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

Abstract

Naphtho[2,3b]thiophene is a linear sulfur containing polycyclic aromatic hydrocarbon. Naphtho[2,3b]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[2,3b]thiophene, exploiting a copper-catalyzed cross coupling to prepare the Bradsher substrate in 3 steps from commercial materials while minimizing redox reactions. Modification of the naphthothiophene scaffold in the 3-position has not previously been reported. 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.

Modular and Regioselective Synthesis of Benzo-Fused Five-Membered Rings Enabled by Co/Ti Synergism

“…In addition to the synthesis of indoles, the Co/Ti bimetallic reagents proved to be effective for the synthesis of benzothiophenes, benzo[ b ]thiophene 1-oxide, and benzo[ b ]thiophene 1,1-dioxide ( 5a – 5h ) (Scheme ). , The previously reported method for synthesizing naphtho[1,2- b ]thiophene 5a faced challenges due to uncontrollable regioselectivity and the necessity for multistep reactions, whereas the current process enabled the production of 5a in a one-pot procedure using commercially available 2-naphthylmagnesium bromide. This efficient approach also showed compatibility with various dielectrophiles such as PhP(O)Cl 2 , PhPCl 2 , (Me) 2 SiCl 2 , (Ph) 2 SnCl 2 , and (EtO) 2 CO, facilitating the achievement of diverse benzo-fused five-membered rings ( 6 – 9 ) with potential applications in acceptable yields. ,, …”