Diels−Alder Reactions of 4-Alkenylthiazoles:  A New Approach to Thiazole Functionalization

• Published in: Journal of organic chemistry 2007-03, Vol.72 (6), p.2097-2105
• Main Authors: Alajarín, Mateo, Cabrera, José, Pastor, Aurelia, Sánchez-Andrada, Pilar, Bautista, Delia
• Format: Article
• Language: English
• Subjects: Alkadienes; Chemistry; Condensed benzenic and aromatic compounds; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Maleic Anhydrides - chemistry; Maleimides - chemistry; Models, Molecular; Naphthoquinones - chemistry; Organic chemistry; Preparations and properties; Thiazoles - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo062417e

Somewhat unexpectedly, the computed highest occupied molecular orbital (HOMO) energies of some 4-alkenylthiazoles afforded values close to those calculated for the Danishefsky−Kitahara and Rawal dienes. In fact, 4-alkenylthiazoles behave as all-carbon dienes in Diels−Alder reactions with the participation of the formal C−C double bond of the thiazole ring and the side-chain double bond. The reactions with N-substituted maleimides, maleic anhydride, and naphthoquinone take place with high levels of stereocontrol to give the corresponding endo-cycloadducts in good to excellent yields. Depending on the dienophile, the cycloadduct further transforms under the reaction conditions through either a 1,3-hydrogen shift, dehydrogenation, or an ene reaction or Michael addition with another molecule of dienophile. These unprecedented results open new synthetic perspectives for the functionalization of the thiazole ring.