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Oxidation via low-energy electron transfer. Development of green oxidation methodology via a biomimetic approach

Final Report Summary - OXLEET (Oxidation via low-energy electron transfer. Development of green oxidation methodology via a biomimetic approach)

The aim of the proposed research project has been to develop novel “green” oxidation methodology that is based on low-energy electron transfer. In the oxidation reactions one of the goals was to use molecular oxygen (air) as the oxidant. In particular, the research has focused on oxidative palladium-catalyzed C-C bond formation and metal-catalyzed C-H oxidation including dehydrogenation reactions using ruthenium and to some extent with iron. One goal has been to develop sustainable catalytic oxidation processes of interest in organic synthesis that also may have industrial applications. One part of the project was devoted to the development of new reoxidation systems inspired by Nature.

The project has dealt with:
(i) Catalytic aerobic oxidative carbocyclization reactions and related C-C bond forming reactions.
(ii) Catalytic oxidation of C-H bonds including dehydrogenation of alcohols and amines
(iii) Efficient reoxidation systems with O2 as stoichiometric oxidant

In this project green oxidation methodology has been developed. One of the important research achievements is the development of novel aerobic oxidations of organic substrates using a principle that is reminiscent of oxidation reactions occurring in Nature.

During the project we have developed a large number of novel oxidative carbocyclizations of enallenes. These reactions are catalyzed by Pd(II) and can often be transformed into an aerobic oxidation by the use of catalytic electron transfer mediators (ETMs). The palladium-catalyzed oxidative carbocyclization of aza-eneallenes combined with an in situ subsequent [4+2]-cycloaddition in tandem afforded useful heterocyclic compounds. The palladium-catalyzed oxidative carbocyclization of enallenes with trapping of the intermediate organopalladium compound with various reagents such as aryl boronic acids (ArB(OH)2) or B2pin2 (pin = pinacolato) afforded new important compound via a second C-C bond formation. An important achievement is the development of an enantioselective Pd-catalyzed oxidative carbocyclization of enallenes.

The extension of the oxidative carbocyclization of enallenes to allenynes has opened up a new type of reactions where the intermediate compound from the carbocyclization is trapped by various reagents such as (i) PhB(OH)2, (ii) B2pin2, (iii) acetylenes, and (iv) carbon monoxide. This leads to an efficient one-pot cascade reaction that provides highly functionalized products.

New aerobic palladium-catalyzed cross-couplings involving C-H activation was developed during the project. In these biomimetic oxidations a quinone and iron(phthalocyanine) were used as the ETMs.

In this project we have also developed an important ruthenium-catalyzed aerobic oxidation system. This coupled catalytic system has a ruthenium complex (e.g. Shvo’s catalyst) as the substrate selective redox catalyst (SSRC) combined with an electron-rich benzoquinone and a metal macrocyclic complex as the electron transfer mediators (ETMs). With this system, novel reactions, e.g. aerobic lactonizations (from diol) and lactamizations (from aminoalcohol), were developed.

We have also developed new catalytic dynamic kinetic resolution (DKR) systems based on metal-catalyzed racemization and enzymatic resolution. Mechanistic studies were carried out on our cyclopentadienyl-ruthenium dicarbonyl catalyst and we were able to prove (by the use of 13CO) that CO dissociation occurs during racemization to give the active catalyst. One important achievement, which we see a small breakthrough in DKR, is the co-immobilization of the racemization catalyst and the enzyme inside the cavities of siliceous mesocellular foam (MCF). This leads to a hybrid DKR catalyst for amines that can do racemization and resolution at the same time. We have termed this device “and artificial metalloenzyme” that makes a “deracemization” of the amine.