Carbene reactivity from alkyl and aryl aldehydes.

Zhang, Lumin; DeMuynck, Bethany M; Paneque, Alyson N; Rutherford, Joy E; Nagib, David A · Science · 2022

basic_science · Level V

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Abstract

Carbenes are highly enabling reactive intermediates that facilitate a diverse range of otherwise inaccessible chemistry, including small-ring formation and insertion into strong σ bonds. To access such valuable reactivity, reagents with high entropic or enthalpic driving forces are often used, including explosive (diazo) or unstable (<i>gem</i>-dihalo) compounds. Here, we report that common aldehydes are readily converted (via stable α-acyloxy halide intermediates) to electronically diverse (donor or neutral) carbenes to facilitate >10 reaction classes. This strategy enables safe reactivity of nonstabilized carbenes from alkyl, aryl, and formyl aldehydes via zinc carbenoids. Earth-abundant metal salts [iron(II) chloride (FeCl<sub>2</sub>), cobalt(II) chloride (CoCl<sub>2</sub>), copper(I) chloride (CuCl)] are effective catalysts for these chemoselective carbene additions to σ and π bonds.