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Synthetic Applications and Methodological Developments of Donor-Acceptor Cyclopropanes

Citation

Goldberg, Alexander F. G. (2013) Synthetic Applications and Methodological Developments of Donor-Acceptor Cyclopropanes. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9W9576V. http://resolver.caltech.edu/CaltechTHESIS:02202013-172928174

Abstract

Donor–acceptor cyclopropanes are a versatile class of synthetic intermediates, compatible in a broad range of ring-opening reactions and formal cycloadditions, and employed in numerous natural product syntheses. We have developed new Lewis acid mediated cycloadditions for the synthesis of five-membered heterocycles, and applied existing a transition metal catalyzed cyclopropane cycloaddition method toward the synthesis of complex alkaloids.

First, described is the development of a Lewis acid mediated (3 + 2) cycloaddition of donor–acceptor cyclopropanes with isocyanates, isothiocyanates and carbodiimides. This reaction was found in certain cases to proceed with excellent stereochemical fidelity, providing access to an array of enantioenriched thioimidates and amidines.

Second, we targeted the Melodinus alkaloids for total synthesis due to their unique structural features. Synthetic efforts toward scandine, the parent of the natural product family, are detailed herein. Our approach features a palladium catalyzed formal (3 + 2) cycloaddition of a vinyl cyclopropane and a β-nitrostyrene to rapidly assemble the central cyclopentane core of the natural product. Initial efforts focused on the synthesis and application of a 1,1-divinylcyclopropane to the formal (3 + 2) cycloaddition reaction, whereas later work entailed the use of a mono-vinylcyclopropane with the goal of installing the second requisite vinyl group at a later stage using modern C–H functionalization technologies.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Cyclopropane; Melodinus Alkaloid; Scandine; Meloscine; Cycloaddition; Thioimidate; Lactam; Amidine; Ortho-Quinone Methide; Asymmetric Alkylation; (3 + 2)
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Mixed availability, specified at file level
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Grubbs, Robert H. (chair)
  • Peters, Jonas C.
  • Reisman, Sarah E.
  • Stoltz, Brian M.
Defense Date:29 May 2013
Funders:
Funding AgencyGrant Number
Natural Sciences and Engineering Research Council of Canada UNSPECIFIED
Projects:Lewis Acid Mediated (3 + 2) Cycloadditions of Donor–Acceptor Cyclopropanes with Heterocumulenes, Progress toward the Total Synthesis of Scandine and the Melodinus Alkaloids
Record Number:CaltechTHESIS:02202013-172928174
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:02202013-172928174
DOI:10.7907/Z9W9576V
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7487
Collection:CaltechTHESIS
Deposited By: Alexander Goldberg
Deposited On:07 Jun 2013 23:22
Last Modified:18 May 2017 22:48

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