Copper‐Catalyzed Aerobic Oxidative CH Functionalizations: Trends and Mechanistic Insights

Abstract

The selective oxidation of C-H bonds and the use of O(2) as a stoichiometric oxidant represent two prominent challenges in organic chemistry. Copper(II) is a versatile oxidant, capable of promoting a wide range of oxidative coupling reactions initiated by single-electron transfer (SET) from electron-rich organic molecules. Many of these reactions can be rendered catalytic in Cu by employing molecular oxygen as a stoichiometric oxidant to regenerate the active copper(II) catalyst. Meanwhile, numerous other recently reported Cu-catalyzed C-H oxidation reactions feature substrates that are electron-deficient or appear unlikely to undergo single-electron transfer to copper(II). In some of these cases, evidence has been obtained for the involvement of organocopper(III) intermediates in the reaction mechanism. Organometallic C-H oxidation reactions of this type represent important new opportunities for the field of Cu-catalyzed aerobic oxidations.

Oxidative Coupling – Bonding between Two Nucleophiles

“…In the following several years, replacing the organometallic reagents with various C-H or X-H nucleophiles to achieve greener oxidative couplings such as R 1 -H/R 2 -M 2 and R 1 -H/R 2 -H dominated the research area, in which numerous outstanding works have been reported [12][13][14][15]. Especially, transition-metal-catalyzed oxidative R 1 -H/R 2 -H coupling with air or O 2 as the oxidant is no doubt an ideal approach for bond formations [16,17].…”

Practical Pd(TFA)2-Catalyzed Aerobic [4+1] Annulation for the Synthesis of Pyrroles via “One-Pot” Cascade Reactions

“…On the other hand, the transition-metal-catalyzed sp 2 C-H amination reaction is one of the most demanding procedures to form C-N bonds [36,37]. In recent years, various late transition metal catalysts such as Pd [38][39][40][41], Ru [42], Rh [43], Ir [44], and Cu [45] have been applied in sp 2 C-H bond amination. Within this methodology, Pd-catalyzed intramolecular aza-Wacker-type oxidative reactions represent one crucial route to produce a range of 5-membered N-containing heterocycles [46][47][48][49][50][51].…”

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

“…Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Therefore, many attempts are made to develop methods that use cheap catalysts, benign conditions and oxygen or air as terminal oxidant 10 . Many organic compounds react slowly with oxygen from air in autoxidation reactions which can functionalize C-H bonds by effectively inserting O 2 , forming a hydroperoxide moiety 11,12 .…”