Polar Hetero-Diels−Alder Reactions of 4-Alkenylthiazoles with 1,2,4-Triazoline-3,5-diones:  An Experimental and Computational Study

• Published in: Journal of organic chemistry 2008-02, Vol.73 (3), p.963-973
• Main Authors: Alajarín, Mateo, Cabrera, José, Pastor, Aurelia, Sánchez-Andrada, Pilar
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo7021668

The hetero-Diels−Alder reactions of 4-alkenylthiazoles with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) lead to new heteropolycyclic systems in excellent yields and high levels of stereocontrol through an exclusively suprafacial approach. 4-Alkenylthiazoles with a stereogenic center placed at the alkenylic substituent react with PTAD giving the corresponding chiral cycloadducts in moderate diastereomeric excesses. The stereochemical course is dominated by the steric interactions at the two diastereomeric transition states. A computational study of these processes with structurally simpler reagents has been carried out. A concerted pathway via a highly asynchronous transition state is preferred for 2-unsubstituted 4-vinyl and 4-styrylthiazoles. However, two alternative and equally likely pathways, concerted and stepwise, have been found to be followed by 2-methyl- or 2-phenyl-substituted 4-styrylthiazoles. The concerted pathway features a highly asynchronous transition state. For the stepwise pathway, the rate-determining step is the first one, as the energy barrier for the second step is virtually nonexistent.