The Rich Legacy and Bright Future of Transition‐Metal Catalyzed Peroxide Based Radical Reactions

Abstract

This personal account is mainly focused on the author's involvement in the field of transition metal‐catalyzed peroxide based radical reactions. Over the past decades, radical chemistry has flourished and become crucial in contemporary synthetic organic chemistry. Owing to the presence of a single electron in one orbital, radicals are very unstable and react very fast. To carry out desired transformations and to control the side reactions the stabilizations of these radicals is essential. Fortunately, the implementation of a suitable transition metal and peroxide combination into the radical reactions have proved beneficial. Transition metals not only stabilizes the radicals but also protects them from being quenched by undesired homo‐coupling or fragmentation. Transition metal‐catalyzed radical‐radical reactions provide an innovative way for the construction and derivatization of carbocycles and heterocycles. The objective of this review is to give an overview of the construction and derivatization of heterocycles through the lens of radical chemistry, mainly focusing on research work done by our group.

Double-Site Binding and Anti-/Pro-oxidation of Luteolin on Bovine Serum Albumin Mediated by Copper(II) Coordination

“…The obviously increased antioxidation reactivity of Cu­(II)–Lut in CO formation during the oxidation of BSA may arise from the increased radical scavenging reactivity of Lut by Cu­(II) coordination as we observed previously in a homogeneous solution . The pro-oxidation effect of Cu­(II) was explained as the catalyzed dissociation of hydroperoxide ROOH by Cu­(II) to form more oxidizing radicals as in eqs and . , in which ROOH was suggested to form from hydrogen abstraction from BSA by ROO • generated from the pyrolysis of AAPH. Cu­(II) initially coordinated to BSA at the Asp-Thr-His triad in the N-terminal changed into double-site coordination at two pockets by complexation with Lut, which converted Cu­(II) from a pro-oxidant into a protein antioxidant.…”

“… 24 The pro-oxidation effect of Cu(II) was explained as the catalyzed dissociation of hydroperoxide ROOH by Cu(II) to form more oxidizing radicals as in eqs 3 and 4 . 56 , 57 in which ROOH was suggested to form from hydrogen abstraction from BSA by ROO • generated from the pyrolysis of AAPH. Cu(II) initially coordinated to BSA at the Asp-Thr-His triad in the N-terminal changed into double-site coordination at two pockets by complexation with Lut, which converted Cu(II) from a pro-oxidant into a protein antioxidant.…”

Recent advances in TBHP‐promoted heterocyclic ring construction via annulation/cyclization

“…In addition to these TBHP is used in oxidative synthesis of substituted pyrimido[4,5‐ d ]pyrimidines from N ‐uracil amidines and methylarenes under metal free conditions [63], for the solvent‐free oxidation of cyclohexane [64], one‐pot synthesis of indolizines using TBHP as the methylene source under metal‐free condition [65], regioselective N ‐alkylations and arylations of tetrazoles [66], intermolecular CDC amination [67], differential peroxidation of terminal and internal alkenes and other miscellaneous reactions [68, 69].…”