Total synthesis of (+)-yatakemycin

Abstract

A convergent total synthesis of (+)-yatakemycin was accomplished by a 20-step sequence in 13% overall yield. The regioselective ring opening of (S)-epichlorohydrin with a 2,6-dibromophenyllithium derivative enabled us to introduce a chiral carbon center, which was required for the stereoselective construction of the cyclopropane ring. The five aryl-nitrogen bonds in (+)-yatakemycin were constructed by a mild copper-mediated aryl amination that utilized the combination of CuI with CsOAc. The efficient and chemoselective debenzylation of aryl benzyl ether with BCl 3 in the presence of pentamethylbenzene was developed. With these new methodologies, the subgram-scale synthesis of (+)-yatakemycin was achieved. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.