東華大學圖書館 |

Co(III)-Catalyzed Synthesis of Homoallylic Alcohols and Light-Mediated, Highly Diastereoselective Epimerization of Saturated N-Heterocycles.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Co(III)-Catalyzed Synthesis of Homoallylic Alcohols and Light-Mediated, Highly Diastereoselective Epimerization of Saturated N-Heterocycles./
作者:	Shen, Zican.
面頁冊數:	1 online resource (648 pages)
附註:	Source: Dissertations Abstracts International, Volume: 84-09, Section: B.
Contained By:	Dissertations Abstracts International84-09B.
標題:	Organic chemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29394776click for full text (PQDT)
ISBN:	9798371973948

Co(III)-Catalyzed Synthesis of Homoallylic Alcohols and Light-Mediated, Highly Diastereoselective Epimerization of Saturated N-Heterocycles.
Shen, Zican.

Co(III)-Catalyzed Synthesis of Homoallylic Alcohols and Light-Mediated, Highly Diastereoselective Epimerization of Saturated N-Heterocycles. - 1 online resource (648 pages)

Source: Dissertations Abstracts International, Volume: 84-09, Section: B.

Thesis (Ph.D.)--Yale University, 2022.

Includes bibliographical references

Both transition-metal catalysis and photocatalysis are useful and versatile platforms for developing novel synthetic methodologies. The first two chapters of this dissertation will discuss the development of cobalt(III)-catalyzed C-H bond additions with dienes and carbonyls to access homoallylic alcohols. The third and fourth chapters describe the light-mediated, highly diastereoselective epimerization of saturated nitrogen heterocycles via reversible hydrogen atom transfer (HAT).Chapter 1 describes an efficient CoIII-catalyzed three-component strategy to prepare homoallylic alcohols containing acyclic quaternary centers is disclosed. This transformation enables the introduction of two C-C σ bonds through C-H bond activation and sequential addition to internally substituted dienes and a wide range of aldehydes and activated ketones. Isoprene and other internally monosubstituted dienes are effective inputs, with the reaction proceeding with high diastereoselectivity for those substrate combinations that result in more than one stereogenic center. Moreover, the opposite relative stereochemistry can be achieved by employing 1,2-disubstituted dienes. A mechanism for the transformation is proposed based upon the relative stereochemistry of the products and studies with isotopically labeled starting materials.Chapter 2 describes a highly diastereoselective three-component C-H bond addition across butadiene and ketones is described. This transformation provides homoallylic tertiary alcohols through the formation of two C-C σ bonds and with complete selectivity for an E-alkene isomer. The reaction exhibits good scope with respect to activated ketone inputs, including highly strained cyclic and electron-deficient cyclic and acyclic ketones. Additionally, high diastereoselectivities were achieved for alcohols prepared from unsymmetrical ketones.Chapter 3 describes a combined photocatalytic and HAT approach for the light- mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di- to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as N-alkyl and aryl derivatives were effective epimerization substrates. The observed diastereoselectivities correlate with the calculated relative stabilities of the isomers. Demonstration of reaction reversibility, luminescence quenching, deuterium labeling studies, and quantum yield measurements provide information about the mechanism.Chapter 4 describes the first photocatalyzed epimerization of morpholines and piperazines. This method proceeds by reversible HAT and provides an efficient strategy for editing the stereochemical configurations of these saturated nitrogen heterocycles, which are prevalent in drugs. More stable morpholine and piperazine isomers are obtained from synthetically accessible but less stable stereoisomers, and a broad scope is demonstrated in terms of substitution patterns and functional group compatibility. The observed distributions of diastereomers correlate well with the calculated relative energies of the diastereomer pairs. Mechanistic studies, including luminescence quenching, deuterium labeling reactions, and determination of reversibility support a thiyl radical mediated HAT pathway for epimerization. Investigation of piperazine epimerization led to the development of new thiol free conditions for the highly stereoselective epimerization of N,N'-dialkyl piperazines.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798371973948Subjects--Topical Terms:

523952
Organic chemistry.
Subjects--Index Terms:

Homoallylic alcoholsIndex Terms--Genre/Form:

