Chiral thiazolidines in the enantioselective ethylation of aldehydes: An experimental and computational study.

Abstract A library of new chiral thiazolidines was prepared starting from l -cysteine and d -penicillamine in a simple, one-step procedure. 2-Arylthiazolidines were obtained, as diastereoisomeric mixtures, with good yields and in short reaction times, through a new and greener procedure, using microwave irradiation. Their use as chiral ligands in the enantioselective ethylation of aromatic aldehydes was studied and optimized, originating good to excellent conversions and ee up to 94% in 6 h. A series of heteroaromatic and aliphatic substrates were also enantioselectively ethylated with success, with ee up to 77%. The distinct opposite chirality in l -cysteine and d -penicillamine makes the use of these ligands an interesting approach for obtaining both the (S) and (R) enantiomers of the chiral alcohols, compounds with potential applications in the area of fine chemistry. NMR studies were carried out using a diastereoisomeric mixture of thiazolidines, allowing the identification of the most stable structure. Computational studies confirmed this result and also gave important insight into the species involved in the catalytic cycle of the enantioselective alkylation. Graphical abstract d -Penicillamine and l -cysteine derived thiazolidines were obtained through a simple microwave procedure and used in the enantioselective alkylation of aldehydes with diethylzinc, giving (S) and (R) enantiomers of the product alcohols with ee up to 94%. NMR and computational studies gave important insight into the species involved in the catalytic cycle. Image 1 Highlights • Chiral thiazolidines prepared from l -cysteine/ d -penicillamine with MW irradiation. • Enantioselective ethylation of aromatic aldehydes gave ee up to 94%. • Enantioselective ethylation of heteroaromatic/aliphatic substrates gave ee up to 77%. • Interesting approach for obtaining both the (S) and (R) chiral alcohols. • NMR and Computational studies gave insight into catalytic species. [ABSTRACT FROM AUTHOR]