The Research Of Some Highly Atom-economic Substitution Reactions

Nucleophilic substitution reaction represents one of the most oimportant and useful reaetions in organic chemistry, but these reactions inevitably generated byproduct, which decreased its atom-economy. This thesis has achieved two types of nucleophilic substitution reactions with high atom-economy, which have found application in the construction of some useful building blocks at the same time.1) The nucleophilic substitution reactions of3-hydroxyoxindoles is developed to synthesis the3-alkylthiooxindoles and3-alkoxyoxindoles,.the thiols and alcohols are used as the nucleophile. The only byproduct of such reaction is low molecular weight H2O, which not only made the reaction high atom-economy but environmentally friendly. The study reveals that a variety of3-substituted3-(alkylthio)oxindoles or3-alkoxyoxindoles could be obtained in good to excellent yield under the catalysis of HClO4. The thus obtained product can be easily elaborated. A Hg(C104)2’3H20catalyzed tandem Sakurai-Hosomi/(thio)ether formation reaction was also developed using isatin as the start materials.2) An byproduct salt promoted tandem nucleophilic substitution/Krapcho reaction is developed, using dimethyl or diethyl fluoromalonate and methyl2-fluoro-2-(phenylsulfonyl)acetate as the pre-nucleophile, NaH as base and different halides as the electrophile, medium to excellent yield could be obtained for a variety of a-fluoro ester and sulfones. The in-situ generated salt from the nucleophilic substitution reactions served as the promoter for the following Krapcho reaction without any treatment, thus the atomic utilization of the whole tandem reaction was efficiently raised.This thesis also included the utilization of ESI to study the mechanism of organic reactions. ESI/MS/MS instrument was used to capture the key intermediate of a thiourea catalyzed nucleophilic substitution reaction and the [3+2] cycloaddition reaction of tetra-substituted alkenes. Additionally, qualitative and semi-quantitative analysis of the solvent effect in Mukaiyama-aldol reaction were also conducted. Through this analysis, we can intuitive found that the low yield of the desired Mukaiyama-aldol products in MeOH were attributed to the presence of substantial side reactions and the deterioration of silyl enol ether, which could be well avoided using H2O as the solvent.