Doubly stereoconvergent construction of vicinal all-carbon quaternary and tertiary stereocenters by Cu/Mg-catalyzed propargylic substitution

The construction of vicinal, congested stereocenters with high selectivities is of general utility in chemistry. Here the authors report a doubly-stereoconvergent, Cu/Mg-catalyzed asymmetric propargylic substitution reaction to convert simple starting materials to products with vicinal tertiary and all-carbon quaternary stereocenters in high yields and excellent diastereo- and enantioselectivities The construction of vicinal, congested stereocenters with high selectivities is of general utility in chemistry. To build two such stereocenters in one step from readily available starting materials is very desirable, but remains challenging. We report here a doubly stereoconvergent, Cu/Mg-catalyzed asymmetric propargylic substitution reaction to convert simple starting materials to products with vicinal tertiary and all-carbon quaternary stereocenters in high yields and excellent diastereo- and enantioselectivities. Both the nucleophiles and the electrophiles employed in this transformation are racemic. This reaction uses earth abundant metal catalysts, operates under ambient conditions, and demonstrates broad substrate scope. The products of this reaction are functional group rich and synthetically versatile. Key to the success of this development is the devise of a Cu/Mg dual catalytic system and the identification of a bulky tridentate pyridinebisimidazoline (PyBim) ligand.

Automated summary

The authors report a doubly-stereoconvergent, Cu/Mg-catalyzed asymmetric propargylic substitution reaction that can selectively construct products with vicinal congested stereocenters. This reaction uses readily available starting materials, environmentally friendly catalysts, and has a broad substrate scope.