Synthesis of Multisubstituted Silyloxy-based Donor-Acceptor Cyclobutanes by an Acid-Catalyzed [2+2] Cycloaddition

This account summarizes our recent efforts on the acid-catalyzed [2+2] cycloaddition of silyl enol ethers with ,-unsaturated esters, giving donor-acceptor (D-A) cyclobutanes and their related reactions. The cycloaddition generally produces multisubstituted cyclobutanes in good yields with high diastereoselectivity. We found that aluminum Lewis acids and triflic imide (Tf2NH) had good catalytic activity. The retro [2+2] cycloaddition proceeded at higher reaction temperatures, and in some cases, diastereoselectivity switching of cycloadducts was observed. A microflow protocol was established for Tf2NH-catalyzed [2+2] cycloaddition. Although the cycloaddition usually requires cryogenic conditions in a batch reactor, the microreactor system enabled the production of D-A cyclobutanes, even at ambient temperature. [2+2] Cycloaddition of allylsilanes and alkyl enol ethers, instead of silyl enol ethers, afforded the corresponding D-A cyclobutanes.