Copper‐Catalyzed Reductive N‐Alkylation of Amides with N‐Tosylhydrazones Derived from Ketones

Abstract

A CuI-catalyzed reductive coupling of ketone-derived N-tosylhydrazones with amides is presented. Under the optimized conditions, an array of N-tosylhydrazones derived from aryl-alkyl and diaryl ketones could couple effectively with a wide variety of (hetero)aryl as well as aliphatic amides to afford the N-alkylated amides in high yields. The method represents the very few examples for reliably accessing secondary and tertiary amides through a reductive N-alkylation protocol.

Transition Metal Catalyzed Insertion Reactions with Donor/Donor Carbenes

“…NÀHa nd PÀHi nsertions with donor/donor copper carbenes are reported to proceed by similar mechanisms (Figure 7). [41][42][43] Tosylhydrazones react with base to generate diazo intermediates 54,w hich subsequently form metal carbenes in the presence of acopper(I) catalyst. Thecopper-(I) catalyst is produced in situ from reduction by the diazo precursor.…”

“…[67] Xu and co-workers were able to exploit this chemistry for the synthesis of amides (Table 4, entries 5-6). [42,68] Unfortunately,inmost of these examples using copper catalysts, b-hydride elimination is common. Most recently,Che and coworkers were able to demonstrate NÀHi nsertion reactions with iron porphyrin catalyst 38,affording various tertiary and secondary amines in good yields from donor/donor carbenes (Table 4, entries 7-8).…”

Transition Metal Catalyzed Insertion Reactions with Donor/Donor Carbenes

“…N−H and P−H insertions with donor/donor copper carbenes are reported to proceed by similar mechanisms (Figure 7). [41–43] Tosylhydrazones react with base to generate diazo intermediates 54 , which subsequently form metal carbenes in the presence of a copper(I) catalyst. The copper(I) catalyst is produced in situ from reduction by the diazo precursor [44, 45] .…”

“…Impressively, Hamze and co‐workers demonstrated that their procedure was highly chemoselective for N−H insertion over O−H moieties present in the substrate; [18, 41] Sivasankar and co‐workers were able to accomplish a similar result with catalyst 30 [67] . Xu and co‐workers were able to exploit this chemistry for the synthesis of amides (Table 4, entries 5–6) [42, 68] . Unfortunately, in most of these examples using copper catalysts, β‐hydride elimination is common.…”

Copper‐catalyzed one‐pot coupling reactions of aldehydes (ketones), tosylhydrazide and 2‐amino(benzo)thiazoles: An efficient strategy for the synthesis of N‐alkylated (benzo)thiazoles

“…Compared with aldehyde‐derived N ‐tosylhydrazones, the N ‐tosylhydrazones derived from ketones are less effective in the cross‐coupling reaction, probably as a result of the steric hindrance of ketones . To expand the utility of this protocol, the N ‐alkylation of non‐benzo‐fused 2‐aminothiazoles with various ketones was also studied (Table ).…”