Selective reduction of secondary amides to imines catalysed by Schwartz's reagent

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Donnelly, Liam J. and Berthet, Jean‐Claude and Cantat, Thibault (2022) Selective reduction of secondary amides to imines catalysed by Schwartz's reagent. Angewandte Chemie International Edition, 61 (33). e202206170. ISSN 1521-3773 (https://doi.org/10.1002/anie.202206170)

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Abstract

The partial reduction of amides is a challenging transformation that must overcome the intrinsic stability of the amide bond and exhibit high chemoselective control to avoid overreduction to amine products. To address this challenge, we describe a zirconium-catalysed synthesis of imines by the reductive deoxygenation of secondary amides. This reaction exploits the excellent chemoselectivity of Schwartz's reagent (Cp2Zr(H)Cl) and utilises (EtO)3SiH as a mild stoichiometric reductant to enable catalyst turnover. The reaction generally proceeds with high yields (19 examples, 51 to 95 % yield) and tolerates a variety of functional groups (alkene, ester, nitro, etc.). Stoichiometric mechanistic investigations suggest the regeneration of the active [Zr]−H catalyst is achieved through the metathesis of Si−H and Zr−OR σ-bonds.

ORCID iDs

Donnelly, Liam J. ORCID logoORCID: https://orcid.org/0000-0003-3342-4902, Berthet, Jean‐Claude and Cantat, Thibault;
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