Synthesis Of Benzonitriles And ?-pyrones & Cycloaddition Reactions Of Aza-oxyallyl Cations

Heterocyclic compounds are frequently presented in numerous natural products and drug molecules, and play a critical role in organic and pharmaceutical chemistry. Exploring and developing a novel method for synthesis of heterocyclic compounds and discovering new structures are one of key researches in chemical community. Based on our own research interests on heterocycle synthesis, this thesis focused on the development of new synthetic methodologies and new models. The details are summarized as following:In the first part, we have developed a new NHC-catalyzed [4+2]-benzannulation protocol to assemble the benzonitrile framework by using enones and enals. N-Heterocyclic carbene attacked ?,?-unsaturated aldehydes, followed oxidized by external oxidant, to yield?,?-unsaturated acyl azolium. The reactions of enones and cinnamaldehydes were selected as model reactions for further optimization. The stucture of N-Heterocyclic carbene, different oxidants and bases, the effect of solvents have been investigated. In the process of substrate scope examination, we found that substituents have little influence on the reaction efficiency,the corresponding products were obtained in good to high yields. Further transformations,such as hydrolysis, reduction, Suzuki coupling, have been made to afford the corresponding benzene derivatives. Eventually, we proposed possible mechanism of N-Heterocyclic carbene-catalyzed convenient benzonitrile assembly and stimulated us to explor other medicinally relevant products on the basis of the theoretical and experiments.The work of chapter 2 was carried out on the basis of the first part. ?,?-Unsaturated acyl azolium can be generated by the initial redox reaction/protonation of the Breslow intermediate derived from ynals,and reacted with pyridinium or isoquinolinium ylides via 1,4-addition. The a-pyrone products were obtained when the pyridine or isoquinoline acted as the leaving group. 3-Phenylpropiolaldehyde and pyridinium ylide were chosed as model substrates, the results of substrates scope indicated that the aryl-alkynals and alkyl-/aroyl-substitued pyridinium ylides were tolerated and reacted smoothly to afford the corresponding a-pyrones in moderate to good yield. Finally, a postulated catalytic cycle for this NHC-catalyzed process was rendered as well. In a short summary, we have described an effective strategy for the synthesis of 4,6-disubstituted a-pyrones.In the third chapter, we turned our attention to the study of aza-oxyallyl cation. A dehydrohalogenation of a-haloamides could provide the aza-oxyallyl cationic intermediate in situ, and reacted with aldehydes smoothly to afford oxazolidinones. Given the importance of oxazolidinones, we further explored the model reaction and optimized the reaction conditions. When the reaction was performed in the presence of 2.0 equiv of Na2CO3 and hexafluoroisopropanol (HFIP) as solvent, the desired product was obtained in almost quantitative yield. Further investigations on the feasibility of our protocol indicated that substituent pattern and electronic nature of substrates have limited effects on reaction conversion. To further demonstrate the utility of this methodology, we carried out a gram-scale synthesis and further transformations. A possible mechanism was proposed and inspired us to seek novel cycloaddition reactions via the use of aza-oxyallyl cations.The chapter four described a [3+3] cycloaddition of aza-oxyallyl cations with nitrones.We employed 4-(dimethylamino)pyridine as base in hexafluoroisopropanol (HFIP) at room temperature or heated to 50 ? to generate 1 ,2,4-oxadiazine-5-ones or 1,4,2-dioxazinan-5-ones in excellent yield. 36 Examples were endured well under the standard condition and the corresponding products were produced in moderate to excellent yields. In order to address the viability of this reaction, we found that the N-O bond can be cleaved efficiently and provided the parent N-H substituted 1,2,4-oxadiazine-5-one in good yield. At last, a plausible mechanism of [3+3] cycloaddition of aza-oxyallyl cations with nitrones was proposed.