Green Synthesis Of Hydropyrrolo-thiazole Compounds By Catalytic Asymmetric Cycloaddition

As a result of the application of the traditional chemical technology,many of the major benefits in public health and standard of our life have arisen.On the other hand,the ecological environment for mankind caused serious pollution and destruction.The aim of green chemistry is to reduce hazards across all the life-cycle stages.Green chemistry is the important means to solve the problem of chemical pollution.Green synthetic chemistry,containing the atom economy,efficient catalyst,green solvent,green raw materials,and so on,has received more and more attention.Hydropyrrole and purine are key structural units found in a large number of natural products and biologically active molecules.Therefore,developing new strategies to prepare hydropyrrole and purine compounds have important academic significance and potential applied value.In this paper,with the main purpose of the atom economy of reaction,we developed a few new green synthesis approach to synthesize hydropyrrole and purine compounds by using highly selective catalysts and environmentally friendly solvents.The main contents are as follows:1.Green synthesis of hydropyrrolo[2,1-b]thiazole compounds via catalytic asymmetric dearomative cycloaddition reactions with high atom economy.We have successfully developed a highly enantioselective dearomative [3+2] cycloaddition reaction of benzothiazoles with cyclopropane-1,1-dicarboxylates.In the presence of a Pybox-MgI2 catalyst,the cycloaddition reaction afforded a series of hydropyrrolo[2,1-b]thiazole compounds in excellent enantioselectivity(up to 97% ee)and yields(up to 97%).The reaction displays a general scope for both cyclopropanes and benzothiazoles.Significantly,a simple kinetic resolution rather than a dynamic kinetic resolution process dominates for the cycloaddition reaction.There is clearly a match scenario about the ligand and substrate,the benzothiazole selectively reacts with the(R)-enantiomer of the cyclopropane in the presence of chiral ligand.In addition,a highly efficient kinetic resolution of 2-substituted cyclopropane-1,1-dicarboxylates was also realized,providing a facile way to access both enantiomers of hydropyrrolo[2,1-b]thiazole compounds.The results of greenness assessment showed that this highly enantioselective cycloadditon reaction catalyzed by MgI2 was a high atomic economic reaction.Meanwhile,the E-factor and the Mass Intensity were reduced remarkably.2.Green synthesis of 3,3-disubstituted oxindoles with important bioactivity via domino Heck reaction in water.In this study,palladium-catalyzed domino Heck reactions were developed in water.Using DBU as base,the desired domino Heck–Sonogashira reaction of N-(2-iodophenyl)acrylamides with terminal alkynes proceeded well in the presence of Pd(PPh3)4 in water,gaving the corresponding products.The reactions provided products in excellent yields with a broad substrate tolerance.A series of 3-(4-aminobut-2-ynyl)oxindole derivatives with an all-carbon quaternary center at the 3-position were easily synthesized.The target product was readily converted into a pharmaceutically active molecule,which is used as a 5-HT7 receptor antagonist.The results of greenness assessment showed that the Mass Intensity of this reaction was close to 1,and the E-factor was close to zero,which proved the strategy is a new green synthesis route for the construct oxindoles.3.Improving the atom economy of the functionalization of purines via highly regioselective three-component domino Heck coupling reactionA highly regioselective three-component domino Heck-Negishi coupling reaction based on 6-chloropurine derivatives has been developed.It is the first time that organozinc reagents were used to trap an alkylpalladium intermediate of 6-chloropurine derivatives with olefins for the synthesis of purine compounds with complex carbon chain substituents at C6.In all cases,this three-component domino Heck-Negishi reactions exhibited excellent levels of regioselectivity,and only α-position products were found.Compared with the direct cross-coupling reaction,the atom economy of this three-component domino reaction was higher.Meanwhile,the Mass Intensity and the E-factor were low.More importantly,the products with the diversity and complexity of the structure were realized from the raw materials with simpler structure,which is difficult for the classic cross-coupling reactions.