Modular Synthesis of Lamellarins via Regioselective Assembly of 3,4,5-Differentially Arylated Pyrrole-2-carboxylates

A modular synthesis of lamellarins via 3,4,5-differentially arylated pyrrole-2-carboxylate intermediates has been developed. The key reactions employed are Br–Li exchange–methoxycarbonylation of 2,5-dibromo-1-(<i>tert</i>-butoxycarbonyl)-1<i>H</i>-pyrrole (<b>1</b>) followed by palladium-catalyzed iterative Suzuki–Miyaura coupling of the pyrrole core. The 3,4,5-triarylpyrrole <b>4</b> thus synthesized was readily converted to 5,6-saturated lamellarin L (<b>2</b>) and 5,6-unsaturated lamellarin N (<b>3</b>) via lactonization followed by annulation of the pyrrole nitrogen and lateral aromatic ring at C5 using 2-bromoethyl phenyl sulfide or bromoacetaldehyde dimethyl acetal as two-carbon homologation agents. In principle, this strategy allows the production of diverse lamellarins in short steps with high yields using readily accessible arylboronic acids as aromatic modules