241, R=Ph) led to a six-membered scandium phosphazine complex. With the aid of an internal phosphine nucleophile, the neutral scandium Lewis acid of (241, R=Ph) abstracted the halide from an organic bromide to give the acyclic zwitter-ion Br(ArO)2Sc−–O–CMe2–CH2–+PPh2Bn.226
Triarylphosphines and group 13 Lewis acids (LA) were surveyed as FLP components for the monodefluorination of gem-difluoromethyl groups of various substrates which led to the formation of α-fluoroalkylphosphonium salts [(RCHF)PAr3]+ [LA-F]− (R=Ar, Alk, Het; Ar=Tolo, Ph, Mes; LA=B(C6F5)3, Al(C6F5)3·C7H8, AlBr3, BF3. (OEt2)). These salts were used in Wittig reaction protocols to generate a variety of monofluoroalkenes in moderate to high yields.319 The chemistry of a range of FLPs based on 1,1′-bis(di(pentafluorophenyl)boryl)ferrocene and various tertiary phosphines (along with C- and N-centered Lewis bases) in the presence of H2O, NH3, CO2 and cyclohexylisocyanate has been investigated.320
The use of a P/B FLP strategy allowed interception of the 1,3-addition products of mesityl nitrile-N-oxide (an effective oxidizing reagent for phosphines), and betaines (311) and (312) were isolated and studied.321
3.2 Oxidation of phosphorus atoms
3.2.1 Formation of phosphine oxides, sulfides and selenides
Oxidation of phosphines with elemental S8, grey selenium, or H2O2 led to the formation of their P=S, P=Se, and P=O derivatives. These reactions were used for the synthesis of sulfides, selenides and oxides of cyclic propargylic monophosphadiynes (313) and diphosphadiynes.35 Tertiary phosphine oxides, sulfides and selenides (314) with a variety of methylthiophenyl substituents277 and selenides of triptycene-type borate- and silyl-phosphines (315),180 tris(pyridyl)phosphines (316),264 phosphinoferrocene sulfonate (317)153 and diphenylphosphinomethylthioanilide (318)322 were also obtained by the usual methods, namely by the interaction of corresponding phosphines with hydrogen peroxide, elemental sulfur or selenium in the appropriate solvent (toluene, CHCl3, CH2Cl2). The mechanochemical technique of ball milling has been applied to the solventless and eco-friendly synthesis of chalcogenides (sulfides and selenides) of a variety of tertiary phosphines and bisphosphines including the compounds bearing amino groups and different azaaryl substituents.323 A number of Se-derivatives of diphenyphosphino ferrocenes (319) were obtained by reaction of tertiary bisphosphines with KSeCN in the presence or in absence of DABCO.178
The interaction of P/Sc compound (241, R=Ph) with elemental sulfur led to the formation of corresponding phosphine sulfide (320) in 88% yield; (320) had a six-membered heterocyclic structure with the soft donor sulfur bonding to scandium center.226
The oxidation of phosphine (61) and bisphosphine (53) bearing three or four neighbouring phosphine sulphide groups (see Section 2.1) with a 30% aqueous solution of H2O2 gave corresponding phosphine oxides (321) and (322).69
Tert-butyl peroxide in the presence of DABCO was used to obtain the phospholyloxide (323, X=O) from the borane-protected phosphole (90) (see Section 2.2) in 68% yield. Reactions of borane-protected dibenzophospholyl amino esters (90) with sulfur/DABCO mixture under anaerobic conditions gave corresponding sulfides (323, X=S) in 64–90% yields.97
Phthalocyanines (248) (see Section 2.5.8) bearing four or eight phosphino groups which are directly linked to macrocycle periphery, have been oxidized with mCPBA in chloroform or with elemental sulfur (in chloroform or toluene) to give corresponding chalcogenides (324).101
Corresponding phosphine oxides were formed as a result of H2O2-oxidation of phosphinohelicene (259) (see Section 2.6),241 N-[2-(diphenylphosphino)benzylidene]-2-(pyridine-2′-yl)ethylamine (193, Ar=Ph, R=(CH)2Py-2) (see Section 2.5.4)183 bis(m-anisyl)- and bis(p-anisyl)phenylphosphines.22
The mono-oxide of bis(di-tert-butylphosphino)methane (325),324 E- and Z-isomeric oxides of E-enamine-functionalized 1,3,5-triaza-7-phosphaadamantanes (326) and (327),325 the oxide of phosphine-peptide (SarGly) conjugate (328),256 thiazolyl- and benzothiazolyl-3-thienylphosphine oxides (329)282 and 1-oxo-1-pyridylphospholanes (330)326 were also obtained analogously.
