Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides by alkenylmetal reagents

The development of efficient methods, particularly catalytic and enantioselective processes, for the construction of all-carbon quaternary stereocentres is an important (and difficult) challenge in organic synthesis, due to the occurrence of this motif in a range of bioactive molecules. One conceptually straightforward and potentially versatile approach is the catalytic enantioconvergent substitution reaction of a readily available racemic tertiary alkyl electrophile by an organometallic nucleophile; however, examples of such processes are rare. In this report, we demonstrate that a nickel-based chiral catalyst achieves enantioconvergent couplings of a variety of tertiary electrophiles (cyclic and acyclic α-halocarbonyl compounds) with alkenylmetal nucleophiles to form quaternary stereocentres with good yield and enantioselectivity under mild conditions in the presence of a range of functional groups. These couplings, which likely proceed via a radical pathway, provide access to an array of useful families of organic compounds, including intermediates in the total synthesis of two natural products, (−)-eburnamonine and madindoline A.