Stereoselective Synthesis of Thiochroman-4-ones by Ring Transformation of Chiral 5-Ylidene-1,3-dioxan-4-ones with 2-Bromothiophenol via Bromo−Lithium Exchange

The reaction of (E)- or (Z)-5-ylidene-1,3-dioxan-4-one (1) and 2-bromothiophenol, followed by bromo-lithium exchange with nBuLi, provides a new access to optically active thiochroman-4-ones 4 and 5. Stereoselective conjugate addition occurs in the first step and the resulting 5-(1-phenylsulfanylalkyl)-1,3-dioxan-4-ones 2 and 3 undergo ring transformation to thiochroman-4-ones by attack of the lithiated phenyl ring at the dioxanone carbonyl carbon atom, cleaving off pivalaldehyde. If reactants with a (Z)-configuration are used, a retro-aldol reaction occurs in the ring transformation step, thus affording the 3-unsubstituted thiochroman-4-ones 5 rather than 3-(1-hydroxyethyl)-thiochroman-4-ones 4. This phenomenon can be rationalized by the steric congestion in the intermediate enolate 7.