The oxidation of bisphosphine (41) (see Section 2.1) allowed the design of bis(phosphine oxide) DPOBBPE (331) as a host material for OLEDs which worked efficiently in a blue fluorescent device due to good solubility, high photoluminescence quantum yield and good film properties.57
Non-photochromic phosphine (258) (TrPEP) (see Section 2.6) was oxidized to the corresponding photochromic phosphine-oxide (332) (TrPEPO), the oxidation of the phosphine turning-on the fluorescence. This feature can be used for accurate H2O2 sensing by phosphines.244 The oxidation of donor–acceptor-appended phosphines (181) (see Section 2.5.3) led to phosphine oxides (333); these phosphines were able to function as time-resolved turn-on fluorescence sensors for H2O2.31
H2O2-oxidation of bisphosphine with acenaphthene-5,6-diyl moiety led to the corresponding bis(phosphine oxide) (334). Its monophosphoryl analogue was unexpectedly obtained after the decomposition of a Co complex of the initial phosphine, accompanied by aerobic oxidation of one molecule of ligand.327
The high reactivity of tertiary phosphines against oxygen has been used for the decomposition of H2O2 by triphenylphosphine, and this may be used to remove H2O2 from proton-exchange membranes.328
The photochemical co-oxidation of triphenylphosphine, tris(o-tolyl)phosphine, trimesitylphosphine in the presence of tris(p-bromophenyl)amine under irradiation and a dry oxygen stream was mechanistically studied and different paths of co-oxidation mechanism were described.329
Triphenylphosphine reacted with anhydrous dinitrogen trioxide, N2O3, giving the corresponding phosphine oxide (when pure toluene was used as solvent) or a hydrogen bonded adduct, HNO3*(O)PPh3 between the oxide and nitric acid.330
3.2.2 Staudinger-related reactions
Staudinger-related reactions between azides and phosphines, with the formation of highly reactive iminophosphorane ylides, are important in organic chemistry due to their chemoselectivity, high efficiency, and mild reaction conditions. Reactions between iminophosphoranes and aldehydes have become a powerful tool in small molecule organic synthesis strategies due to the absence of metal catalysts, mild reaction conditions, and relatively high yields of the imine products. Iminophosphoranes can also react with other carbonyl compounds, such as ketones, esters, thioesters, amides, and anhydrides, providing an effective method for construction of C–N bonds, including CN double bonds.
A very fast interaction of a dansyl-dye conjugated triaryl phosphine (199) (see Section 2.5.5) with 4-azidotetrafluorobenzoic acid conjugated maleimide led to the corresponding water-stable phosphinimine (335). This highly efficient Staudinger reaction was successfully used for a chemoselective fluorescence labeling of proteins and nucleic acids by the successive treatment of these substrates with the corresponding azide and the phosphine (199).195 The treatment of bis(diphenylphosphino)-dimethylphosphinine (277) (see Section 2.6) with mesityl azide led to the corresponding bis(iminophosphorano)phosphinine.271 Fast Staudinger reactions between bis-(perfluoroaryl azides) and bis-phosphines led to polyphosphazenes (336) which showed a high thermal stability.199 Imidazo[1,5-a]-pyridinium salt (337) (a precursor of a bifunctional iminophosphorane-N-heterocyclic carbene ligand) was readily obtained by an efficient three-component coupling reaction between 5-bromoimidazo[1,5-a]pyridinium bromide, sodium azide, and triphenylphosphine according to a SNAr/Staudinger reaction sequence.331 A new representative of chiral bifunctional iminophosphorane organosuperbases (338) with thiourea fragment was prepared by the treatment of tris(p-methoxyphenyl)phosphine with the corresponding thiourea-functionalized azide as an organocatalysts for the diastereoselective Michael addition.332
An efficient formation of water- and air-stable aza-ylides has been achieved using the Staudinger reaction between electron-deficient aromatic azides such as 2,6-dichlorophenyl azide and various triarylphosphines. The reaction has been successfully applied to chemical modification of proteins in living cells.333
A sensitive near-infrared fluorescent probe, azido hemicyanine, for the detection of tris(2-carboxyethyl)phosphine (TCEP), via a Staudinger ligation, has been developed. It provided a good selectivity for TCEP among thiols and natural amino acids.334
