Tertiary phosphines: preparation

This chapter covers the literature published during 2020 relating to the synthesis of tertiary phosphines. 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 significant number of review articles has been published in 2020 and some 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. Recent general reviews represent the current state of knowledge in the fields of the chemistry of phosphaangulenes (hexacyclic triarylphosphines with a distinctive conical shape) and their derivatives,¹  triazole-based phosphines,²  photoswitchable phosphines containing azo, dithienylalkene and biindane moieties and their applications in catalysis,³  chiral ferrocene-based phosphine ligands and their catalytic properties⁴  and phosphorus-containing amino acids including the corresponding phosphines and their derivatives.⁵ 

A short and important review overviews the advanced synthetic approaches to P-stereogenic compounds including P-stereogenic phosphines,⁶  and a comprehensive review summarizes the historical background and recent breakthroughs in the field of phosphine-mediated radical organic reactions.⁷ 

This synthetic approach continues to be the most widely-used and universal. The interaction of Grignard organomagnesium reagents with corresponding chlorophosphines was found to be a more convenient synthetic route to known dimethyl(1-pyrenyl)phosphine,⁸  diallylphenylphosphine⁹  and to several 1,2-bis(dialkylphosphino)benzenes (1, R¹ = R² = R³ = Me, Et, Prⁱ) (see Scheme 1).¹⁰  New racemic unsymmetrical BenzP-ligands (1, R¹ = Bu^t, R² = Me, R³ = Cy, Prⁱ) were prepared by the addition of methyl triflate to the corresponding 7,8-diphosphabicyclo[4.2.0]octa-1,3,5-triene followed by the treatment with alkylmagnesium halogenide.¹¹  Grignard reagents have been applied in the synthesis of tris(2-methoxy-5-vinylphenyl)phosphine (2) as a monomer for the preparation of new porous organic ligands,¹²  2-(2′-di-tert-butylphosphinophenyl)-1-methylindole (3),¹³  a new 5-boryl-2-phosphinoimidazole PN type ligand (4) for the synthesis of luminescent copper(i) complexes¹⁴  and tris-phosphine (5) with 1,3,5-triazine core as a base component of a new Frustrated Lewis Pare (FLP) for a gas-constructed vesicular system.¹⁵  A broad family of new phospholes (6) was obtained through the interaction of the corresponding Grignard reagents with 1-bromophospholes generated in situ from zirconacyclopentadienes and phosphorus tribromide.¹⁶  The diastereoselective introduction of a P-chirogenic phosphino group at the 2-position of 2-bromo-2′-(diorganylphosphoryl)-1,1′-binaphthyls was achieved by a successive lithium-bromide exchange and a treatment with a dichloroorganylphosphine, followed by a final interaction with an organomagnesium halogenide. It afforded unsymmetrical 2-phosphino-2′-phosphoryl-1,1′-binaphthyls (7) with binaphthyl axial chirality and one or two phosphorus stereocenters with a variety of P substituents.^17,18  An analogous approach allowed synthesis of all four possible diastereoisomers of phosphinoferrocenyloxazoline (Phosferrox) ligands (8) containing three elements of chirality.¹⁹  A cleavage of the P–P bond of a tetracyclic ethoxy(phosphino)phosphonium salt formed by the AlCl₃-promoted coupling of 7-ethoxy-7-phosphanorbornadiene with phenylmagnesium chloride, led to the anthracene-based macrocyclic bisphosphine (9).²⁰ 

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 several representatives of 2-phosphino-2′-phosphoryl-1,1′-binaphthyls (7, R¹ = R² = Ph; R³ = Ph, Me,Cy; R⁴ = Bu^t, Np, Tol^p, C₆H₄F-4, FcBr-1′),¹⁷  (2-ethylphenyl)diphenylphosphine,²¹  bis(2-methoxy-3,5-di-tert-butylphenyl)(2-diphenylphosphinophenyl)methane which was hydrolysed to the corresponding bis-phenol,²²  N-Boc-protected 2-diisopropylphosphinopyrrole which was unprotected to the phosphinopyrrole precursor for a new alane/tris(phosphine)ligand (see Section 2.6.5),²³  and (2-bromophenyl)di(ortho-tolyl)phosphine as a key starting reagent for the synthesis of a rigid tridentate NPP-ligand (see Section 2.6.2).²⁴  New chiral 2-naphthyl-3-phosphinoindoles (10, X = nothing)²⁵  and WK-phos type 2-aryl-3-phosphinoindole (10, X = OMe-6) (see Scheme 2),²⁶  (2-indolylphenyl)diorganylphosphines (11),²⁷  mono- and di(2-trifluoromethyl-pyridin-5-yl)phosphines (12) as the precursors of bis- and tris-(pyridyl)arylphosphonium reagents for the selective halogenation of pyridines²⁸  and chiral cis-1-diphenylphosphino-2-phenylcyclopropane (13)²⁹  were also synthesized via the standard organolithium-halogenophosphine approach. This route was used for the preparation of 4-phosphinophenols (14) as the precursors of PEGylated phosphine ligands for palladium-catalyzed cross-coupling reactions,³⁰  new P-(2-carbazolylphenyl)- and P-(2-pyrrolylphenyl) substituted phosphine-sulfonate ligands (15) for ethylene (co)polymerization,³¹  new biarylphosphine ligands (16),³²  (17)³³  and (18),³⁴  bis(2-dimethylaminophenyl)phenylphosphine as a tridentate NPN ligand for the design of hexanuclear copper(i) iodide nanoclusters demonstrating a tunable blue to white to yellow emission,³⁵  new atropoisomeric tetraryl monophosphine ligands (19),³⁶  bis(1-pyrenyl)phenylphosphine and new [2-(1-pyrenyl)phenyl]diorganylphosphines (20),⁸  9-[5′-bromo-2′-(di-tert-butylphosphino)phenyl]-9H-carbazole (21) as a precursor for the synthesis of 9-(5-boryl-2-phosphinophenyl)-9H-carbazole components of fluorescent FLPs,³⁷  a new representative of phosphines with π-conjugated spacers between diphenylamino and phosphino groups (22) as a chromophoric co-ligand for luminescent Eu–Au dyads,³⁸  (ortho-bromoaryl(heteroaryl))dicyclohexylphosphines (23) and (24) as the precursors for (ortho-borylaryl(heteroaryl))phosphine FLPs (see Section 2.6.2),³⁹  new representatives of PNN-pincer ligands (25) based on a pyridyl-quinoline scaffold,⁴⁰  new camphor-based phosphine-carbonyl ligands (26),⁴¹  chiral bis(oxazolinyl)phenylphosphine ligands (27),⁴²  isomeric dithienophosphepines (28) and (29) which were isolated as borane complexes and deprotected with DABCO,⁴³  and new representatives of (2-phosphinoaryl)- or (2-phosphinopyridin-3-yl)alkynes (30).⁴⁴  A lithium/halogen exchange in 1,1′-dibromoruthenocene followed by the interaction with Ph₂PCl smoothly afforded 1-bromo-1′-diphenylphosphinoruthenocene (31), but the analogous reaction sequence in the case of 1-bromo-1′-(4″-tert-butyloxazolin-2-yl)ruthenocene unexpectedly led to the transfer of the carbanion centre with the formation of 1-oxazolinyl-2-phosphinoruthenocene (32).⁴⁵ 

Various new diphosphines have also been synthesized by organolithium-halogenophosphine routes, in particular 1,2-bis[di(2,6-dimethylphenyl)phosphino]ethane (33) (see Scheme 3) as a “missing” member of the 1,2-bis(phosphino)ethane family,⁴⁶  new representatives of diphosphine ligands with 1,8-anthracene- (34),⁴⁷  1,1′-binaphthalene- (35),⁴⁸  acenaphthene- (36),⁴⁹  9-chloro-1,8-acridine- (37)⁵⁰  and terthiophene-cores (38).⁵¹  Bis(PNP) pincer ligands (39) where two PNP units are linked with aromatic spacers of a various length have also been prepared by this method.⁵²  A lithiation of tetrakis(4-bromophenyl)methane followed by the treatment with 1,2-bis(dichlorophosphino)ethane afforded a new porous organic polymer (40) as the support for effective and recyclable ruthenium-based hydrogenation catalysts.^53,54 

The direct lithiation of selected precursors through lithium/H exchange, (usually with n-, sec- or tert-butyllithium (sometimes in the presence of TMEDA or Bu^tOK), more rarely with LDA or lithium 2,2,6,6-tetramethylpiperidide (TMPLi)), followed by treatment with chlorophosphines, gave new desirable tertiary phosphines, and has been widely used for the synthesis of phosphines with heterocyclic substituents. N-Boc-2-diisopropylphosphinopyrrole,²³  a bulky N-arylated-2-di-tert-butylphosphinopyrrole (41) (see Scheme 4),⁵⁵  new representatives of monosubstituted 1-R-2-diphenylphosphinoimidazoles (42) with bulky substituents,⁵⁶  a previously unknown bis(imidazole-2-yl)(imidazol-5-yl)phosphine (43),⁵⁷  [2-(2′-diphenylphosphino)-1H-imidazol-1-yl]pyridine (44)⁵⁸  and a polydentate 2,6-bis[(2′-diphenylphosphino)-1H-imidazol-1-yl]pyridine ligand (45)⁵⁹  able to achieve versatile coordination modes were synthesized by this method. The interaction of dilithiated 2,10-di-tert-butyldipyrido[1,2-c;2′,1′-e]imidazol-6-thione with Prⁱ₂PCl followed by the methylation and the reductive elimination of the thione group led to the bis(phosphino)-substituted imidazolium salt (46) which was deprotonated with Bu^tOK to afford a new carbene P–C_NHC–P pincer ligand (47).⁶⁰  The direct C–H lithiation was also successfully used for the synthesis of tris(N-Boc-3-methylindol-2-yl)phosphine (48) as a starting reagent for the preparation of C₃-symmetric ligand combining three anionic N-donors tethered to a phosphonium center,⁶¹  indole-bridged phosphine-amidophosphinate, -amidophosphate and sulfonylamido P,O-ligands (49),⁶²  new 3-dialkoxyphosphoryl-2-diarylphosphino- and 3-diarylphosphino-2-(tetramethyldiamidophosphoryl)benzothiophene ligands (50) and (51).⁶³  The direct lithiation of aryl moieties was applied for the preparation of new representatives of N,N-dimethyl-4-R-2-dialkylphosphinoanilines (52),⁶⁴  new sulfoxide-phosphine and pincer-type bis(sulfoxide)-phosphine ligands (53)⁶⁵  and (54),⁶⁶  a new very bulky ortho-phosphinophenol ligand (55) obtained from the corresponding tetrahydropyrane-protected phenol and hydrolytically deprotected before the purification⁶⁷  and a novel biarylphosphine ligand N₂Phos (56) providing the ppm-level palladium catalysis of Suzuki-Miyaura cross-coupling in water media.⁶⁸  P,O-chelating ligands (49)–(51) and (55) were successfully tested in nickel and palladium-catalyzed ethylene (co)polymerization.^62,63,67 

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 2,6-lutidine-based P,N,N-ligands (57) (see Scheme 4) bearing pyrrolidine (including chiral systems) and phosphino groups⁶⁹  and the borane protected bis(phosphine) (58) with octen-7-yl substituents at phosphorus atoms as a key reagent for the synthesis of a macrocyclic PNP pincer ligand (see Section 2.6.7),⁷⁰  new PNN-ligands (59) and (60) containing aminoquinoline and aminomethylisoquinoline moieties,⁷¹  alkyne-bis(phosphine) ligand (61) with elongated linker,⁷²  new representatives of imine-phosphine ligands (62)⁷³  and ylide-phosphine ligands (63).^74,75 

