Copper-Catalyzed Amide Radical-Directed Cyanation of Unactivated C_sp³–H Bonds

Abstract

A method for site-selective intermolecular δ/ε-Csp 3–H cyanation of aliphatic sulfonamides is developed using TsCN as the cyanating reagent, catalyzed by a Cu­(I)/phenanthroline complex. The mild, expeditious, and modular protocol allows efficient remote Csp 3–H cyanation with good functional group tolerance and high regioselectivity. Mechanistic studies indicate that the reaction might proceed through a Cu­(I)-mediated N–F bond cleavage to generate an amidyl radical, 1,5-HAT, and cyano group transfer of the resulting carbon radical with TsCN.

Chiral Piperidines from Acyclic Amines via Enantioselective, Radical-Mediated δ C–H Cyanation

“…Otherwise, this might lead to a background racemic reaction. 28 If successful, we envisioned this approach for stereoselective interception of an intramolecular HAT based on N-centered radicals could enable the asymmetric synthesis of a wide variety of remotely functionalized amines and heterocycles.…”

Visible‐Light‐Driven Remote C−H Chlorination of Aliphatic Sulfonamides with Sodium Hypochlorite

“…Recently, new applications have been found for the HLF type reactions to enable the site-selective C(sp 3 )À H functionalization in an atomeconomical and step-economical fashion. [2] In this context, great process has been made by applying this strategy to CÀ H alkylation, [3] arylation, [4] alkynylation, [5] trifluoromethylation, [6] cyanation [7] and introduction of hetero atom centered functional groups. [8] Notably, employment of visible light photoredox catalysis allows nitrogen-centered radicals to be generated conveniently under mild and environmental-friendly conditions, [9] which renders the HLF CÀ H functionalization strategy more attractive from the view point of green chemistry.…”

Recent Advances in Copper-Catalyzed Radical C–H Bond Activation Using N–F Reagents

“…On the other hand, in 2019 Zhang and co-workers designed a protocol that allowed efficient remote Csp 3 -H bond cyanation of aliphatic sulfonamides, using TsCN as the cyanating reagent and a Cu(I)/phenanthroline complex as catalyst (Scheme 20a). 31 The system showed good functional group tolerance and high regioselectivity. They proposed that the N-fluorotosylamide is reduced with Cu(I) by a single-electron-transfer (SET) mechanism to generate amidyl radical and a (FCu II CN)L n complex (Scheme 20b).…”