Tandem Isomerization Reaction of Alkynes: Total Synthesis of Alpha-Yohimbine

Abstract

Bicyclic guanidine was found to be effective for the transformation of alkynes to allenoates. Based on this, a tandem isomerisation intramolecular-aza-Michael reaction was developed to form useful heterocycles under mild conditions. This efficient method was applied to the synthesis of functionalized piperidine with good yields. Enantioselective tandem isomerisation intramolecular-aza-Michael reaction of alkynyl-amide led to an axially chiral lactam of high enantioselectivity when a chiral guanidine was used as the catalyst. A guanidine catalyzed tandem isomerisation intramolecular-Diels-Alder reaction was also developed to form useful hydroisoquinoline derivatives under mild conditions. The IMDA products have been obtained in moderate to high enantiomeric purity. This efficient method was successfully applied to the catalytic enantioselective total synthesis of (+)-alpha-yohimbine.