Abstract
Naphtho[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.
Keywords
naphtho[2,3-
b]thiophenes - Bradsher cyclization - copper catalysis - cross-coupling - lithiation
