Chiral Crotylsilane-Based Approach to Benzoquinoid Ansamycins:  Total Synthesis of (+)-Macbecin I

A highly convergent total synthesis of the antitumor antibiotic (+)-macbecin I ( 1 ) has been achieved through the homologation of the aldehyde 3 (C5−C21 aromatic fragment) to the E,Z -dienoate 2 by employing a sequential olefination strategy. Subsequent macrolactonization and a final two-step oxidation sequence were the principle steps used to complete the synthesis. Six of the seven syn-stereochemical relationships (C6−C7, C10−C11, and C14−C15) were introduced using our asymmetric crotylation bond construction methodology. The C12 stereocenter was introduced by an alkoxy-directed hydroboration reaction. An alternative strategy for introducing the C10 stereo center via a diastereoselective hydroboration reaction of 1,1-disubstituted olefin 6b provided a more atom efficient approach to intermediate 7 .