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Development of Nickel-Catalyzed Asymmetric Reductive Cross-Coupling Reactions

Citation

Poremba, Kelsey Elizabeth (2019) Development of Nickel-Catalyzed Asymmetric Reductive Cross-Coupling Reactions. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ZW64-GJ97. https://resolver.caltech.edu/CaltechTHESIS:05222019-135022700

Abstract

Asymmetric reductive cross-electrophile coupling is a powerful method to forge C–C bonds and access enantioenriched small molecules, which can be further functionalized to access scaffolds present in natural products and bioactive pharmaceutical agents. However, an innate challenge of this methodology is identifying a chiral catalyst that achieves optimal cross-selectivity and stereocontrol. Herein, we report studies on the asymmetric cross-coupling of C(sp3) electrophiles, such as benzyl chlorides, α-chloroesters, and N-hydroxyphthalimide esters, with several classes of C(sp2) electrophiles.

We describe the asymmetric Ni-catalyzed reductive cross-coupling of (hetero)aryl iodides and benzyl chlorides to prepare enantioenriched 1,1-diarylalkanes. As part of these studies, a new chiral bi(oxazoline) ligand, 4-HeptylBiOX, was developed to obtain products in synthetically useful yield and enantioselectivity. This novel ligand is demonstrated to expand the substrate scope of these stereoconvergent reductive cross- couplings to include the asymmetric cross-coupling of α-chloroesters with aryl iodides, and sterically hindered N-hydroxyphthalimide esters with alkenyl bromides. Model studies have been initiated to study the application of these reactions toward the total synthesis of cylindrocyclophane natural products.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:nickel, catalysis, reductive cross-coupling, enantioselective
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Reisman, Sarah E.
Thesis Committee:
  • Stoltz, Brian M. (chair)
  • Reisman, Sarah E.
  • Fu, Gregory C.
  • Peters, Jonas C.
Defense Date:23 April 2019
Funders:
Funding AgencyGrant Number
NSFDGE 1144469
Record Number:CaltechTHESIS:05222019-135022700
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:05222019-135022700
DOI:10.7907/ZW64-GJ97
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/jacs.7b01705DOIArticle adapted for Chapter 2
https://doi.org/10.1021/acs.orglett.7b00793DOIArticle adapted for Chapter 4
ORCID:
AuthorORCID
Poremba, Kelsey Elizabeth0000-0002-7446-257X
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11531
Collection:CaltechTHESIS
Deposited By: Kelsey Poremba
Deposited On:23 May 2019 16:09
Last Modified:04 Oct 2019 00:25

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