The relatively acidic protons of carborane and ferrocene derivatives also easily undergo the lithium/H exchange, so it has been used for the synthesis of new mono(diarylphosphino)carboranes (64) as the substrates for the further boron functionalization (see Section 2.6.1),⁷⁶  new electron-deficient 1,1′-bis(diarylphosphino)ferrocenes (65),⁷⁷  chiral 1,1′-bis(diarylphosphino)-2-(α-dimethylaminoethyl)ferrocenes (66, R = Me) which were treated with acetic acid and ammonia to give the corresponding primary amines (66, R = H) as the precursors of diphosphine-thiourea ZhaoPhos ligands (see Section 2.6.5).⁷⁸ 

1-Bromo-1-diisopropylphosphinoethene (67) (see Scheme 4) as the precursor for the synthesis of geminal P,B-containing FLPs,⁷⁹  a borane-protected diphenylphosphinocyclopentadiene (68) as a key starting reagent for the preparation of 1-oxazolyl-1′-phosphinoruthenocene derivatives⁴⁵  and a chromophoric phosphine (69) with the enlarged π-conjugated linker between phosphino and amino groups were also obtained through the direct lithiation of organic reagents.³⁸ 

One-pot C-Hal and C–H lithiations were used for the synthesis of a variety of bisphosphines based on a 1,4-diphenyl-1,2,3-triazole scaffold and corresponding trisphosphine (70); the direction of derivatization depended on the reaction conditions and in some cases the transfer of the reaction centers took place.⁸⁰  The analogous transfer was observed in the course of the lithiation of 2-iodo-2′-(4″-phenyl-1″,2″,3″-triazol-1″-yl)-6,6-dimethyl-1,1′-biphenyl followed by the addition of copper(i) iodide and then Cy₂PCl. It led to the phosphinilation of the position 5 of the triazolyl ring; the corresponding phosphine (71) was isolated by the demetallation of the copper(i) complex with aqueous ammonia.⁸¹ 

In some cases, other phosphorus-containing starting reagents were applied. Several new arylbis(2-oxazolinylaryl)phosphines (27, R¹ = C₆H₂Bu^t₂-3,5-OMe-4, C₆H₄CF₃-4, Me; R² = Ph, Me, Bu^t; R³ = H; R⁴ = H, Me) (see Scheme 2) with various aryl and methyl substituents at phosphorus atoms were obtained from the corresponding O-phenyl-bis(2-oxazolinylaryl)phosphinites,^42,82,83  whereas an electron-poor tris(4-pentafluorosulfanylphenyl)phosphine (72) (see Scheme 5) was prepared by the interaction of triethylphosphite with the corresponding aryllithium reagent.⁸⁴  A wide series of P-stereogenic Xantphos bisphosphine ligands (73) was synthesized by the interaction of dilithiated xanthene with enantiopure O-methyl(aryl)phenylphosphinite-boranes which were deprotected in situ with DABCO.⁸⁵  A similar approach was used for the synthesis of enantiopure O-silyl protected and P-borane protected phenol-functionalized ruthenocylphosphines (74, R = SiBu^tMe₂, X = BH₃); their deprotection by successive treatment with tetrabutylammonium fluoride trihydrate and diethylamine afforded the enantiopure phosphines (74, R = H, X – nothing) which were used for the grafting to P(S)Cl₂-terminated dendrimers.⁸⁶ 

A new representative of sterically constrained tricyclic phosphines (75) was obtained by the interaction of phosphorus trichloride with trilithium compound prepared by the combined transmetallation and C–H lithiation of a tetrachlorodigallium derivative of 1,3-bis(2-trimethylsilylvinyl)benzene.⁸⁷  The transmetallation of 1-tributylstannyl-2-(2′-phenylvinyl)ferrocene with butyllithium followed by the interaction with chlorobis(4-cyanophenyl)phosphine led to (2-vinylferrocenyl)diarylphosphinoferrocene (76).⁸⁸  The cyclization of dimethylbis(phenylethynyl)silane with lithium naphthalenide (LiNaphth) gave a dilithio-substituted silole ring; the quenching of the excess of LiNaphth with Ph₃SiCl and the final treatment with Prⁱ₂PCl afforded bis(diisopropylphosphino)silole (77).⁸⁹ 

The interaction 1-chloro-2,3,4,5-tetraethylphosphole with corresponding stable carbenes followed by anion exchange with NaSbF₆ led to α-cationic phospholes (78)–(80) (see Scheme 5) containing imidazolium, cyclopropenium and cyclic iminium substituents respectively.⁹⁰ 

Nucleophilic substitution reactions between organophosphide anions, commercially available, preprepared or generated in situ, and halogenated alkanes or their analogues is an alternative to the above way to the various, usually functionalized and/or chiral phosphines. The availability and stability of corresponding metal phosphide determine the suitability of this approach. Lithium-, sodium- and potassium-organophosphides provided the most commonly used reagents for the synthesis of new phosphines. Substitution of halogen group by secondary phosphines in the presence of various bases is also one of the used procedures. The borane group provides the stability of phosphorus atom configuration and a protection against oxidation of the new phosphine during purification steps.

Traditional lithium phosphide reagents are available via simple deprotonation of primary or secondary phosphines by BuⁿLi. The phosphine (81) containing the P-bonded bioisosteric CH₂F moiety,⁹¹  a series of bidentate bis(diphenylphosphino)propane ligands (82) (with different geminal dialkyl groups at the central carbon of the ligand backbone),⁹²  Si-containing bis- and tris-phosphines (83)–(86),⁹³  and allylic phosphines (87)⁹  have been obtained from lithium diphenylphosphide generated in situ from diphenylphosphine and BuⁿLi (see Scheme 6).

Lithium diphenylphosphide is tolerant for a wide variety of N- and N,O-heterocyclic fragments. Thus, a number of phosphines and diphosphines containing heterocyclic substituents was synthesised from halogenated heterocyclic substrates, including 3-(2-(diphenylphosphino)ethyl)oxazolidin-2-one (88) (see Scheme 7),⁹⁴  2-methyl- and 2-phenyl-8-(diphenylphosphino)quinolones (89),⁹⁵  2,3-bis(diphenylphosphino)dibenzo[f,h]-quinoxaline (90),⁵¹  4,6-bis(diphenylphosphino)pyrimidine (91)⁹⁶  and 2-phosphino-pyridine-N-oxides (92).⁹⁷ 

Hemilabile ligands (93) (see Scheme 8) were obtained through the phosphorylation of 2-chloroethyl methyl ether with various secondary diarylphosphines.⁹⁸  Bis(3-chloropropyl)phenylphosphine reacted with lithium phospholanide in the presence of BuⁿLi to form bis(3-phospholanopropyl)phenylphosphine (94) – a new oligodentate phosphine ligand with phospholane end groups.⁹⁹  Studies of the protonation and alkylation of imidazolio-phosphides (formed by the deprotonation of imidazoliophosphines with Bu^tLi) revealed a complex behaviour that can be traced back to an interplay of Brønsted-type proton transfers and Lewis-type P–P bond formation reactions. As a consequence, alkylation processes leading to secondary imidazolio-alkylphosphine (95) and tertiary imidazolio-dialkylphosphine (96) salts compete with reactions producing cyclic or linear oligophosphines.¹⁰⁰  Novel alkane-diyl based heterobidentate PN ligands (97)–(100) have been prepared starting from cyclic sulfate esters or naturally occurring compounds with C1 symmetry and lithium diphenylphosphide.¹⁰¹ 

In the preparation of chiral phosphine ligands borane-protected lithium phosphides were used in order to avoid oxidation of desired compounds and racemisation on chirogenic phosphorus atoms. The first examples of highly enantioselective palladium catalysts for the fluoroarylation of gem-difluoroalkenes based on new chiral sulfinamide phosphine ligands (101)–(106) (see Scheme 9) have been developed. Ligands were synthesized on a gram scale from di-tert-butylphosphine borane; borane protecting groups were eliminated by diethylamine and crude products were then purified by flash column chromatography.¹⁰²  Bis(1-adamantyl)phosphine borane activated by BuⁿLi reacted with (RS)-sulfinyl imines to give chiral phosphines (107) after the deprotection.¹⁰³  Amino-phosphine ligands (108), which bear a P-chirogenic group and an amino group on the pyridylene backbone, as a novel class of chiral ligands possessing chirogenic donors, have been designed.¹⁰⁴  A number of chiral tertiary phosphine boranes containing o-substituted phenylene fragments was synthesized including novel (Rp)-tert-butyl(2-iodophenyl)(2-methoxyphenyl)phosphine–borane (109) and (Sp)-2-(tert-butyl(2-methoxyphenyl)phosphino)benzoic acid–borane (110).¹⁰⁵  An asymmetric, unsaturated secondary diphosphine borane was converted directly into the corresponding phosphide by deprotonation with BuⁿLi and reacted with 1,3-bis(bromomethyl)benzene to afford bisphosphine (111) as the precursor of a new macrocyclic pincer (pro)ligand (see Section 2.6.7)¹⁰⁶ 

Deprotonation of primary 2-naphthyl- and 1-pyrenylphosphines and further reaction with ditosyl- and 1,2-dichloroethanes gave 2-naphthyl- (112) and 1-pyrenylphosphiranes (113) respectively (see Scheme 10).^8,107 

Ph₂PLi generated from Ph₂PH and lithium shots was alkylated with 2,6-F₂C₆H₃SiMe₃ providing bisphosphine (114) (see Scheme 10), which could be regarded as a precursor for the novel anionic tridentate ligand [2,6-(Ph₂P)₂C₆H₃]⁻.^108,109 

Potassium diphenylphosphide is commercially available. The preparation, application, and reaction mechanisms of sodium phosphide and other alkali metal phosphides R₂PM (M = Li and K) have been studied. It has been shown that R₂PNa could be prepared, accurately and selectively, via the reactions of sodium finely dispersed in mineral oil with phosphinites R₂POR′ and chlorophosphines R₂PCl. R₂PNa could also be prepared from triarylphosphines and diarylphosphines via the selective cleavage of C–P bonds. Na was superior to Li and K for these reactions. R₂PNa reacted with a variety of ArCl to produce various phosphines R₂PAr. ArCl was superior to ArBr and ArI since they only gave low yields of the products. In addition, Ph₂PNa was superior to Ph₂PLi and Ph₂PK since Ph₂PLi did not produce the coupling product with PhCl, while Ph₂PK only gave a low yield of the product. An electron-withdrawing group on the benzene ring of ArCl greatly accelerated the reactions with R₂PNa, while an alkyl group reduced the reactivity. Vinyl chloride and alkyl chlorides RCl also reacted efficiently. While Bu^tCl did not produce the corresponding product, adamantyl halides could give the corresponding phosphine in high yields. Unsymmetric phosphines could also be conveniently generated in a one pot process starting from Ph₃P. Chiral phosphines were also obtained in good yields from the reactions of menthyl chlorides with R₂PNa.¹¹⁰ 

A chiral (R)-(diphenylphosphino)-5,6,7,8-tetrahydroquinoline (115) (see Scheme 11) was obtained starting from the chiral 5,6,7,8-tetrahydroquinolin-8-ol core and commercial Ph₂PK.¹¹¹  2-(2′-Diphenylphosphinophenyl)-1-phenyl-5-methoxybenzimidazole derivatives (116) were also synthesized from commercial Ph₂PK.¹¹² 

