Journal of the American Chemical Society· 2026Q1
Enantioselective Defluorinative C(sp2)–H Allylation of Acrylamides Enabled by CpxRh(III) Catalysis
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- Q1SCImago
- 2026year
Short summary
A chiral CpxRh(III) catalyst enables the direct, enantioselective synthesis of fluorinated skipped 1,4-dienes from acrylamides and allylic difluorides, achieving up to 99% yield and 99% ee.
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Key points
- Developed a convergent strategy merging asymmetric alkenyl C(sp2)–H functionalization with defluorinative coupling.
- Enables direct, enantioselective synthesis of fluorinated skipped 1,4-dienes from acrylamides and amide-substituted allylic difluorides.
- Achieves high efficiency and stereocontrol, with yields up to 99% and enantiomeric excess (ee) up to 99%.
- Mechanistic studies suggest a pathway involving C–H activation, migratory insertion, and β-fluoride elimination.
- Demonstrates divergent cascade reactivity with ester-derived allylic difluorides to form chiral 2-piperidones with high selectivity.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Chiral fluoroalkenes are high-value synthetic targets; however, the development of efficient catalytic asymmetric methods for their assembly from abundant precursors remains a formidable challenge. Herein, we report a convergent strategy that merges asymmetric alkenyl C(sp2)–H functionalization with defluorinative coupling, enabling the direct, enantioselective synthesis of fluorinated skipped 1,4-dienes from readily available starting materials. Facilitated by a chiral CpxRh(III) catalyst, this enantioselective olefin–olefin cross-coupling leverages abundant acrylamides and amide-substituted allylic difluorides to provide streamlined access to a structurally diverse array of enantioenriched fluorinated 1,4-dienes with high efficiency and excellent stereocontrol (up to 99% yield, 99% ee). Mechanistic studies suggest that the transformation proceeds via a sequence of site-selective alkenyl C–H activation, enantioselective migratory insertion, and β-fluoride elimination. Remarkably, ester-derived allylic difluorides induce divergent cascade reactivity, allowing efficient construction of valuable chiral 2-piperidones with excellent enantio- and diastereoselectivity. This step-economical protocol offers a versatile platform for the rapid construction of complex fluorinated motifs from simple chemical feedstocks.
The authors' abstract, as published at the source. Journal of the American Chemical Society, 2026 · DOI ↗
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