Quaternary Stereocenters via an Enantioconvergent Catalytic S(N)1 Reaction

The unimolecular nucleophilic substitution (S(N)1) mechanism figures prominently in every introductory organic chemistry course. In principle, stepwise displacement of a leaving group by a nucleophile via a carbocationic intermediate allows for the construction of highly congested carbon centers. However, the intrinsic instability and high reactivity of the carbocationic intermediates render it very difficult to control product distributions and stereoselectivity in reactions proceeding via S(N)1 pathways. Here we report asymmetric catalysis of an S(N)1-type reaction mechanism resulting in the enantioselective construction of quaternary stereocenters from racemic precursors. The new transformation relies on the synergistic action of a chiral hydrogen bond donor (HBD) catalyst with a strong Lewis acid promoter to mediate the formation of tertiary carbocationic intermediates at low temperature and achieve high levels of control over reaction enantioselectivity and product distribution. The work presented here provides a foundation for the enantioconvergent synthesis of other fully-substituted carbon stereocenters.