Interrupted Nazarov Cyclization on Silica Gel

摘要

The Nazarov cyclization of allenyl vinyl ketones is a facile process that takes place under very mild conditions of acid catalysis. We recently reported the reaction that is summarized in eq 1. Addition of propargyllithium species 1 to amide 2 led to enone 3 that underwent cyclization to 4 on a silica gel chromatography column (hexanes/EtOAc). Isomerization of 3 presumably led to an allenyl vinyl ketone that cyclized spontaneously. Although a variety of enones related to 3 underwent this cyclization efficiently, we were puzzled by our observation that conversion of 3 to 4 failed to take place in the absence of solvent. It is desirable to minimize the use of organic solvents in synthesis both for reasons of economy as well as to mitigate any adverse environmental impact. Exposure of 3 to dry silica gel for 10 h resulted in recovery of the starting material. We reasoned that if isomerization of 3 to the allene could be induced, perhaps in the presence of added base, cyclization in the absence of solvent would quickly follow. This proved to be the case.