Part I : Reoptimized Phase-transfer Catalytic Alkylation of α-acetylthiomalonate Part II : Application and Confirm the Absolute Configuration of α-benzoxy-α-alkylmalonate

enantioselective synthesis;asymmetric phase-transfer catalysis;α-acetylthio-α-alkylmalonate;quaternary carbon center;α-benzoxy-α-alkylmalonate;derivatization;615

약학대학 약학과 ;

University:서울대학교 대학원

关键词: enantioselective synthesis;    asymmetric phase-transfer catalysis;    α-acetylthio-α-alkylmalonate;    quaternary carbon center;    α-benzoxy-α-alkylmalonate;    derivatization;    615;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/133673/1/000000142085.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Part I :Organosulfur compounds are widely present in bioactive natural products and pharmaceuticals. The C-S bond formation is basic approach to synthesize the organosulfur compound. Among the C-S bond formation, construction of sulfur-bearing chiral quaternary carbon center is the most challenging target. There have been many synthetic methods for construction of sulfur-bearing chiral quaternary carbon center, but most of them were reactions through the sulfa nucleophile attack. However, these conventional methods have limitations in preparing sulfa nucleophiles and modifying its substrates.In 2011, our research team reported novel synthetic method for chiral α,α-dialkylmalonates in high chemical yield and optical yield by asymmetric phase-transfercatalyzed alkylation of modified malonates in the presence of chiral quaternary ammonium salts, and successfully proved its value by application of the natural product total synthesis and bioactive chemical block synthesis. To expand the research scope, we designed new substrate bearing heteroatoms to malonate’s α–position especially sulfur. Into this new sulfur bearing substrate, we tried to insert the various electrophiles via asymmetric phase-transfer catalytic alkylation. As a result, enantioselective alkylation of tert-butyl diphenylmethyl α-acetylthiomalonate was accomplished through asymmetric phase-transfer catalysis in the presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide as chiral catalyst and 50% KOH (aq) as base solution, toluene as organic solvent at -20 oC reaction temperature to afford the corresponding α-acetylthio-α-alkylmalonates in high chemical (up to 99%) and optical yields (up to 98%ee).Part II :In 2013, our research team developed enantioselective synthetic method for α-benzoyloxy-α-alkylmalonates via PTC alkylation. The asymmetric PTC α-alkylation of α-benzoxymalonate produced the corresponding α-benzoxy-α-alkylmalonates with high chemical (up to 99 %) and optical (up to 93 %ee) yields. However, we didn’t try the derivatization of α-benzoxy-α-alkylmalonates and we couldn’t get the absolute configuration by X-ray crystallography. Accordingly, we have been proceeded the derivatization of α-benzoxy-α-alkylmalonates.We could synthesize the chiral β-hydroxydiester, α,β-dihydroxyester, α,β-epoxyester, and 1,2-diol via multiple steps of reaction. From this applications we could confirm the absolute configuration of chiral α-benzoxy-α-alkylmalonate. The absolute configuration of α-benzoxy-α-alkylmalonate was assigned as R by the chemical conversion to a known compound 1,2-diol.