A concise total synthesis of the azaphenanthrene alkaloid eupolauramine

A six-step total synthesis of the azaphenanthrene alkaloid eupolauramine 1 has been achieved using combinational metalation-cyclization tactics. The s ynthetic route involved first the construction of the azaisoindolinone 9 by aryne-mediated cyclization of he phosphorylated pyridocarboxamide 7 and su bsequent dephosphorylation. Metalation of 9 followed by connection of the h ydroxybenzyl appendage and E1CB anti-elimination allowed the formation of t he halogenoarylmethylene azaisoindolinone 4 in the exclusive E-form. Oxidat ive radical cyclization gave rise to the azaphenanthrene skeleton and regio selective bromination of 3 induced the incorporation of the bromine atom at the 6-position of the azaphenanthrene lactam. Ultimate replacement of the bromine atom of 2 by the methoxy functionality by sequential transmetalatio n, in situ oxidation, and O-methylation of the phenolic derivative 14 compl eted the synthesis of the target natural product eupolauramine.