Stereodivergently asymmetric synthesis of chiral phosphorus compounds by synergistic combination of ion-pair catalyst and base

Stereodivergently constructing the designed products having adjacent multi-stereocenters via a given reaction, with excellent control of both absolute and relative configurations, presents one of the substantial hurdles in asymmetric catalysis. Herein, we report a precisely stereodivergent asymmetric protocol by synergistic combination of phosphonium-involved ion-pair catalysis and base for accessing to chiral phosphorus compounds bearing two adjacent chiral centers particularly containing an acidic protonated enantioenriched carbon atom, having broad functional group compatibility in both dynamic and thermodynamic processes under mild reaction conditions. Two keys for the success in constructing these stereoisomers with high levels of regio-, diastereo-, and enantioselectivities were contained: firstly, the precise stereo-control in providing dynamic products was enabled by bifunctional phosphonium salt catalyst with semi-enclosed cavity; secondly, the readily stereospecific transformation of adducts from dynamic to thermodynamic version was initiated by achiral base. All four stereoisomers could be readily accessed even in gram-scale in high yields with maintaining excellent stereoselectivities, illustrating the potential of this synergistic catalytic methodology in organic synthesis. Moreover, mechanistic studies including density functional theory (DFT) calculations and control experiments provide insights into the mechanism.

Automated summary

A precise stereodivergent asymmetric protocol using phosphonium-involved ion-pair catalysis and base has been developed to access chiral phosphorus compounds with adjacent chiral centers. This methodology shows good compatibility with various functional groups and can produce high yields of four stereoisomers with excellent stereoselectivities, demonstrating its potential in organic synthesis.