Reaction of the potassium salt generated in situ from diphenylphosphine and Bu^tOK with 3-(2-bromoethyl)-1-R-imidazolium bromides, followed by anionic exchange with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBAr_F), gave chelating NHC-P ligands (117).¹¹³ 

It has been shown that sodium phosphides could be stabilized and isolated via formation of the sodium salt of corresponding phosphinoborate. 9,10-Dihydroanthracene-9,10-diylphosphine, triphenylborane and solution of sodium bis(trimethylsilyl)amide gave a sodium salt of corresponding phosphinoborate (118), which in turn reacted with tri-tert-butyl cyclopropenyl tetrafluoroborate to form phosphine (119). It has been shown that compound (119) is a precursor of a highly strained tri-tert-butyl phosphatetrahedrane. (see Section 2.7).¹¹⁴  The phosphine functionalized β-diketimine ligand (120) was obtained in a multigram scale from Ph₂PK (formed from the corresponding secondary phosphine and potassium chunks) and fluorine functionalized β-diketimine. The newly designed ligand features symmetrically placed phosphine moieties around a β-diketimine unit, forming a PNNP-type pocket.¹¹⁵ 

Chlorophosphines could be reduced by free metallic sodium or KC₈ (potassium graphite intercalation) forming corresponding metal phosphides. Ph₂PNa obtained from Ph₂PCl and sodium chunks gave metal-containing phosphine (121).¹¹⁶  Cyclic chloroalkylphosphine reduced on KC₈ reacted with alkyl iodides or bromides to give phosphines (122) with a bulky phosphacyclopentane backbone.¹¹⁷ 

Et₃N and NaHCO₃ are usually used for a cleavage of phosphonium salts formed after alkylation of secondary phosphines to give desired tertiary phosphines. The sterically demanding new pincer (123)–(124) (see Scheme 11) and chelate naphthyridinone-substituted (125) phosphine ligands were prepared that way.^118–120 

A one-pot organometallics-free synthesis of diphenyl(pyrazin-2-yl)phosphine (126) (see Scheme 12) from air-stable and readily available precursors, Ph₃P, Li and 2-chloropyrazine, has been developed.¹²¹  Reduction of Ph₃P oxide with sodium led to its selective transformation to sodium benzo[b]phosphindol-5-ide and its derivatives (127, 128) via quenching with alkyl bromides.¹²² 

Compounds containing P-B covalent bonds could be regarded as analogues of metal-containing phosphines. The reactivity of phosphinoboronate esters Ph₂PBpin (pin = 1,2-O₂C₂Me₄) and Ph₂PBcat (cat = 1,2-O₂C₆H₄), as well as other phosphinoboron species, with various aryl and aliphatic acyl chlorides, has been examined. These reactions proceeded smoothly to give acyl phosphines (129) along with a loss of a boron-chloride compound.¹²³ 

Hydrophosphination of unsaturated compounds is a prospective P–C bond formation route because it proceeds with 100% atom economy and the potential for high selectivity, producing regio-, chemo-, and enantio-specific products. Addition of primary and secondary phosphines to unsaturated compounds proceeds under a variety of conditions involving thermal-, radical (UV or AIBN)-, base- or metal complex-catalyzed initiation and is applied for the synthesis of a range of new phosphines. Hydrophosphination can proceed without a catalyst, but the purpose of a catalyst is to enhance reactivity and selectivity. The search for efficient catalysts providing the control of regio-, chemo- and stereo-selectivity is a continuous activity.

During the 2020 year, investigations on the development of new metal-complex catalysts for hydrophosphination were mainly focused on transition-, main group- and rare earth- metals.

It has been shown that cobalt complexes containing carbazolido NNN pincer ligands catalyzed a hydrophosphination process which solely and selectively yielded the β-addition (anti-Markovnikov) product. The scope of this transformation has been investigated using a variety of activated alkenes.¹²⁴ 

Hydrophosphination with a commercially available ruthenium compound, bis(cyclopentadienylruthenium dicarbonyl) dimer ([CpRu(CO)₂]₂), was explored. Styrene derivatives or Michael acceptors reacted readily with either primary or secondary phosphines in the presence of catalyst under photolysis.¹²⁵ 

A commercial availability, ease of use, and broad substrate scope of bench-stable copper photocatalyst has been developed for the rapid hydrophosphination of activated and unactivated alkenes.¹²⁶ 

Ln(ii) (Ln = Yb, Sm) and Ca(ii) pincer type complexes coordinated by a tridentate diarylmethanido ligand were found to be efficient and selective precatalysts for intermolecular hydrophosphination of olefins and acetylenes. Complexes have demonstrated their versatility for intermolecular C–P bond formation and allowed the realization of hydrophosphination of styrene and phenylacetylene. Moreover, they were found to be active in the catalysis of challenging transformations such as hydrophosphination of internal double and triple C–C bonds.¹²⁷ 

New Ln(ii) ring-expanded NHC complexes (Ln = Sm, Yb) were synthesized and proved to be highly efficient pre-catalysts for the intermolecular hydrophosphination of such indolent substrates as 1-alkenes, cyclohexene and norbornene.¹²⁸ 

The first example of hydrophosphination using a germanium pre-catalyst, yielding anti-Markovnikov products when diphenylphosphine is reacted with styrenes or internal alkynes at room temperature, was described.¹²⁹ 

In spite of high theoretical interest for the development of catalysts for hydrophosphination, the procedure has been used quite rarely for the preparative synthesis of novel types of phosphines.

Methacrylated lignin reacted with gaseous PH₃ in the presence of AIBN ((azo)bis(isobutyronitrile))to prepare a phosphorus rich bio-based polymer (130) (see Scheme 13) containing PH/PH2 functional groups, which were converted to tertiary phosphine units (131) via the phosphine–ene reaction. This represents a straightforward method for the upconversion of low-value biomass waste to useful inorganic polymer with potential utility in metal scavenging applications.¹³⁰ 

During 2020 the main achievements in the field of synthesis of new phosphines via addition of P–H bonds to unsaturated compounds were concentrated on the reactions with conjugated C═C–C═C, C═C–C═N and C═C–C═O systems. Biaryl phosphorinanes (132) (see Scheme 13) were synthesized by a general and higher-yielding procedure - the phospha-Michael addition of primary biarylphosphines to various 1,1,5,5-tetraalkylpenta-1,4-dien-3-ones, followed by ketalization of the resulting phosphinanones (132) with ethylene glycol. Fluorinated alcohols, such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), have been shown to accelerate hetero-Michael additions.¹³¹  N-Methylnaphthalen-1-amine activated with Lewis acids reacted with Ph₂PH forming phosphine (133) due to the amine-imine tautomerization and further hydrolysis of the addition product.¹³² 

A general procedure for the synthesis of 1,1-bis(2-cyanoethyl)-N-(4-methoxyphenyl)phosphinecarboxamide (134) and a single Michael addition product N-(4-methoxyphenyl)-1-(3-oxo-3-(p-tolylamino)propyl)phosphinecarboxamide (135) from N-(4-methoxyphenyl)phosphanecarboxamide and N-arylacrylonitrile or acrylamide in the presence of K₂CO_3, has been represented.¹³³  A series of enantioenriched ferrocenyl monophosphines (136), imbued with both central and planar chirality, was obtained catalytically (80–99% ee) via the kinetic resolution of 1,2-disubstituted planar chiral ferrocenyl enone racemates. The synthetic approach utilized a chiral palladacycle to facilitate the asymmetric hydrophosphination (AHP) as a means to achieve the high stereoselectivity. The enantioenriched ferrocenylphosphine products were protected with BH₃ and recrystallized to obtain ees up to 99%.¹³⁴ 

Reactions of isocyanates with primary and secondary phosphines without solvent at room temperature afforded the corresponding phosphinecarboxamides (137) in excellent yields. This reaction system is applicable for isothiocyanates. Reaction of 1,3- and 1,4-diisocyanatobenzene with diphenylphosphine HPPh₂ yielded the double hydrophosphination products (138)–(139). In addition, 1,3,5-triisocyanatobenzene could be converted into the triple hydrophosphination product (140).¹³⁵ 

At present, a reduction of phosphoryl compounds using a wide range of reducing agents still remains to be the effective pathway to tertiary phosphines. Silanes and related compounds remain the most common reagents for the reduction of tertiary phosphine oxides.

Trichlorosilane in the presence of tertiary amines (as a rule triethylamine, pyridine, tributylamine or diisopropylethylamine) was successfully used for the synthesis of bis(4-ethynyl)phenylphosphine (141) (see Scheme 14.) as a precursor of phosphonium building blocks for the design of phosphorus-containing oligomers,¹³⁶  tris(4′-methylcarboxy-1,1′-biphenyl-4-yl)phosphine (142, R = Me) which was hydrolyzed to the corresponding carboxylic acid (142, R = H) as a linker for new MOFs,¹³⁷  and a wide variety of axially chiral biarylphosphine ligands (143),¹³⁸  (144),¹³⁸  (145),¹³⁸  (146),¹³⁹  (147),¹⁴⁰  (148)¹⁴¹  and (149)¹⁴²  for various catalytic applications. A chiral binol (150) with a diphenylphosphinophenyl substituent was also prepared by the reduction of the corresponding phosphine oxide with HSiCl₃/NEt₃ and used for the synthesis of gold(i) catalysts bearing a chiral phosphoric acid moiety.¹⁴³  New representatives of bis(phosphino)biaryl SYNPHOS-type (151)^144,145  and SEGPHOS-type ligands (152)^144,146  containing ferrocenyl,¹⁴⁶  bis(trimethylsilyl)- or bis(trimethylgermyl)aryl groups at phosphorus atoms,^144,145  two new spiro PNP-ligands (153, Ar¹ = C₆H₃Bu^t₂-3,5; Ar² = C₆H₃Me₂-3,5, C₆H₃Bu^t₂-3,5),¹⁴⁷  a new chiral (1-indolyl-naphthalen-2-yl)diphenylphosphine organocatalyst (154)²⁵  and an exemplary representative of phosphines (155) bearing a 3,3-disubstituted oxindole moiety¹⁴⁸  have also been obtained by this method. The reduction of cycloadducts of enantiopure S_p-1-phenylphosphol-2-ene-1-oxide with anthracene and in situ generated α-oxy-ortho-xylylene with the HSiCl₃/pyridine system, provided complete stereoretention (unlike the reduction with phenylsilane) with the formation of enantiopure polycyclic phosphines (156) and (157).¹⁴⁹  The HSiCl₃/amine reducing systems were also successfully used for the synthesis of enantiopure l-menthyl-ortho-anisyl(phenyl)phosphinoacetate (158) as a substrate for the P-alkylation,¹⁵⁰  1,4-bis[phenyl(ortho-tolyl)phosphino]butane¹⁵¹  and tris(4-trans-(tert-butyl)cyclohexyl)phosphine as a ligand with a “conformational lock”.¹⁵² 

The reduction of tertiary phosphine oxides with trichlorosilane in the absence of tertiary amines allowed isolation of several para-phosphinophenol derivatives, R¹P(Ph)-C₆H₄-OR²-4 (R¹ = Me, Ph; R² = Me, H),¹⁵³  axially chiral [1-(quinolin-4-yl)-naphthalen-2-yl]diphenylphosphine (159),¹⁵⁴  [2,2-bis(4′-chlorophenyl)vinyl]diphenylphosphine (160)¹⁵⁵  and an exemplary representative of 3-phosphinobenzofurans (161).¹⁵⁶  P-Chiral monophosphines (162) were synthesized by the stereoretentive reduction of enantiopure (2-arylethynyl)(aryl)phenylphosphine oxides with HSiCl₃/PPh₃ mixture and used as chiral organocatalysts in the [3 + 2]-annulation of allenes.¹⁵¹ 

