1,2-Redox Transpositions of Tertiary Amides

Abstract

Reactions capable of transposing the oxidation levels of adjacent carbon atoms enable rapid and fundamental alteration of a molecule's reactivity. Herein, we report the 1,2-transposition of the carbon atom oxidation level in cyclic and acyclic tertiary amides, resulting in the one-pot synthesis of 1,2-and 1,3-oxygenated tertiary amines. This oxidation level transfer was facilitated by the careful orchestration of an iridium-catalyzed reduction with the functionalization of transiently formed enamine intermediates. A novel 1,2-carbonyl transposition is described, and the breadth of this redox transposition strategy has been further explored by the development of aminoalcohol and enaminone syntheses. The diverse β-functionalized amine products were shown to be multifaceted and valuable synthetic intermediates, accessing challenging biologically relevant motifs.

Asymmetric Deoxygenative Functionalization of Secondary Amides with Vinylpyridines Enabled by a Triple Iridium-Photoredox-Chiral Phosphoric Acid System

“…According to the above results and previous reports, ,, a plausible mechanism was proposed as illustrated in Scheme b. First, an Ir-catalyzed semireduction of the amide generates O -silylated hemiaminal I , which on elimination of the silanol further evolves to the imine intermediate II . , On the other hand, the photoredox catalyzed radical process is triggered by a single-electron reduction of the excited *DPZ with trace HE-1 • , which may be generated from *HE-1 and imine II under blue LED irradiation . The α-amino radical V is formed via proton-coupled electron transfer (PCET), followed by a radical addition with protonated alkene III to afford intermediate VI .…”

“…In this context, the deoxygenative transformation of readily available amides, occurring widely in numerous bioactive molecules and materials, is in high demand for rapid generation of various amines . In recent years, significant progress has been made in this area, primarily including the reductive functionalization of amides via electrophilic activation, controlled hydride reduction, and transition-metal-catalyzed reduction of amides, which generally involved transformation of the less reactive amides into some types of highly electrophilic species (iminiums or imines), and thus may be captured by nucleophiles to afford the corresponding α-functionalized amines (Scheme a-i). In addition, several elegant strategies involved in a single electron transfer (SET) process were also disclosed for amide functionalization.…”

“…Although great progress has been made in the deoxygenative transformation of the amides, − asymmetric functionalization of amides to chiral amines is rarely explored (Scheme a-iii). In 2021, asymmetric reductive cyanation and phosphonylation of secondary amides were demonstrated by the Huang group .…”

“…There was no notable signal apart from the peaks for silane or the amide (Figure 2-i vs ii in the Supporting Information (SI)). As a comparison, adding both silane and [Ir­(COE) 2 Cl] 2 to the solution of 1a in toluene- d 8 and stirring the mixture for 30 min, new signals assigned to imine intermediate 4 appeared on the spectrum (Figure 2-iii in the SI), which was probably produced via the intermediacy of silylhemiaminal. , Notably, no desired product 3aa was detected when the reaction was run in the dark vessel (Scheme a), while imine intermediate 4 was detected in 90% yield, suggesting that light irradiation is necessary for the coupling process.…”

Regioselective oxidative cleavage of conjugated dienes to access α,β-unsaturated nitriles

“…6 This field was initially reported by Luisi and Bull 6 and has experienced significant growth in the last five years. 7 Recently, Morandi's group developed a nitrogen atom insertion method for indole and indene skeletons to produce quinazolines and isoquinolines, respectively (Scheme 1c). 8 This method involved the use of ammonium carbamate and hypervalent iodine( iii ), generating an N -iodonium-aziridine intermediate from an electrophilic nitrene iodonium species ( I ) that reacted with the CC double bond in the arenes.…”