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4‐Alkenyl‐2‐aminothiazoles: Smart Dienes for Polar [4 + 2] Cycloadditions
Author(s) -
Alajarin Mateo,
Cabrera Jose,
SanchezAndrada Pilar,
Orenes RaulAngel,
Pastor Aurelia
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201201185
Subject(s) - chemistry , regioselectivity , zwitterion , stereospecificity , cycloaddition , stereoselectivity , selectivity , stereochemistry , computational chemistry , organic chemistry , medicinal chemistry , molecule , catalysis
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.