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Computational and Experimental Studies in Selective Organocatalysis- [electronic resource]
Computational and Experimental Studies in Selective Organocatalysis- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214101224
- ISBN
- 9798380848060
- DDC
- 547
- 저자명
- Wagen, Corin.
- 서명/저자
- Computational and Experimental Studies in Selective Organocatalysis - [electronic resource]
- 발행사항
- [S.l.]: : Harvard University., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(354 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-05, Section: B.
- 주기사항
- Advisor: Jacobsen, Eric.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Chemical synthesis has transformed the ability of scientists and engineers to interact with the molecular world. Yet despite almost two centuries of considerable effort, small-molecule synthesis remains a challenging task. Hundreds of new reactions are discovered every year, but few possess the requisite selectivity and generality needed to be useful for routine synthesis, and elucidation of their mechanism and underlying catalytic principles is rarely conducted. In this work, we describe a variety of efforts at the interface of organic, computational, and analytical chemistry which seek to address the linked problems of discovering selective organocatalysts and understanding the mechanism by which they operate.In Chapter 1, we report the development of a new analytical method that combines chiral stationary phase supercritical fluid chromatography with mass spectrometry-based detection to enable enantiodetermination of pooled crude reaction mixtures, greatly increasing analytical throughput. This advance allows us to perform multi-substrate screening to discover catalysts possessing good substrate scope, which we demonstrate in the optimization of a Bronsted acid catalyst for the enantioselective Pictet-Spengler reaction.In Chapter 2, we disclose the results of a mechanistic study aimed at understanding a hydrogen chloride/hydrogen-bond donor co-catalyzed Prins cyclization of alkenyl aldehydes which exhibited dramatic rate acceleration compared to the background reaction. Our studies reveal that the catalyst reacts with hydrogen chloride to form a new chiral acid in situ with a higher pKa than hydrogen chloride, which nevertheless reacts faster owing to favorable catalyst-controlled positioning of the chloride anion to electrostatically stabilize the major transition state.In Chapter 3, we report a computational study of our group's regio- and stereoselective glycosylation of minimally protected glycosyl acceptors. The computational model described- the first of hydrogen-bond-donor-catalyzed glycosylation of glycosyl phosphate donors-contains features of the transition state previously hypothesized on the basis of experimental results, and lends support to the proposed "4H" binding mechanism.In Chapter 4, we describe the development of an enantioselective protio-semipinacol reaction of unactivated vinylic cyclopropanols. Motivated by the question of how high enantioselectivity can be achieved in a low-barrier 1,2-rearrangement, we conduct an experimental and computational mechanistic investigation and come to the surprising conclusion that protonation to form a formally achiral carbocation in fact exerts stereocontrol over the subsequent rearrangement step: the rearrangement is so rapid that the carbocation is locked in a given chiral conformation, rendering the rearrangement effectively stereospecific. Finally, in chapter 5 we detail a spectroscopic and computational study of solutions of hydrogen chloride in diethyl ether, aimed at assigning the solution structure of hydrogen chloride. In situ IR spectroscopy, combined with density-functional theory and molecular dynamics, provides evidence for the existence of oxonium ions formed from complete proton transfer to diethyl ether. This observation explains the often-inhibitory effect of diethyl ether on hydrogen chloride-catalyzed reactions and has intriguing implications for catalyst design.
- 일반주제명
- Organic chemistry.
- 일반주제명
- Computational chemistry.
- 일반주제명
- Analytical chemistry.
- 키워드
- Organocatalysis
- 키워드
- Catalysts
- 기타저자
- Harvard University Chemistry and Chemical Biology
- 기본자료저록
- Dissertations Abstracts International. 85-05B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798380848060
■035 ▼a(MiAaPQ)AAI30526688
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a547
■1001 ▼aWagen, Corin.▼0(orcid)0000-0003-3315-3524
■24510▼aComputational and Experimental Studies in Selective Organocatalysis▼h[electronic resource]
■260 ▼a[S.l.]:▼bHarvard University. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(354 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-05, Section: B.
■500 ▼aAdvisor: Jacobsen, Eric.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aChemical synthesis has transformed the ability of scientists and engineers to interact with the molecular world. Yet despite almost two centuries of considerable effort, small-molecule synthesis remains a challenging task. Hundreds of new reactions are discovered every year, but few possess the requisite selectivity and generality needed to be useful for routine synthesis, and elucidation of their mechanism and underlying catalytic principles is rarely conducted. In this work, we describe a variety of efforts at the interface of organic, computational, and analytical chemistry which seek to address the linked problems of discovering selective organocatalysts and understanding the mechanism by which they operate.In Chapter 1, we report the development of a new analytical method that combines chiral stationary phase supercritical fluid chromatography with mass spectrometry-based detection to enable enantiodetermination of pooled crude reaction mixtures, greatly increasing analytical throughput. This advance allows us to perform multi-substrate screening to discover catalysts possessing good substrate scope, which we demonstrate in the optimization of a Bronsted acid catalyst for the enantioselective Pictet-Spengler reaction.In Chapter 2, we disclose the results of a mechanistic study aimed at understanding a hydrogen chloride/hydrogen-bond donor co-catalyzed Prins cyclization of alkenyl aldehydes which exhibited dramatic rate acceleration compared to the background reaction. Our studies reveal that the catalyst reacts with hydrogen chloride to form a new chiral acid in situ with a higher pKa than hydrogen chloride, which nevertheless reacts faster owing to favorable catalyst-controlled positioning of the chloride anion to electrostatically stabilize the major transition state.In Chapter 3, we report a computational study of our group's regio- and stereoselective glycosylation of minimally protected glycosyl acceptors. The computational model described- the first of hydrogen-bond-donor-catalyzed glycosylation of glycosyl phosphate donors-contains features of the transition state previously hypothesized on the basis of experimental results, and lends support to the proposed "4H" binding mechanism.In Chapter 4, we describe the development of an enantioselective protio-semipinacol reaction of unactivated vinylic cyclopropanols. Motivated by the question of how high enantioselectivity can be achieved in a low-barrier 1,2-rearrangement, we conduct an experimental and computational mechanistic investigation and come to the surprising conclusion that protonation to form a formally achiral carbocation in fact exerts stereocontrol over the subsequent rearrangement step: the rearrangement is so rapid that the carbocation is locked in a given chiral conformation, rendering the rearrangement effectively stereospecific. Finally, in chapter 5 we detail a spectroscopic and computational study of solutions of hydrogen chloride in diethyl ether, aimed at assigning the solution structure of hydrogen chloride. In situ IR spectroscopy, combined with density-functional theory and molecular dynamics, provides evidence for the existence of oxonium ions formed from complete proton transfer to diethyl ether. This observation explains the often-inhibitory effect of diethyl ether on hydrogen chloride-catalyzed reactions and has intriguing implications for catalyst design.
■590 ▼aSchool code: 0084.
■650 4▼aOrganic chemistry.
■650 4▼aComputational chemistry.
■650 4▼aAnalytical chemistry.
■653 ▼aOrganocatalysis
■653 ▼aChemical synthesis
■653 ▼aHydrogen chloride
■653 ▼aMass spectrometry
■653 ▼aCatalysts
■690 ▼a0490
■690 ▼a0219
■690 ▼a0486
■71020▼aHarvard University▼bChemistry and Chemical Biology.
■7730 ▼tDissertations Abstracts International▼g85-05B.
■773 ▼tDissertation Abstract International
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16933255▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
