Transition‐Metal‐Free α Csp³−H Cyanation of Sulfonamides

Abstract

This report describes the site-selective α-functionalization of sulfonylamide derivatives through the in-situ generation of imine intermediates. The NÀ F sulfonylamides, which could facilitate the elimination to generate imines, are coupled with TBACN to efficiently and mildly afford αamino cyanides. Comparing with Strecker reaction, this transformation offers a complementary strategy to efficiently construct α-amino cyanides from direct α CÀ H functionalization of sulfonylamindes. The reaction is also characterized by broad substrate scope and flash chromatography column free workup. More importantly, the new two-electron pathway to generate imines through manipulation of the leaving group allows us to achieve excellent α site-selectivity.

Copper-Mediated Radical Fluorine-Atom Transfer to Sulfonyl Radical: A Dramatic 4-Methoxypyridine 1-Oxide Ligand Effect

“…( 4) To improve the efficiency further, both the solvent and SO 2 source were evaluated, albeit with no improvement. Giving that byproduct 7a might be formed through the 1,2-addition of SO 3 2− to imine intermediate, as well as the previous example that L 7 can serve as a base 22 to promote the 1,2-elimination of 1a to generate an imine 23 we thought that the addition of a suitable additive that could inhibit the basicity of ligand L 7 might increase the yield. We were delighted to see that adding one equivalent of Selectfluor has a positive influence.…”

C(sp3)−H Functionalization Using Chlorine Radicals

“…) [13] with the assistance of heat or light to make an active radical species for C( sp 3 )−H bonds breaking (Figure 2B). These methods also cover non‐radical pathways including hydride atom transfer that convert C( sp 3 )−H bonds to the related carbocations (Figure 2B‐IV) [6] through 1,n‐HT and nucleophilic attack at the α‐position of heteroatom assisted C( sp 3 )−H bonds [14] …”

“…These methods also cover non-radical pathways including hydride atom transfer that convert C(sp 3 )À H bonds to the related carbocations (Figure 2B-IV) [6] through 1,n-HT and nucleophilic attack at the αposition of heteroatom assisted C(sp 3 )À H bonds. [14] In addition to the abovementioned methods, there is a fast-growing field in CÀ H bond functionalization methodologies that use electric current as a driving force to break CÀ H bonds through appropriate mediators. [15] These protocols can be divided into two main classes: 1) direct and 2) indirect electrochemical methods.…”

Fluoroamide-Directed Regiodivergent C-Alkylation of Nitroalkanes

“…20 This reaction is hampered by the electron-deficient protecting group on the nitrogen atom, which has a much lower electron density than an amine. Very recently, the groups of Zhang21 and Loh22 independently reported base-promoted fluoroamide-directed α-C−H cyana-…”

“…This reaction is hampered by the electron-deficient protecting group on the nitrogen atom, which has a much lower electron density than an amine. Very recently, the groups of Zhang and Loh independently reported base-promoted fluoroamide-directed α-C–H cyanations (Scheme B, left). These elegant reactions offer a modern orthogonal approach to well-known δ-C–H functionalization protocols involving 1,5-HAT.…”