The α-tertiary amine motif drives remarkable selectivity for Pd-catalyzed carbonylation of β-methylene C–H bonds

Abstract

The selective C–H carbonylation of methylene bonds, in the presence of traditionally more reactive methyl C–H and C(sp2)–H bonds, in α-tertiary amines is reported.

DP4-AI automated NMR data analysis: straight from spectrometer to structure

“…7). [50][51][52][53][54][55] This test set has been designed to include natural Fig. 7 Figure illustrating the 47 molecules utilized to evaluate the performance of DP4-AI.…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…The reaction proceeds smoothly even when sterically congested α-tertiary amines are selected as starting materials. 1156 Accordingly, a large panel of β-lactams may now be accessed from simple, non-protected and non-prefunctionalised aliphatic amines. In addition to the carbonylation reactions, Gaunt and coworkers described in 2017 alkenylation reactions ( Scheme 180D ).…”

Heterocycle Synthesis through Pd‐Catalyzed Carbonylative Coupling

“…This palladium‐catalyzed methodology, starting from a range of structurally different amines ( N ‐ethyl‐substituted ATAs, N ‐methyl‐substituted ATAs, N ‐benzyl‐substituted ATAs, etc. ), was applied to deliver a number of highly functionalized bicyclic β ‐lactam derivatives 12 in moderate to excellent yields (Scheme ) …”

“…Moreover, in 2017 studies about catalytic processes that target specific C-H bonds have highlighted that α-tertiary amines (ATAs) underwent exclusive carbonylation at the -methylene C-H bond, also in the presence of usually more reactive C-H bonds such as methyl C(sp 3 )-H and C(sp 2 )-H (Scheme 8). [26] This selective C-H carbonylation is driven by the bulky α-carbon atom on one side of the amine motif that probably could promote preferential -methylene C-H activation towards cyclopalladation reaction. This palladium-catalyzed methodology, starting from a range of structurally different amines (Nethyl-substituted ATAs, N-methyl-substituted ATAs, N-benzylsubstituted ATAs, etc.…”

“…), was applied to deliver a number of highly functionalized bicyclic -lactam derivatives 12 in moderate to excellent yields (Scheme 8). [26] Scheme 8. N-Ethyl-substituted ATA as substrate for selective Pd-catalyzed carbonylation of -methylene C-H bond.…”