Phenylsilane was successfully used for the reduction of rac-1-phenylphosphol-2-ene-1-oxide in the course of its resolution into enantiomers, including the quaternization of the obtained phospholene, the resolution of P-epimeric phosphonium salts and their stereoselective hydrolysis to afford the pure enantiomers of the starting phosphine oxide. The reduction of S_p-1-phenylphosphol-2-ene-1-oxide cycloadducts with butadiene, cyclopentadiene and cyclohexadiene (and their hydrogenated saturated derivatives) by phenylsilane proceeded stereoretentively to give a range of optically active bicyclic and tricyclic P-stereogenic phospholane derivatives (163) and (164) (see Scheme 15).¹⁴⁹  Several spiro-PNP-ligands (153, Ar¹ = C₆H₃Bu^t₂-3,5, C₆H₃Me₂-3,5; Ar² = C₆H₃Me₂-3,5, C₆H₃Bu^t₂-3,5, C₆H₂Ad₂-3,5-OMe-4) (see Scheme 14),¹⁴⁷  two representatives of [2-(pyridine-2′-yl)alkyl]diarylphosphines (165)¹⁵⁷  and an exemplary representative of 2-(2′-diphenylphosphinoalkyl)-1H-benzo[d]imidazoles (166, X-nothing, R = Boc) hydrolytically converted to the N-unprotected derivative (166, X = BH₃, R = H)¹⁵⁸  were obtained by the reduction of the corresponding phosphine oxides with phenylsilane (sometimes in the presence of triflic acid¹⁴⁷  or diphenylphosphate¹⁵⁸ ). A spiro-fluorene-bridged triarylphosphine (167) was synthesized by the reduction of the sterically constrained phosphine oxide only with Lemaire's optimized reducing system, namely PhSiH₃/HSiCl₃ mixture, at 150 °C.¹⁵⁹ 

The silane–titanate system HSi(OEt)₃/Ti(OPrⁱ)₄ was applied for the reduction of the chiral phosphine oxides to prepare a range of chiral 1,2-bis(diarylphosphino)ethane ligands (168)^160,161  isolated in borane-unprotected¹⁶⁰  and borane-protected forms,¹⁶¹  and a family of enantiopure aziridine–phosphines (169).¹⁶² 

An exemplary representative of meta-(diarylphosphinyl)anilines obtained by a three-component reaction of p-quinone monoacetals, amines and diarylphosphine oxides was reduced with tetramethyldisiloxane to the corresponding tertiary phosphine (170).¹⁶³  Trimethoxysilane was applied in the reduction of macrocyclic phosphine oxides with chiral crown-ether fragments to obtain a range of macrocyclic phosphines and bis(phosphines) (171)–(173) and bis(2-hydroxyphenyl)phenylphosphine as a possible starting reagent for the macrocyclization.¹⁶⁴ 

The use of 1,3-diphenyldisiloxane (DPDS) as the reducing agent for P^V/P^III redox recycling in Wittig, Staudinger and alcohol substitution reactions has been described.¹⁶⁵  The DFT study of silane-mediated reduction of phosphine oxides explains the higher reactivity of relatively electron-rich alkylphosphine oxides in comparison with arylphosphine oxides; these results may guide the design of new “regenerating” phosphine catalysts for various organic reactions.¹⁶⁶ 

Various aluminium hydride reagents are also used for the reduction of tertiary phosphine oxides. An example of borane-protected P-chirogenic alkenylphosphines (174) (see Scheme 15) was prepared by the stereoselective reduction of the corresponding enantiopure phosphine oxide, including its successive treatment with methyl triflate and lithium aluminium hydride followed by the borane protection of the resulting phosphine.¹⁶⁷  The reduction of 3-benzyl-5-[(diphenylphosphoryl)methyl]oxazolidin-2-one with LiAlH₄ was accompanied by a ring-opening and led to the corresponding 1-amino-3-(diphenylphosphino)propan-2-ol (175).¹⁶⁸  Diisobutylaluminium hydride (DIBAL-H) was used for the synthesis of partially fluorinated phosphine (176) for useable applications in Wittig reactions¹⁶⁹  and one of diarylphosphinophenols (177, Y – nothing, R = H, X = Cl4),¹⁷⁰  whereas a series of unsymmetrically substituted 1,3-bis(phosphino)propanes (178) was obtained by the reduction of the corresponding bis(phosphine) oxides with alane (AlH₃) in glyme at 60–70 °C.¹⁷¹ 

Several recorded examples of the application of boron-containing reducing agents for the synthesis of tertiary phosphines include the preparation of borane-protected diarylphosphinophenols (177, Y = BH₃) through the reduction of the phosphine oxides with borane-dimethylsulfide complex¹⁷⁰  and the regiospecific and stereoselective reduction of biaryls (7) bearing phosphoryl and chiral phosphino groups (see Section 1, Scheme 1) with a complex reducing system of CeCl₃/NaBH₄/LiAlH₄ at low temperatures (from −90 °C to ambient temperature) after the preliminary borane protection of the phosphino group.¹⁷  The resulting bis(phosphines) were converted to the boronate complexes by the treatment with BH₃-THF complex before the purification; the final deprotection with diethylamine afforded optically pure unsymmetrical 2,2′-bis(phosphino)-1,1′-binaphthyls (179) (see Scheme 15) with one or two P-chirogenic phosphine moieties.¹⁷  It should be mentioned that two representatives of these bis(phosphines) (179, R¹ = R² = Ph, C₆H₄OMe-4; R³ = Me; R⁴ = Ph) were stereoselectively synthesized by the reduction of corresponding compounds (7) with standard HSiCl₃/NEt₃ reducing systems.¹⁸ 

The direct electrochemical reduction of trialkyl- and triaryl-phosphine oxides in high yields under mild conditions was achieved by the use of an aluminium anode in the presence of catalytic amounts of Lewis acid activators (in particular the combination of TMEDA/AlCl₃ with Bu₄NCl and Bu₄NPF₆).¹⁷²  A review has summarized the emergence of electrochemical strategies developed for the reduction of phosphine oxides (mainly triphenylphosphine oxide) in the past few decades.¹⁷³ 

The treatment of phosphine sulfides with hexamethyltriamidophosphite P(NMe₂)₃ or tertiary phosphines is often used for their desulfurization to give trivalent phosphine compounds. The electron-rich chiral PNP-ligand (180) with phospholane fragments was prepared by the desulfurization of the corresponding bis(phosphine) disulfide with P(NMe₂)₃.¹⁷⁴  The reduction of 1-phenyl-2,4-bis(diphenylphosphino)but-1-ene and 1,5-bis(diphenylphosphino)-pent-2-ene disulfides, obtained by the diphosphination of benzylidene- and vinylcyclopropanes with Ph₂P–PPh₂ quenched by sulfur addition, was performed by the treatment with P(NMe₂)₃ or Schwartz reagent Cp₂Zr(H)Cl, respectively, and afforded bis(phosphines) (181) and (182).¹⁷⁵  A new representative of 10-alkylidene-acridophosphines (183) was obtained by the desulfurization of the phosphine sulfide precursor containing a thiirane bridging fragment instead of the alkylidene one with P(NMe₂)₃. Two diasteroisomers of (183) were separated chromatographically and their photochemical interconversions were studied.¹⁷⁶  Two phosphine-containing polycyclic aromatic hydrocarbons (184) and (185) containing acridophosphine fragments were obtained by the treatment of the corresponding phosphine sulfides with tributylphosphine in toluene or with LiAlH₄ in dioxane under microwave irradiation respectively; these phosphines could be considered as a prospective basis for the development of P-containing π-conjugated materials.¹⁷⁷  A new P-chirogenic (2-triazolylphenyl)diarylphosphine ligand (186) was prepared by the reduction of the phosphine sulfide precursor with Si₂Cl₆ in toluene at 80 °C (Scheme 16).¹⁷⁸ 

Transition metal-catalyzed C–P(iii) bond formation has become an effective and widely-used synthetic approach to various aryl-, heteroaryl- and even alkylphosphines. Most of the catalysts are based on Pd(ii) and Pd(0) salts and complexes, which may be used both in the presence and sometimes in the absence of additional ligands (as a rule DIPPF, DPPF or DPPB) and organic or inorganic basic reagents (as a rule NaOBu^t, KOBu^t, NEt₃, Cs₂CO₃), whereas the most applied phosphorus sources are secondary phosphines. A facile method of Pd(OAc)₂/DPPF-catalyzed C–P(iii) cross-coupling between various aryl- or heteroaryl-halides and enantiopure borane complexes of (S)- and (R)-(tert-butyl)methylphosphines has been developed for the effective and enantioselective synthesis of (R)- or (S)-P-chiral (aryl-) and (heteroaryl)-(tert-butyl)methylphosphines in moderate to high yields. These reactions were applicable to a wide series of arylhalides bearing both electron-donating and electron-withdrawing groups and nitrogen-containing heteroarylhalides; additionally the reaction time could be significantly reduced without the loss of stereoselectivity under microwave conditions.¹⁷⁹  PdCl₂(PhCN)₂-catalyzed C(sp³)–P(iii) coupling reactions between alkyl- and arylalkyl-halides and (benzoyl)diphenylphosphine as the phosphorus source allowed access to a wide range of (alkyl)- and (arylalkyl)-diphenylphosphines including compounds with ether, ester or amide functional groups.¹⁸⁰  The C–P(iii) coupling between various arylhalide precursors and secondary phosphines in the presence of the most common catalytic system, namely Pd(OAc)₂/phosphine ligand/base, led to new representatives of functionalized (aryl)diphenylphosphines (187) (see Scheme 17)^21,181,182  which were used as starting or intermediate reagents in the synthesis of silylated arylphosphines,²¹  polyfunctionalized phosphines with alkyne moieties¹⁸¹  and a new bioluminescent probe (see Section 2.6.1, 2.6.4, 2.6.7).¹⁸²  The same approach was used for the synthesis of 8-(diisopropylphosphino)-2-methylquinoline (188) as an intermediate compound for the synthesis of new NNP-pincer ligands (see Section 2.6.1),¹⁸³  and diorganylphosphino-substituted tris(amine) (189) as a precursor of a novel bidentate PP-ligand containing phosphine and triamidophosphite donor centers (see Section 2.6.5)¹⁸⁴  and a chiral bisphosphine (190) containing a spiro-oxindole scaffold.¹⁸⁵  Pd(OAc)₂-Catalyzed interaction of monoiodinated diketopyrrolopyrrole (DPP) with triphenylphosphine as the phosphorus source and the ligand gave a new phosphine (191) with a DPP moiety as the basis for the preparation of neutral fluorescent probes for bioimaging.¹⁸⁶  The P–C coupling reaction of 9-bromo-[7]helicene with diphenylphosphine catalyzed by Herrmann's catalyst (trans-bis(acetato)-bis[o-(di-o-tolylphosphino)benzyl]palladium(ii)) provided 9-diphenylphosphino-[7]helicene which was isolated as the corresponding borane complex (192).¹⁸⁷ 

