Photoinduced copper-catalysed deracemization of alkyl halides

Abstract

Deracemization is an emerging strategy for generating enantioenriched compounds wherein the two enantiomers of a readily available racemic starting material are transformed into a single enantiomer, typically through the action of a light-induced catalyst1,2. Excellent proof of principle for this potentially powerful approach to asymmetric catalysis has been described3–8; nevertheless, substantial challenges have not yet been addressed, including the exploitation of carbon–heteroatom (rather than only carbon–hydrogen and carbon–carbon) bond cleavage to achieve deracemization, as well as the development of processes that provide broad classes of useful enantioenriched compounds and tetrasubstituted stereocentres. Here we describe a straightforward method that addresses these challenges, using a chiral copper catalyst, generated in situ from commercially available components, to achieve the photoinduced deracemization of tertiary (and secondary) alkyl halides through carbon–halogen bond cleavage. Mechanistic studies (including the independent synthesis of postulated intermediates, photophysical, spectroscopic and reactivity studies, and density functional theory calculations) provide support for the key steps and intermediates in our proposed catalytic cycle, as well as insight into the origin of enantioselectivity. A chiral copper catalyst, generated in situ from commercially available components, can be used to achieve photoinduced deracemization of alkyl halides through carbon–halogen bond cleavage.