Cooperative catalysis by carbenes and Lewis acids in a highly stereoselective route to γ-lactams

Abstract

Enzymes are a continuing source of inspiration for the design of new chemical reactions that proceed with efficiency, high selectivity and minimal waste. In many biochemical processes, different catalytic species, such as Lewis acids and bases, are involved in precisely orchestrated interactions to activate reactants simultaneously or sequentially. This type of ‘cooperative catalysis’, in which two or more catalytic cycles operate concurrently to achieve one overall transformation, has great potential in enhancing known reactivity and driving the development of new chemical reactions with high value. In this disclosure, a cooperative N-heterocyclic carbene/Lewis acid catalytic system promotes the addition of homoenolate equivalents to hydrazones, generating highly substituted γ-lactams in moderate to good yields and with high levels of diastereo- and enantioselectivity. In nature, enzymes can orchestrate the combination of several different catalytic species, but mimicking this with synthetic catalysts is often problematic due to undesirable interactions between the catalysts. Here, an N-heterocyclic carbene and a Lewis acid cooperate to catalyse the efficient formation of γ-lactams.

Cite this article

Raup, D., Cardinal-David, B., Holte, D. et al. Cooperative catalysis by carbenes and Lewis acids in a highly stereoselective route to γ-lactams. Nature Chem 2, 766–771 (2010). https://doi.org/10.1038/nchem.727

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