Synthesis of multi-substituted cyclobutenes: Cyclic strategy for [2+2] cycloaddition of ketene silyl acetals with propiolates

Cyclic ketene silyl acetals were utilized for [2 + 2] cycloaddition with propiolates to prevent an undesired electrocyclic ring opening reaction. Trimethylaluminum catalyzed this cycloaddition to afford the cyclobutene derivatives in high yields. The advantage of this reaction was highlighted by the successful application of beta-substituted propiolates to afford the multi-substituted cyclobutenes. Furthermore, we applied this methodology to the late stage functionalization of natural product artemisinin. (C)2017 Elsevier Ltd. All rights reserved.