First highly regio- and diastereoselective [3+2] cycloaddition of chiral nonracemic Fischer carbene complexes with azomethine ylides: an enantioselective synthesis of (+)-rolipram.
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 (+/-)-menthol and (-)-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 (-)-8-phenylmenthol 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.
Barluenga
J
J
Instituto Universitario de Química Organometálica Enrique Moles, Unidad Asociada al CSIC, Universidad de Oviedo, Spain. barluenga@sauron.quimica.uniovi.es
Fernández-Rodríguez
M A
MA
Aguilar
E
E
Fernández-Marí
F
F
Salinas
A
A
Olano
B
B
D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D020889:Rolipram / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D000928:Antidepressive Agents; D007202:Indicators and Reagents; D020889:Rolipram