A combined experimental and computational study reveals a crossover between conventional cross-coupling and carbene insertion pathways in a Pd catalyzed C(sp2)–H insertion

IF 7.6 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Chemical Science Pub Date : 2025-03-18 DOI:10.1039/d5sc00777a

Arushi Tyagi, Kritika Gaur, Anubhav Goswami, Arko Seal, Mayuk Joddar, Garima Jindal

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Abstract

Computational (DFT and DLPNO-CCSD(T)) calculations along with experimental tools (deuterium labelling, kinetic studies using VTNA, ESI-HRMS and UV) are used to probe the mechanism of a Pd(II)-catalyzed enantioselective carbene insertion into C(sp²)–H of indole. Using deuterium labelling studies, we demonstrate the intermediacy of a metal-hydride species, which contrasts with mechanistic routes for other transition metals (Rh, Fe, Au, Cu, etc.). Our VTNA study reveals the order to be one in both diazo and indole, which along with microkinetic modelling aligns well with the computationally predicted mechanism. The mechanism is further supported by the detection of the most stable intermediate in the catalytic cycle using ESI-HRMS. An investigation into the origin of stereoselectivity using DLPNO-CCSD(T) presents a new paradigm, wherein stereocontrol arises during the formation of the Pd carbene itself as opposed to proton transfer steps found for all other metal catalysts.

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来源期刊

Chemical Science CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

14.40

自引率

4.80%

发文量

1352

审稿时长

2.1 months

期刊介绍： Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.