4‐Alkenyl‐2‐aminothiazoles: Smart Dienes for Polar [4 + 2] Cycloadditions1. Issue 3 (6th December 2012)

• Record Type: Journal Article
• Authors: Alajarin, Mateo; Cabrera, Jose; Sanchez‐Andrada, Pilar; Orenes, Raul‐Angel; Pastor, Aurelia
• Is Part Of: European journal of organic chemistry. Issue 3(2013)
• Page Start: 474
• Page End: 489
• Publication Date: 2012-12-06
• Subjects: Cycloaddition -- Cyclization -- Nitrogen heterocycles -- Zwitterions -- Reaction mechanisms; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201201185
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: An exhaustive investigation into the [4 + 2] cycloadditions of 4‐alkenyl‐2‐aminothiazoles with a wide range of dienophiles has been carried out. 4‐Alkenyl‐2‐aminothiazoles act as good in‐out dienes, reacting with dienophiles bearing electron‐withdrawing groups. The heteroannulations, typically conducted under mild conditions, were endo ‐selective when cyclic dienophiles were used, and regioselective when the reactions are conducted with unsymmetrical dienophiles. The endo ‐selective processes presumably take place by concerted but highly asynchronous mechanisms. In contrast, the low levels of endo selectivity and the lack of stereospecificity in the reactions with certain acyclic dienophiles indicate a stepwise mechanism with a zwitterion as the most plausible intermediate. The course of the reaction changes when the highly reactive PTAD and TCNE are used as dienophiles, since in these cases, only addition products were obtained. Calculations of the HOMO and LUMO energy values of representative 4‐alkenyl‐2‐aminothiazoles, and the results of π‐facial diastereoselective processes by using chiral substrates are also disclosed. Abstract : 4‐Alkenyl‐2‐aminothiazoles act as in‐out dienes in [4 + 2] cycloadditions with a wide variety of dienophiles. The reactions were endo ‐selective when cyclic dienophiles were used and regioselective with unsymmetrical dienophiles. A stepwise mechanism is proposed for the cycloadditions with acyclic dienophiles.