Stereoselective synthesis of thiochroman-4-ones by ring transformation of chiral 5-ylidene-1,3-dioxan-4-ones with 2-bromothiophenol via bromo-lithiumexchange

The reaction of (E)- or (Z)-5-ylidene-1,3-dioxan-4-one (1) and 2-bromothiop henol, 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-phenylsulfanylalky l)-1,3-dioxan-4-ones 2 and 3 undergo ring transformation to thiochroman-4-o nes by attack of the lithiated phenyl ring at the dioxanone carbonyl carbon atom, cleaving off pivalaldehyde. If reactants with a (Z)-configuration ar e used, a retro-aldol reaction occurs in the ring transformation step, thus affording the 3-unsubstituted thiochroman-4-ones 5 rather than 3-(l-hydrox yethyl)-thiochroman-4-ones 4. This phenomenon can be rationalized by the st eric congestion in the intermediate enolate 7.