Site-Selective Remote Radical C-H Functionalization of Unactivated C-H Bonds in Amides Using Sulfone Reagents
Yong Xia+, Lin Wang+, and Armido Studer*
Organisch-Chemisches Institut Westf-lische Wilhelms-Universit-t Corrensstrasse 40, 48149 Mfnster (Germany)
E-mail: studer@uni-muenster.de
—Angew Int. 2018 12940-12944
Recommended by Qilin Li_PDM
ABSTRACT: A general and practical strategy for remote siteselective functionalization of unactivated aliphatic C-H bonds in various amides by radical chemistry is introduced. C-H bond functionalization is achieved by using the readily installed N-allylsulfonyl moiety as an N-radical precursor. The in situ generated N-radical engages in intramolecular 1,5-hydrogen atom transfer to generate a translocated C radical which is subsequently trapped with various sulfone reagents to afford the corresponding C-H functionalized amides. The generality of the approach is documented by the successful remote C-N3, C-Cl, C-Br, C-SCF3, C-SPh, and C-C bond formation. Unactivated tertiary and secondary C-H bonds, as well as activated primary C@H bonds, can be readily functionalized by this method.
Scope of the reaction-azidation
Scope of the reaction-sulfone-type radical-trapping reagent
γ-C-H azidation of amides
Remote C-H alkenylation
Proposed Mechanism
Summary and Comments:
In summary, Prof. Armido Studer and co-workers presented a method for radical C(sp3)-H functionalization of unactivated C-H bonds in various benzamides. Site-selective remote radical generation is achieved by 1,5-HAT to in situ generated amidyl radicals. The allylsulfon-amide moiety serves as a stable and valuable amidyl radical precursor, which is easily attached to the substrate. In contrast to most HLF-type reactions, various functionalities can be introduced at the remotely generated C radical by simply varying the radical-trapping reagents. This versatility is shown for azidation, chlorination, bromination, trfluoromethylthiolation, phenylthiolation, cyanation, and alkenylation. The substrate scope is broad, as cascades work efficiently for C-H modification of unactivated tertiary and secondary, as well as activated primary C-H bonds.
Moreover, the strategy introduced can also be applied to the γ-C-H functionalization of amides.