We report here that tetrasubstituted olefins (vi in Scheme I) are also good substrates for the asymmetric dihydroxylation (AD) process. As shown in Table I the enantiomeric excesses are generally in the fair to excellent range for the cases examined.Moreover, the best ligands for the tetrasubstituted olefins are the PYR-1 and PHAL-2 classes, which taken together are also the best ligands for four (i, ii, iv and v) of the five remaining olefin types. Only c/s-olefins (ill) require a unique ligand (IND,3 Scheme I) and still have yielded no examples exceeding the 90% ee mark.These successful catalytic AD's of tetrasubstituted olefins are noteworthy on two counts: 1) catalytic osmylations of tetrasubstituted alkenes, asymmetric or otherwise have been extremely rare4 due to turnover problems at the osmate ester stage of the cycle; and 2) we had long believed that at least one of the olefinic substituents had to be a hydrogen atom in order to fit into a crowded region of the AD transition state.5
In an attempt to improve the effectiveness and duration of the action of diltiazem (1), a 1,5-benzothiazepine calcium channel blocker, its derivatives (2) with halogen substituents on the fused benzene ring were synthesized. These compounds were evaluated for their effects on vertebral and coronary blood flows and antihypertensive activity. The structure-activity relationships are discussed. The 8-chloro derivative ((+)-2b), the most potent compound in this series, was selected for clinical evaluation as a cerebral vasodilating and antihypertensive agent.
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