Synthesis of tri- and tetrasubstituted stereocentres by nickel-catalysed enantioselective olefin cross-couplings

Asymmetric transition-metal catalysis has had a far-reaching impact on chemical synthesis. However, non-precious metal-catalysed strategies that provide direct entry to compounds with enantioenriched trisubstituted and fully substituted stereogenic centres are scarce. Here we show that a sterically encumbered chiral N-heterocyclic carbene-Ni(O) catalyst, in conjunction with an organotriflate and a metal alkoxide as hydride donor, promotes 1,2-hydroarylation and hydroalkenylation of diverse alkenes and 1,3-dienes. Replacing the metal alkoxide with an organometallic reagent allows installation of two different carbogenic motifs. These multicomponent reactions proceed through regio- and enantioselective carbonickelation followed by carbon-nickel bond transformation, providing a streamlined pathway towards enantioenriched carbon- or heteroatom-substituted tertiary or quaternary stereogenic centres. Through selective carbofunctionalizations, enantiodivergent access to opposite enantiomers may be achieved using the same catalyst antipode. The method enables practical access to complex bioactive molecules and other medicinally valuable but synthetically challenging building blocks, such as those that contain deuterated methyl groups.

Automated summary

Asymmetric transition-metal catalysis has a significant impact on chemical synthesis, but non-precious metal-catalysed strategies for enantioenriched compounds with multiple stereogenic centers are rare. This study presents a sterically encumbered chiral N-heterocyclic carbene-Ni(O) catalyst, combined with an organotriflate and a metal alkoxide as hydride donor, to promote 1,2-hydroarylation and hydroalkenylation reactions of various alkenes and 1,3-dienes.