Stereoselective thio-Michael/aldol tandem reaction to alpha,beta-unsaturated esters

A mixture of lithium thiophenolate, alpha,beta-unsaturated ester, and aldeh yde in CH2Cl2 afforded Michael/aldol tandem adducts, beta-hydroxy-alpha-(1- phenylthioalkyl) eaters, in moderate to good yields with a high syn-aldol s electivity. The reaction proceeded effectively when CH2Cl2 or ether was use d as a solvent. The countercation of thiolate proved important; lithium cat ion provided the best results. The stereoselectivity and yield of the adduc ts greatly depended on the steric size of the ester group. Lithium selenola te, generated in situ by treatment of diphenyldiselenide with methyllithium , brought similar results, whereas alkoxide was too inert for the reaction. Application of the reaction to methacrylate provided a useful method to fo rm a quaternary carbon center on a similar stereoselective level. In the re action with crotonates, on the other hand, the anti-Michael selectivity dom inated over the syn-aldol selectivity. The tandem adduct was useful for the stereoselective preparation of trisubstituted tetrahydrofuran via radical cyclization, whose configuration was found to be 2,3-trans-3,5-trans.