Control of Six Contiguous Stereocenters in an Asymmetric Organocatalytic One-Pot Michael/Michael/Aldol Addition Sequence

The asymmetric organocatalytic one-pot synthesis of polyfunctionalized cyclohexanes is described. Starting from beta-keto esters, nitroalkenes and a,beta-unstaturated aldehydes and employing a bifunctional norephedrine-based thiourea catalyst, six contiguous stereocenters including one quarternary center are generated. The one-pot protocol follows a Michael/Michael/aldol addition sequence and affords the highly substituted cyclohexanes in moderate to very good yields (22-70%), diastereomeric ratios of dr>95:5 and excellent enantioselectivities of 91-99% ee.