Stereoselective synthetic approaches to highly substituted cyclopentanes via electrophilic additions to mono-, di-, and trisubstituted cyclopentenes

Electrophilic additions to allylically substituted alkenes are of broad synthetic utility. The control of stereoselectivity in such reactions has attracted considerable interest. However, the effect of allylic and homoallylic substituents in cyclopentenyl systems has not been investigated systematically. Studies on a series of mono, di-, and trisubstituted cyclopentenes are reported in which trans-vicinal-additions favor a syn-selective approach of electrophiles to the cyclopentene system. The formal addition of HOBr, HOCl, CH(3)SCl, and dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF)/NaN(3) with a variety of cyclopentene substrates has been carried out, and the effects of various allylic substituents on these selectivities have been examined. Additions of HOBr, HOCl, and DMTSF to highly functionalized substrates proceed predictably with syn selectivity, giving predominantly or exclusively one product. Methanesulfenyl chloride additions are less predictable, but can be tuned by suitable alteration of solvent and substrate. Results have proven useful in total syntheses of (+)-trehazolin and (+)-allosamidin.