Periodic Reporting for period 1 - Photo2Bio (Photo-Organocatalytic CO2 Valorisation into Bioactive Added-Value Molecules)
Reporting period: 2021-02-01 to 2023-01-31
Carbon dioxide (CO2) is naturally present in the Earth's atmosphere. However, over the past century, human activities such as burning of fossil fuels, deforestation, and industrial processes have greatly increased the amount of CO2 in the atmosphere, leading to a range of environmental and health problems. One of the most significant problems associated with CO2 production is climate change. CO2 and other greenhouse gases trap heat in the atmosphere, leading to a warming of the Earth's surface. This warming can cause a severe weather events, and changes to ecosystems that can threaten biodiversity. Overall, the production of CO2 is a major environmental problem that has significant implications for human health as well as the health of the planet. The CO2 reduction is mitigating the effects of climate change as it is a greenhouse gas that traps heat in the Earth's atmosphere, leading to rising temperatures and changes in weather patterns. CO2 emission form power plants and vehicles, also emit other pollutants that can harm human health. Reducing CO2 emissions can help to improve air quality and reduce the negative health impact of air pollution. Thus, the reducing CO2 emissions provides numerous benefits, including mitigating climate change, improving air quality, enhancing energy security. In this sense, European Union (EU) policies have promoted improvements in resource efficiency, supporting the shift towards a low-carbon economy for a sustainable growth. The main objective of Photo2Bio project is to exploit the potential of visible light photoredox catalysis and organocatalysis for the development of conceptually now and innovative methodologies for the valorisation of CO2 into value added chiral biomolecules which will offer a new platform for the structural complexity in an environmentally benign way.
In discovery phase of the project, we have synthesised structurally different aziridine from as corresponding stilbene. In our investigation, benzyl diphenyl aziridine was subjected for cycloaddition reaction with CO2 using acridinium as visible light absorber organo-photoredox catalyst in acetonitrile using with blue led. However, in initial trials did not give the desired product. Therefore, we have attempted a set of experiment of aziridines with CO2 with different photoredox catalysis but in all cases same result was obtained. Activation of CO2 is a challenging task due to its kinetic and thermodynamic stable nature. Hence only a few methods, either by metal complexation or by organocatalysis, for its activation and transformation have been reported. At this stage, we have focused our work for activation of CO2 using nitrogen based organocatalysis. We have synthesised a chiral Guanidine based Organocatalyst and attempted the cycloaddition of aziridines with CO2 activated with chiral bicyclic guanidine catalyst, but similar results with formation of tri-benzyl amine were observed using different photocatalyst and solvent. Hence, in our further studies, we have modified the strategy by replacing the aziridines by 2H-aziridine and used the organo-photocatalytic conditions using visible light as energy source to trap the CO2. we have prepared the azirines by reported procedure and attempted a reaction of 2,3-diphenyl azirines with CO2 in acetonitrile the presence of acridinium as photocatalyst using blue LED of 456 nm. After irradiation of 6 hours surprisingly the formation of desired product was observed in moderate yield of 36 %. To check the generality of the reaction we have further move to test the reaction with 2(4-Methoxyphenyl)-3-phenyl-azirines with CO2 under same reaction conditions. It was our delight to isolate the product in similar yield. Currently we are working on this protocol with border substrate scope and their manipulation to biomolecules. During the investigation of cycloaddition of CO2 with aziridines the tri-phenyl aziridine was isolated as side product in a very low yield, which supports for formation of azomethine ylide intermediate. In continuation of our research work, we have envisioned to capture the azo-ylide by the use of dipolorophiles. To evaluate this hypothesis, we have attempted a reaction of triphenyl aziridine with dimethyl acetylene dicarboxylate (DMED) using DCA as photocatalyst in acetonitrile and it was delight to isolate the desired cycloadduct in good yield. To our delight, the aziridines having benzyl, methoxy benzyl, fluoro benzyl, aryl, and benzhydryl on nitrogen participated smoothly in the reaction to give the product in good yield. The generality of the cycloaddition of aziridines was also explored for the various alkenes as dipolorophiles. We have found that the dipolorophiles such as alkenes, aldehydes, di- aza compounds, melamides smoothly participate in the reaction and afford structurally different pyrrolidine, oxazolidine, and amino sulfonate.
The carboxylic acid is a privileged motif present in a large number of biologically active molecules. In the discovery phase of the project an photocarboxylation for synthesis of phenylacetic acid by use of CO2 and visible light has been developed by use of organophotoredox catalyst (4CzIPN) and different in combination with organic base. The feasibility and efficiency of reaction were studied under varying reaction conditions by use of different photoredox catalyst and solvent. . Applying these optimised conditions, we explored the scope for preparation of aryl and heteroaryl compounds with primary, secondary and tertiary benzylic carboxylic acids in moderate to good yields. The process was applicable to differently substituted DHPs, both with electron withdrawing and electron donating groups on the aryl ring, and also with different aryl and heteroaryl rings.
The carboxylic acid is a privileged motif present in a large number of biologically active molecules. In the discovery phase of the project an photocarboxylation for synthesis of phenylacetic acid by use of CO2 and visible light has been developed by use of organophotoredox catalyst (4CzIPN) and different in combination with organic base. The feasibility and efficiency of reaction were studied under varying reaction conditions by use of different photoredox catalyst and solvent. . Applying these optimised conditions, we explored the scope for preparation of aryl and heteroaryl compounds with primary, secondary and tertiary benzylic carboxylic acids in moderate to good yields. The process was applicable to differently substituted DHPs, both with electron withdrawing and electron donating groups on the aryl ring, and also with different aryl and heteroaryl rings.
The aforementioned section clearly expressed the design and development of innovative scientific methodologies by use of different discipline of organic synthesis such as photocatalysis, organocatalysis and CO2 valorisation. This approach provides a new mechanistic and synthetic platform for targeting structural complexity using by photocatalytic activation of small molecule along with CO2 fixation as (C1) building block in an environmentally respectful way. The scientific results achieved during work on photo2bio project towards synthesis of structurally complex phenyl acetic acid derivatives by use of CO2 as renewable source and visible light as green energy source contribute to two highly valued objectives by sustainable use of CO2 (greenhouse gas) and overcome the big lack of application towards the generation of bioactive molecules using this highly abundant inexpensive gas. Additionally, developing an innovative Protocol for synthesis of pyrrolidine, pyrrole and amino acids by photocatalytic small molecule activation via efficiently harnesses the energy of visible light to produce biomolecules is in line with the European approach to attaining sustainable chemistry. The societal impact of this project can be used as the key concept and communicated to the target lay community in terms of valorisation of a waste product to provide valuable compounds and development of unexplored methods to access bioactive molecules with possible pharmaceutical application. The CO2 valorisation will be beneficial in the public health by reducing harmful pollutants that are released in the atmosphere cases respiratory illness and other health problem caused by air pollutions.