Diastereoselective Three-Component Vinylogous Mannich Reaction of Nitrogen Heterocycles, Acyl/Sulfonyl Chlorides, and Silyloxyfurans/pyrroles

A one-step,
3-component vinylogous Mannich reaction of trimethylsilyloxyfuran
or N-protected tert-butyldimethylsilyloxypyrrole
with a variety of nitrogen-containing heterocycles in the presence
of diverse electrophiles is described. The reaction products were
generally obtained in high yields and as a single diastereoisomer
having the (R*,R*) relative configuration
based on crystallographic studies of several derivatives. Several
azaheterocycles were successfully used for this reaction, such as
isoquinolines, quinoline, phenanthridine, quinazoline, phthalazine,
and β-carboline, and electrophiles included acetyl chloride,
methyl chloroformate, methyl chloromalonate, 2-bromobutanoyl chloride,
and arylsulfonyl chlorides. The products of the vinylogous Mannich
reactions were subjected to further transformations, leading to highly
functionalized and stereochemically defined tetracyclic derivatives
that are valuable building blocks for the preparation of natural products
or medicinal agents.