Chemistry of amido radicals: intramolecular hydrogen abstraction as related to amido radical configurations

Abstract

Model bromamides were photolysed to investigate the reactivity of intramolecular C-5 hydrogen abstraction (from the nitrogen atom) of the corresponding amidyl radicals and of the cyclization of the resulting C-bromides. The observed results are discussed in terms of stereoelectronic as well as energetic considerations. In the former C-5 hydrogen abstraction, the reactivity difference between semi-rigid trans and cis-oriented reaction centers is only slightly in favor of the latter; the small difference is interpreted as due to the planar ground state Π amidyl radical structure with a low N—CO twisting barrier (4-5 kcal/mol). This interpretation is supported by the efficient C-5 hydrogen abstraction in N-bromo-N-alkyltoluamides, since a rigid planar amidyl radical does not allow the methyl C—H bond to colinearly approach the Π orbital. In marked contrast, there are large reactivity differences in the cyclization of C-bromides derived from these intramolecular H—Br exchanges; these arise from the requirement of colinearity of the approaching and departing bonds. Thus this requires the coplanar orientation of the C—CH3 and C—CO bonds and this is the source of the reactivity differences.

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“…In 2016, the Knowles and Rovis groups independently published concurrent reports of the remote, δ-selective, C­(sp 3 )–H alkylation of amides with electron-deficient olefins. , In these publications, an amidyl radical, generated through formal homolysis of the amide N–H bond, is leveraged to undergo selective 1,5-HAT to abstract from a distal C­(sp 3 )–H bondanalogous to the classical Hofmann–Löffler–Freytag (HLF) reaction. − The resulting C -centered radical is then trapped by a Michael acceptor in a Giese-type reaction, forming a new C–C bond remote to the site of N–H activation. While both groups utilize the innate reactivity of the amidyl radical to achieve site selectivity in C–H bond activation, the two groups applied distinct, yet complementary approaches to the generation of the amidyl radical.…”

Synthesis of Lactones via C–H Functionalization of Nonactivated C(sp3)–H Bonds

“…Nevertheless, the extraordinary properties of nitrogen-centered radicals and the high selectivity of radical hydrogen abstractions still inspire scientists to develop novel methods for controlled oxidation in a variety of applications . Since the 1960s, there have been reports that amidyl radicals can in principle be used to form γ-lactones via hydrogen abstraction . Nevertheless, such a lactonization has not found application in synthesis.…”