Issue 6, 2017

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

Abstract

An in-depth computational mechanistic probe of the CuH-mediated hydroamination of internal arylalkynes with an archetype hydroxylamine ester and hydrosilane by a (Xantphos)CuH catalyst (Xantphos ≡ {P^P} ≡ 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) is presented. This first comprehensive computational study of the CuH-mediated electrophilic alkyne hydroamination has identified the most accessible pathway for the rival avenues for direct and reductive hydroamination. The mechanistic picture derived from smooth energy profiles obtained by employing a reliable computational protocol applied to a realistic catalyst model conforms to all available experimental data. The crucial vinyl- and alkylcopper intermediates were found to display a distinct chemodivergence in their reactivity towards amine electrophile and alcohol, which ensures the successful formation of α-branched alkylamines together with (E)-enamines. On the one hand, the vinylcopper is somewhat preferably approached by the alcohol, thereby rendering the reductive hydroamination avenue favourable in the presence of both amine electrophile and alcohol. In contrast, the greater kinetic demands for protonation versus electrophilic amination predicted for the alkylcopper prevents the reductive hydroamination avenue to become non-productive. Electronically modified hydroxylamine esters are found to influence the chemoselectivity in reactivity towards amine electrophile and alcohol achievable for the vinyl- and alkylcopper, thereby offering an opportunity for process improvement.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
10 Mar 2017
Accepted
27 Mar 2017
First published
28 Apr 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 4410-4423

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

S. Tobisch, Chem. Sci., 2017, 8, 4410 DOI: 10.1039/C7SC01107E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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