Highly Chemoselective Esterification from O‐Aminoallylation of Carboxylic Acids: Metal‐ and Reagent‐Free Hydrocarboxylation of Allenamides

Abstract

Metal-free hydrocarboxylation of allenamides with various functionalized carboxylic acids were achieved with complete regio-and stereocontrol (> 49:1). This environmentally compatible transformation affords g-acyloxyenamides with exclusive E-selectivity.E lectron rich, electron poor,a liphatic, aryl, and heterocyclic carboxylic acids all gave excellent yields (avg. 89 %, 47 examples). We demonstrate the synthetic potentialo ft his transformation in the late-stage modification of complex natural carboxylic acids and simple modification of the products to three-carbon synthons with ample opportunity for further diversification. DFT studies revealed that the reaction occurs in as tepwise mannert hrough the intermediacy of ac onjugated iminum species, which is rapidly captured by the carboxylate ion, resulting in the observed linear selectivity.

Construction of C–N and C–O bonds based on N-allenamide functionalization

“…In 2020, Park et al 45 described a metal-free hydrocarboxylation of terminal N -allenamides 34 . Conjugated iminiums 155 were formed through the activation of N -allenamides 34 with carboxylic acids 134 .…”

Postpolymerization modification of sterically demanding poly(methacrylic acid) with allene sulfonamides

“…The direct esterification of carboxylic acids with allene sulfonamides under mild conditions without any catalyst or activating agent was recently reported by Park et al 12 Deprotonation of the -COOH moiety by the allen sulfonamides produces a nucleophilic carboxylate and an electrophilic iminium that couple quickly. The allene sulfonamides is highly reactive toward various carboxylic acids, including sterically congested tertiary ones.…”

Acetate Assistance in Regioselective Hydroamination of Allenamides: A Combined Experimental and Density Functional Theory Study

“…Control experiments without HFIP or NaOAc demonstrated their importance; without HFIP, no conversion of 1a was observed, and a large amount of γ-HFIP adduct 5 was detected when NaOAc was not used (entries 12 and 13, respectively). Additionally, an OAc-based Brønsted acid (AcOH) was less effective than NaOAc, producing a mixture of linear acetate adduct 8 and HFIP adduct 5 (entry 14). This result provides a useful reference point for the reaction that would proceed through an intermediate different from the iminium intermediate.…”

“…Our curiosity about this reaction arose from our ongoing efforts to alter allenamides, particularly by controlling the accessible reaction intermediates. , The mechanism by which an H + or E + activator operatesin the context of the functionalization of allenamides without metalsis evident from its extensive history; it is widely accepted that the reaction occurs by forming a conjugated iminium species (Scheme B, top), the nature of which affects the selectivity of nucleophile interception. This process gives rise to two regioisomeric products: a 1,2-addition product and a 1,4-addition product, which depend not only on the nature of the iminium intermediates (int A H/X ) but also on the nucleophile (Scheme B, bottom).…”