Stereoselective Synthesis of Isoxazolidines via Copper-Catalyzed Alkene Diamination

Abstract

A convenient copper-catalyzed intramolecular/intermolecular alkene diamination reaction to synthesize 3-aminomethyl-functionalized isoxazolidines under mild reaction conditions and with generally high levels of diastereoselectivity was achieved. This reaction demonstrates that previously underutilized unsaturated carbamates are good [Cu]-catalyzed diamination substrates. Sulfonamides, anilines, benzamide, morpholine, and piperidine can serve as the external amine source. This relatively broad amine range is attributed to the mild reaction conditions. Reduction of the N–O bond could also be achieved, revealing the corresponding 3,4-diamino-1-alcohols efficiently.

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

“…Lower reaction temperature facilitated employment of a catalytic diamination with more electron-rich exogenous amines. 67 Electron-rich amines are susceptible to oxidation (to give imines, for example) by copper(II) salts at elevated temperatures. 68 They can also contribute to catalyst poisoning.…”

“…1.3 V). A summary of experimentally determined oxidation potentials of related amines determined by us 73 and Dinnocenzo 74 is shown in Scheme 25. Oxidation of the amines would form aminyl radical cations while homolysis of the R 2 N-[Cu(II)] bond, the proposed path for “direct” formation of aminyl radicals under our reaction conditions, would form a neutral aminyl radical, so the systems are not identical.…”

Copper-catalyzed aminoalkynylation of alkenes with hypervalent iodine reagents

“…Our investigation of this alkene aminoalkynylation reaction began with unsaturated amide 1a ( Table 1 ), a model substrate that was demonstrated to undergo effectively copper-catalyzed aminocyclization in our previous studies. 8c , 9h , 10 We chose ethynylbenziodoxolones (EBX) as the alkynyl precursors, as they have been successfully used in different alkynylation reactions with nucleophiles, 11 C–H bonds, 12 carbon radicals, 13 and olefins. 5 Encouragingly, aminoalkynylation product 3aa was formed in 69% yield in the presence of Cu(OTf) 2 in CH 3 CN at 80 °C (entry 1).…”

“…15 In pathway A, the reaction may be initiated by the coordination of copper catalyst with alkene 1a followed by the intramolecular aminocupration. 10 The resulting alkyl–Cu intermediate II may undergo a reversible C–Cu( ii ) homolysis to form radical intermediate III , which would subsequently attack the α-position of the alkynyliodonium salt 2a . Finally, the β-elimination of intermediate IV would lead to product 3 and regeneration of the copper catalyst.…”

Vicinal difunctionalization of carbon–carbon double bond for the platform synthesis of trifluoroalkyl amines

“…In general, the diamination reaction of alkenes requires radical or oxidative conditions, which permit the introduction of Natoms in form of azide, sulfonamide, urea, and amide functionalities, while easily oxidizable alkyl-and aryl-amines are introduced by transition metal-assisted and -catalyzed methods limited to few examples 1,[26][27][28] . Regarding the abundant N-atom sources, nucleophilic difunctionalization of alkenes with simple amines without the use of transition metals would be a cornerstone to improve structural diversity of diamine synthesis.…”