Anderson Lab at UChicago Chemistry (@jsandersonlab.bsky.social)

Asymmetric Synthesis of Tertiary Alkyl Boronates via Ligand-Controlled Enantioconvergent Homologation 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. https://pubs.acs.org/doi/10.1021/jacs.6c04941