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STRAIN-ENABLED PHOSPHINATION AND FLUORINATION REACTIONS

Milligan, John (2018) STRAIN-ENABLED PHOSPHINATION AND FLUORINATION REACTIONS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Chapter one of this thesis discusses the hydrophosphination of carbodiimides with secondary phosphine boranes. These reactions provide access to phosphaguanidine boranes, which have previously not been studied. A cyclic carbodiimide was also prepared, and hydrophosphination of this substrate provided access to structurally unique phosphaguanidines that bear resemblance to cyclophanes. Chapter two delineates the extension of this hydrophosphination method to functionalize strained carbocycles, namely bicyclo[1.1.0]butanes. The scope and stereoselectivity of this transformation was investigated, and further transformations of the cyclobutyl phosphine products were conducted. Studies on the addition of aromatic and heteroaromatic thiols to bicyclo[1.1.0]butanes are also described in this chapter. Chapter three describes a strain-relieving deoxyfluorination of bicyclo[1.1.0]butyl alcohols. The products of these transformations are fluorinated methylenecyclobutanes, which can be oxidatively transformed into cyclobutanones. Bicyclo[1.1.0]butyl amides were also subjected to fluorination with a high degree of diastereoselectivity. Chapter four details the development of bicyclo[1.1.0]butyl amides as potential androgen receptor antagonists for the treatment of castration-resistant prostate cancer. In the course of these medicinal chemistry studies, an acid-mediated isomerization of bicyclo[1.1.0]butanes to cyclobutenes was discovered.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Milligan, Johnjam350@pitt.edujam350
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWipf, Peterpwipf@pitt.edu
Committee MemberBrummond, Kaykbrummon@pitt.edu
Committee MemberWilcox, Craigdaylite@pitt.edu
Committee MemberBusacca, Carlcarl.busacca@boehringer-ingelheim.com
Date: 28 June 2018
Date Type: Publication
Defense Date: 8 March 2018
Approval Date: 28 June 2018
Submission Date: 30 March 2018
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 446
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: hydrophosphination, fluorination, bicyclo[1.1.0]butane, strained rings
Date Deposited: 28 Jun 2018 18:28
Last Modified: 28 Jun 2018 18:28
URI: http://d-scholarship.pitt.edu/id/eprint/34056

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