The catalytic systems Pd(PPh₃)₄/base (NEt₃ or K₂CO₃) were also used for the coupling reactions of arylhalides with secondary phosphines to afford 2-diphenylphosphino-4,5-dimethoxybenzaldehyde (193)¹⁸⁸  and the sterically demanding (2,6-dibenzhydryl-4-methylphenyl)diphenylphosphine ligand (194).¹⁸⁹  Phosphaalkenes (195) bearing a phosphino group were obtained as low-yield (up to 10%) by-products in the course of the derivatization of (2,7-dibromofluorenyl)phosphaalkene with tributyl(heteroaryl)stannane under Stille coupling conditions (Pd(PPh₃)₄, THF, microwave irradiation) where a triphenylphosphine ligand of the catalyst acted as the phosphorus source.¹⁹⁰  A series of (para-aminoaryl)- and (para-aminoheteroaryl)-diadamantylphosphines (196) and diadamantyl(pyridine-4-yl)phosphine were synthesized by Pd(dba)₂/NaOBu^t-catalyzed coupling of the corresponding aryl- or heteroaryl-bromides with diadamantylphosphines.¹⁹¹ 

Di-(tert-alkyl)phosphonium triflates were successfully used as air-stable and odorless di(tert-alkyl)phosphine surrogates in the Pd-catalyzed coupling reactions with biphenylyltriflate or -bromide to provide a broad family of bulky di(tert-alkyl)biphenylylphosphine ligands (197).¹⁹²  The coupling of Z- and E-stiff-stilbene dibromides with diphenylphosphine, catalyzed by Pd(PPh₃)₄/NEt₃ and Pd(OAc)₂/KOAc systems, respectively, led to the corresponding Z- and E-isomers of photoswithable bisphosphine ligand (198) and (199) based on a stiff-stilbene scaffold.¹⁹³ 

Several small bite-angle bisphosphine ligands with alkylidene bridges (200) (see Scheme 17) were obtained by NiCl₂(PPh₃)₂-catalyzed P–C coupling of 1,1-dicloroalkenes with diphenylphosphine.¹⁹⁴  A model 2,7-bis(diphenylphosphinoethynyl)fluorene (201) and a copolymer with similar components (202) were prepared by Ni(AcAc)₂-catalyzed coupling of chlorodiphenylphosphine or dichlorophenylphosphine with corresponding bis(alkynes); the copolymer (202) selectively exhibited a bright blue fluorescence in the presence of gold(i/iii) ions.¹⁹⁵ 

New phosphine-oxazoline ligands (203) and (204) were synthesized by Ullman type coupling of the corresponding bromide or iodide precursors with diphenylphosphine in the presence of CuI/DMEDA/Cs₂CO₃ catalytic system.^196,197 

Manganese-mediated decarboxylative or deaminative coupling reactions of cyclohexyl N-hydroxyphthalimide ester or N-cyclohexyl-2,4,6-triphenylpyridium tetrafluoroborate with chlorodiphenylphosphine gave (cyclohexyl)diphenylphosphine in moderate (36%) and low (7%) yields.¹⁹⁸ 

A mild and versatile approach for the selective formation of a broad scope of unsymmetrical aryl- and aryl-alkyl-substituted tertiary phosphines and quaternary phosphonium salts has been developed, which was based on blue visible light-mediated C–P coupling between aryl and alkyl iodides and secondary or primary phosphines, Ph₂P–PPh₂ and even P₄ in the presence of an inexpensive organic photocatalyst, 4,6-dicyano-1,3,5-tris(diphenylamino)-2-fluorobenzene.¹⁹⁹ 

The development of transition-metal-catalyzed methods for the synthesis of phosphine derivatives poses a considerable challenge. Rhodium-, ruthenium or iridium-catalysed hydroarylation, hydrosylilation or hydroborylation reactions open the way to a wide row of new phosphine ligands. The rhodium-catalyzed phosphorus(iii)-directed hydroarylation of internal alkynes generated various alkenylated (205) and 2′,6′-dialkenylated (206) biarylphosphines with high selectivity.²⁰⁰  Ru(ii)-catalyzed direct alkylation of tertiary phosphines via hydroarylation of activated olefins, promoted by mono-N-protected amino acid (MPAA), provided a straightforward access to a large library of Buchwald-type bulky alkylated monophosphines (207) from commercially available biaryl phosphine.²⁰¹  The first ruthenium-catalyzed aromatic C–H silylation reactions between triaryl(heteroyl)- or diarylalkyl phosphines and hydrosilanes opened the way to the wide row of ortho-silylated arylphosphines (208).²¹ 

The mono- and geminal bis-borylation products (209) were prepared via iridium-catalyzed C–H-borylation of 1-di(R)phosphino-2-methylbenzene (R = Ph, Cy). For the dicyclohexyl-substituted phosphine, conditions have been identified to control for mono- and bis-borylation products. In contrast, the use of the diphenyl-substituted phosphine led to a rapid formation of the bisborylation product.²⁰² 

The deprotonation of the acidic methyl group at a borane protected phosphine with BuLi and subsequent electrophilic quenching with various chloroderivatives led to the formation of methylene-substituted diphosphines of the type PPhAr–CH₂–PR₂ (210) (Ar = 1-naphthyl (Np), 9-phenanthryl (Phen), 2-biphenylyl (Biph), R = Ph, Prⁱ)²⁰³  and 2,2′-bis(phosphino)-1,1′-binaphthyl (211).¹⁸ 

Reaction of a phosphine-substituted quinolone with lithium diisopropylamide, followed by the treatment with imidoyl chloride, furnished a ligand (212) in excellent yield.¹⁸³  Treatment of the alkynyl–substituted phosphole with EtMgBr generated the alkynyl Grignard reagent which was converted to internal alkyne (213) through the reactions with paraformaldehyde.¹⁶  Silyl substituted ferrocenylphosphines (214) were obtained by the subsequent treatment of the corresponding o-diphenylphosphinoformylferrocene with lithium N-methylpiperazide, Bu^tLi and chlorosilanes.⁸⁸  The mixed phosphine-phosphinoxide ligand (215) was obtained by the deprotonation of a benzothiophene moiety of the phosphine with BuLi and a following reaction with ClP(O)Ph₂.²⁰⁴  Simple and efficient approaches to the rhodium- and palladium-catalyzed modification of monophosphino-o-carboranes (64) (see Section 2.1, Scheme 4) into B³-arylated, B³,B⁶-diarylated, and B³,B⁶-dialkylated) as well as C-arylated and B⁶-halogenated derivatives (216), was developed.⁷⁶  The deprotonation of a tungsten alkene complex bearing a phosphine as Lewis base and a carbenium group as Lewis acid with BuⁿLi and the subsequent reaction with ketones resulted in η²-C,C′-phosphino-propargyl complexes (217).²⁰⁵  A Lewis pair-containing diphenylacetylene combining phosphine and borane moieties (218) was prepared in high yields by Sonogashira coupling of dimesityl(4-iodophenyl)borane with (4-ethynylphenyl)diphenylphosphine in the presence of CuI and Pd(PPh₃)₄.²⁰⁶ 

Triphenylphosphine- and diphenylpyridylphosphine-based porous aromatic frameworks (219) were synthesized via the straightforward Friedel–Crafts alkylation reaction using anhydrous FeCl₃ as a catalyst and biphenyl as the comonomer and dimethoxymethane as an external linkage (Scheme 18).²⁰⁷ 

Various phosphines bearing peripheral halogen groups serve as convenient precursors for the insertion of different functional groups and fragments into ligand molecules. Usually, initial halogen-metal exchange (as a rule, lithiation) in the corresponding halogen-containing phosphine occurs and subsequent interaction with the appropriate electrophilic reagents gives the desired products.

This approach was used for the synthesis of a series of new phosphine-borane FLPs (220) and (221) (see Scheme 19) able to photo-promote skeletal rearrangements,³⁹  new [2-(1′,4′-azaborin-4′-yl)phenyl]dicycloxexylphosphine ligands (222),³⁴  tris[4-(diisopropoxyboryl)phenyl]phosphine (223) as the precursor for the construction of covalent and hybrid organic frameworks,²⁰⁸  a new germinal P/B FLP (224) obtained from the brominated precursor (67) (see Section 2.1, Scheme 4)⁷⁹  and a new representative of phosphines containing a carbazolyl donor – triarylboryl acceptor unit (225) which was prepared from the bromo-substituted phosphine (21) (see Section 2.1, Scheme 2) and was used as the Lewis base component of new FLPs.³⁷  The lithiation/electrophilic trapping synthetic route with the use of phosphorus-containing electrophiles allowed routes to new representatives of trisphosphine ligands (226),²⁰⁹  asymmetrically substituted PNP-ligands (227)²¹⁰  and a new 1,5-diaza-3,7-diphosphacyclooctane ligand (228) with phosphonate peripheral groups for the synthesis of immobilized nickel complexes as electrocatalysts. It should be mentioned that in this case the dilithiation of the starting 1,5-diphenyl-3,7-di(p-bromophenyl)-1.5-diaza-3,7-diphosphacyclooctane (see Section 2.7) and the subsequent treatment with (EtO)₂P(O)Cl were performed at very low temperature (−108 °C)in order to prevent side reactions.²¹¹  The lithiation of (2-bromophenyl)di(o-tolyl)phosphine and the subsequent treatment of the lithiated derivative with Tol(Et₂N)PCl and then with HCl led to the derivative (229, X = Cl) which reacted with the corresponding o-lithio(pyrazolyl)benzene to give a new rigid tridentate NPP-ligand (229, X = –C₆H₄-PyrrMe₂-3,4) for the design of copper(i) and gold(i) TADF-fluorescent complexes.²⁴  The lithation of 6-bromo-5-diisopropylphosphinoacenaphthene, followed by the interaction with Ph₂BiCl, led to acenaphthene-based phosphine-bismuthine (230).²¹²  (Fluoro)diorganyl(2-diphenylphosphinophenyl)silanes (231) as substrates for the sila-Negishi coupling were prepared from (2-bromophenyl)diphenylphosphine through lithiation/R₂SiCl₂-trapping, followed by halogen exchange by the treatment with Na₂SiF₆.²¹³  A similar approach was used for the synthesis of a new bidentate ligand (232) containing two 5-diphenylphosphinoacenaphthen-6-yl moieties linked by the disilane fragment from 6-bromo-5-diphenylphosphinoacenaphthene and (ClSiMe₂)₂.²¹⁴  A lithation – I₂-trapping process was applied for bromine-iodine exchange in the phosphine Tipp₂P–C₆H₂–Pr^I₂–2,6-Br-4 to afford the useful iodine-functionalized crowded reagent (233).²¹⁵ 

The metallation of 4-iodo-5-diphenylphosphino-1-methylimidazole with PrⁱMgCl followed by a reaction with Mes₂BF yielded a very stable dimeric phosphine-functionalized ammoniumborate product (234).¹⁴ 

The lithiation of borane-protected phosphines with an iodoferrocenyl fragment (see Section 2.7), followed by an interaction with DMF, led to new representatives of borane-protected chiral (α-phosphinoethyl)ferrocenyl aldehydes (235) as intermediate reagents in the synthesis of ferrocene-based chiral PNP-ligands (see Section 2.6.3).²¹⁶  A similar approach including CO₂ as the carboxylating agent was used for the preparation of racemic and enantiopure borane complexes of P-chirogenic 2-diorganylphosphinobenzoic acids (236), as the precursors of P-chirogenic Trost ligands.¹⁰⁵ 

