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December 3, 2025Organic Letters3 citations

Rh(III)-Catalyzed Strain-Release-Enabled C–H Alkenylation/4+1 Annulation of Benzamides with Alkylidenecyclobutanes

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XLXinxing LiuYMYuan-Jie MengZYZifeng Yang

Key Points

  • C-H activation improves the synthesis of 3-methyleneisoindolin-1-one derivatives with varied conditions.
  • Key reaction conditions facilitated a broad substrate scope in benzamides and alkylidenecyclobutanes.
  • Observational analysis across multiple reactions indicates sustained synthetic utility through late-stage modifications.
  • Supports further exploration of C1 synthons in complex pharmaceutical scaffolds for efficient drug development.

Abstract

A Rh(III)-catalyzed strain-release-enabled C-H alkenylation/4+1 annulation of benzamides with alkylidenecyclobutanes is described, enabling the efficient construction of 3-methyleneisoindolin-1-one derivatives. This protocol uniquely integrates Rh(III)-catalyzed C-H activation with strain-release ring-opening of alkylidenecyclobutanes, representing a rare example in which alkylidenecyclobutanes serve as C1 synthons in 4+1 annulation. Moreover, by subtly modifying the reaction conditions, Rh(III)-catalyzed C-H alkenylation was also achieved. This strategy features broad substrate scope and holds promise for late-stage functionalization of pharmaceutically relevant scaffolds. Its synthetic utility is further highlighted by scaled-up experiments and diverse downstream transformations.

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Cite This Study

Liu et al. (2025) studied this question.

synapsesocial.com/papers/694025842d562116f28fe718https://doi.org/10.1021/acs.orglett.5c04392
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