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

Emily K. Burke; Erin N. Welsh; Katherine N. Robertson; Alexander W. H. Speed

doi:10.1055/a-2004-1093

Synthesis, Table of Contents

Synthesis 2023; 55(15): 2406-2414
DOI: 10.1055/a-2004-1093

paper

Special Issue dedicated to Prof. David A. Evans

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

Emily K. Burke‡

^aDalhousie University, Chemistry Department, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada

,

Erin N. Welsh‡

^aDalhousie University, Chemistry Department, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada

,

Katherine N. Robertson

^bSaint Mary’s University, Department of Chemistry, 923 Robie Street, Halifax, NS, B3H 3C3, Canada

,

Alexander W. H. Speed ∗

^aDalhousie University, Chemistry Department, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada

› Author Affiliations

Abstract

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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

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References

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