CuH-Catalyzed Selective N-Methylation of Amines Using Paraformaldehyde as a C1 Source

Abstract

Copper hydride (CuH) complexes have been proposed as key intermediates in synthesis and catalysis. Herein, we developed a highly efficient strategy for CuH-catalyzed N-methylation of aromatic and aliphatic amines using paraformaldehyde and polymethylhydrosiloxane (PMHS) under mild reaction conditions. The reaction proceeded smoothly without additives to furnish the corresponding N-methylated products using cyclic­(alkyl)­(amino)­carbene (CAAC)­CuH as a reaction intermediate, which results from a reaction between PMHS and (CAAC)­CuCl.

C−N Bond Formation Using Paraformaldehyde as C1 Source – Recent Advances

“…In 2023, Wang et al used CuH as a catalyst, hydrogenated silane acting for reduction media, and the polyformaldehyde acting for C1 medium in the selective N-methylation of Nmethylaniline. [86] Compared with formerly published inhomogeneous catalysts used to perform the N-methylation reaction, this homogeneous CuH catalytic structure is characterized by gentle reaction conditions, a wide range of substrates, and yields up to 99 % or more.…”

SnCl2-catalyzed multicomponent coupling: synthesis of 1,3-oxazolidine derivatives using paraformaldehyde as a C1 feedstock

“…Paraformaldehyde, a polymeric form of formaldehyde, is one of the simplest C1 feedstocks containing C, O, and H atoms and is widely used in diverse functionalization processes. 11–15 It offers unique benefits over formaldehyde in terms of stability, handling, transit, and storage. Furthermore, paraformaldehyde can be utilized as a source of methylene (–CH 2 –), CO, and hydroxymethyl (–CH 2 OH–) units, which serve as key building blocks for many organic molecules.…”