Selective and Catalytic Hydrocarboxylation of Enamides and Imines with CO₂ to Generate α,α‐Disubstituted α‐Amino Acids

Abstract

The first catalytic hydrocarboxylation of enamides and imines with CO to generate valuable α,α-disubstituted α-amino acids is reported. Notably, excellent chemo- and regio-selectivity are achieved, significantly different from previous reports on β-carboxylation of enamides, homocoupling or reduction of imines. Moreover, this transition-metal-free procedure exhibits low loading of an inexpensive catalyst, easily available substrates, mild reaction conditions, high efficiency, facile scalability and easy product derivatization, providing great potential for application in organic synthesis, pharmaceutical chemistry, and biochemistry.

Reductive radical-polar crossover: traditional electrophiles in modern radical reactions

“…In 2018, the group of Da-Gang Yu reported a highly chemoand regioselective visible-light-mediated carboxylation of enamides and imines for the synthesis of a,a-disubstituted aamino acids (Scheme 5). 10 An a-amino anion is formed via two consecutive reductions of an imine intermediate by the excited state photocatalyst. This anion then adds to carbon dioxide to form the a-amino acid product.…”

Improved Conditions for the Visible-Light Driven Hydrocarboxylation by Rh(I) and Photoredox Dual Catalysts Based on the Mechanistic Analyses

“…Concomitantly, difunctionalizations of alkenes such as thiocarboxylation (Ye et al, 2017), carbocarboxylation and silylcarboxylation (Yatham et al, 2017; Hou et al, 2018a) have also been developed by incorporating an appropriate radical precursor with CO 2 . Furthermore, in addition to unsaturated hydrocarbons, various substrates such as aryl and alkyl halides (Meng et al, 2017; Shimomaki et al, 2017), amines (Seo et al, 2017a), imines and enamides (Fan et al, 2018; Ju et al, 2018) have been carboxylated with CO 2 by photoredox catalysis so far (for review, see Yeung, 2019). These examples demonstrated wide applicability of the photoinduced electron transfer to carboxylation reactions.…”

Syntheses of α‐Amino Acids by Using CO2 as a C1 Source

“…The synthesis of α‐amino acids from enamines and imines under visible‐light irradiation (with a blue LED) was demonstrated by Yu and co‐workers in 2018 (Scheme ) . In this case, 4CzIPN and i Pr 2 NEt were employed as a photoredox catalyst and sacrificial reductant, respectively.…”