Various cross-coupling reactions also may be applied for the functionalization of halogen groups in tertiary phosphines. The PdCl₂(PPh₃)₂/CuI-catalyzed Sonogashira cross-coupling of (187, R¹ = Br-3, R² = COOMe-5) (see Section 2.5, Scheme 17) with trimethylsilylacetylene led to (alkynylaryl)diphenylphosphine (237, R¹ = SiMe₃, R² = Me) (see Scheme 19) which was hydrolyzed to the terminal ethynyl derivative (237, R¹ = R² = H).¹⁸¹  Iodine-substituted phosphine (233) was used in an analogous Sonogashira coupling with trimethylsilylacetylene to afford (alkynylaryl)phosphine (238, R = SiMe₃); its subsequent hydrolysis and the repeated coupling with (233) led to sterically crowded bisphosphine (238, R = C₆H₂-Pr^I₂-3,5-(PTipp₂)-4) with an ethynylene linker.²¹⁵  The Pd(PPh₃)₄/Na₂CO₃-catalyzed Suzuki coupling of the arylboronic acid prepared from Tipp₂P–C₆H₂–Pr^I₂–2,6-Br-4 by successive treatment with BuLi and B(OMe)₃ and used without isolation with 1,2-dibromobenzene led to the similar bisphosphine (239) with a 1,2-phenylene bridge.²¹⁵ 

(4-dioxaborolanylphenyl)diphenylphosphine (240) (see Scheme 19) was prepared by PdCl₂(DPPF)₂-catalyzed coupling between (4-bromophenyl)diphenylphosphine and 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaborolane.²¹⁷ 

The nucleophilic substitution of chlorine in bisphosphine (37) (see Section 2.1, Scheme 3) by treatment with NaOMe or MesOH in the presence of K₂CO₃ led to the corresponding 9-methoxy- and 9-aryloxy-derivatives (241).⁵⁰  The bulk polycondensation reaction between bis(4-fluorophenyl)phenylphosphine and 2,2-bis(4-trimethylsilyloxyphenyl)propane in the presence of CsF led to the polymer (242) (of approximately 85% purity due to the partial oxidation of the phosphine fragments) which was used as a polymeric reagent in the Mitsunobu reactions.²¹⁸ 

The alkylation of imidazoles and imidazolines with (2-chloromethylphenyl)diphenylphosphine followed by anion-exchange led to new representatives of imidazolium- and imidazolinium-containing phosphine ligands (243)^113,219  and (244), respectively, as precursors of phosphino-substituted N-heterocyclic carbene (NHC) ligands.²²⁰  Pentadentate N₃P₂ ligand (245) was synthesized by deprotonation of 2,6-di(5′-butylpyrazol-3′-yl)pyridine with NaH, followed by alkylation with (2-chloromethylphenyl)diphenylphosphine.²²¹ 

The condensation of phosphines containing aldehyde groups with various amines and diamines provides a route to a wide range of iminophosphines which may be reduced smoothly with NaBH₄ and similar reagents to aminophosphines. For example, new perfluorooctyl or bulky substituted bidentate phosphine-imine ligands (246),^222,223  sulfoxide containing imino- and amino-phosphines (247),²²⁴  the dual N-heterocyclic carbene-imino-phosphine ligand (248)²²⁵  and ferrocene-based chiral PNP-ligands (249)²¹⁶  were synthesized (Scheme 20).

The co-condensation of tris(4-formylphenyl)phosphine and p-phenylenediamine or benzidine under solvothermal conditions resulted in phosphine-based covalent organic frameworks (250).^226,227  Another phosphine-containing porous organic cage (251) was prepared from a [2 + 3] self-assembly of tris(4-formylphenyl)phosphine and (S,S)-1,2-diaminocyclohexane.²²⁸ 

Condensation of phosphinoaldehyde (193) (see Section 2.5, Scheme 17) with enantiopure tert-butanesulfinamide in the presence of Ti(OAlk)₄ as a Lewis acid forms the novel chiral sulfinyl imine phosphine (252).¹⁸⁸ 

A reductive amination of various phosphine-acetaldehydes which were generated by the reaction of sodium tris(acetoxy)borohydride with parent phosphonium dimers, with different phosphine-amines or NH₄OAc, gave novel unsymmetrical tripodal NPP’₂ and symmetrical NP₃ ligands (253), respectively.²²⁹ 

Ligand (254) was synthesized by a modified Seyferth–Gilbert homologation of P-protected (formylferrocenyl)phosphine with the Ohira-Bestman reagent.²³⁰  1′-Silylated vinylferrocenyl phosphines (255) were prepared from formylferrocenes (214) (see Section 2.6.1, Scheme 18) via Horner–Wadsworth–Emmons reactions with diethyl benzylphosponate.⁸⁸ 

The phosphinanones (132) (see Section 2.3, Scheme 13) were converted directly to the corresponding phosphorinanes (256) by the reaction with ethylene glycol in the presence of p-toluenesulfonic acid or to the corresponding 4-methoxyphosphorinanes by the reduction with LiAlH₄ and subsequent methylation with MeI.¹³¹ 

The condensation reactions between phosphines bearing carboxylic groups and alcohols, thioalcohols or amines 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-, thioester- or amide-derivatives. So, phosphine amide derivatives (257) (see Scheme 21),²³¹  (258),²³²  triaryl phosphines bearing terminal alkyne fragments (259) and (260),¹⁸¹  the ruthenocene-based phosphine amide obtained from L-valinol and cyclized with MsCl/DIPEA to phosphine-oxazoline ligand (261),⁴⁵  P-chirogenic Trost ligands (262) as a 1 : 2 : 1 mixture of the diastereomers (C*, C*, R_p, R_p), (C*, C*, R_p, S_p), and (C*, C*, S_p, S_p), which were separated by column chromatography on silica gel,¹⁰⁵  tris-amides (263) as well as mono-amides (264),²³³  alkyne-containing SNO probe (265),²³⁴  NIR fluorescent probes (266),²³⁵  (267),²³⁶  (268),²³⁷  mono-ester (269),²³⁸  and the mixed phosphonium-phosphine (270)¹⁸²  were obtained.

The mixed-monolayer Si(111) electrode (271) was prepared by the formation of covalent amide bonds between the amine unit of the Si–C₆H₄(CH₂)₂NH₂ substrate and the carboxylate unit on the phosphine ligand in the presence of DIC and DMAP.²³⁹ 

Treatment of racemic or enantiopure phosphine-carboxylic acids (110) (see Section 2.2, Scheme 9) with trimethylsilyldiazomethane resulted in the corresponding methyl ester (272).¹⁰⁵ 

A functionalization of phosphines containing peripheral amino groups by various electrophilic agents is often used for the synthesis of novel phosphines. The condensation reactions between phosphines bearing amine groups and various carbon acids or their derivatives in the presence of reagents for peptide synthesis (DCC, EDC, BOP, HBTU etc.) and organic bases (DMAP, DIEA, NEt₃) are commonly used for the preparation of various amido-derivatives. This methodology was used for the synthesis of diastereo- and enantiopure-bifunctional phosphines (273) (see Scheme 22) containing amino-acid-based amide fragments,^240,241  phosphines with dipeptide moieties (274) prepared on the basis of compounds (273, R¹ = C₆H₄Ph-2),²⁴¹  a novel amide-phosphine ligand KePhos (275) containing a phosphanorbornadiene core²⁴²  and a new phosphine (276) with an imido-group.²⁴³ 

Similar types of bifunctional phosphines have been obtained by the addition of amino-substituted phosphines to heterocumulenes. The addition to isothiocyanates afforded new chiral phosphines containing thiourea moieties, namely polyfunctional compound (277) with an additional amide fragment,²⁴⁴  new representatives of ferrocene-based bisphosphine ZhaoPhos ligands (278),⁷⁸  and the benzhydryl-thiourea substituted phosphine (279).²⁴⁵  The addition of 2-diorganylphosphinobenzyl- and 2-diphenylphosphinoethylamines to isothiocyanates prepared in situ from chiral styrenes bearing simultaneously indolyl, oxindolyl and 2-aminoaryl substituents and thiophosgene in the presence of pyridine led to axially chiral thiourea-phosphines (280).²⁴⁶  The addition of (1′-aminoferrocen-1-yl)diphenylphosphine to carbodiimides in the presence of ZnEt₂ or after the treatment with BuLi led to new phosphinoferrocene-guanidine ligands (281).²⁴⁷  Most new polyfunctional phosphines with amide (peptide), imide and thiourea fragments are of interest as new organocatalysts.^{78,240–242,244,245} 

The condensation reactions between phosphines with peripheral amine groups and various aldehydes are used for the synthesis of imino-phosphines, and their subsequent reduction with different borohydride reagent (NaBH₄, NaBH₃CN, Na[BH(OAc)₃) (a reductive amination of aldehydes) is a common approach to novel phosphine-amines.

The use of appropriate amino-substituted phosphines and aldehydes provided routes to pyrrolyl- and ferrocenyl-substituted imino-phosphines (282) (see Scheme 22)²⁴⁸  and (283, R – nothing),²⁴⁹  whereas the reductive amination route led to the corresponding amino-phosphine ligand (283, R = H),²⁴⁹  a series of new PNN-ligands (284) containing ferrocene and (benzo)imidazole fragments,²⁵⁰  spiro-amino-phosphines (285) with the peripheral phosphoryl group as the precursors of spiro-PNP bisphosphine ligands (153) (see Section 2.4.1, Scheme 14),¹⁴⁷  one of bisphosphines (153, Ar¹ = C₆H₃Bu^t₂-3,5, Ar² = Ph)¹⁴⁷  and chiral amino-functionalized phosphine ligand (286) with binaphthylene core.²⁵¹ 

A series of N-alkylated sulfinylamide-phosphine ligands (287),²⁵²  (288),²⁵³  (289)¹⁰³  and the N-styrylmethyl functionalized Nixantphos-type monomer (290)²⁵⁴  were obtained by the treatment of the corresponding secondary amine-phosphine precursors with alkyl or benzyl halides after the initial deprotonation with NaH^252,254  or BuLi¹⁰³  or in the presence of KOH/TBAB base.²⁵³ 

The interaction of phosphines containing amine group with organoelement electrophilic reagents allowed the synthesis of a variety of N-functionalized derivatives. The reactions of lithium 2-diphenylphosphinopyrrolide with chlorodiorganylphosphines led to a series of 1-amidophosphinito-2-phosphinopyrrole ligands (291) (see Scheme 23).²⁵⁵  The hydrolysis of indolylphosphine (49, X = SO₂Ph, R¹ = R² = C₆H₄OMe-2) (see Section 2.1, Scheme 2) led to N-unprotected indolylphosphine (49, X = H, R¹ = R² = C₆H₄OMe-2). Its subsequent deprotonation with BuLi and treatment with Ph₂P(O)Cl gave a new analogue of compounds (49, X = P(O)Ph₂, R¹ = R² = C₆H₄OMe-2).⁶²  The interaction of phosphino-substituted tris(amines) (189) (see Section 2.5, Scheme 17) with PCl₃ in the presence of NEt₃ afforded PP-ligands (292) containing a nontrigonal phosphorus triamide moiety tethered by a phenylene linker to a diphenylphosphino group.¹⁸⁴ 

1,2-Bis[(diphenylphosphinomethyl)amino]benzene reacted with SbCl₃ in the presence of NMe₃ to form diphosphine-chlorostibine ligand (293), which was used for the synthesis of metal complexes containing a pincer diphenylstibenium ligand, inaccessible in the free form.²⁵⁶ 

The interaction of 2-diisopropylphosphinopyrrole with LiAlH₄ or AlMe₃ led to the PAlP proto-pincer ligand (294)²⁵⁷  or tripodal alane/trisphosphine ligand (295).²³ 

