A Convergent Total Synthesis of the Michellamines

A convergent total synthesis of the anti-HIV michellamines ( 1 ) is described. The tetraaryl skeleton of the michellamines was constructed by formation first of the inner (nonstereogenic) biaryl axis and subsequently of the two other (stereogenic) axes in a highly convergent manner. The key transformation features a double Suzuki-type cross-coupling reaction between binaphthalene ditriflate 26 and isoquinolineboronic acid 35 . Ditriflate 26 is synthesized in six steps starting from diene 6 and 2,6-dibromobenzoquinone ( 9 ) in 21% overall yield. For large scale production of 26, a substantially shortened version of an existing procedure for the preparation of bisnaphthoquinone 13 was also developed, which allows for the preparation of 13 from benzoquinone and diene 6 in five steps and 67% overall yield. Binaphthoquinone 13 was subsequently converted into ditriflate 26 in three steps and 67% overall yield. By the described synthetic strategy, michellamines A ( 1a ) and B ( 1b ) are produced ( 1a: 1b = 1:2.5) in 24.6% overall yield from diene 6 . Curiously, none of the nonnaturally occurring atropoisomer 1c is formed.