Stereoselective Thio-Michael/Aldol Tandem Reaction to α,β-Unsaturated Esters

A mixture of lithium thiophenolate, α,β-unsaturated ester, and aldehyde in CH2Cl2 afforded Michael/aldol tandem adducts, β-hydroxy-α-(1-phenylthioalkyl) esters, in moderate to good yields with a high syn-aldol selectivity. The reaction proceeded effectively when CH2Cl2 or ether was used as a solvent. The countercation of thiolate proved important; lithium cation provided the best results. The stereoselectivity and yield of the adducts greatly depended on the steric size of the ester group. Lithium selenolate, 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 form a quaternary carbon center on a similar stereoselective level. In the reaction with crotonates, on the other hand, the anti-Michael selectivity dominated 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.