TiCl4-Mediated Reactions of the Silyl Ketene Acetals Derived from N-Methylephedrine Esters: An Asymmetric Variant of the Mukaiyama Reaction

Article abstract of DOI:10.1021/jo00389a021

The TiCl4-mediated reaction between silyl ketene acetals 2 and benzaldehyde was chosen as a model for mechanistic studies.The influence of the silyl ketene acetal double-bond geometry, the C-1/C-2 relative configuration of N-methylephedrine, and different modes of addition and molar ratios of reagents on the stereochemical outcome of the reaction was investigated.On the basis of these results and of literature data, an octahedral, six-coordinate titanium complex was proposed as the transition-structure model.This model helps to rationalize some of the experimental data (e.g., the anti-syn ratios with aldehydes and imines).The TiCl4-mediated additions of the E silyl ketene acetal derived from (1R,2S)-N-methylephedrine propionate 1 (R=Me) to racemic 3-(benzyloxy)-2-methylpropionaldehyde (11) (kinetic resolution), (+)-(S)-11 (mismatched pair), and (-)-(R)-11 (matched pair) were studied.In the matched pair case three contiguous stereocenters were established with complete selectivity.The Mukaiyama-Michael additions of 1 (R = Me) to vinyl ketones were also studied.By this route α-methyl-δ-keto esters were obtained in 72-75 percent ee.