Cooperative Al(salen)-pyridinium catalysts for the asymmetric synthesis of trans-configured β-lactones by [2+2]-cyclocondensation of acylbromides and aldehydes: investigation of pyridinium substituent effects.
[reaction: see text] The intramolecular, nucleophile-catalyzed, aldol lactonization (NCAL) process merges catalytic, asymmetric carbocycle synthesis with beta-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-beta-lactones. This methodology uniquely provides beta-lactone-fused cyclopentanes and cyclohexanes readied for further transformations.