Alleviating Catalyst Decay Enables Efficient Intermolecular C(sp³)–H Amination under Mechanochemical Conditions

Abstract

The implementation of an energetically distinct mechanical activation strategy in catalysis has unlocked exciting opportunities for sustainable organic synthesis. Differing from the primary synthetic endeavors to explore reaction diversity that mechanochemistry can substitute the conventional solution-based protocols and probe essential reaction kinetics and thermodynamics, herein we investigate the origin of enhanced catalytic stability and performance under ball milling by taking Rh 2 (esp) 2 -catalyzed intermolecular C−H amination as a study case. Significant alleviation of catalyst decay was observed. Mechanistic studies revealed that single-electron oxidation of the Rh II dimer and solvent oxidation are largely circumvented, thereby alleviating the decay of metal catalysts. Also, the present work has delineated the first mechanochemical C(sp 3 )−H amination, which accommodates a host of hydrocarbons and complex natural products with economized precious catalysts under solvent-free conditions, thus substantially enriching the repertoire of mechanosynthesis.

Mechanochemical Direct Fluorination of Unactivated C(sp3)−H Bonds

“…The transformation required a high temperature (112.5 °C) to afford monochloromethane as the major product [7] . Wu, Zhong, and coworkers demonstrated the mechanochemical amination of aliphatic C( sp 3 )−H bonds, adopting the developed solution‐based Rh 2 (esp) 2 ‐catalyzed reactions (esp=α,α,α′,α′‐tetramethyl‐1,3‐benzenedipropionic acid) [8] . The reaction proceeded in a short time (2.5 h vs 4–6 h for the solution reaction) with a low catalyst loading (0.2–0.5 mol% vs 1.0–2.0 mol% for solution reactions) [9]…”

“…[7] Wu, Zhong, and coworkers demonstrated the mechanochemical amination of aliphatic C(sp 3 )À H bonds, adopting the developed solution-based Rh 2 (esp) 2 -catalyzed reactions (esp = α,α,α',α'-tetramethyl-1,3-benzenedipropionic acid). [8] The reaction proceeded in a short time (2.5 h vs 4-6 h for the solution reaction) with a low catalyst loading (0.2-0.5 mol% vs 1.0-2.0 mol% for solution reactions). [9] The introduction of fluorine into organic molecules constitutes a crucial transformation reaction in organic synthesis.…”

Recent Advances in C—H Bond Functionalization under Mechanochemical Conditions

“…通过比较作者发 现, 虽然在溶剂中反应可以得到更高的收率, 但是球磨 中反应不需要额外加热, 反应时间短等优势也极为突 出. 2021 年, 钟芳锐课题组 [44] 报道利用机械化学方法 可以提高催化剂的稳定性并促进其催化性能, 实现机械 力促进的 C(sp 3 )-H 胺化反应(Scheme 24). 以醋酸碘苯 为氧化剂, 碳酸氢钠为助磨剂, 仅需 0.5 mol%铑催化剂, 该反应在研磨 2.5 h 后即可得到 89%的收率.…”

Rh(ii)-catalyzed Doyle–Kirmse reaction: access to unprotected 3-allyl/3-allenyl-3-(thio)oxindoles

“…10 However, most Doyle–Kirmse reactions use ester-derived diazo reagents, 11 and few cases use heterocyclic diazo reagents. 12 Considering the great interest in the oxindole nucleus as the structural motif of many biologically active compounds and clinically used pharmaceuticals, and as part of our ongoing study on the development of efficient Rh( ii ) catalytic chemistry, 13 we envisaged that N–H unprotected diazoindolinones could be transferred into metal carbene intermediates efficiently under a low catalyst-loading Rh( ii ) catalyst, which subsequently undergoes the Doyle–Kirmse reaction exclusively. Allyl sulfides act as both sulfenylating and allylating reagents, and facilely furnish modified C-3 bifunctional 3-allyl-3-(phenylthio)indolin-2-ones (Scheme 1c).…”