eprintid: 34056
rev_number: 11
userid: 3207
dir: disk0/00/03/40/56
datestamp: 2018-06-28 18:28:30
lastmod: 2019-06-28 05:15:03
status_changed: 2018-06-28 18:28:30
type: thesis_degree
succeeds: 33899
metadata_visibility: show
contact_email: jam350@pitt.edu
item_issues_id: thesis_degree_versioning
item_issues_type: thesis_degree_versioning
item_issues_description: ETD 34056 is using versioning.
item_issues_timestamp: 2018-03-31 06:02:13
item_issues_status: discovered
item_issues_count: 1
eprint_status: archive
creators_name: Milligan, John
creators_email: jam350@pitt.edu
creators_id: jam350
title: STRAIN-ENABLED PHOSPHINATION AND FLUORINATION REACTIONS
ispublished: unpub
divisions: sch_as_chemistry
full_text_status: public
keywords: hydrophosphination, fluorination, bicyclo[1.1.0]butane, strained rings
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.
date: 2018-06-28
date_type: published
pages: 446
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_chair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Wipf, Peter
etdcommittee_name: Brummond, Kay
etdcommittee_name: Wilcox, Craig
etdcommittee_name: Busacca, Carl
etdcommittee_email: pwipf@pitt.edu
etdcommittee_email: kbrummon@pitt.edu
etdcommittee_email: daylite@pitt.edu
etdcommittee_email: carl.busacca@boehringer-ingelheim.com
etd_defense_date: 2018-03-08
etd_approval_date: 2018-06-28
etd_submission_date: 2018-03-30
etd_release_date: 2018-06-28
etd_access_restriction: 1_year
etd_patent_pending: FALSE
thesis_type: dissertation
degree: PhD
citation:   Milligan, John  (2018) STRAIN-ENABLED PHOSPHINATION AND FLUORINATION REACTIONS.  Doctoral Dissertation, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/34056/1/Milligan_ETD_2018_3.pdf