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
a   Dalhousie University, Chemistry Department, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada
,
Erin N. Welsh
a   Dalhousie University, Chemistry Department, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada
,
Katherine N. Robertson
b   Saint Mary’s University, Department of Chemistry, 923 Robie Street, Halifax, NS, B3H 3C3, Canada
,
a   Dalhousie University, Chemistry Department, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada
› Institutsangaben
This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) through a Discovery Grant (2017-04297), an Idea to Innovation Grant (I2IPJ 523283-18), and the CREATE­ Training Program in BioActives (510963). Newfoundland and Labrador (Labrador’s Post-Secondary Student Support Program) and the Nova Scotia Graduate Scholarship are thanked for graduate funding to E.N.W.


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.

Supporting Information



Publikationsverlauf

Eingereicht: 16. November 2022

Angenommen nach Revision: 26. Dezember 2022

Accepted Manuscript online:
26. Dezember 2022

Artikel online veröffentlicht:
25. Januar 2023

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