Optically active 1,5-benzothiazepin-4-ones by ring transformation of 5-ylidene-1,3-dioxan-4-ones with 2-aminothiophenol

Optically active cis- and trans-3-(1-hydroxyethyl)-1,5-benzothiazepin-4-one s 4 and 5 have been synthesised by ring transformation of (E)- and (Z)-5-yl idene-1,3-dioxan-4-ones 1 with 2-aminothiophenol. Stereoselective conjugate addition of the -SH group of 2-aminothiophenol to the Michael system of th e chiral 5-ylidene-1,3-dioxan-4-one 1, catalysed by BuLi, gave adducts 2 an d 3. The stereochemical mode of attack can be rationalised by hydrogen bond ing of the attacking 2-aminothiophenolate with the oxygen atoms of the diox anone ring. Treatment of the adducts 2 and 3 with ethylmagnesium bromide af forded ring transformation by attack of the amino group at the carbonyl car bon atom cleaving the dioxanone ring. The resulting 3-(1-hydroxyethyl)-1,5- benzothiazepin-4-ones 4 and 5 represent structural analogues of Diltiazem(R ), a widely used drug in the treatment of hypertension.