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

Nélia C.T. Tavares, César T. Neves, Bruce F. Milne, Dina Murtinho, Alberto A.C.C. Pais, M. Elisa Silva Serra* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Organometallic Chemistry
Early online date9 Oct 2018
Publication statusPublished - 30 Dec 2018

Bibliographical note

Acknowledgements and Funding Sources
Thanks are due to Coimbra Chemistry Centre (CQC), supported by the Portuguese Agency for Scientific Research, Fundação para a Ciência e a Tecnologia (FCT) through Project Nº 007630 UID/QUI/00313/2013, co-funded by COMPETE2020-UE. Nélia C. T. Tavares and Bruce F. Milne also thank FCT for funding (PhD grant PD/BD/128496/2017 and project CENTRO-01-0145-FEDER-000014, 2017–2020, respectively). We thank Prof. Fernando Nogueira and the Laboratory for Advanced Computing (LCA) of the University of Coimbra for technical support and computer time allocated to this project. We also acknowledge the UC-NMR facility for obtaining the NMR data (

Data Availability Statement

Supplementary data to this article can be found online at


  • Alkylation
  • Asymmetric catalysis
  • Microwave synthesis
  • Thiazolidine
  • Computational studies


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