Application Of 4-Alkyl/Acyl Substituted Hantzsch Ester As Radical Reagent In Organic Synthesis

Hantzsch esters,a class of 1,4-dihydropyridine(DHP)compounds,have proven to be a versatile class of electron donors and proton sources.They often worked as reductants in organic hydrogenation reactions and photoredox reactions.In recent years,the research of 4-alkyl/acyl-1,4-dihydropyridine compounds as alkyl/acyl radical donor reagents made great progress and has thus been widely concerned.This research mainly focused on the addition reactions of corresponding radicals to carbon-carbon double bonds or nitrogen-nitrogen double bonds,and the substitution reactions of heterocyclic compounds by using 4-substituted Hantzsch esters as alkylation/acylation reagents.In the first chapter,the background of radical chemistry and photochemistry in organic synthesis were introduced.Radical chemistry was an important branch of organic chemistry.Due to the continuous progress of chemical technology,photochemistry currently played a pivotal role in organic synthesis.The applications of 4-substituted Hantzsch esters as radical donors in organic synthesis were also described.In the end,the synthetic strategies of Hantzsch esters were summarized.In the second chapter,the photochemical addition protocol to the dehydroamino acids using 4-acyl-1,4-dihydropyridine as acyl radical donors was established.4-acyl-1,4-dihydropyridine could form excited state easily upon light irradiation,which then underwent homolysis to generate acyl radicals.In this system,the role of 4-acyl-1,4-dihydropyridines were proved to be“tailor-made”as it not only offered nucleophilic acyl radicals upon irradiation with simple blue LED,but also acted as reductants in the single electron transfer process,converting the radical intermediates to the corresponding anion species.The photochemical acylation modification of chiral amino acid substrates and tripeptides was realized.The amino acid products were derivatized to the oxime compounds successfully,while the coupling product was obtained through the Suzuki-Miyaura reaction as well.In the third chapter,the acylation addition reaction system of 4-acyl-1,4-dihydropyridine as acyl radical donors to azodicarboxylate was established.Similarly,4-acyl-1,4-dihydropyridines were able to generate acyl radicals easily upon visible light irradiation.A series of acyl hydrazide derivatives were easily prepared from dialkyl azodicarboxylates.The advantages of this protocol including mild reaction conditions,broad substrates scope,accessibility in scale-up synthesis and good yields.In the fourth chapter,the direct alkylation and acylation reaction system of 2 H-indazole by 4-alkyl/acyl-1,4-dihydropyridine was established.Applying silver nitrate/sodium persulfate as catalysts,this strategy could be used for selective substitution of 2H-indazole in C3 position under mild conditions.This method displayed broad substrates scope and afforded the target 3-alkyl/acyl-2 H-indazole derivative in good yields.This strategy could be also used in gram-scale synthesis;it achieved the target synthesis of bioactive molecules successfully as well as simplifying its synthesis steps.In the fifth chapter,a series of 1,4-disubstituted thiazoles and benzothiazoles were synthesized by the oxidation system of iodine/tert-butyl hydroperoxide.This strategy worked with L-cysteine esters and O-aminothiophenol as the nitrogen and sulfur source respectively,achieving the one-pot cyclization-oxidation cascade.A diverse range of aliphatic/aromatic aldehydes were amenable to this transition-metal free protocol,which provided an alternative method to access thiazole-containing compounds.In summary,the substitution and addition reactions of 4-alkyl/acyl substituted Hantzsch ester as radical reagents were studied.As a novel type of free radical donor,4-substituted Hantzsch esters have stability,availability and low toxicity when compared to organometallic reagents.Such reagents could provide corresponding alkyl/acyl radicals through mild oxidation or under photochemical conditions.This thesis mainly reported alkyl/acyl radicals generated by 4-substituted Hantzsch esters to perform addition reaction with unsaturated substrates and carry out substituent modifications of heterocyclic compounds’C-H bonds.