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Although chelation-assisted C–H olefination has been intensely investigated, Pd( ii )-catalyzed C–H olefination reactions are largely restricted to acrylates and styrenes. Here we report a quinoline-derived ligand that enables the Pd( ii )-catalyzed olefination of the C(sp 2 )–H bond with simple aliphatic alkenes using a weakly coordinating monodentate amide auxiliary. Oxygen is used as the terminal oxidant with catalytic copper as the co-oxidant. A variety of functional groups in the aliphatic alkenes are tolerated. Upon hydrogenation, the ortho -alkylated product can be accessed. The utility of this reaction is also demonstrated by the late-stage diversification of drug molecules.
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This content will become publicly available on July 24, 2026
Boron-mediated modular assembly of tetrasubstituted alkenes
Abstract Alkenes are a central part of organic chemistry1–3. However, although most alkenes are easy to prepare, the controlled synthesis of tetrasubstituted alkenes, those with four groups around the central C=C bond, remains challenging1–5. Here we report the boron-mediated assembly of tetrasubstituted alkenes with complete control of the double-bond geometry. The migrating group and electrophile add syn across the alkyne. Mild oxidation leads to intermediate borinic esters6, which can be isolated and purified or reacted directly in a range of transformations, including cross-couplings and homologation reactions. In particular, subjecting the intermediate borinic esters to Zweifel7,8olefination conditions can give either retention or inversion of the double-bond geometry, depending on whether base is present or not. Different positional and stereoisomers of the tetrasubstituted alkenes can be easily accessed, highlighting the breadth and versatility of the method. This was showcased through its successful application to the rapid synthesis of drug molecules and natural products with high yield and stereocontrol. Not only does this method provide efficient access to the long-standing challenge of the stereocontrolled synthesis of tetrasubstituted alkenes but it also introduces new concepts related to the intervention of non-classical borenium ions in the Zweifel olefination.
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- Award ID(s):
- 2400056
- PAR ID:
- 10647582
- Publisher / Repository:
- NPG
- Date Published:
- Journal Name:
- Nature
- Volume:
- 643
- Issue:
- 8073
- ISSN:
- 0028-0836
- Page Range / eLocation ID:
- 975 to 982
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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