Double diastereoselective, nucleophile-catalyzed aldol lactonizations (NCAL) leading to beta-lactone fused carbocycles and extensions to beta-lactone fused tetrahydrofurans.

A double diastereoselective variant of the nucleophile-catalyzed aldol lactonization (NCAL) process is described. This strategy delivers beta-lactone-fused carbocycles with good to excellent diastereoselectivities using cinchona alkaloid catalysts with enantioenriched aldehyde acids, which gave low diastereoselectivity based on substrate control alone. beta-Lactone-fused tetrahydrofurans are also prepared for the first time via the NCAL process; however, diastereoselectivity was only modestly improved when applying double diastereodifferentiation to these systems.