A modular synthesis of the lamellarin family of natural products has been developed that is based on the application of three iterative halogenation/cross-coupling reaction sequences. The ability to halogenate the pyrrole core in a regioselective fashion, even in the presence of highly electron-rich aryl substituents, has been established. The compatibility of Suzuki coupling conditions with free alcohols and phenols in the boronic acids has been employed to reduce the number of protection/deprotection steps. Indeed, the presence of a free phenol on boronic acid 3 has been determined to be critical for the successful final coupling in route to lamellarin G trimethyl ether, since protected versions fail to undergo coupling.
A Modular Synthesis of the Lamellarins: Total Synthesis of Lamellarin G Trimethyl Ether
Handy, ST., Zhang, Y., & Bregman, H. (2004). A Modular Synthesis of the Lamellarins: Total Synthesis of Lamellarin G Trimethyl Ether. Journal of Organic Chemistry, 69(7), 2362-2366. https://doi.org/10.1021/jo0352833