Zwitterions Mediated Carbon-Carbon And Carbon-Heteroatom Bond-Forming Reactions

Carbon-carbon and carbon-heteroatom bond-forming reactions are central to organic synthesis. Zwitterions resulting from the addition of nucleophiles to activatedπsystems, although known for a long time, have not been recognized adequately by researchers. In this thesis, based on the review aiming at developments of zwitterions in synthesis using pyridine, tertiary amine, phosphine and N-heterocyclic carbenes as nucleophiles, we have described several N-methylimidazole engaged carbon-carbon and carbon-nitrogen bond-forming reactions and thiazole carbene mediated three-component tandem reactions. The details are summarized as following:1. The zwitterion derived from the addition of N-methylimidazole to DMAD was investigated and intercepted by a ketene. In this process, we have discovered a novel N-methylimidazole catalyzed two-component reaction. Dimethyl (Z)- and (E)- succinates can be synthesized in moderate yields under mild conditions. In the meantime, we proposed a mechanism for this catalytic reaction. According to the possible formation of intermediate B, we designed a disubstituted ketene of more function to re-capture the zwitterion. In this process, we have discovered a three-component tandem reaction leading to the formation of 6-vinyl-1,3a-diazapentalene derivatives. The ketene was found act as a one-carbon component in the reaction to form a five-membered ring.2. We captured the zwitterions derived from the addition of thiazole carbene to aldehyde using DMAD, and developed a facile and effective synthesis of highly substituted 3-aminofuran derivatives via a novel multicomponent reaction of thiazole carbenes, aldehydes and DMAD in moderate to good yields. It is ascertained the whole tandem reaction sequence pivots on the nucleophilicity of thiazole carbenes, and the solubility of thiazolium precursors has an enormous effect on the reactions. Moreover, an improved overall economy of the process could be achieved by using 4-methylthiazolium salts as carbene precursors. Furthermore, the reaction seems to be applicable to various aldehydes, besides aromatic aldehydes,α,β-unsaturated aldehydes and some aliphatic aldehydes could also complete the reaction smoothly.3. A novel zwitterion derived from the addition of thiazole carbene to ketene was discovered and captured by an activated alkyne. In this process, we developed a facile and efficient three-component tandem reaction involving thiazole or benzothiazole carbene, disubstituted ketene and activated alkyne. A highly substituted ring system containing furo[2,3-c]thiazepine core can be generated from simple and readily accessible starting materials via this methodology. In this reaction, the first example of 1,3-addition to ketene was observed. Furthermore, the synthetic utilities of these unique polyheterocyclic compounds were demonstrated via their Diels-Alder reactions with benzynes to furnish thiazepine-fused 7-oxanorbornadiene derivatives in excellent yields.