Non-conjugated dienes were dihydroxylated using the commercially available osmium tetroxide AD-mix-a reagent resulting in highly regioselective dihydroxylation of the terminal olefin rather than the internal, more substituted olefin. These findings now allow for the use of allylmetal reagents on substrates where preexisting internal olefins are present. The resultant dial can be cleaved to the aldehyde allowing for subsequent transformations. This selectivity is controled by a steric effect imposed by the allylic silyl ether adjacent to the internal olefin. 0 1997 Elsevier Science Ltd.
Recently we reported the synthesis of stipiamide, a new multi-drug resistance reversal agent, together with 6,7-dehydro-stipiamide, a non-natural and more potent variant.' The anti-1,2-hydroxymethyl functionality was made using Brown's crotyl boration procedure.* It was found to be superior in yield and selectivity to analoguos asymmetric aldol methods' (sch. 1). Selective cleavage of the primary olefin in the presence of the tri-substituted oletin then became a necessity. Previous osmium tetroxide dihydroxylation studies of simple non-conjugated dienes by Sharpless Corey' and others6 have shown conclusively that the more substituted, internal olefin is selectively oxidized. Selective diene oxidation in favor of the least substituted olefin has been reported by Danishefsky using stoichiometric osmium tetroxide.' More recently, a catalytic version with NM0 (N-methylmorpholine N-oxide) has been used with moderate selectivity. ' When this procedure resulted in poor yield and selectivity with our substrate, we reasoned that use of a larger ligand on osmium might favor oxidation Scheme 1 0 1) crotyl-QTBS borane_ ""r(' 2) protect