Triiodide‐Mediated δ‐Amination of Secondary C−H Bonds

Abstract

The δ C-H amination of unactivated, secondary C-H bonds to form a broad range of functionalized pyrrolidines has been developed via a triiodide (I3−)-mediated strategy. By in situ (i) oxidation of sodium iodide and (ii) sequestration of the transiently generated iodine (I2) as I3−, this approach precludes undesired I2− mediated decomposition that can otherwise limit synthetic utility to only weak C-H bonds. The mechanism of this triiodide-mediated cyclization of unbiased, secondary C-H bonds, via thermal or photolytic initiation, is supported by NMR and UV-Vis spectroscopic data and intercepted intermediates.

Directed γ-C(sp3)–H Alkylation of Carboxylic Acid Derivatives through Visible Light Photoredox Catalysis

“…modified Hofmann-Löffler-Freytag reaction 10 ), generates a γ-carbon centered radical. These radicals largely end up as halogenated 11 or cyclized product, 12 due to high reactivity of the excess halogen reagents within the systems.…”

Directed β C–H Amination of Alcohols via Radical Relay Chaperones

“…3 However, metal-based approaches typically afford γ selectivity, due to requisite metallacycle geometries. 4 As part of our program to develop radical relay strategies for selective C–H functionalization, 5 we hypothesized that an open-shell pathway might enable valuable, synthetic complementarity.…”

“…Each imidate was then subjected to our recently developed, triiodide-based C–H amination conditions (Scheme 1). 5 Gratifyingly, these mild conditions (NaI, PhI(OAc) 2 ) convert all three imidates ( 1 – 3 ) to the desired oxazoline heterocycles ( 4 – 6 ), albeit with divergent efficiencies (e.g., trace to quantitative), reflecting a difference in stability of the imidate intermediates, as well as their respective N-centered radicals. Fortunately, trichloroacetimidate 3 affords C–H amination product 6 , quantitatively.…”

“…Longer alcohols with unbiased, secondary β C–H bonds ( 34 , 35 ) provide even greater efficiency–consistent with our observation that triiodide-based C–H amination enables methylene functionalization. 5 Orthogonal functionality is tolerated under these mild, radical-mediated conditions, including ethers, esters, and amines ( 36 – 38 ). Secondary alcohols can also undergo β -amination ( 39 , 40 ), complementary to metal-mediated approaches.…”

An Iodine‐Mediated Hofmann‐Löffler‐Freytag Reaction of Sulfoximines Leading to Dihydroisothiazole Oxides

“…This constraint was overcome by Suá rez, who implemented neutral reaction conditions by using iodobenzene diacetate (PIDA) to generate the nitrogen radical, which is the key intermediate in the HLF chemistry. [4] In 2015, Herrera devised a chemoselective intramolecular functionalization of Niodosulfonamides for the synthesis of aminated fivemembered heterocycles. [3] Similarly, Nagib developed a protocol for the CÀH functionalization of unbiased amines to pyrrolidines using an I 3 --based system.…”