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Methodological Developments and Synthetic Applications of Strained Rings and Allylic C-H Functionalization of Hindered Substrates

Citation

O'Connor, Nicholas R. (2017) Methodological Developments and Synthetic Applications of Strained Rings and Allylic C-H Functionalization of Hindered Substrates. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9JS9NF6. http://resolver.caltech.edu/CaltechTHESIS:03072017-164212272

Abstract

Formal dipolar cycloadditions of cyclopropanes and aziridines are useful methods for the formation of carbo- and heterocycles. Given our group’s previous interest in this area, we sought to expand the scope of strained ring cycloadditions by employing heterocumulenes as dipolarophiles. This thesis describes our development of Lewis acid catalyzed formal (3 + 2) cycloadditions between donor–acceptor cyclopropanes and isocyanates, isothiocyanates, and carbodiimides to furnish various five-membered heterocycles. Enantioenriched cycloadducts can be accessed through a stereospecific reaction if enantiopure substrates are employed. We also present a method to access more highly nitrogenated heterocycles by replacing donor–acceptor cyclopropanes with activated aziridines. These aziridines react smoothly with isothiocyanates and carbodiimides in the presence of zinc Lewis acids to afford iminothiazolidine and iminoimidazolidine products in good yields. Our efforts to apply a cyclopropane cycloaddition toward the total synthesis of the indole alkaloid calophyline A are also described.

In addition, a method for the activation of sterically hindered allylic C–H bonds is presented. Despite numerous recent advances in the functionalization of allylic C–H bonds and the general utility of these transformations, reactions of sterically hindered substrates remain challenging. In this thesis we describe the development of a novel system for the palladium(II)-catalyzed allylic C–H acetoxylation of α-allyl lactams. We believe the lactam moiety may act as a directing group to aid in the palladation of these generally unreactive substrates. During optimization, we also discovered enal products were formed if water was added. These conditions represent the first example of a transition metal catalyzed C–H oxidation system with tunable selectivity over the extent of oxidation.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:cyclopropanes; aziridines; cycloadditions; allylic; oxidation
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Fu, Gregory C. (chair)
  • Agapie, Theodor
  • Reisman, Sarah E.
  • Stoltz, Brian M.
Defense Date:13 February 2017
Record Number:CaltechTHESIS:03072017-164212272
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:03072017-164212272
DOI:10.7907/Z9JS9NF6
Related URLs:
URLURL TypeDescription
http://onlinelibrary.wiley.com/doi/10.1002/ijch.201500089/epdfDOIArticle adapted for chapter 1
http://pubs.acs.org/doi/abs/10.1021/ol302494nDOIArticle adapted for chapter 2
http://onlinelibrary.wiley.com/doi/10.1002/chem.201303699/abstract?sDOIArticle adapted for chapter 3
http://onlinelibrary.wiley.com/doi/10.1002/anie.201504007/abstractDOIArticle adapted for chapter 5 and appendix 10
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10088
Collection:CaltechTHESIS
Deposited By: Nicholas O'Connor
Deposited On:15 Mar 2017 17:44
Last Modified:14 Sep 2017 16:47

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