Hydrogen Atom Transfer (HAT)-Triggered Iron-Catalyzed Intra- and Intermolecular Coupling of Alkenes with Hydrazones: Access to Complex Amines

Abstract

A novel methodology for the coupling of alkenes with aldehyde-or ketone-derived Cbzhydrazones to form a new CC bond through a radical process is described. The sequence comprises an initial in situ generation of an iron hydride followed by a hydrogen atom transfer to an alkene, a coupling with a hydrazone and a final reduction of the nitrogencentered radical. Hydrogenation of the obtained hydrazines renders amines, including valuable tert-alkyl amines.

Catalytic Radical–Polar Crossover Reactions of Allylic Alcohols

“…Metal hydride-mediated radical reactions provide a highly chemoselective means for hydrofunctionalization of alkenes with Markovnikov selectivity. , The intermediate alkyl radicals or their equivalents can react with a variety of atom and group transfer reagents, undergo addition into multiple bonds, and engage in cross-coupling reactions to introduce new functionalities and connectivity patterns. Recent reports demonstrate that the radical formation can be combined with subsequent oxidation to generate corresponding electrophilic intermediates, which can be captured with oxygen and nitrogen nucleophiles to produce cyclic and acyclic ethers, lactones, and saturated nitrogen heterocycles. − The radical–polar crossover nature of these processes can be expected to considerably expand the scope of the radical hydrofunctionalizations and offer the advantage of chemoselectivity when compared to the corresponding acid-catalyzed reactions.…”

Olefin Amine (OLA) Reagents for the Synthesis of Bridged Bicyclic and Spirocyclic Saturated N-Heterocycles by Catalytic Hydrogen Atom Transfer (HAT) Reactions

“…In prior work from our group, we have established that C-centered radicals, generated by single-electron oxidation of organosilicons or organostannes, undergo additions to unactivated imines. In order to access more complicated ring structures, we sought alternative methods for radical generation and turned to the well-known Mukaiyama hydration of olefins and further developments by Carreira, Boger, Baran, Shenvi, Shigehisa, Herzon, Bradshaw and others to a growing number of Mn-, Fe-, and Co-catalyzed radical hydrofunctionalizations of olefins . These reactions are generally based on the Halpern mechanism featuring carbon-centered radicals generated from the olefins by hydrogen atom transfer (HAT) via metal hydride (MH) species.…”

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

“…More recently, the Bradshaw group has been exploring the potential use of tosyl hydrazones in reductive couplings with olefins initiated via metal hydride atom transfer [ 96 – 97 ]. In 2020, they realized that formal hydroalkylated products could be obtained by coupling substituted tosyl hydrazones with olefins ( Scheme 29 ) [ 98 ], similarly to the hydromethylation protocol developed by Baran [ 95 ] ( Scheme 28 ).…”