Arynes as synthetic linchpins towards the construction of diversely functionalized natural product skeletons

Despite growing interest in 2,1,3-benzothiadiazole (BTD) as an integral component of many functional molecules, methods for the functionalization of its benzenoid ring have remained limited, and many even simply decorated BTDs have required de novo synthesis. We show that regioselective Ir-catalyzed C−H borylation allows access to versatile 5-boryl or 4,6-diboryl BTD building blocks, which undergo functionalization at the C4, C5, C6, and C7 positions. The optimization and regioselectivity of C−H borylation are discussed. A broad reaction scope is presented, encompassing ipso substitution at the C−B bond, the first examples of ortho-directed C−H functionalization of BTD, ring closing reactions to generate fused ring systems, as well as the generation and capture reactions of novel BTD-based heteroarynes. The regioselectivity of the latter is discussed with reference to the Aryne Distortion Model.

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Aryne Aminohalogenation Using Protic Amines Enabled by Halogen Transfer

Gavin,

Anderson,

Roberts

2024

Org. Lett.

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Methods for aryne difunctionalization have been the focus of recent research, but one limitation is the use of nucleophiles with proton sources. Herein, we demonstrate the use of halogen transfer reagents to enable protic amines in aryne aminohalogenation difunctionalizations in up to 86% yield. This method uses amines and arynes with a variety of N-heterocyclic scaffolds. Through a variety of derivatizations, the synthetic utility of these products is demonstrated.

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Arynes as synthetic linchpins towards the construction of diversely functionalized natural product skeletons

Abstract: Arynes are a privileged class of reactive intermediates in synthetic organic chemistry, and their unusual reactivities have been the subject of engrossing research interest. Recently, arynes-based synthetic innovations have been...

Cited by 3 publications

References 54 publications

Fragmentation Reactions

Fragmentation Reactions

Derivatization of 2,1,3-Benzothiadiazole via Regioselective C–H Functionalization and Aryne Reactivity

Aryne Aminohalogenation Using Protic Amines Enabled by Halogen Transfer

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