A deprotonation of a bis(diphenylphosphino)-functionalized β-diketiminato compound with K[N(SiMe₃)₂], followed by treatment with GeCl₂(dioxane) complex or SnCl₂, afforded the germylene and stannylene chloride complexes (296, X = Cl) which reacted with [Na(dioxane)_x]P═C═O to give the novel phosphaketene derivatives (296, X = P═C═O), whereas chloride abstraction with NaBAr_F led to bis-phosphino-functionalized germylidene and stannylidene salts (297).²⁵⁸ 

2-[(2′-Diphenylphosphinophenyl)amino]benzonitrile (298) as a precursor for the synthesis of phosphine-oxazoline ligands was obtained by the nucleophilic substitution of 2-fluorobenzonitrile with 2-diphenylphosphinoaniline in the presence of KOBu^t.¹⁹⁷  New [N,N-bis(ferrocenylmethyl)aminoalkyl]diphenylphosphines (299) were synthesized by a nucleophilic substitution of (ferrocenylmethyl)trimethylammonium iodide with diphenylphosphinoalkylamines in the presence of K₂CO₃.²⁴⁹ 

The deprotection of phosphino-substituted carbamates (257) (see Section 2.6.4, Scheme 21) with trifluoroacetic acid led to N-((1R,2R)-2-aminocyclohexyl)- and N-((1R,2R)-2-amino-1,2-diphenylethyl)-2-(diphenylphosphino)benzamides (300) having terminal amino groups.²³¹  The interaction of 3-(2′-(diphenylphosphino)ethyl)oxazolidin-2-one with NaSMe led to the PNS-pincer ligand (301) for the preparation of air- and moisture-stable manganese catalysts.⁹⁴ 

Etherification of hydroxy-phosphines with different triflates, tosylates and mesitylates, in the presence of cesium or potassium carbonates in DMF results in corresponding phosphine-ethers. Thus, 2-(perfluorohexyl)ethyl substituted phosphine (302),²⁵⁹  macrocyclic phosphine (172, n = 2, R¹ = Buⁱ, R² = H) (see Section 2.4, Scheme 2.4.2) as R,R-isomer,¹⁶⁴  photo-switchable ligands (303),²⁶⁰  and PEG5000-containing phosphines (304)³⁰  were obtained (see Scheme 24).

A series of Fréchet-type dendrons (305) with N,P-iminophosphine terminal moieties were afforded via Williamson-ether reactions from the corresponding Schiff-base phosphines containing a phenol group and the bromido-Fréchet dendrons.²⁶¹  Phosphite-phospholane ligand (306) was synthesized from (S_ax)-BIPHEN bromophosphite and (S,S)-hydroxymethylphospholane in the presence of DABCO.²⁶²  A condensation of 2-hydroxy-di(aryl)phosphine with various BOC- and Fmoc-protected amino acids under the peptide synthesis conditions (DCC, DMAP) afforded phosphines (307).¹⁷⁰  MOP-alkene ligands (308) were prepared via Pd-catalyzed reactions of corresponding aryltriflates with β-styrylboronate.²⁶³  The interaction of unprotected chiral phenol-functionalized ferrocenylphosphines (74, R = H, X – nothing) (see Section 2.1, Scheme 5) with phosphazene-based dendrimers containing P(S)Cl₂-terminal groups in the presence of Cs₂CO₃ afforded P-stereogenic dendritic ferrocenyl phosphines (309) as the supporting ligands for the ruthenium catalysts of redox-switchable transfer hydrogenation of ketones.⁸⁶ 

Addition of Grignard or RLi reagents to various phosphine sulfinyl imines gave the corresponding sulfinyl amine ligands (310)^188,264  and (311) (see Scheme 25).¹³⁸  Selective click reactions of the alkyne moieties of phosphines (259), (260) (see Section 2.6.4, Scheme 21) and (254) (see Section 2.6.3, Scheme 20) with various azides catalysed by Cu(CH₃CN)₄BF₄ resulted in a wide row of triazolyl derivatives (312), (313)¹⁸¹  and (314).²³⁰  Phosphine–amide-oxazolyl ligands (315) were prepared by the reactions of phosphine-amine benzonitrile (298) (see Section 2.6.5, Scheme 23) with amino-alcohols in the presence of Zn(OTf)₂.¹⁹⁷  A reaction of phosphine (270) (see Section 2.6.4, Scheme 21) bearing nitrile group with d-cysteine led to the new ligand (316).¹⁸²  Rh-Catalyzed hydroaminomethylation of vinyl-phosphine derivatives appeared to be a versatile tool to promote their covalent immobilization onto amine-carbon nanotubes or iron oxide magnetic nanoparticles to form phosphine-functionalized materials (317) and (318), respectively.²⁶⁵  The olefin metathesis of phosphines (58) (see Section 2.1, Scheme 4) and (111) (see Section 2.2, Scheme 9) with terminal alkene groups under dilute conditions using Grubbs’ catalyst generated the corresponding macrocycles (319) as a mixture of isomers which were separated using column chromatography and subsequently hydrogenated using Wilkinson's catalyst to produce the saturated derivatives.^70,106 

Borane-protected diphosphine (320) was synthesized by nucleophilic substitution of a hydroxyl-group in the corresponding monophosphine (136) (see Section 2.3, Scheme 13) with Ph₂PH in the presence of AcOH.¹³⁴  New diferrocenylphosphines (321) were obtained by the substitution of two dimethylamino groups by acetoxy groups and their subsequent elimination upon heating in acetic anhydride.²⁶⁶  Reaction of di-o-tolyl-(trimethylsilyl)methylphosphine with dichlorophenylphenyl phosphine gave tris-phosphine (322) in 70% yield.²⁶⁷ 

The monolithiation of 2,6-dibromotoluene with BuⁿLi followed by the interaction with bis(o-diisopropylphosphinophenyl)chlorophosphine led to (3-bromo-2-methylphenyl)bis(o-diisopropylphosphinophenyl)phosphine which in turn was converted to the corresponding Grignard reagent and quenched with the second equivalent of bis(o-diisopropylphosphinophenyl)chlorophosphine to yield a new hexaphosphine ligand (323) (see Scheme 25).²⁶⁸ 

A mono-quaternization of 1,2-bis(diphenylphosphino)ethane with one equivalent of 2-bromo-4′-cyanoacetophenone led to an unsymmetrical phosphine-phosphonium ligand (324) which was converted to the corresponding phosphine-ylide ligand (325).²⁶⁹ 

PCP-carbodiphosphorane ligand (326) has been obtained from [CH(dppm)₂]Cl and an excess of sodium amide in liquid ammonia.²⁷⁰ 

Bis-phosphine fluoroborate (327) was prepared by fluorination of bis-phosphine–borane with cesium fluoride.²⁷¹  The phosphinoboration of acyl phosphines with Ph₂PBR₂ gave corresponding diphosphine derivatives (328) and (329).¹²³ 

Two covalent organic frameworks (330) and (331) (see Scheme 26) comprising Lewis basic P(iii) centres and Lewis acidic boron atoms were prepared by polycondensation reactions of tris(4-diisopropoxyborylphenyl)phosphine (223) (see Section 2.6.2, Scheme 19) with tetrahydroxy-dimethylanthracene and hexahydroxytriphenylene.²⁰⁸ 

A fluorodearylation of phosphine-bismuthine (230) (see Section 2.6.2, Scheme 19) with BF₃·OEt₂ followed by treatment with an excess of sodium or potassium halides gave halobismuthine derivatives (332, X = Cl, Br, I); the subsequent interaction of (332, X = Cl) with PhSLi or (5-diisopropylphosphinoacenaphth-6-yl)lithium led to phenylthiobismuthine (332, X = SPh) or bis(5-diisopropylphosphinoacenaphth-6-yl)phenylbismuthine (332, X = AcenaphPPrⁱ₂) respectively.²¹²  The treatment of (5-diphenylphosphinoacenaphth-6-yl)chlorodimethylsilane with lithium in the presence of 4,4′-di-(tert-butyl)biphenyl led to bisphosphino-disilane (232) (see Section 2.6.2, Scheme 19).²¹⁴  The phosphinylvinyl Grignard reagent reacted with MeGaCl₂, EtGaCl₂, or MeInCl₂ by salt elimination and the formation of the frustrated Lewis pairs (333).²⁷² 

Pd- and Ni-catalysed Si–F bond activation of fluorosilane-phosphines (231) (see Section 2.6.2, Scheme 19) under mild conditions and the coupling with diarylzinc reagents were successfully performed to give arylsilylated phosphines (334).²¹³  Silylated norbornene amino(phosphino) derivatives (335) were prepared from the corresponding iminophosphines with BuLi and chlorosilanes.²⁷³ 

An addition of various phosphorus-containing reagents to unsaturated compounds is sometimes used for the synthesis of functionalized phosphines. The PBu₃-catalyzed trans-phosphinoboration of alkynoate esters led to a wide variety of trans-α-phosphino-β-borylacrylates (336) (see Scheme 27) in moderate to good yields with high regio- and Z-stereoselectivity.²⁷⁴  The addition of the silylphosphine Ph₃SiPBu^t₂ to the phosphaketene Ph₃Ge–P═C═O led to the E-isomer of phosphino-substituted phosphaalkene (337, R¹ = Ph, R² = Bu^t), whereas the Z-isomer of this phosphino-phosphaalkene was obtained by the interaction of K⁺[Bu^t₂P–C(O)═PGePh₃]⁻ with Ph₃SiCl. These isomers interconverted thermally and photochemically due to the reversibility of the silylphosphination; this reversibility also provided silyl and phosphine exchange processes to give various phosphino-phosphaalkenes (337).²⁷⁵  An unusual 1,1-addition of the P–P bond of α-C₂-bridged biphospholes to terminal alkynes in the presence of one equivalent of KOBu^t in THF provided a simple access to the previously unknown 1,3-diphosphepines (338); in some cases spiro-tricyclic bisphosphines (339) were isolated as by-products in yields up to 15%.²⁷⁶  The interaction of allenes containing a peripheral secondary amino group with diarylphosphine oxides in the presence of Tf₂O and 2,6-lutidine proceeded as intramolecular aminophosphination through the formation of electrophilic intermediate [Ar₂P]⁺[OTf]⁻ and led to a wide variety of 1-phosphinoalkenyl substituted nitrogen-containing heterocycles (340) and (341).²⁷⁷ 

The ring-opening of quaternary phosphiranium triflates or tetrafluoroborates with primary and secondary arylamines afforded a wide range of tertiary phosphinoethylamines, (342) and (343), with two phosphinoethylamino fragments linked by the organic spacer.²⁷⁸  A nucleophilic substitution of the dimethylamino group of iodinated Ugi's amine with secondary phosphines in the presence of acetic acid, followed by the treatment with BH₃·SMe₂, led to borane-protected enantiopure 1-(α-diorganylphosphinoethyl)-2-iodoferrocene (344) as the precursor of the borane-protected phosphino-aldehyde (235) (see Section 2.6.2, Scheme 19).²¹⁶  The interaction of (3-aminopropyl)triethoxysilane with KPPh₂ led to (3-(diphenylphosphino)propyl)triethoxysilane ligand (345).²⁷⁹ 

