Multigram-scale synthesis of a gem-difluoro-substituted 4,5,6,7-tetrahydrobenzo[c]thiophen-4-one heterocycle via oxidative chlorination and radical Smiles rearrangement

Henry, Martyn C. and Anderson, Jack Q. and Jamieson, Craig (2023) Multigram-scale synthesis of a gem-difluoro-substituted 4,5,6,7-tetrahydrobenzo[c]thiophen-4-one heterocycle via oxidative chlorination and radical Smiles rearrangement. Synlett, 34. ISSN 0936-5214 (https://doi.org/10.1055/a-2153-7341)

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Abstract

We report an optimized synthetic route towards a functionalized 4,5,6,7-tetrahydrobenzo[c]thiophene heterocycle bearing a gem-difluoromethylene moiety in 4 steps with an overall yield of 43%. The CF2 fragment was incorporated using a building block approach, by coupling an appropriate fluorinated alcohol with a C-3 sulfonyl chloride, synthesized via oxidative chlorination of an exocyclic benzyl thioether. Visible-light-mediated Smiles rearrangement of the resulting fluorosulfonate ester then furnishes the desired fluorinated thiophene scaffold.

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