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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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Asymmetric intermolecular allylic C–H amination of alkenes with aliphatic amines
Aliphatic allylic amines are found in a great variety of complex and biorelevant molecules. The direct allylic C–H amination of alkenes serves as the most straightforward method toward these motifs. However, use of widely available internal alkenes with aliphatic amines in this transformation remains a synthetic challenge. In particular, palladium catalysis faces the twin challenges of inefficient coordination of Pd(II) to internal alkenes but excessively tight and therefore inhibitory coordination of Pd(II) by basic aliphatic amines. We report a general solution to these problems. The developed protocol, in contrast to a classical Pd(II/0) scenario, operates through a blue light–induced Pd(0/I/II) manifold with mild aryl bromide oxidant. This open-shell approach also enables enantio- and diastereoselective allylic C–H amination.
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- Award ID(s):
- 1955663
- PAR ID:
- 10473947
- Publisher / Repository:
- AAAS
- Date Published:
- Journal Name:
- Science
- Volume:
- 378
- Issue:
- 6625
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- 1207 to 1213
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1126/science.abq1274
