Tobisch Sven
University of St Andrews , School of Chemistry , Purdie Building, North Haugh, St Andrews , UK KY16 9ST . Email:
Chem Sci. 2017 Jun 1;8(6):4410-4423. doi: 10.1039/c7sc01107e. Epub 2017 Apr 28.
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 ()-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 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.
本文展示了通过(Xantphos)CuH催化剂（Xantphos ≡ {P^P} ≡ 4,5-双（二苯基膦基）-9,9-二甲基氧杂蒽）对内部芳基炔烃与原型羟胺酯和硅烷进行的CuH介导的氢胺化反应进行的深入计算机理探究。对CuH介导的亲电炔烃氢胺化反应的首次全面计算研究确定了直接氢胺化和还原氢胺化竞争途径中最可行的途径。通过将可靠的计算协议应用于实际催化剂模型获得的平滑能量分布得出的机理图景与所有现有实验数据相符。发现关键的乙烯基铜和烷基铜中间体在对胺亲电试剂和醇的反应性上表现出明显的化学发散性，这确保了α-支链烷基胺与()-烯胺的成功形成。一方面，醇对乙烯基铜的进攻稍占优势，从而使在胺亲电试剂和醇同时存在的情况下还原氢胺化途径更有利。相比之下，预测烷基铜进行质子化亲电胺化的动力学要求更高，这使得还原氢胺化途径不会变得无产物。发现电子修饰的羟胺酯会影响乙烯基铜和烷基铜对胺亲电试剂和醇的反应性中的化学选择性，从而为工艺改进提供了机会。
