An Update on Distal C(sp³)−H Functionalization Involving 1,5‐HAT Emerging from Nitrogen Radicals

Abstract

Methods to selectively functionalize any one sp 3 CÀ H bond among all others, has been well documented in literature. Radical reactions, which are essentially mild reaction conditions has provided a significant improvement over the standard functionalization pathways. Although radical recombinations are fast and feasible, the selectivity is always guided by the electronic biasness in the system. 1,n-Hydrogen atom transfer (HAT) reactions are extremely useful in determining regioselectivity, the involvement of a 1,5-HAT protocol made the reaction pathway energetically much more favourable to functionalize the desired remote C(sp 3 )À H bond. In this review we are going to give a brief overview of the methods involved in the functionalization of distal aliphatic CÀ H bond by 1,5-HAT transformation pathway.Scheme 5. Homolyzation of amide NÀ H bond to trigger 1,5-HAT using iridium photocatalyst. Scheme 6. Rh-catalyzed asymmetric HLF type reaction.

Photoinduced regioselective difluorination of secondary inert C(sp3)–H bonds in sulfonamides via 1,5-hydrogen-atom transfer

“…Using the modified Hofmann-Löffler-Freytag (HLF) reaction involving 1,5-hydrogen-atom transfer (1,5-HAT) is a potent and promising way to activate inert C(sp 3 )-H bonds, [45][46][47][48][49][50] which can functionalize remote C-H bonds in a site-selective manner. [51][52][53][54][55][56][57][58][59][60][61] Recently, we reported a novel approach for the inert C(sp 3 )-H bond functionalization of free alcohols by employing this strategy with various heteroarenes as coupling partners. 62 Inspired by this work and our previous relevant research studies, [63][64][65][66][67] we hypothesized that using a 1,5-HAT strategy might enable two consecutive fluorinations at the same position of a substrate (Fig.…”

Palladium‐Catalyzed Cycloisomerization of 1,6‐Allene‐Ene via [1,8]‐Sigmatropic Hydrogen Shift of Allylic C−H

“…The subsequent hydrogen atom transfer(HAT) is highly depended on bond dissociation energy (BDE) and thermodynamic stability of C-centred radical(tertiary > secondary > primary), which delivered more stable intermediate via 1,n-HAT (Scheme 1B). [12][13][14][15][16][17][18][19] On the other hand, the palladium(II) catalyzed Csp 3 -H bonds activation mediated via directing group have been well developed while some of the directing group are not removable (Scheme 1C-I). Allylic C-H functionalization has been considered as a solution of directly providing allylic compounds with reagents in advance (Scheme 1C-II).…”

“…Recently, palladium radical involved catalysis was realized via single electron transfer oxidative addition to form C‐centred radicals. The subsequent hydrogen atom transfer(HAT) is highly depended on bond dissociation energy (BDE) and thermodynamic stability of C‐centred radical(tertiary > secondary > primary), which delivered more stable intermediate via 1,n‐HAT (Scheme 1B) [12–19] . On the other hand, the palladium(II) catalyzed Csp 3 ‐H bonds activation mediated via directing group have been well developed while some of the directing group are not removable (Scheme 1C–I).…”

Formal γ-C(sp3)–H Activation of Ketones via Microwave-Promoted and Iminyl-Radical-Mediated 1,5-Hydrogen Atom Transfer

“…Thus, only traps that afford readily oxidizable adducts can be employed. Clearly, the generation of iminyl radicals by methods that do not rely on SET would increase the scope of HAT-mediated γ-C–H activation …”