Stereoselective synthesis of 1,2-disubstitued βeta-amino alcohols and amino thiols

Roth, Aaron

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https://hdl.handle.net/2142/108470 Copy

Description

Title

Stereoselective synthesis of 1,2-disubstitued βeta-amino alcohols and amino thiols

Author(s)

Roth, Aaron

Issue Date

2020-07-14

Director of Research (if dissertation) or Advisor (if thesis)

Denmark, Scott E

Doctoral Committee Chair(s)

Denmark, Scott E

Committee Member(s)

• Sarlah, David
• Hergenrother, Paul
• Mehta, Angad

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Lewis base Catalysis, Stereoselective, Enantioselective

Abstract

This thesis covers the development and implementation of two distinct methodologies, both of which provide access to enantiomerically enriched, vicinally functionalized products. Chapter 1 provides background and a brief introduction of the activation of Group 16 Lewis acids by Lewis bases. Chapter 2 details a method for the catalytic, enantioselective, intermolecular, 1,2-sulfenoamination of alkenes. Functionalization is achieved through the intermediacy of an enantioenriched, configurationally stable thiiranium ion generated by Lewis base activation of a readily available sulfur electrophile. An expedited reaction optimization was achieved by employing multivariate Design of Experiment optimization ultimately resulting for a diverse set of anilines and benzylamines react with different styrenes to afford products in good yield and stereoselectivity. Downstream manipulation of the products is facilitated by deprotonation of the amines to enable carbon-sulfur bond cleavage. Chapter 3 of this thesis covers the identification of a method amenable to the rapid construction of diverse libraries of 1,2-amino alcohols. A number of methods are examined prior to the identification of 1,2-conjugate addition of aryl and alkyl lithium reagents to Ellman sulfonimines. The use of lithium reagents is key to overcome modest diastereoselectivity and poor reaction rates. A brief scope is explored and stereochemical models are discussed.

Graduation Semester

2020-08

Type of Resource

Thesis

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http://hdl.handle.net/2142/108470

Copyright and License Information

Copyright 2020 Aaron Roth

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