Abiotic reduction of ketones with silanes catalyzed by carbonic anhydrase through an enzymatic zinc hydride

Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes would react through abiotic intermediates like these, then the scope of enzyme-catalyzed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyze hydride transfers from silanes to ketones with high enantioselectivity and report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalyzed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformations in molecular catalysis and biocatalysis.