The Synthesis Of Aryl Alkyl Ethers And Chiral Oxime Ethers

Ethers belong to an important class of oxygen-containing compounds. They exist widely in a large amount of natural products and therapeutic agents with biological and pharmacological activities. Hence, the construction of ethers by the information of C-O bond has caused high concern from organic synthetic chemists. Even though the methods of synthesizing ethers have been widely studied, the development of novel reagents and the exploration of efficient strategies applied for the synthesis of ethers would be worthy and challenging.Based on these, we use the highly activative arynes generated in situ from o-(trimethylsilyl)aryltriflates and fluoride source reacted with dimethyl sulfoxide (common solvent) and a-bromo ketones (esters or amide) to afford multisubstituted methyl aryl thioethers through a three-component coupling reaction. Investigation of the reaction parameters (such as the fluoride source and additive, ratio of the two substrates, temperature, reaction time etc.) gave the optimal reaction conditions. With the optimal conditions, a wide range of precursors of arynes and electrophilic bromides were investigated to probe the generality of the three-component reaction. We have studied systematiclly the influence of electronic and hindered effects of arynes on the reaction regio selectivity and yield as well as the influence of electronic and hindered effects of electophilic bromides on the reaction yield. What’s more, we carried out the labeling experiments using deuterium-labeled and O18-labeled dimethyl sulfoxide, and found that the oxygen of newly formed C-O bond and methylthio group originated from dimethyl sulfoxide. Notably, dimethyl sulfoxide can serve as carbon source, oxygen source or methylthiolation reagent solely, but there is no report on dimethyl sulfoxed serves as oxygen source and methylthiolation reagent simultaneously in one single step.In view of the importance of oxime ethers in pesticidal moleculars as well as special biological and pharmacological activities of chiral moleculars, we applied β-CF3-β-disubstituted nitroalkenes as Michael acceptors, p-methoxybenzaldehyde oxime as Michael donor for synthesizing chiral oximes containing trifluoromethyl group through an asymmetric Oxa-Michael addition under quinine-derived bifunctional thiourea catalyst. It is worth mentioning that the reaction can construct a hetero-quaternary carbon center. Investigation of the reaction parameters (such as the bifunctional catalysts, catalyst loading, ratio of the two substrates, temperature, reaction time etc.) gave the optimal reaction conditions. Under optimal conditions, a wide range of β-CF3-β-disubstituted nitroalkenes were examined to probe the generality of the asymmetric Oxa-Michael additon. We have studied systematiclly the influence of electronic and sterically hindered effects of β-CF3-β-disubstituted nitroalkenes on the reaction yield and enantioselectivity. According to the absolute configuration of product and previous works about the activated model of nitroalkene with bifuncional catalyst, a plausible sterochemical model was proposed.