Browse

상전이 촉매 반응을 통한 tert-butyl oxycarbamates의 입체 선택적인 aza-Michael Reactions
Enantioselective aza-Michael Reactions of tert-butyl oxycarbamates via Phase-Transfer Catalyst

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
반정우
Advisor
박형근
Issue Date
2020
Publisher
서울대학교 대학원
Description
학위논문(석사)--서울대학교 대학원 :약학대학 약학과,2020. 2. 박형근.
Abstract
β-Amino carbonyl 골격은 β-lactams을 포함하여 amino alcohols, diamines, β-amino acids 등 다양한 질소 함유 중간체에서 중요한 구조를 차지하고 있다. 본 연구실에서는 상전이 촉매 반응(Phase-Transfer Catalysis)을 이용하여 tert-butyl benzyloxycarbamate와 electron-deficient olefins 들을 대상으로 한 aza-Michael addition을 성공적으로 보고한 바 있다. 50% aqueous potassium hydroxide(KOH) 와 toluene 용매 조건으로 상전이 촉매 반응을 진행하였을 때, 높은 수율(>99%)을 얻었다.
본 연구에서는 cyclic β-Amino carbonyl 골격을 입체 선택적으로 합성하기 위해 tert-butyl benzyloxycarbamate와 2-cyclohexen-1-one을 기질로 PTC aza-Michael reaction을 진행하였다. 다양한 상전이 촉매를 사용하여 0oC 에서 높은 광학수율 (87% ee)을 보이는 상전이 촉매를 발견하였다. 이렇게 확립한 상전이 촉매를 사용하여 tert-butyl oxycarbamates 14가지와 cyclic enones 9가지를 대상으로 phase-transfer catalytic aza-Michael addition을 진행하였다.
최종적으로 tert-butyl (naphthalene-2-ylmethoxy)carbamate와 2-cyclohexen-1-one을 기질로 aza-Michael reaction을 진행하였을 때 높은 수율 (>99%)과 높은 광학수율 (98% ee)을 얻을 수 있었다. 이는 촉매와 기질간의 상호작용에 기인한 것으로 보이며, 다음과 같은 3가지 상호작용이 관여하고 있음을 제안해보았다. (Ion-pair interaction, π-π interaction, Hydrogen-bonding interaction). 또한, TFA acidic 조건과 Hydrogen & Pd/C 조건하에서 선택적으로 deprotection을 진행하여, cyclic β-amino carbonyl 골격을 chiral하게 갖고 있는 천연물을 합성하기 위한 전구 물질로 활용 가능함을 확인하였다.
β-Amino carbonyl is an important structure in various nitrogen-containing intermediates, including β-lactams, amino alcohols, diamines, β-amino acids etc. In this lab, we have successfully reported aza-Michael reaction with tert-butyl benzyloxylcarbamate and electro-deficient olefins with a phase-transfer catalyst. High chemical yield (99%) was achieved via phase-transfer catalysis using 50% aqueous potassium hydroxide as base and toluene as solvent.
In our research, we firstly conducted phase-transfer catalytic aza-Michael reaction with tert-butyl benzyloxylcarbamate and 2-cyclohexen-1-one. We could find specific phase-transfer catalyst that shows a high optical yield (87% ee) at 0 oC. This established phase-transfer catalyst was used to carry out phase-transfer catalytic aza-Michael reactions with 14 types of tert-butyl oxycarbamates and 9 cyclic enones.
Finally, high yields (>99%) and high optical yields (98% ee) were obtained when the tert-butyl(naphthalene-2-ylmethyl)carbamate and 2-cyclohexen-1-one were used. This is due to the interactions between catalysts and substrates. And we suggest that the following three interactions are involved (Ion-pair interaction, π-π interaction, Hydrogen-bonding interaction).
In addition, the selective deprotection, the objective of designing the cyclic chiral β-amino carbonyl structure, in TFA acidic and Pd/C conditions was confirmed. We suggest that it is available as a precursor to natural substances that contain β-amino carbonyl structure.
Language
kor
URI
http://dcollection.snu.ac.kr/common/orgView/000000159201
Files in This Item:
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Master's Degree_약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse