Chiral N-Arylsulfonyl-N'-perfluoroalkylphospho-ramidimidate Catalysts Enable Asymmetric Friedel–Crafts Alkylation of Arenes via Cyclopropylcarbinyl Cations

Abstract

The high reactivity and transient nature of non-stabilized sp³-hybridized carbocations have long limited their application in enantiocontrolled transformations. In particular, the difficulty in regulating their lifetime and stereochemical environment has posed a fundamental challenge for asymmetric catalysis. Here, we report a catalytic strategy that addresses these challenges by harnessing cyclopropylcarbinyl cations as reactive yet controllable intermediates. These cations, known for their propensity to undergo rapid rearrangement, are strategically stabilized and directed within a chiral ion-pairing framework. Despite their rarity in asymmetric catalysis, these electrophiles enable highly enantioselective asymmetric Friedel–Crafts alkylation reactions when paired with newly developed phosphoramidimidate catalysts functioning as chiral Brønsted acids. The confined chiral environment provided by these catalysts effectively governs carbocation rearrangement pathways, allowing for precise stereochemical control. This method delivers excellent enantioselectivity and yields across a broad range of arenes, highlighting its generality in arene functionalization. Unlike conventional methods requiring substrate preactivation, our approach directly utilizes alcohol as electrophile precursors, forming water as the sole byproduct through an S_N1-type mechanism. The catalytic system promotes selective desymmetrization of prochiral substrates, converting simple and readily available starting materials into structurally complex chiral products. Importantly, controlled rearrangement of cyclopropylcarbinyl cations plays a key role in expanding molecular diversity without sacrificing enantioselectivity. Overall, this strategy significantly broadens the electrophile scope accessible in asymmetric synthesis. By integrating rearrangement control and chiral Brønsted acid catalysis, the present work establishes a new paradigm for exploiting highly reactive carbocation intermediates. These findings not only advance asymmetric catalysis but also open new avenues for enantiocontrolled transformations involving nonclassical carbocation chemistry.

Keywords

Phosphoramidimidate catalysts / Cyclopropylcarbinyl cations / Chiral Brønsted acid / Asymmetric Friedel-Crafts alkylation / Arene functionalization / Asymmetric catalysis / Rearrangement / Desymmetrization

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