The method for constructing C–S bonds is very important in organic synthesis. Here a new sulfenylation method to generate flavone thioether derivatives was developed by employing aromatic or alkyl halides, S powder and Na2S2O3 as reactants. Good yields of regioselective Calkyl–S and Caryl–S-substituted flavones were generated under relatively environmentally friendly and simple conditions. This method might be potentially applicable to large scale production, and it enriches current sulfenylation methods.

A novel and highly regioselective ammonium iodide-induced nonradical sulfenylation method for the construction of a C–S bond was developed via C–H functionalization. With DMSO or R1SO2NHNH2 as a sulfenylating agent, MeS- and R1S-substituted flavone derivatives were obtained in good yields. This method enriches current C–S bond formation chemistry, making it a highly valuable and practical method in pharmaceutical industry.

Coumarin and flavone derivatives are highly valuable molecules in drug discovery. Here, two new regioselective cross-dehydrogenation couplings of coumarins and flavones with different ethers via C(sp3)–H functionalization processes were developed, generating new ether-substituted derivatives not previously reported. These reactions proceeded well via radical mechanisms and provided the corresponding products in good yields.

Two radical-mediated cascade couplings of N-alkyl-N-methacryloylbenzamides with different ethers and arylsulfonohydrazides to generate ether- and arylsulfonyl-substituted isoquinoline-1,3(2H,4H)-dione derivatives were developed. Both casccades proceeded via initially triggered functionalization of the alkene functions of the N-alkyl-N-methacryloylbenzamides, followed by ortho radical cyclizations onto the aromatic ring to give isoquinoline-1,3(2H,4H)-dione derivatives in good yields. These highly functionalized drug-like molecules will be valuable in drug discovery in the future.

A series of seven- and eight-membered ring –N,O–, –N,N–, and –N,S–sultams were effectively synthesized via tandem reactions involving oxa-, aza-, and thia-Michael addition to vinyl sulfonamides. These reactions are summarized here since they enrich current synthetic methodologies for sultams and provide a good example of sultam diversity-oriented synthesis. All reactions proceeded under relatively mild and environmentally friendly conditions, and all these reactions are quite suitable for the rapid preparation of sultam compound libraries, which are valuable for biological activity explorations.

A cascade reaction between N-alkyl-N-methacryloylbenzamide and aryl aldehydes was developed to generate isoquinoline-1,3(2H,4H)-dione derivatives. The reaction involves oxidative cross-coupling of the activated alkene from the N-alkyl-N-methacryloylbenzamide with the aldehyde functional group (–CHO), followed by radical addition to the aromatic ring to afford isoquinoline-1,3(2H,4H)-dione derivatives in good yields under mild reaction conditions without either metal catalysts or organic solvents involved.

A diversity-oriented syntheses by coupling three electron-deficient olefins (vinyl sulfonamides, methacrylamides, and methyl acrylates, respectively) with aryl aldehydes via C(sp2)–H functionalization were reported. These reactions gave four different skeletal products respectively under environment-friendly and mild conditions. All these reactions are highly regioselective and effective, very suitable for the preparation of synthetic building blocks and compound library, the results will enrich current coupling chemistry of olefins with aldehydes and can be applied to other chemistry areas as well.Keywords: aldehydes; C(sp2)−H functionalization; diversity-oriented synthesis; environmentally friendly; olefin; regioselective

A benzoylation/substitution/desulfonylation/cyclization cascade reaction giving oxindole derivatives was discovered. The reaction used aromatic aldehydes and N-alkyl-N-(phenylsulfonyl)methacrylamides as starting materials, and proceeded under mild conditions without using toxic metal catalysts. 3-Methyl-3-aroyloxindole derivatives were formed in good yields.

From vinyl sulfonamides as precursors to vinyl sulfonamide epoxides, two cascade reaction protocols were developed to synthesize eight-membered ring sultams in water. These protocols employ intermolecular Michael addition by NaOH or NaHS in water, followed by rapid proton transfer and intramolecular 8-endo-tet epoxide ring-opening to give medium-size sultams selectively in one-pot. Novel core structures and high synthetic efficiency make these cascade reactions highly suitable for sultam library production. Both reactions proceeded well and afforded the respective sultams in good yields under environmentally friendly conditions.Keywords: eight-membered ring compound; Michael addition; parallel synthesis; sulfonamide; sultam

A cascade reaction between N-alkyl-N-methacryloylbenzamide and aryl aldehydes was developed to generate isoquinoline-1,3(2H,4H)-dione derivatives. The reaction involves oxidative cross-coupling of the activated alkene from the N-alkyl-N-methacryloylbenzamide with the aldehyde functional group (–CHO), followed by radical addition to the aromatic ring to afford isoquinoline-1,3(2H,4H)-dione derivatives in good yields under mild reaction conditions without either metal catalysts or organic solvents involved.