Asymmetric Synthesis of Bicyclic β-Lactones via the Intramolecular, Nucleophile-Catalyzed Aldol Lactonization:  Improved Efficiency and Expanded Scope

The intramolecular, nucleophile-catalyzed, aldol lactonization (NCAL) process merges catalytic, asymmetric carbocycle synthesis with β-lactone synthesis. The application of modified Mukaiyama reagents to this process led to greatly improved conversion and efficiency (70−82% yield) and shorter reaction times with no diminution of enantioselectivity (91−98% ee). The process was extended to several new aldehyde−acid substrates leading to new bicyclic-β-lactones. This methodology uniquely provides β-lactone-fused cyclopentanes and cyclohexanes readied for further transformations.