Lithium-iodine exchange initiated intramolecular additions : application of a novel annulation protocol to the total synthesis of (±)-mangicol F
department or school: Science, Faculty of
department or school: Chemistry, Department of
data provider: DSpace
degree campus: UBCV
creator: Harrison, Christian L.
issued: 2009-11-27T23:44:46Z
issued: 2004
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: This dissertation is divided into two sections: methodological work and application of one of the developed methods to the total synthesis of the racemic version of naturally occurring mangicol F. In the first section, the possibility of effecting intramolecular conjugate addition reactions initiated by lithium-iodine exchanges was explored. The required substrates for the initial study were cyclic α,β-unsaturated ketones (Michael acceptors) bearing alkenyl iodide functionalized sidechains. The preparation of such substrates began with the facile hydriodination of acetylenic esters, supplying alkyl Z-iodoalkenoates such as 66, which were subsequently converted (in two steps) into their corresponding allylic bromides. Alkylation of cyclic vinylogous esters such as 45 with allylic bromides 44 afforded compounds such as 46 which were converted into the required enone substrates, 47. Stereoselective intramolecular conjugate additions of the anions of these substrates, generated by lithium-iodine exchange reactions, were cleanly effected at -78 °C in the presence of the additives TMSC1 and HMPA, furnishing czs-fused bicyclic ketones of general structure 48 in very good yields. In addition, this methodology was extended to the formation of tricyclic ketones (ie. 59 and 61) via the use of cyclic alkenyl iodides (58) and aryl iodides (60), respectively. The substrates required for the second methodology project were the vinylogous ester intermediates (46). Intramolecular addition of alkenyl anions, generated by lithium-iodine exchange, to the carbonyl function of the vinylogous esters furnished, after an acid-promoted hydrolysis-dehydration protocol, bicyclic dienones of general structure 50 in excellent yields. This methodology was extended to the formation of tricyclic compounds such as aryl enone (172) and furyl enone (177) via the use of aryl iodide (143) and furyl iodide (162) substrates, respectively. To commence the work described in the second part of this dissertat…
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note: LITHIUM-IODINE EXCHANGE INITIATED INTRAMOLECULAR ADDITIONS: APPLICATION OF A NOVEL ANNULATION PROTOCOL TO THE TOTAL SYNTHESIS OF (±)-MANGICOL F. by Cristian L. Harrison B. Sc. (with honours), Concordia University, 1996 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Department of Chemistry) W e accept this thesis as conforming to the required s tandard THE UNIVERSITY OF BRITISH COLUMBIA Spring 2004 © Cristian L. Harrison i 11 Abstract This dissertation is divided into two sections: methodological work and application of one of the developed methods to the total synthesis of the racemic version of naturally occurring mangicol F . In the first section, the possibility of effecting intramolecular conjugate addition reactions initiated by lithium-iodine exchanges was explored. The required substrates for the initial study were cyclic a,p-unsaturated ketones (Michael acceptors) bearing alkenyl iodide functionalized sidechains. The preparation of such substrates began with the facile hydriodination of acetylenic esters, supplying alkyl Z-iodoalkenoates such as 66, which were subsequently converted (in two steps) into their corresponding allylic bromides. Alkylation of cyclic vinylogous esters such as 45 with allylic bromides 44 afforded compounds such as 46 which were converted into the required enone substrates, 47. Stereoselective intramolecular conjugate additions of the anions of these substrates, generated by lithium-iodine exchange reactions, were cleanly effected at -78 °C in the presence of the additives T M S C 1 and H M P A , furnishing czs-fused bicyclic ketones of general structure 48 in very good yields. In addition, this methodology was extended to the formation of tricyclic ketones (ie. 59 and 61) via the use of cyclic alkenyl iodides (58) and aryl iodides (60), respectively. The substrates required for the second methodology project were the vinylogous ester intermedia…
has type: Thesis/Dissertation
date issued: 2004-05
is shown at: 10.14288/1.0061170
language: eng
degree discipline: Chemistry
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/15931