Chapter 10: Demystifying the Soai Reaction1
Published:28 Oct 2022
S. V. Athavale and S. E. Denmark, in Asymmetric Autocatalysis: The Soai Reaction, ed. K. Soai, T. Kawasaki, and A. Matsumoto, The Royal Society of Chemistry, 2022, ch. 10, pp. 199-238.
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Displaying robust asymmetric amplification, extraordinary sensitivity toward initial chiral imbalances, a capacity for statistical symmetry breaking, and a natural predisposition to evolve towards homochirality, the sui generis Soai reaction stands as a monumental challenge for mechanistic elucidation. The recent discovery of amplifying autocatalysis in a related pyridine system proved that only one nitrogen atom is necessary for the Soai phenomenon. Spectroscopic enquiries led to a ‘pyridine assisted cube-escape’ model for the generation of the active square-macrocycle-square (SMS) tetrameric alkoxide aggregate. Further kinetic and computational studies suggested that this homochiral cluster facilitates enantioselective alkylation of the substrate through a floor-to-floor binding pathway. Such binding is naturally precluded in the heterochiral tetramer, providing a basis for the non-linear effect in the reaction. The strategy of mixed catalyst–substrate experiments provided an opportunity to dissect structural contributions in the Soai reaction and revealed new aspects of (auto)catalyst function. Finally, a study of three related autocatalytic systems allowed an assessment of the role played by the strength of nitrogen–zinc interactions in influencing autocatalytic progression. By providing a logic for autocatalyst evolution and function, these findings address longstanding questions about the Soai reaction and provide new observations that should stand as a test for alternative mechanistic proposals.