Practical Aerobic Oxidations of Alcohols and Amines with Homogeneous Copper/TEMPO and Related Catalyst Systems

Abstract

Alcohol and amine oxidations are common reactions in laboratory and industrial synthesis of organic molecules. Aerobic oxidation methods have long been sought for these transformations, but few practical methods exist that offer advantages over traditional oxidation methods. Recently developed homogeneous Cu/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidinyl-N-oxyl) and related catalyst systems appear to fill this void. The reactions exhibit high levels of chemoselectivity and broad functional-group tolerance, and they often operate efficiently at room temperature with ambient air as the oxidant. These advances, together with their historical context and recent applications, are highlighted in this minireview.

Cu‐Catalyzed Cyanation of Arylboronic Acids with Acetonitrile: A Dual Role of TEMPO

“…Av ariety of arylboronic acids 1b-g with electron-donating groups (R = Me, OMe, OBn, tBu,r espectively) on the aryl ring furnished the corresponding products 2b-g in 71-97 %y ields ( Table 2, entries 1-6). More electron-rich boronic acids 1o-1 q,w hich contained two electron-donating substituents, worked more efficiently to give the products 2o-q in 81-99 %y ields ( Table 2, entries [14][15][16]. Additionally,i tw as observed that electron-withdrawing substituents (R = 4-OCF 3 ,4 -CF 3 ,4 -COOMe, 4-F) were tolerated under the reaction conditions;h owever,t he corresponding products 2j-l,r were afforded in lower yields ( Table 2, entries 9-11a nd 17).…”

“…Accordingly,t hese results indicated that not only the CÀCN bond but also the NÀOb ond has been cleaved in compound 6.I ncidentally,d uring NÀOb ond cleavage, TEMPO might serve as an oxidantasw ell. [15,19] On the basis of the above mechanistic studies, we have proposed ac atalytic cycle for the Cu/TEMPO system (Scheme 3). Twop athways for the formation of TEMPOÀCH 2 CN (6)a re possible.…”

“…Along with itsu se as ar adicalt rapping reagent, TEMPO has been used as am ild oxidanti nt ransition-metal-catalyzed coupling reactions. [15] Recently,w er evealed that TEMPOc an be used as Scheme1.Catalytic cyanation strategy using acetonitrile as the "CN" source.…”

Aerobic Oxidations in Continuous Flow

“…In stark contrast, oxidations using air or molecular oxygen theoretically produce water as the only by-product. Therefore, considerable effort has been invested in the development of catalytic protocols to explore the applicability of these environmentally benign alternatives [46][47][48][49].…”

“…Furthermore, the possibility for fine-tuning of the active material by, for example, ligands often accesses a broader scope compared to metallic species or salts used in heterogeneous catalysis. Over the past years a plethora of effective aerobic oxidation protocols utilizing homogeneous Scheme 11 Catalyst preparation using a PEG (a) and a 2,2 0 -dipyridylamine (b) unit for immobilization of Pd nanoparticles Aerobic Oxidations in Continuous Flow palladium or copper catalysis have been developed [49,105,106]. These contributions are almost exclusively small-scale laboratory reactions predominantly carried out in a flask equipped with an O 2 -filled balloon.…”