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. 2022 Apr 26;13(20):5913-5919.
doi: 10.1039/d2sc01959k. eCollection 2022 May 25.

Facile synthesis of amides via acceptorless dehydrogenative coupling of aryl epoxides and amines

Yaoyu Liang  1 , Jie Luo  1 , David Milstein  1
Affiliations

Facile synthesis of amides via acceptorless dehydrogenative coupling of aryl epoxides and amines

Yaoyu Liang et al. Chem Sci. .

Abstract

The synthesis of amides is significant in a wide variety of academic and industrial fields. We report here a new reaction, namely acceptorless dehydrogenative coupling of epoxides and amines to form amides catalyzed by ruthenium pincer complexes. Various aryl epoxides and amines smoothly convert into the desired amides in high yields with the generation of H2 gas as the only byproduct. Control experiments indicate that amides are generated kinetically faster than side products, possibly because of the facile activation of epoxides by metal-ligand cooperation, as supported by the observation of a ruthenium-enolate species. No alcohol or free aldehyde are involved. A mechanism is proposed involving a dual role of the catalyst, which is responsible for the high yield and selectivity of the new reaction.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Synthesis of amides from epoxides.
Fig. 1
Fig. 1. Mechanistic aspects of the reaction. (a) Investigation of the generation of byproducts 3a′ and 4, and the possibility of converting into 3a. (b) The correlation between reaction time and yields of 3a (standard conditions), 3a′ (without catalyst), and 4 (without amine). (c) Control experiments for excluding the participation of H2. (d) Control experiments for excluding the generation of free aldehyde. (e) The active catalytic species of amidation reaction. (f) Formation of Ru-enolate intermediates Ru-6 in the reaction. (g) Formation of Ru-8 and its reversible conversion into Ru-9.
Scheme 2
Scheme 2. Proposed mechanism.
See this image and copyright information in PMC

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