Efficient pyrrole synthesis using double nucleophilic addition to alpha,beta-unsaturated imines with plural nucleophiles

摘要

2,3,5-Trisubstituted pyrroles were prepared in a regioselective manner using the double nucleophilic addition of alpha,alpha-dialkoxy ketene silyl acetals and ketene sily thioacetals or trimethylsilyl cyanide to alpha,beta-unsaturated imines followed by acid- promoted cyclization and oxidation with DDQ. Using this methodology an imidazole glycerol phosphate dehydratase inhibitor ( IGPDI) possessing a monopyrrole aldehyde moiety was synthesized.