The first example of PdII‐catalyzed γ‐C(sp3)−H functionalization of aliphatic and benzoheteroaryl aldehydes has been developed using a transient ligand and an external ligand, concurrently. A wide array of γ‐arylated aldehydes were readily accessed without preinstalling internal directing groups. The catalytic mechanism was studied by performing deuterium‐labelling experiments, which indicated that the γ‐C(sp3)−H bond cleavage is the rate‐limiting step during the reaction process. This reaction could be performed on a gram scale, and also demonstrated its potential application in the synthesis of new mechanofluorochromic materials with blue‐shifted mechanochromic properties.
Sulfamate Esters Guide Selective Radical‐Mediated Chlorination of Aliphatic C−H Bonds
Masked alcohols are particularly appealing as directing groups because of the ubiquity of hydroxy groups in organic small molecules. Herein, we disclose a general strategy for aliphatic γ‐C(sp3)−H functionalization guided by a masked alcohol. Specifically, we determine that sulfamate ester derived nitrogen‐centered radicals mediate 1,6‐hydrogen‐atom transfer (HAT) processes to guide γ‐C(sp3)−H chlorination. This reaction proceeds through a light‐initiated radical chain‐propagation process and is capable of installing chlorine atoms at primary, secondary, and tertiary centers.
more » « less- NSF-PAR ID:
- 10047885
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie
- Volume:
- 130
- Issue:
- 1
- ISSN:
- 0044-8249
- Page Range / eLocation ID:
- p. 302-305
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract The first example of PdII‐catalyzed γ‐C(sp3)−H functionalization of aliphatic and benzoheteroaryl aldehydes has been developed using a transient ligand and an external ligand, concurrently. A wide array of γ‐arylated aldehydes were readily accessed without preinstalling internal directing groups. The catalytic mechanism was studied by performing deuterium‐labelling experiments, which indicated that the γ‐C(sp3)−H bond cleavage is the rate‐limiting step during the reaction process. This reaction could be performed on a gram scale, and also demonstrated its potential application in the synthesis of new mechanofluorochromic materials with blue‐shifted mechanochromic properties.
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Abstract The Mizoroki–Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3)−H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β‐, γ‐, and δ‐C(sp3)−H sites. The use of an easily installed/removed Si‐based auxiliary enables selective I‐atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible‐light‐mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.
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