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Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

preprint
submitted on 04.09.2020 and posted on 07.09.2020 by Arup Mondal, Manuel van Gemmeren
Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

Funding

Emmy Noether Programme (DFG)

Otto Hahn Award (Max Planck Society)

WWU Münster

History

Email Address of Submitting Author

mvangemmeren@uni-muenster.de

Institution

Westfälische Wilhelms-Universität Münster

Country

Germany

ORCID For Submitting Author

0000-0003-3080-3579

Declaration of Conflict of Interest

There are no conflicts of interest.

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