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ENANTIOSELECTIVE CYCLOPROPANATIONS OF ALLENES AND THEIR APPLICATION TO THE TOTAL SYNTHESIS OF CLAVINE ALKALOIDS

McCabe, Stephanie R (2018) ENANTIOSELECTIVE CYCLOPROPANATIONS OF ALLENES AND THEIR APPLICATION TO THE TOTAL SYNTHESIS OF CLAVINE ALKALOIDS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The first section of this thesis describes the development of an enantioselective synthesis
of terminally unsubstituted methylenecyclopropanes. The key feature of this approach is a Rh2(STBPTTL)
4-mediated catalytic asymmetric cyclopropanation of unsubstituted allene to produce
enantioenriched methylenecyclopropanes bearing alkyl or activated ester functionalities. This
method was successfully applied to the enantioselective total synthesis of cycloclavine.
The second section of this thesis describes the development of an improved 12
steps/5.2% overall yield racemic total synthesis of the clavine alkaloid cycloclavine. The first
enantioselective total syntheses of the unnatural enantiomer (–)-cycloclavine and the natural
enantiomer (+)-cycloclavine were also accomplished in 8 steps/7.1%(brsm) overall yield and 8
steps/4% overall yield, respectively. Noteworthy features of this approach include a strainpromoted
intramolecular Diels-Alder reaction followed by a highly regioselective aerobic α,β-
dehydrogenation to form a key enone intermediate in >99.5:0.5 er after crystallization.
Additional noteworthy features include the enone 1,2-addition of a novel TEMPO-carbamate
aminomethyl carbanion and an IMDAF reaction to install the indole core. The mechanism of
thermolysis of the new TEMPOC amine protecting-group was investigated. Finally, the natural
and unnatural enantiomers were evaluated for their ability to bind to several neurotransmitter
receptors in radioligand binding assays.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
McCabe, Stephanie Rsrm99@pitt.edusrm990000-0001-9773-4796
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWipf, Peterpwipf@pitt.edupwipf0000-0001-7693-5863
Committee MemberCurran, Denniscurran@pitt.educurran0000-0001-9644-7728
Committee ChairKoide, Kazunorikoide@pitt.edukoide0000-0001-8894-8485
Committee ChairJanjic, Jelenajanjicj@duq.edu0000-0002-0539-8359
Date: 27 September 2018
Date Type: Publication
Defense Date: 4 May 2018
Approval Date: 27 September 2018
Submission Date: 10 June 2018
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 352
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: total synthesis, cycloclavine, allene
Date Deposited: 27 Sep 2018 19:56
Last Modified: 27 Sep 2018 19:56
URI: http://d-scholarship.pitt.edu/id/eprint/34612

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