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

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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