Copper‐Catalyzed Oxidative Amination and Allylic Amination of Alkenes

Abstract

Enamines and enamides are useful synthetic intermediates and common components of bioactive compounds. A new protocol for their direct synthesis by a net alkene C–H amination and allylic amination by using catalytic CuII in the presence of MnO2 is reported. Reactions between N-aryl sulfonamides and vinyl arenes furnish enamides, allylic amines, indoles, benzothiazine dioxides, and dibenzazepines directly and efficiently. Control experiments further showed that MnO2 alone can promote the reaction in the absence of a copper salt, albeit with lower efficiency. Mechanistic probes support the involvement of nitrogen-radical intermediates. This method is ideal for the synthesis of enamides from 1,1-disubstituted vinyl arenes, which are uncommon substrates in existing oxidative amination protocols.

Stereoselective and Regioselective Synthesis of Heterocycles via Copper-Catalyzed Additions of Amine Derivatives and Alcohols to Alkenes

“…72 These amidyl radicals appear to be electron-poor and to react faster with electron-rich styrenes. Related reactions of amidyl radicals with alkenes and alkanes have been reviewed.…”

“…72 1,1-Disubstituted styrenes provide higher yields than monosubstituted styrenes; this argues against activation of the alkene by [Cu] since a metal typically prefers lower steric hindrance. 1,1-Diarylalkenes in particular are excellent radical acceptors.…”

Palladium-Catalyzed Intermolecular Oxidative Amination of Alkenes with Amines, Using Molecular Oxygen as Terminal Oxidant

“…Oxidative coupling for the formation of nitrogen-containing compounds such as enamines using metal-catalyzed oxidative amination of olefins by dioxygen, known as the aza-Wacker reaction, has been the subject of considerable research [10][11][12][13][14][15][16][17][18]. Although significant developments in aza-Wacker-type reactions have been achieved, the existing aza-Wacker process generally requires non-basic nitrogen nucleophiles such as carboxamides, carbamates, and sulfonamides as amination reagents, under relatively high oxygen pressures (4-10 atm.)…”

Stereoselective Synthesis of Isoxazolidines via Copper-Catalyzed Alkene Diamination

“…Thus, endo cyclization of aminyl radical VI onto its 1,1-disubstituted alkene to produce a tertiary carbon radical (not shown) that suffers oxidation to give alkene 5 is more favorable than the C–N bond formation involving carbon radical IV ′, which would lead to a diamine product. 19 The presence of a ring-opening pathway (such as IV ′ to VI ) could also account, at least in part, for the low observed enantioselectivity (eq 1), since the aminyl radical would produce a racemic product upon exocyclization to give a carbon radical like IV (Scheme 1). We have previously observed low enantioselectivity in related reactions where substrates can access a more-stabilized aminyl radical and where the carbon radical must engage in a relatively higher energy subsequent bond formation.…”