First Highly Regio- and Diastereoselective [3+2] Cycloaddition of Chiral Nonracemic Fischer Carbene Complexes with Azomethine Ylides: An Enantioselective Synthesis of (+)-Rolipram

✍ Scribed by José Barluenga; Manuel A. Fernández-Rodríguez; Enrique Aguilar; Félix Fernández-Marí; Alejandro Salinas; Bernardo Olano

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 213 KB
• Volume: 7
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/1521-3765(20010817)7:16<3533::aid-chem3533>3.0.co;2-e

✦ Synopsis

A new procedure for the synthesis of 1,3,4-trisubstituted and 1,4-disubstituted pyrrolidin-2-one derivatives in an enantioselective fashion is reported. The 1,3-dipolar cycloaddition of (AE)menthol and (À)-8-phenylmenthol derived Fischer alkoxy alkenyl carbene complexes with in situ generated functionalized azomethine ylides gives the corresponding cycloadducts as chelated tetracarbonyl Fischer carbene complexes. Only one regioisomer is detected in all cases, and the diastereoselectivity of the reaction is very high when (À)-8phenylmenthol derived carbenes are employed. Oxidation and further transformation of the cycloadducts provide an easy access to pyrrolidin-2-ones. The anti-inflammatory and antidepressant drug ()-Rolipram is readily prepared in four steps in a 20 % overall yield by taking advantage of this newly developed methodology.