Dehydrogenative Conversions of Aldehydes and Amines to Amides Catalyzed by a Nickel(II) Pincer Complex

Abstract

A C-N cross-coupling approach involving oxidative amidations of aromatic aldehydes in the presence of an amide-based nickel(II) pincer catalyst (2) is demonstrated. Upon optimization, quick reaction times (15 min) and an ideal temperature (25 °C) were established and implemented for the conversion of 33 different amide products using only 0.2 mol% of catalyst. Moderate to good turnover numbers (TONs) were obtained for secondary benzamide products, and moderate TONs were obtained for tertiary benzamide products, with the highest turnover number calculated for the 4-chloro-N-(3-phenylpropyl)benzamide product (4i, 309). Gas chromatographic–mass spectrometric (GC–MS) analysis also indicates the formation of alcohols in different reactions, indicating an oxidative amidation process. Kinetic studies were performed by varying the amount of catalyst, aldehyde, LiHMDS base, and amine substrate to determine the order of reaction for each component. Benzaldehyde and benzaldehyde-d6 were reacted with benzylamine, and the kH/kD ratio was determined to understand the rate-determining step. Isotope labeling further revealed that deuterium was being transferred to both the alcohol side product and the target amide product. With the help of kinetic data and UV–visible spectra, a mechanism for the amidation process via the catalyst (2) is proposed through a Ni(I)–Ni(III) pathway.

Keywords

• amides
• oxidative amidation
• aldehyde
• amine
• nickel(ii) pincer catalyst
• C-N cross-coupling