Direct synthesis of 2-oxo-acetamidines from methyl ketones, aromatic amines and DMF via copper-catalyzed C(sp³)–H amidination

Abstract

A convenient method for the synthesis of 2-oxo-acetamidines from methyl ketones using aromatic amines and DMF as nitrogen sources is reported via copper-catalyzed C(sp 3 )-H amidination. Various methyl ketones react readily with aromatic amines and DMF, producing 2-oxo-acetamidines in yields of 47 to 92%. This protocol features the simultaneous formation of C-N and C]N bonds using DMF and aromatic amines as two different nitrogen sources. It thus provides an efficient approach to construct acyclic amidines via three C(sp 3 )-H bond amidination. Based on the preliminary experiments, a plausible mechanism of this transformation is disclosed.

A Journey from June 2018 to October 2021 with N,N-Dimethylformamide and N,N-Dimethylacetamide as Reactants

“…According to control experiments, R 1 COCH2NMe2 produced from radical pathways involving the carbamoyl radical I4 and the aminyl radical I5, is an intermediate of the reaction. The Liu/Guo team disclosed the synthesis of 2-oxo-acetamidines from a mixture of methyl ketones and anilines in DMF containing peroxide, base, and Cu II catalyst under oxygen atmosphere (Scheme 11) [43]. According to control experiments, R 1 COCH 2 NMe 2 produced from radical pathways involving the carbamoyl radical I 4 and the aminyl radical I 5 , is an intermediate of the reaction.…”

Generation and Aerobic Oxidation of Azavinyl Captodative Radicals

“…A control reaction under the optimized conditions where the amine was replaced with water (Scheme ) gave the same product 17 , suggesting that hydrolysis of HMDS to ammonia was the culprit. Notably, similar amidine derivatives have been previously prepared only in the presence of metal catalysts …”

N,N-Dimethylformamide: An Versatile Organic Synthetic Reagent

“…Scheme 7 为该反应可能的反应机理. [17] (Scheme 17). 反应是在碱性条件下通过 CuCl 2 催化氧化 C(sp 3 )-H 键实现, 涉及一个单电子转移, 用 DMF 充当 Me 2 N 源(Scheme 18).…”