The Carbonylation of Organic Compounds by Visible Light Photoredox Catalysis
AffiliationSchool of Chemistry
Document TypePhD thesis
Access StatusOpen Access
© 2020 Nenad Micic
Palladium-catalysed alkoxy- and aminocarbonylation of aryl (pseudo)halides provides efficient access to aromatic esters and amides. The broad application of this approach has been restricted by functional group tolerance, high reaction temperatures and moderate catalyst efficiency. Free-radical carbonylation is a complementary approach not confined by the same inherent limitations of palladium-catalysed carbonylative cross-coupling methodology. The development of free-radical carbonylation has been hindered by the ability to selectively generate the carbon-centred radical species and the high pressures of carbon monoxide required to drive the carbonylation step. This thesis describes the development of visible light photoredox-catalysed alkoxy- and aminocarbonylation of aryl (pseudo)halides. Visible light photoredox-catalysis is a potent method to generate carbon-centred radicals selectively under mild reaction conditions. Aryl radicals can be trapped by carbon monoxide to afford carbonyl compounds. Continuous flow chemistry is utilised throughout, employing tube-in-tube semipermeable membrane reactor technology, to enable precise control over reactions conditions and safe use of carbon monoxide. Chapter 1 introduces carbonylation and elaborates on carbonylative cross-coupling of aryl (pseudo)halides. It further introduces continuous flow processing in synthetic chemistry (flow chemistry) and details the application of flow chemistry to carbonylative cross-coupling and photochemical reactions. Chapter 2 established a continuous flow platform for high pressure gas-liquid photochemistry. The flow system consisted of a pumping module, a reagent delivery module, a Teflon AF-2400 tube-in-tube reactor for saturation of the reaction stream with carbon monoxide, a photoreactor and pressure regulation devices. The photoredox-catalysed alkoxycarbonylation of aryl diazonium salts was selected to evaluate the performance of the flow system. It was determined that excellent yields of the benzoate ester could be achieved at significantly lower partial pressures of carbon monoxide and processing time than in batch. Chapter 3 details the development of a free-radical annulative addition/alkoxycarbonylation cascade reaction. The developed methodology was applied to the synthesis of a diverse library of novel 3-acetate functionalized 2,3-dihydrobenzofurans from widely accessible allyl aryl diazonium ethers. Application of the previously established continuous flow system enabled dilute reaction conditions to effectively control the propagation of competitive intermolecular radical addition side reactions without compromising on reaction throughput or space-time yield. Chapter 4 describes the development of photoredox-catalysed aminocarbonylation of aryl halides. The developed methodology was applied to the synthesis of both electron rich and electron deficient benzamides at room temperature. Spectroscopic and theoretical computational studies were conducted to elucidate the reaction mechanism. A novel tandem photoredox catalytic manifold was proposed that features the transformation of Ir(dtbbpy)(ppy)2]PF6 in the presence of DIPEA to generate a distinct highly reducing Ir-complex capable of engaging energy demanding aryl halides. Chapter 5 provides a summary of the work described in this thesis. Supplementary data is included in the appendix.
Keywordscarbonylation; carbon monoxide; catalysis; organic chemistry; synthetic chemistry; flow chemistry; continuous flow processing; photocatalysis; photoredox-catalysis; small molecule synthesis
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