Eco-friendly Green Oxidation And Reduction Of C-C Unsaturated Bonds Without Transition Metal-catalyst

In today’s chemical production process,many crucial functional group conversion processes inevitably depend on the use of transition metal-catalysts.For example,the dihydroxylation of olefins usually requires the participation of noble metals such as ruthenium and osmium.In principle,olefins also rely on transition metals such as palladium and platinum for catalytic hydrogenation.Moreover,the construction of C-C bonds,such as the typical Suzuki and Negishi reactions,require the use of transition metal-catalysts such as palladium and nickel.Although most transition metal-catalysts have the advantages of high efficiency and stability,their shortcomings cannot be ignored.First of all,mining and excessive use of heavy metal salts have caused severe damage to the already fragile ecological environment due to difficulty in recycling.Secondly,in the pharmaceutical and other fields,there is a risk of heavy metal residues in the use of transition metal-catalysts in the production process.Importantly,China has strict control over the amount of metal residues in pharmaceutical production.However,the long-term cumulative effect still lays hidden dangers for human health.Therefore,the development of green synthetic methods and the reduction of the use of transition metals are not only the main concern of current organic synthesis research but also very critical for the field of environmental scienceIn an attempt to overcome the disadvantages mentioned above associated with transition metal-catalysis,the current study explored eco-friendly green oxidation and reduction of C-C unsaturated bonds.It then developed a series of green organic synthesis methods without the participation of transition metals.Specifically,it includes the cis-dihydroxylation reaction of olefins,reductive isomerization reaction of olefins,and synthesis of nitrogen heterocyclic using conjugated alkynes as starting material.The content of the current dissertation is presented in four chapters with three contributing areasFirstly,potassium permanganate was used as an oxidant and imidazolium salt as a phase transfer catalyst to develop a method for efficiently synthesizing cis-dihydroxy compounds.In the traditional cis-dihydroxylation reaction,it is usually necessary to introduce noble metals such as osmium tetroxide as a catalyst to achieve mild oxidation of the double bond.Potassium permanganate,as a kind of cheap oxidant,has the disadvantages of poor solubility in organic solvents and causes overoxidation in the aqueous medium.To overcome the problem of poor solubility of potassium permanganate,it has been reported that an equivalent phase transfer reagent is usually added for ion exchange to improve the solubility of permanganate ions,thereby achieving the effect of increasing the reaction yield.Based on the concept of green chemistry,we synthesized a series of imidazolium salt phase transfer catalysts.As previously reported,we further realized the catalytic cycle of phase transfer reagents.The amount of catalyst was only 10 mol%.After optimizing the conditions,we synthesized a series of cis-dihydroxy compounds with a reaction yield of up to 95%.Further research found that the reaction has a good substrate scope for most electron-deficient olefins.Interestingly,even polysubstituted olefins were processed smoothly,and concomitant cis-dihydroxylated products were obtained in high yields.To reflect the practicability of this reaction,we synthesized the key dihydroxy intermediate of the drug sofosbuvir under gram-scale conditions.Because of the mild reaction conditions and easy workup procedure,it has good potential for industrial scale production.Secondly,a method was developed for the rapid construction of of γ-keto esters through a cascade strategy without the involvement of transition metals.In contrast to the traditional multistep approach,the most attractive and robust quality of cascade reaction is the sequential bond-forming transformations in a single operation without isolation of intermediates,particularly with those unstable or nonisolable intermediates,thereby saving costs and reducing pollution.Commercially available propargyl esters and aryl aldehydes along with Bis(pinacolato)diboron were used as starting materials,which directly undergoes through alkyne-aldehyde reductive C-C coupling involving borylation,protodeboronation,and olefin isomerization,resulting in γ-keto ester products.The key intermediate(i.e.,γ-hydroxy-α，β-acetylenic esters)was produced in the 1st step of reaction under the action of the base.The reaction involved four steps in series,and y-keto ester products were synthesized in moderate yields of up to 63%.In addition to propargyl esters,propargyl amides were also smoothly participated in the preparation of the corresponding y-keto amide compounds.By investigating the substrate scope of this reaction,it was found that all kinds of substituted aryl aldehyde substrates can react smoothly.Still,alkyl aldehydes cannot participate in the reaction.Through in-situ NMR experiments and control reactions,we studied the mechanism of the reaction and gave an assumption on the four-step series reaction.Notably,the starting materials of this method are easily available,and the conditions are mild,which provides a way for quickly constructing y-keto ester products.Thirdly,a green method for synthesizing polysubstituted pyrrole compounds was developed using conjugated alkyne as the starting material,T-chloramine as the oxidant and nitrogen source,and iodine as the co-oxidant.The synthesis of nitrogen heterocycles by the amination of the conjugated alkyne is a well-established strategy.Nevertheless,most of the reported work relies on transition metals such as gold and copper as Lewis acid to activate the alkyne to achieve the reaction,under harsh conditions.Therefore,elemental iodine was used to activate the alkyne to induce the attack of T-chloramine on the alkyne,thereby further achieving the cyclization product.Based on this green method,a series of highly functionalized pyrrole compounds were synthesized with a moderate yield of up to 65%.The reaction was carried out with 1,2-dichloroethane as the solvent at 70℃ under mild conditions.The obtained pyrrole compound had iodine atoms at the 3 and 4 positions,which could be used for further derivatization.Through substrate expansion,we found that the substituents on the aromatic ring have little effect on the reaction,whether conjugated alkyne with the electron-withdrawing group or electron-donating group participated in the reaction.