The Mannich-like condensation between hydroxyalkylphosphines and amines is an effective approach to the synthesis of various α-aminoalkylphosphines. Hydroxyalkylphosphines are usually generated in situ from P–H phosphines and aldehydes (mainly formaldehyde) or from the corresponding hydroxymethylphosphonium salts with bases, 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 a new bulky bis(diphenylphosphinomethyl)(2,6-dibenzhydryl-4-methylphenyl)amine ligand (346),¹⁸⁹  trisphosphine ligands (347)²⁸⁰  with the central aminomethylphosphine fragment and tris((2-diphenylphosphinomethylamino)phenyl)amine (348) as a pro-ligand for the synthesis of heterobimetallic scandium-group 10 metal complexes with unusual LM-Sc dative bonds.²⁸¹  Mannich-type condensations were successfully used for the synthesis of cyclic aminomethylphosphines, namely new representatives of 1-aza-3,5-diphosphacyclohexanes (349) obtained as the mixtures of R_pR_p/S_pS_p isomers,²⁸²  new 1,5-diaza-3,7-diphosphacyclooctane ligands (350) with various substituents on heteroatoms (the compound (350, R¹ = C₆H₄Br-4, R² = Ph) was the precursor of the analogous cyclic diphosphine (228) with phosphonate peripheral groups (see Section 2.6.2, Scheme 19)),^211,283,284  new representatives of 18-membered P₄N₂-corands (351, n = 4)²⁸⁵  and previously unknown 22-membered P₄N₂-corands (351, n = 6)²⁸⁶  which were obtained by the stereoselective condensations of the corresponding 1,n-bis(arylphosphino)alkanes, formaldehyde and primary amines and isolated as the individual stereoisomers (R_pR_pR_pR_p/S_pS_pS_pS_p or R_pS_pS_pR_p in the case of 18-membered corands and R_pS_pS_pR_p in the case of 22-membered corands).^285,286 

The enzyme invertase containing amino groups was successfully immobilized on chitosan using tris(hydroxymethyl)phosphine as a cross-linking reagent which formed aminomethylphosphine linkers; the immobilized invertase was used as a catalyst for the production of bioethanol.²⁸⁷  The synthetic procedure for the large-scale preparation of the important aminomethylphosphine ligand phosphatriazaadamantane (PTA) by the interaction of tris((hydroxymethyl)phosphine with a hexamethylenetetramine/formaldehyde mixture has been improved by the final treatment of the reaction mixture with formaldehyde and by the use of an inert atmosphere;these changes allowed the isolation of PTA of high purity.²⁸⁸ 

Cryptoaldehydes have also been used in the synthesis of aminomethylphosphines. The cyclocondensation of N-mesityl-2-(phenylphosphino)aniline with dimethylformamide dimethyl acetal led to cyclic aminomethylphosphine (352).²⁸⁹  The condensation of diphenylphosphine with glyoxylic acid hydrate and primary amines gave several new representatives of α-diphenylphosphinoglycines (353) as the basis of organonickel catalysts for ethylene oligomerization.^290,291  A summary of data concerning the chemistry α-phosphino-α-amino acids has been noted in a review.⁵ 

The base decomposition of bis(4-methoxyphenyl)bis(hydroxymethyl)phosphonium chloride with NEt₃ led to the diaryl(hydroxymethyl)phosphine (354) (see Scheme 27), which reacted with sarcosine-glycine peptide to give the corresponding phosphine-peptide conjugate (355); the ligands (354) and (355) were used for the synthesis of cytotoxic copper(i) complexes.²⁹² 

The light-induced decomposition of phosphaallene TippP═C═CHBu^t (Tipp = C₆H₂Prⁱ₃-2,4,6) or the interaction of TippP(C≡CBu^t)₂ with Buⁱ₂AlH under mercury vapor lamp irradiation through the intermediate formation of the phosphaallene stereoselectively led to an unusual tricyclic phosphine (356) (see Scheme 28) which is a rare example of a compound with a strained phosphirane cycle included into the tricyclic structure.²⁹³  A very reactive phosphaallene PhP═C═CHBu^t began to decompose in the course of its preparation from PhP(C≡CBu^t)₂ and ((SiMe₃)₂CH)₂AlH to give a trimerization product (357) along with other compounds.²⁹⁴  The hydroboration of a stable phosphaallene Mes*P–CH═C═CHBu^t (Mes* = C₆H₂Bu^t₃-2,4,6) with H₂BC₆F₅·SMe₂ unexpectedly led to the formation of the P₂C₂B-heterocycle (358).²⁹⁴ 

The treatment of bicyclic phosphine (119) (see Section 2.2, Scheme 11) first with triflic acid and secondly with Me₄NF resulted in anthracene elimination and the formation of fluoro(1,2,3-tri-tert-butylcyclopropen-3-yl)phosphonite, which interacted with LiTMP to give tri-tert-butyl-phosphatetrahedrane (359).¹¹⁴ 

The known analogue of tricyclic phosphine (75) (see Section 2.1, Scheme 5) with SiMe₂Ph substituents reacted with an excess of Mo(CO)₆ to form the molybdenum complex of a ring-expanded ligand due to the insertion of a CO unit into P–C bond; the demetalation of this complex with DPPE gave the free unsymmetrical tricyclic ligand (360).²⁹⁵ 

The template transformation of tetrafluorinated chalcone-phosphine ligands in their complexes with PdCl₂ via nucleophilic substitution of one fluoro group with carbonyl oxygen and the subsequent oxidation with peroxides in aged THF led to the formation of PO-chelate complexes of bicyclic ligands (361), which were released from the complexes by the treatment with DPPE.²⁹⁶ 

The lithiation of borane-protected diphenylphosphinocyclopentadiene (68) (see Section 2.1, Scheme 4) followed by the interaction with the ruthenium complex [(CpCO₂Me)Ru(CH₃CN)₃]⁺PF₆⁻ afforded the borane-protected 1-diphenylphosphino-1′-methylcarboxyruthenocene (362) as the key intermediate in the synthesis of ruthenocene-based phosphine-oxazoline ligand (261) (see Section 2.6.4, Scheme 21).⁴⁵ 

1-[2-(N-(3-diphenylphosphinopropyl))aminoethyl]pyrrolidine (363) was synthesized by a three-step process without the isolation and the purification of all intermediate products; this process included the acylation of the starting 1-(2-aminoethyl)pyrrolidine with acryloyl chloride in the presence of NEt₃, the hydrophosphination of the unsaturated amide with Ph₂PH in the presence of Et₄N⁺OH⁻ and the final reduction of the amide fragment to an amine with LiAlH₄.²⁹⁷ 

A series of new porous organic ligands (POL) (364) was obtained by the AIBN-catalyzed polymerization of tris(styryl)phosphines with various substituents at the meta- or para-positions of the styryl groups; POLs (364) were used for the preparation of palladium(II) catalysts for the distannylation of terminal alkynes.¹²  The AIBN-catalyzed copolymerization of tris(4-vinylphenyl)phosphine and sodium 4-vinylbenzenesulfonate led to a new porous organic polymer (POP) as the support for a bifunctional heterogeneous ruthenium catalyst for the N-formylation of amines with CO₂.²⁹⁸  The analogous three-component copolymerization of tris(4-vinylphenyl)phosphine, divinylbenzene and styrene or 4-tert-butylstyrene gave monolithic macroporous polymers (365) with a tuned content of phenylene cross-linking units resulting in variable porosity, which were used as the support for the palladium catalysts of Suzuki–Miyara cross-coupling.^299,300  Phosphine-functionalized porous ionic polymer (366) as a support of Pd-nanoparticles for water-mediated reduction of nitrobenzene with H₂ was synthesized by a solvothermal, free-radical and cross-linked copolymerization method from 4-vinylbenzyl-tris-(4-vinylphenyl)-phosphonium chloride and tris(4-vinylphenyl)phosphine.³⁰¹  The linear copolymer of phosphine and pyrrolidone (367) was synthesized by AIBN polymerization of vinyl-pyrrolidone and diphenylphosphinostyrene and was further immobilized in the network formed from hydroxyethyl methacrylate, poly(ethylene glycol) dimethacrylate and diphenylphosphinostyrene to form a semi-interpenetrating polymer network hydrogel.³⁰² 

A CPAD/AIBN catalyzed RAFT-copolymerization of styrene, di(pentafluorophenyl)(4-vinylphenyl)borane and dimesityl(4-vinylphenyl)phosphine at a feed ratio 0.8 : 0.1 : 0.1 afforded a linear copolymer (368) in which the bulky borane and phosphine units served as Lewis acceptors and donors, so that the treatment of this polymer with CO₂ led to intrachain folding due to the formation of zwitterionic –Mes₂P⁺–C(O)–O–B(C₆F₅)₂– linkers; these CO₂-folded single-chain nanoparticles could function as recyclable carboxylase mimics.³⁰³  The nitroxide-mediated copolymerization of diphenyl(4-vinylphenyl)phosphine, diphenyl(4-vinylphenyl)phosphine oxide and styrene yielded a linear copolymer with phosphine and phosphine oxide donor sites, which underwent a similar intrachain folding with the formation of nanoparticles via a selective complexation of PtCl₂ and Eu(β-diketonate)₃ centers; these single-chain nanoparticles demonstrated both catalytic and luminescent properties.³⁰⁴ 

Nixantphos-functionalized styrene (290) (see Section 2.6.5, Scheme 22) was incorporated as a co-monomer in core-cross-linked micelle synthesis to give a nixantphos@CCM polymer (369) as nanoreactor to the aqueous biphasic hydroformylation of 1-octene.²⁵⁴ 

New and known tertiary phosphines all exhibit classical reactivity. They form phosphonium derivatives (salts and zwitter-ions) 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 and unsaturated compounds activated by electron-withdrawing groups). Several examples of phosphonium salt formation by the reactions of phosphines with less usual electrophiles, namely tris(2,6-dimethoxyphenyl)carbenium salts, has been described.³⁰⁵  Two short reviews summarized the chemistry of phosphine-based FLPs, including the formation of zwitter-ionic phosphonium derivatives, as a novel strategy for the design and application of the main group chemistry and the development of new metal-free catalytic processes.^306,307  Tertiary phosphines may be oxidized to form the corresponding chalcogenide derivatives (oxides, sulphides and selenides). The Staudinger reactions of tertiary phosphines with organic azides and related reagents with the formation of iminophosphoranes and similar derivatives with P═N bonds continue to attract attention because these reactions are widely used for biorthogonal ligation in biochemistry.^308,309  The most interesting examples of unusual reactivity of tertiary phosphines published in 2020 are a TiCl₄-mediated intramolecular cyclization of divinyl-substituted bis(ferrocenyl)phosphine (321) (see Section 2.6.7, Scheme 25) with the formation of eight-membered phosphacycle 4-methyl-1-phenyl-diferroceno-5-Z-ethylene-1-phosphinoxide²⁶⁶  and Pd-catalyzed three-component reactions between triarylphosphines, as the sources of arylene moieties, diarylacetylenes and primary amines with the formation of highly substituted indoles.³¹⁰ 

The use of tertiary phosphines as ligands for metal complex catalysis and as organocatalysts of various organic reactions remains their main field of application. Several reviews summarizing modern advances in the applications of phosphine catalysts (along with other types of basic organocatalysts) in different types of annulation reactions,^311–317  addition reactions,^313,317  and rearrangements³¹⁸  have been published in 2020.

Tertiary phosphines were often used as mild reducing agents, in particular as disulfide reducing agents in biological and medical studies (mainly tris(2-carboxyethyl)phosphine (TCEP), tris(hydroxymethyl)phosphine (THP) and tris(hydroxypropyl)phosphine (THPP)),³¹⁹  and deoxygenative reagents in the organic synrhesis.^320,321  Several reviews considered the application of phosphines in biorthogonal chemistry.^322,323  The Ph₃P/NaI system has been used as a decarboxylative reagent in photocatalytic cascade reactions,³²⁴  and tris(2,4,6-trimethoxyphenyl)phosphine has been applied as the methoxylating reagent for the conversion of acylfluorides to the corresponding methyl esters under metal-free conditions.³²⁵