Asymmetric [3+2] Cycloaddition Route to Tetrahydrofurans

Significance

Johnson and co-workers report a simple and efficient enantioselective synthesis of tetrahydrofurans 3 through the asymmetric [3+2] cycloaddition of racemic cyclopropanes 1 with aldehydes 2. Optimization of the reaction conditions identified MgI₂/(t-Bu-pybox) as the best system for the stereospecific cycloaddition of one enan­tiomer of the cyclopropane whilst simultaneously promoting interconversion of both enantiomers through dynamic kinetic resolution. Cyclopropanes bearing donating groups are required for ­efficient ring opening and cycloaddition. The ­reaction is tolerant of electron-rich aryl, cinnamyl, linear and branched aliphatic aldehydes, although electron-poor aldehydes gave lower yields presumably due to their poor nucleophilicity. Excellent enantio- and diastereoselectivity was observed in all cases.