Total Synthesis of Pentaketide Ansamycin Microansamycin H

Herein, we report the first total synthesis of pentaketide ansamycin microansamycin H. Key to our success was the endo-selective epoxide-opening O-alkylation to construct the elusive seven-membered benzoxepane core. Due to the electron-rich disposition of the aromatic substrate, our pivotal transformation was hindered by competing electrophilic aromatic substitution at multiple C-based nucleophilic sites that generated kinetically favored products. Judicious choices of transition metal Lewis acid promoters biased toward the formation of the desired oxepane.