542853
Electronic books.

Co(III)-Catalyzed Synthesis of Homoallylic Alcohols and Light-Mediated, Highly Diastereoselective Epimerization of Saturated N-Heterocycles.
LDR:04982nmm a2200361K 4500 001 2363463
005 20231127093409.5
006 m o d
007 cr mn ---uuuuu
008 241011s2022 xx obm 000 0 eng d
020 $a 9798371973948
035 $a (MiAaPQ)AAI29394776
035 $a AAI29394776
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Shen, Zican. $3 3704224
245 1 0 $a Co(III)-Catalyzed Synthesis of Homoallylic Alcohols and Light-Mediated, Highly Diastereoselective Epimerization of Saturated N-Heterocycles.
264 0 $c 2022
300 $a 1 online resource (648 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 84-09, Section: B.
500 $a Advisor: Ellman, Jonathan A.
502 $a Thesis (Ph.D.)--Yale University, 2022.
504 $a Includes bibliographical references
520 $a Both transition-metal catalysis and photocatalysis are useful and versatile platforms for developing novel synthetic methodologies. The first two chapters of this dissertation will discuss the development of cobalt(III)-catalyzed C-H bond additions with dienes and carbonyls to access homoallylic alcohols. The third and fourth chapters describe the light-mediated, highly diastereoselective epimerization of saturated nitrogen heterocycles via reversible hydrogen atom transfer (HAT).Chapter 1 describes an efficient CoIII-catalyzed three-component strategy to prepare homoallylic alcohols containing acyclic quaternary centers is disclosed. This transformation enables the introduction of two C-C σ bonds through C-H bond activation and sequential addition to internally substituted dienes and a wide range of aldehydes and activated ketones. Isoprene and other internally monosubstituted dienes are effective inputs, with the reaction proceeding with high diastereoselectivity for those substrate combinations that result in more than one stereogenic center. Moreover, the opposite relative stereochemistry can be achieved by employing 1,2-disubstituted dienes. A mechanism for the transformation is proposed based upon the relative stereochemistry of the products and studies with isotopically labeled starting materials.Chapter 2 describes a highly diastereoselective three-component C-H bond addition across butadiene and ketones is described. This transformation provides homoallylic tertiary alcohols through the formation of two C-C σ bonds and with complete selectivity for an E-alkene isomer. The reaction exhibits good scope with respect to activated ketone inputs, including highly strained cyclic and electron-deficient cyclic and acyclic ketones. Additionally, high diastereoselectivities were achieved for alcohols prepared from unsymmetrical ketones.Chapter 3 describes a combined photocatalytic and HAT approach for the light- mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di- to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as N-alkyl and aryl derivatives were effective epimerization substrates. The observed diastereoselectivities correlate with the calculated relative stabilities of the isomers. Demonstration of reaction reversibility, luminescence quenching, deuterium labeling studies, and quantum yield measurements provide information about the mechanism.Chapter 4 describes the first photocatalyzed epimerization of morpholines and piperazines. This method proceeds by reversible HAT and provides an efficient strategy for editing the stereochemical configurations of these saturated nitrogen heterocycles, which are prevalent in drugs. More stable morpholine and piperazine isomers are obtained from synthetically accessible but less stable stereoisomers, and a broad scope is demonstrated in terms of substitution patterns and functional group compatibility. The observed distributions of diastereomers correlate well with the calculated relative energies of the diastereomer pairs. Mechanistic studies, including luminescence quenching, deuterium labeling reactions, and determination of reversibility support a thiyl radical mediated HAT pathway for epimerization. Investigation of piperazine epimerization led to the development of new thiol free conditions for the highly stereoselective epimerization of N,N'-dialkyl piperazines.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
650 4 $a Organic chemistry. $3 523952
650 4 $a Chemistry. $3 516420
653 $a Homoallylic alcohols
653 $a Diastereoselectives
653 $a Epimerization
655 7 $a Electronic books. $2 lcsh $3 542853
690 $a 0490
690 $a 0485
710 2 $a ProQuest Information and Learning Co. $3 783688
710 2 $a Yale University. $b Chemistry. $3 2101664
773 0 $t Dissertations Abstracts International $g 84-09B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29394776 $z click for full text (PQDT)