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

Abstract This account summarizes our recent efforts on the acid‐catalyzed [2+2] cycloaddition of silyl enol ethers with α,β‐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 (Tf 2 NH) 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 Tf 2 NH‐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.