Nature Synthesis - An enantioconvergent approach for direct asymmetric insertion of racemic carbon-, oxygen-, nitrogen-, sulfur- and silicon-substituted carbenoids into carbon–boron bonds is...

Tertiary alkyl boronates are highly versatile synthetic intermediates; however, their asymmetric preparation remains challenging and exhibits limitations. Here we report a distinct ligand-controlled strategy for the synthesis of chiral tertiary alkyl boronates via enantioconvergent homologation with racemic tertiary α-thio lithium carbenoids. The enantioselectivity in this process is controlled by chiral hydrobenzoin-derived diether ligands. Both aryl and alkyl boronates give high yield and excellent enantioselectivity (up to >99:1 e.r.), showing good functional group tolerance. Mechanistic studies support an unusual pathway involving ligand-mediated dynamic thermodynamic resolution of racemic carbenoids, followed by rapid ate-complex formation and an indium-mediated stereospecific 1,2-migration. The utility of this strategy is demonstrated in the asymmetric construction of various fully substituted stereocenters and concise modular syntheses of precursors for muscarinic M3 receptor antagonists.

An enantioconvergent approach for direct asymmetric insertion of racemic carbon-, oxygen-, nitrogen-, sulfur- and silicon-substituted carbenoids into carbon–boron bonds is reported, enabled by a class...