A Comprehensive Mechanistic Analysis of Palladium- and Nickel-Catalyzed α,β-Dehydrogenation of Carbonyls via Organozinc Intermediates

Introducing degrees of unsaturation into small molecules is a central transformation in organic synthesis. A strategi- cally useful category of this reaction type is conversion of alkanes into alkenes for substrates with an adjacent electron withdrawing group. An efficient strategy for this conversion has been deprotonation to form a stabilized organozinc intermediate that can be subject to α,β-dehydrogenation through palladium or nickel catalysis. This general reactivity blueprint presents a window to uncover and understand the reactivity of Pd- and Ni-enolates. Within this context, it was determined that β-hydride elimination is slow and proceeds via a concerted syn-elimination. One interesting finding is that β-hydride elimination can be preferred to a greater extent than C–C bond formation for Ni more so than with Pd, which defies the generally assumed trends that β-hydride elimination is more facile with Pd than Ni. Discussion of these findings are informed by KIE experiments, DFT calculations, stoichiometric reac- tions, and rate studies. Additionally, this report details an in-depth analysis of a methodological manifold for practical dehydrogenation and should enable its application to challenges in organic synthesis.