Efficient Synthesis and Functionalization of 3-Bromonaphtho[2,3-b]thiophene

Abstract

AbstractNaphtho[2,3-b]thiophene is a linear sulfur-containing polycyclic aromatic hydrocarbon. Naphtho[2,3-b]thiophene and its derivatives are commonly accessed by a Bradsher cyclization. Synthesis of the Bradsher cyclization substrate typically requires harsh conditions, including several oxidation state changes. Here, we report an improved, multigram synthesis of 3-bromonaphtho[2,3-b]thiophene, exploiting a copper-catalyzed cross-coupling to prepare the Bradsher substrate in three steps from commercial materials while minimizing redox reactions. In this work, the 3-bromonaphthothiophene is further functionalized via lithium–halogen exchange, with the key finding being a specific order of addition in lithiation is required to avoid undesired rearrangement reactions. Transformation to a versatile set of derivatives, including a naphthothiophene-containing chiral amine, is illustrated.