Organocatalyzed reactions in which organic molecules catalyze single or multiple chemical transformations were found to be an efficient synthetic tool for creating various carbon-carbon and carbon-heteroatom bonds throughout the synthesis of a wide range of achiral and chiral acyclic as well as cyclic derivatives. The benefits of organocatalytic reactions include the use of inexpensive and readily available organic compounds as catalysts, as well as increased synthetic efficiency as no metal traces have to be removed at the end of the processes. This last feature is particularly suited to the preparation of biologically relevant compounds that do not tolerate contamination. The continuous-flow approach has recently emerged in the organic chemistry community as an interesting and alternative method to batch processing for performing chemical transformations. This technology has a number of attractive advantages that are related both to the nature of the continuous process and to the small size of the channels in which the reactions occur. These include (i) large surface to volume ratios and enhanced mixing quality; (ii) superior mass and heat transfer and, hence, improved operational safety; (iii) good real-time reaction monitoring by incorporating in-line analytical devices, allowing fast reaction screening and optimization; (iv) improved scalability. Typical drawbacks of organocatalysis such as organocatalyst recycling and the high catalyst loading often required for several transformations may be overcome by the heterogeneization of organocatalysts that allows the set-up of effective continuous-flow procedures endowed with high levels of stereoselectivity and productivity. The majority of the reported studies on asymmetric flow organocatalysis utilize the active catalyst immobilized on either polymeric or inorganic particles as packing material of macro- and micro-reactors. In this thesis are reported batch and continuous-flow synthetic approaches for the formation of carbon-carbon and carbon-heteroatom bonds, mediated by organocatalysts acting via enamine and iminium catalysis, and umpolung reactivity.

L’organocatalisi è un ramo della catalisi che utilizza piccole molecole organiche per promuovere trasformazioni chimiche in cui si ha la formazione di nuovi legami carbonio-carbonio e/o carbonio-eteroatomo. L’impiego di questa metodologia può offrire numerosi vantaggi: gli organocatalizzatori, infatti, sono in grado di operare in condizioni blande, anche in mezzi acquosi, senza richiedere l’utilizzo di metalli di transizione. Quest’ultima caratteristica risulta particolarmente favorevole nel caso della sintesi di composti che non tollerano contaminazione da parte di metalli come i prodotti di interesse farmaceutico e, più in generale, i composti ad attività biologica. Inoltre, gli organocatalizzatori hanno generalmente basso costo e sono facilmente reperibili. La chimica in flusso continuo rappresenta una valida alternativa a quella in condizioni batch grazie ai numerosi vantaggi che derivano sia dalla natura del processo in continuo che dalla piccola dimensione dei canali nei quali avviene la reazione chimica. Tra i possibili benefici si possono ricordare la riduzione dei rischi, la sostenibilità, la facilità di scale-up e la semplicità di automazione/monitoraggio dei normali parametri di reazione (velocità di flusso, temperatura, pressione e stechiometria di reazione). Alcuni svantaggi tipici dell’organocatalisi, come il riciclo dell’organocatalizzatore e l’alto loading spesso necessario per certe trasformazioni, possono essere superati grazie all’eterogeneizzazione degli stessi organocatalizzatori. Questa permette di applicare una procedura in flusso continuo in maniera efficace arrivando a raggiungere alti livelli di stereoselettività e di produttività. La maggior parte degli studi riportati in letteratura riguardanti la sintesi asimmetrica in flusso continuo utilizza catalizzatori supportati su materiale polimerico o su particelle inorganiche, che costituiscono il letto fisso all’interno di macro- o microreattori. In questa tesi sono riportate metodologie batch ed in flusso continuo per la formazione di legami carbonio-carbonio e carbonio-eteroatomo, promosse da organocatalizzatori che agiscono attraverso una catalisi via enammina o ione imminio, oppure sfruttando la reattività di umpolung.

Batch and continuous-flow synthetic processes for the formation of carbon-carbon and carbon-heteroatom bonds

ZAGHI, ANNA
2017

Abstract

Organocatalyzed reactions in which organic molecules catalyze single or multiple chemical transformations were found to be an efficient synthetic tool for creating various carbon-carbon and carbon-heteroatom bonds throughout the synthesis of a wide range of achiral and chiral acyclic as well as cyclic derivatives. The benefits of organocatalytic reactions include the use of inexpensive and readily available organic compounds as catalysts, as well as increased synthetic efficiency as no metal traces have to be removed at the end of the processes. This last feature is particularly suited to the preparation of biologically relevant compounds that do not tolerate contamination. The continuous-flow approach has recently emerged in the organic chemistry community as an interesting and alternative method to batch processing for performing chemical transformations. This technology has a number of attractive advantages that are related both to the nature of the continuous process and to the small size of the channels in which the reactions occur. These include (i) large surface to volume ratios and enhanced mixing quality; (ii) superior mass and heat transfer and, hence, improved operational safety; (iii) good real-time reaction monitoring by incorporating in-line analytical devices, allowing fast reaction screening and optimization; (iv) improved scalability. Typical drawbacks of organocatalysis such as organocatalyst recycling and the high catalyst loading often required for several transformations may be overcome by the heterogeneization of organocatalysts that allows the set-up of effective continuous-flow procedures endowed with high levels of stereoselectivity and productivity. The majority of the reported studies on asymmetric flow organocatalysis utilize the active catalyst immobilized on either polymeric or inorganic particles as packing material of macro- and micro-reactors. In this thesis are reported batch and continuous-flow synthetic approaches for the formation of carbon-carbon and carbon-heteroatom bonds, mediated by organocatalysts acting via enamine and iminium catalysis, and umpolung reactivity.
MASSI, Alessandro
DE RISI, Carmela
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2488074
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