Mechanistic Studies of the Copper-Catalyzed Electrophilic Amination of Diorganozinc Reagents and Development of a Zinc-Free Protocol

Abstract

[reaction: see text] An SN2 mechanism for the copper-catalyzed amination of diorganozinc reagents by O-benzoyl-N,N-dialkylhydroxylamines is supported by following stereochemically defined organometallics through the reaction and by employing the endocyclic restriction test. A copper-catalyzed electrophilic amination of organomagnesium compounds is also described in which the use of zinc halides has been eliminated.

CuH-catalysed hydroamination of arylalkynes with hydroxylamine esters – a computational scrutiny of rival mechanistic pathways

“…Among the multiple mechanistic scenarios imaginable, 16 three plausible pathways for Umpolung electrophilic amination have been characterised commencing from adducts 2· A. A first pathway sees the S N 2-type displacement of the amine electrophile's benzoate leaving group via a classical TS structure to afford transient {P^P}Cu III intermediate 3 , which likely undergoes C–N bond-forming reductive elimination thereafter to deliver PE together with {P^P}Cu I benzoate 4 .…”

“…In the absence of a proton donor, the direct hydroamination avenue is traversed, where 2 couples with the hydroxylamine electrophile (A) to generate ( E )-enamine (PE) and {P^P}Cu I benzoate 4 . This transformation can proceed through various mechanistic pathways, 16 its precise details remain largely elusive thus far. If, however, an alcohol additive (R) is present, the avenue for reductive hydroamination would become available, whereby protonation occurs at 2 to deliver {P^P}Cu I alkoxide 5 and cis -alkene (O).…”

Copper Hydride Catalyzed Hydroamination of Alkenes and Alkynes

“…Tertiary amine product 9 and copper(I) benzoate species 10 are then generated upon rapid reductive elimination. [21] Subsequent work has also demonstrated that N -heterocyclic carbene (NHC) or phosphine ligated copper catalysts can mediate the coupling of aryl boronic esters and silyl ketene acetals with hydroxylamine O- benzoates to form the respective aminated products. [22] …”

Synthesis of amines by the electrophilic amination of organomagnesium, -zinc, -copper, and -lithium reagents

“…Copper-II catalyzed reaction of various N,N-dialkyl-Obenzoylhydroxylamines with organomagnesium reagents have been shown by Champbell and Johnson. 39 RMgX was added slowly (0.15 mmol/min.) to the mixture of aminating reagent and copper catalyst in THF at room temperature.…”

“…4-(Benzoyloxy)piperidine reacts with phenylcopper and diphenylcuprate to furnish aniline in good to high yields (Scheme 33). 39 Diphenylcuprate gives a higher yield than phenylcopper. The organometallic precursor (PhLi, PhMgBr or PhZnCl) used in the preparation of organocopper reagents does not affect the yield, but using a Li 2 CuCl 3 complex instead of a CuBr.SMe 2 complex as copper source leads to an increase in the yield of aniline.…”