A method for the protecting of organic azides from click reactions with alkynes has been reported. The interaction of azides with di(tert-butyl)(p-dimethylaminophenyl)phosphine afforded phosphazides (339), which were stable under click reaction conditions and could be easily converted back to azides by treatment with elemental sulfur.335
A series of new phosphazenes (340) and (341) derived from trifluorodiazoethane and tertiary phosphines or bis-phosphines was synthesized. These phosphazenes reacted with allenyl esters to give unexpected α-iminophosphoranes, which interacted with aldehydes or with acetic acid to give β-enamino esters, so the overall sequence of reactions offered a formal hydrohydrazonation of allenyl esters and did not require the isolation of intermediate phosphazenes.336
Several phosphine-diazomethane derivatives EtOC(O)CHN–NPR3 (R=Ph, Cy, But) were prepared via the reactions of the substituted diazomethane and a phosphine and their Lewis and Brønsted basicities were studied.337
3.3 Miscellaneous reactivity of phosphines
A three-component reaction between triphenylphosphine, dialkylacetylenedicarboxylates and some heterocycles or activated unsaturated compounds, namely 3-arylamino-1-methyl-1H-pyrrole-2,5-diones, 3-alkyl-5-hydroxy-1-phenylpyrazoles or 5-arylidene-1,3-dimethylpyrimidine-2,4,6-triones, as the third reagents, resulted in various triphenylphosphanylidene derivatives: (1-methyl-2,5-dioxo-4-(arylamino)-2,5-dihydro-1H-pyrrol-3-yl)- and pyrazolyl-substituted 3-(triphenyl-λ5-phosphanylidene)succinates (342)338 and (343)339 or triphenylphosphanylidene-7,9-diazaspiro[4.5]dec-1-ene-2-carboxylates (344),340 respectively. All reactions presumably proceeded as domino processes through the initial formation of zwitter-ionic intermediates from triphenylphosphine and the dialkyl acetylene dicarboxylates which interacted with the third reaction component.338–340
A similar reaction of phosphino-substituted ylides, derived from 1,2-bis(diphenylphosphino)ethane and 2-bromoacetophenones, with fullerene C60 and dimethyl acetylenedicarboxylate led to the formation of the new [6,6]-methanofullerene derivatives (345) bearing both α-keto and α, β-ester stabilized phosphorus ylides, which were highly soluble in conventional organic solvents.341
New P-stabilized boryl radicals (346) were obtained by the reduction of the corresponding peri-(phosphinonaphthyl)(bromo)arylboranes with 1% Na(Hg) amalgam in THF.342,343 The most sterically hindered radical (346, R=Ph, Ar=C6H3Mes2-2,6 (Ter)) in solutions existed in the equilibrium with its dimer (347) which was isolated and studied by the X-ray-diffraction analysis.343 Less bulky radicals (346, Ar=Mes, Tipp) reacted with TEMPO to give phosphinonaphthylborinic esters (348) which had open structures without intramolecular P→B interaction, whereas the chlorination of (346, Ar=Mes, Tipp) with Ph3CCl led to (phosphinonaphthyl)chloroboranes (349) with a strong P→B interaction.342,343
The electrochemical oxidation of Zn(ii) 5,15-bis(p-tolyl)-10-phenylporphyrin in the presence of triphenylphosphine led to the meso-substituted triphenylphosphonium porphyrin (350), coordinated by one triphenylphosphine oxide molecule, in good yield (84%).344
The investigation of a powder sample of 2,4-bis(2,4,6-tri-tert-butylphenyl)-1-tert-butyl-3-benzyl-1,3-diphosphacyclobutane-2,4-diyl using muon-(avoided) level-crossing resonance (μLCR) spectroscopy revealed that muonium (the light isotope of a hydrogen radical) added to phosphorus atom of the cyclic P2C2 unit bearing the tert-butyl group to provide a metastable P-heterocyclic radical (351) involving the ylidic MuP(<)=C moiety.345
The actual progress in the field of catalytic activations and transformations of carbon–phosphorus bonds (including P-C bonds of tertiary phosphines) within the coordination sphere of transition metals and of the synthetic application of these reactions has been summarized in a review.346
The organocatalysis of various organic reactions remains the main field of the application of the tertiary phosphines after their use as ligands for metal complex catalysis. Several reviews describing the modern advances in this field have been published in 2018.7,8,347–352 Tertiary phosphines were often used as mild reducing agents, mainly in biological and medical analytical studies. In particular, tris(2-carboxyethyl)phosphine (TCEP) has become a standard reagent in the pre-treatment of biochemical materials for the selective cleavage of disulfide bonds in proteins and nucleic acids.353 The application of tertiary phosphines bearing chromophoric fragments, (including their conjugates with biomolecules) as biologically-compatible fluorogenic probes, has also been developed.354