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DDQ-Mediated Oxidative Oxocarbenium Ion Formation – Method Development and Natural Product Total Synthesis

Han, Xun (2016) DDQ-Mediated Oxidative Oxocarbenium Ion Formation – Method Development and Natural Product Total Synthesis. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is an excellent oxidant for cleaving the carbon–hydrogen bond of allylic (or benzylic) ethers to generat oxocarbenium ions. When DDQ oxidation proceeds in a macrocyclic system that contains a sterically undemanding alkynyl group, the (Z)-geometry oxocarbenium ion dominates due to the geometric constraint of the macrocyclic core. The following nucleophilic addition of the appending enol acetate to this macrocyclic oxocarbenium ion yields the bridged 2,6-trans-disubstituted tetrahydropyran diastereoselectively.

Based on the DDQ oxidation methodology, a one-pot process has been developed to access synthetically challenging spiroketal structures through combining simple dienes and aldehydes. After the initial hetero-Diels-Alder (HDA) reaction, the resulting tetrahydropyranyl enol silyl ethers are subjected to DDQ oxidation. The tetrahydropyranyl oxocarbenium ions are formed immediately, followed by cleavage of the carbon–silicon bonds to produce the enones that go through an oxa-Michael addition to afford the spiroketals in excellent yields.

This one-pot process has been successfully applied to the construction of the spiroketal core during the convergent total synthesis of bioactive natural product bistramide A. The 2,6- trans-tetrahydropyran in the righthand fragment was fast assembled through another novel one- pot process, which is composed of a hydroformylation, cyclization, and acetylation. Currently, our total synthesis of bistramide A holds the shortest synthetic sequence in the literature.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Han, Xunxuh9@pitt.eduXUH9
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFloreancig, Paul Eflorean@pitt.eduFLOREAN
Committee MemberCurran, Dennis Pcurran@pitt.eduCURRAN
Committee MemberHorne, W Sethhorne@pitt.eduHORNE
Committee MemberXie, Xiang-Qunxix15@pitt.eduXIX15
Date: 19 January 2016
Date Type: Publication
Defense Date: 2 December 2015
Approval Date: 19 January 2016
Submission Date: 13 November 2015
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 210
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: oxocarbenium ion, tetrahydropyran, cyclization, natural product, spiroketal
Date Deposited: 19 Jan 2016 20:18
Last Modified: 15 Nov 2016 14:30


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