3-Trifluoroacetyl-quinolin-2(1H)-ones as Carbonyl and Acid Surrogates in the Passerini-/Ugi-Type Reaction

Herein, we report tailored 3-trifluoroacetyl-quinolin-2(1H)-ones (1) as carbonyl and acid surrogates in Passerini- and Ugi-type reactions for the synthesis of alpha-trifluoromethyl-alpha-hydroxy carboxamides (4) and alpha-trifluoromethyl alpha-amino acids (6) in high yields, respectively. The reaction proceeds under mild reaction conditions via an exocyclic carboximidate intermediate (3). The amide group in compound 1 acts as an acid component as well as a reversible oxygen nucleophile to facilitate the reaction.

Automated summary

In this study, tailored 3-trifluoroacetyl-quinolin-2(1H)-ones were used as carbonyl and acid surrogates in Passerini- and Ugi-type reactions to synthesize alpha-trifluoromethyl-alpha-hydroxy carboxamides and alpha-trifluoromethyl alpha-amino acids, achieving high yields under mild reaction conditions via an exocyclic carboximidate intermediate. The amide group in compound 1 acted as both an acid component and a reversible oxygen nucleophile to facilitate the reaction.