Green Synthesis Methods Of C-C Bond Formation Catalyzed By Enzymes Or Photoredox Catalysis

Enzymes are widely found in organisms and play an important role.They have the advantages of efficiency and specificity.In addition,enzymes are biodegradable,environmentally friendly,few byproducts and low energy consumption,so they are attractive green biocatalysts.In recent years,scientists have found that enzymes have the ability to catalyze non-natural reactions or act on non-natural substrates,a phenomenon which was known as enzyme promiscuity.There are many reports on the catalytic promiscuity of enzymes,such as aldol,Michael addition,Mannich,multi-component tandem,Markov addition and asymmetric synthesis of α-cyanamide reactions.The catalytic promiscuity of the enzyme not only broadens the scope of application of the enzyme but also provides a green biocatalytic method for organic synthesis.In this paper,we developed papain-catalyzed aldol reaction for the synthesis of trifluoromethyl tertiary alcohol derivatives,lipase from porcine pancreas and protease from Streptomyces griseus protease catalyzed Michael reaction for the synthesis of rhodanine and 3,3-disubstituted oxidized indole derivatives.Visible light is a cheap accessible,rich source,green and renewable clean energy,which have advantages of green,easy operation,application of huge potential and so on.Presently,photoredox catalysis has been effectively used into the chemical conversion for the synthesis of complicated moleculars.Chlorophyll is the most abundant natural visible-light photocatalyst on Earth,and it is the main visible-light aeceptor in the chloroplasts of most green plants.Photosynthesis is one of the most famous chemical reactions in nature.Plants use sunlight as their energy source to convert C O2 and H2 O into carbohydrates with the help of chlorophyll.As a rich,green and environmentally friendly photosensitizer,chlorophyll was rarely used in photoredox catalysis.In this paper,chlorophyll was used as photocatalyst in cyclization reaction for synthesis of tetrahydroquinoline derivatives induced by visible-light.Some chemical reactions can be carried out smoothly in the absence of catalyst conditions,which greatly reducing the cost of production and the pollution.They meet the requirements of green chemistry,and have important theoretical research and practical value.In this paper,the direct ammoniation reaction was carried out under catalyst-free conditions to form the carbon-nitrogen bond.Aldol reaction is one of the most common carbon-carbon bond formation methods.In the second chapter,we studied the synthesis of trifluoromethyl tertiary alcohol derivatives by papain-catalyzed aldol reaction between trifluoromethyl ketone and aliphatic ketone in organic solvent.The yields range from 50% to 99% and the ee values were up to 30%.And a possible reaction mechanism was proposed.This method broadens the application range of papain and provides a green synthetic pathway for the preparation of trifluoromethyl tertiary alcohol derivatives.Michael addition reaction is one of the basic reactions of carbon-carbon bond formation in organic synthesis,which is used to synthesize drug and complex natural products.In the third chapter of this paper,the enzymatic Michael reaction was studied.We first discovered that the lipase from porcine pancreas exhibited new catalytic promiscuity in catalyzing the Michael reaction between α,β-unsaturated ketones and rhodanines.After optimizing the reaction conditions including solvent,water content,substrate molar ratio,pH,solvent volume,enzyme loading and temperature,the substrate scope was then tested,23 rhodanine derivatives were obtained.The yields range from 50% to 98%,enantioselectivity up to 66%.This new catalytic promiscuity will have important practical significance,and also broadens the application of lipase from porcine pancreas in organic synthesis.In the fourth chapter of this paper,the enzymatic Michael reaction was studied.We first discovered that Streptomyces griseus protease-catalyzed Michael reaction between 3-methylhydroxoles or rhodanines and maleimides.Through a series of conditions optimized,a variety of substrates were able to successfully participate in the reaction,we obtained 19 target products,and the yields range from 50% to 99%.The work broadened the scope of application of enzymes.In the fifth chapter of this paper,we have developed a simple,green and efficient method for the synthesis of tetrahydroquinoline derivatives from N,N-dimethylanilines and maleimides.The method utilizes visible light and oxygen as the green reagents,natural chlorophyll as a green photosensitizer.26 tetrahydroquinoline derivatives were achieved,and the target product yields range from 61% to 98%,while the reaction mechanism was discussed based on control experiments.The construction of carbon-nitrogen bonds is important in organic chemistry.However,the direct amination of C(sp3)-H bond between azodicarboxylate and N,N-dimethylaniline under catalyst free conditions has not been reported.The organic reactions carried out under catalyst-free conditions which are green,economical,easy to handle and under mild conditions are more in line with green chemistry.In the sixth chapter of this paper,the amination reaction of azodicarboxylate and N,N-dimethylaniline under catalyst-free conditions was reported for the first time.The reaction of azo-dicarboxylates and N,N-dimethylanilines with different functional groups went smoothly,and the yields of the ammoniated product range from 58% to 99%.