Cu-catalysed intramolecular radical enantioconvergent tertiary β-C(sp3)–H amination of racemic ketones

Abstract

In contrast to the wealth of enantioselective prochiral C(sp3)–H functionalization that is transition-metal-catalysed, the enantioconvergent transformation of racemic tertiary C(sp3)–H bonds (pKa > 25) still represents a vastly uncharted domain. The mechanistic limitation is partial or complete chirality retention, which is inherent to developed enantioselective C–H functionalization catalysis and poses the major challenge in establishing such a process. To this end, we herein describe the combination of decoupled hydrogen atom abstraction with asymmetric copper catalysis for enantioconvergent tertiary β-C(sp3)–H amination of racemic ketones. This method, when allied with follow-up transformations, provides facile access to a range of enantioenriched compounds featuring quaternary stereocentres. We anticipate that this work will inspire the future design of generally efficient catalysts for enantioconvergent transformations of racemic tertiary C(sp3)–H bonds. Methods for the enantioconvergent tertiary C–H functionalization are scarce, but desired for the construction of valuable compounds. Now, a highly enantioconvergent tertiary β-C(sp3)–H amination of racemic ketones with copper/chiral phosphoric acid dual catalysis is reported.