Study On Amination Reactions Based On Imides, Amidines And Tertiary Amines As Nitrogen Sources

Nitrogen-containing organic compounds are prevalent in natural products, such asamino acids, proteins and alkaloids. The vast majority of clinically used drugs arenitrogen-containing compounds. Therefore, the development of efficient, highlyselective C–N bond formation has become an important research field in organic(synthetic) chemistry.C–H bond functionalization reactions have recently been found to be a powerfulmethod for the formation of C–C and C–X bonds. Among various important C–Nbond construction methods, the direct C–N bond formation reaction between C–H andN–H bonds is the optimal methodology because of avoiding prefunctionalization ofthe substrates, minimum environmental impact and fewer synthetic steps. Recently,transition-metal-catalyzed aminations of C–H bonds, especially Rh, Ru, and Pdsystems for catalytic C H amination with applications in complex molecule synthesis,have been established. However, these aminations are restricted because most oftransition metal catalyst is toxicity and expensive. Therefore, the development ofalternative direct C–H amination reactions, especially inert C(sp3)–H, performed ininexpensive, availability, low toxicity transition metal catalyst or metal-free(organocatalytic) conditions using appropriate nitrogen sources are highly desirable.Nitrogen source is a very important factor for developing the methodology forthe construction of C–N bond. The reactions of aldehydes or ketones with ammonia,primary amines, or secondary amines in the presence of reducing agents to giveprimary, secondary, or tertiary amines, respectively, known as reductive aminations(of the carbonyl compounds) are among the most classic and widely ways in the C–Nbond formation reaction. However, tertiary amines as nitrogen sources have rarelybeen studied in this area. Harsh conditions were required for the additional C–N bondcleavage compared with N–H bond. In addition, reducing agents are also importantfactors in reductive amination. Therefore, reductive amination directly utilizingtertiary amines as both nitrogen source and reducing agent will provide a new way forC–N bond formation reaction.This thesis developed direct C(sp3)–H amination reactions using imides andamidines as nitrogen sources, reductive amination of aldehydes with tertiary anilinesas nitrogen sources. The thesis includes the following three aspects:1. A simple and efficient synthetic way accessing to2-aryl-quinazolines starting from benzylic C–H bond via Cu(OTf)2catalyzed direct benzylic C–N cyclizationutilizing Ag2CO3as oxidant was developed.2. The first example of nBu4NI-catalyzed C–N cross coupling imidation reactionof C(sp3)–H bond of simple ketones and N–H bond in imides with TBHP as anenvironmentally benign oxidant was developed. Various ketones including thesimplest acetone and a diverse range of imides such as phthalimide, succinimide andsaccharin were efficient, which made this imidation reaction very attractive. Thismethodology promises to provide a new pathway for direct imidation of ketones.Based on those results, we have also developed nBu4NI-catalyzed amination ofbenzylic C–H bonds under the same conditions. Various toluene derivatives and adiverse range of imides were efficient.3. An unprecedented oxidant-selectfluor mediated direct reductive amination oftertiary anilines and aldehydes was developed, in which simple tertiary amines actedas both nitrogen sources and reducing agents. The nucleophilic addition of carbonylgroup to the in situ generated iminium ion intermediate was involved, which hadnever been reported.