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Abstract Transition metal catalysis plays a pivotal role in transforming unreactive C–H bonds. However, regioselective activation of distal aliphatic C–H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C–H bond in the presence of methyl C–H is underexplored. Here we show activation of a methylene C–H bond in the presence of methyl C–H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C–H bond activation. Computational studies suggest that reversible C–H activation is followed by β-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C–O cyclization, and subsequent β-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C–H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules.
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This content will become publicly available on July 29, 2026
Carbon–Carbon Bond Formation Mediated by an Iron(0)–Olefin Pincer Complex
Abstract C–H functionalization is a highly appealing strategy for accessing complex molecular structures. Herein, we show that π-tethered pincer ligands can engage in C–H activation when coordinated to iron. These reactions result in C(sp2)–C(sp2) bond formation through oxidative coupling and β-hydride elimination/reductive elimination pathways with alkynes and isocyanides.
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- Award ID(s):
- 2102517
- PAR ID:
- 10649762
- Publisher / Repository:
- Thieme
- Date Published:
- Journal Name:
- Synthesis
- Volume:
- 57
- Issue:
- 16
- ISSN:
- 0039-7881
- Page Range / eLocation ID:
- 2521 to 2529
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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