Site‐Specific C(sp³)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions

Abstract

The utilization of N-centered radicals to synthesize nitrogen-containing compounds has attracted considerable attention recently,d ue to their powerfulr eactivities and the concomitant construction of CÀNb onds.H owever,t he generation and control of N-centered radicals remain particularly challenging.W er eport at ethering strategy using SOMO-HOMO-converted distonic radical anions for the site-specific aminations of imidates and amidines with aid of the noncovalent interaction. This reaction features aremarkably broad substrate scope and also enables the late-stage functionalization of bioactive molecules.F urthermore,t he reaction mechanism is thoroughly investigated through kinetic studies, Raman spectroscopy, electron paramagnetic resonance spectroscopy, and density functional theory calculations,r evealing that the aminations likely involve direct homolytic cleavage of NÀHbonds and subsequently controllable 1,5 or 1,6 hydrogen atom transfer.

Site‐Specific C(sp3)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions

“…Ultimately, the benzocyclic structure was found to be optimal for the intramolecular amination (56,7 6%, > 20:1 dr), and the cisdiastereoselectivity of 56 was also confirmed by the X-ray crystallographic analysis. [32] Furthermore,the late-stage functionalizations of the derivatives from the dehydrocholesterol and carbohydrate were performed successfully as well (57 and 58). Having successfully achieved the synthesis of the oxazoline and dihydro-1,3-oxazine derivatives (Figure 4a (Figure 5, bottom).…”

“…In the further investigation, alcohols with the tertiary b CÀHb onds (23-25)a nd secondary alcohols (26, 27,b oth trans, > 20:1 dr;a nd 28, cis, > 20:1 dr) were b-aminated efficiently.T he trans-diastereoselectivity of b amino alcohol 26 was confirmed by the X-ray crystallographic analysis. [32] Notably,t he products with hydrolysis-sensitive substituents (29 and 30)were isolated as the oxazolines.Furthermore,the late-stage aminations of the small-molecule drug derivatives, carbohydrate analogue,a nd steroid-derived substrates were also successful in moderate to excellent yields (31-35,u pt o 99 %). [32] It was found that the introduction of the Natom to substrates bearing both 1,5-HATand benzylic 1,6-HATs ites realized the selectively b-aminations (39-41)d ue to that the generated radicals can be stabilized by the orbital overlap of al one pair on an adjacent heteroatom.…”

“…[32] Notably,t he products with hydrolysis-sensitive substituents (29 and 30)were isolated as the oxazolines.Furthermore,the late-stage aminations of the small-molecule drug derivatives, carbohydrate analogue,a nd steroid-derived substrates were also successful in moderate to excellent yields (31-35,u pt o 99 %). [32] It was found that the introduction of the Natom to substrates bearing both 1,5-HATand benzylic 1,6-HATs ites realized the selectively b-aminations (39-41)d ue to that the generated radicals can be stabilized by the orbital overlap of al one pair on an adjacent heteroatom. [17] As au nique bioisostere for the phenyl ring, [18] o-carborane was investigated which replaced phenyl groups with the three-dimensional aromaticity.T he successful b-amination and the following aromatization generate product 44 with ap henyl group rather than -CCl 3 .…”

Organic radicals with inversion of SOMO and HOMO energies and potential applications in optoelectronics

“…Complementing these molecular material applications, organic radicals with SHI have recently been claimed as key intermediates for regiospecific reaction of C(sp 3 )H-amination and photocatalytic allylation, providing alternative directions for organic synthesis. 80,81 Design strategies for SHI radicals Numerous molecular systems have been reported to show SHI. However, a clear understanding of the electronic factors that lead to this specific electronic configuration has been lacking.…”

Visible Light Driven and Copper-Catalyzed C(sp3)–H Functionalization of O-Pentafluorobenzoyl Ketone Oximes

“…Intramolecular HAT mediated by nitrogen-centered radicals constitutes a valuable tool for the site-selective C­(sp 3 )–H functionalization of organic compounds. , In this context, much attention has been focused recently toward applying the iminyl-radical-mediated intramolecular 1,5-HAT to the preparation of benzene-fused cyclohexanones, nitrogen heterocycles, β-amino alcohols, and γ-functionalized ketones . Encouraged by these achievements, we set out to develop new C­(sp 3 )–H functionalization methods on the basis of this chemistry.…”