Dissertation/Thesis Abstract

Multicomponent Cyclization Reactions: A General Approach to Dibenzocyclooctadiene Lignan Natural Products
by Gong, Wei, Ph.D., The Ohio State University, 2012, 531; 10630971
Abstract (Summary)

Aiming at finding a general and broadly applicable route to dibenzocyclooctadiene (DBCOD) lignans, an important class of natural products with wide-ranging biological activities, we applied Pd-catalyzed bis-metallative cyclizations mediated by a [B-Sn] reagent, 1-trimethylstannyl-2,5-dimethyl-2,5-diazaborolidine, to access the core DBCOD systems.

2,2'-Dipropargyl biphenyls are suitable precursors of [B-Sn] reagent mediated cyclizations and their acetylene moieties can be installed by addition of lithium acetylides to 2'-substituted biphenyl aldehydes. Most of these acetylide additions are highly stereoselective and chelating models have been proposed to rationalize their stereochemical results. The viability of the [B-Sn]-mediated cyclizations of these dipropargyl biphenyls depends on the chirality of the biphenyl scaffolding and the configuration of the propargylic center. Models based on steric arguments can be used to rationalize the stereochemical outcomes in successful cyclizations, and the reluctance in others to undergo the cyclization.

A racemic synthesis of steganone was achieved from a 1,2-bisalkylidenecyclooctadiene prepared via the [B-Sn]-mediated cyclization. A novel AD-mix mediated tandem process quickly led to the formation of the key lactone, which was converted to steganone after three steps.

Eight fully substituted DBCOD lignans, including compounds such as kadsuralignan B, tiegusanin D, and schizanrin F, with a tertiary center at C7, were first synthesized using an intermediate prepared by the [B-Sn]-mediated cyclization. The unique conformations of DBCOD intermediates are crucial for different reactivities of certain functional groups (e.g., C-C double bonds, hydroxyl and carbonyl groups), which can explain the stereochemical outcome of related transformations, for example, the hydrogenation reactions, Mitsunobu reactions, electrophilic additions to C-C double bonds and nucleophilic additions to carbonyl groups. The conformations of DBCODs containing C6 and/or C9 carbonyl groups are also discussed based on experimental data. We provide a general approach to the syntheses of highly functionalized DBCOD lignan natural products (>100) and unnatural analogs with different configurations and/or oxidation states at C6, C7, C8 and C9.

Indexing (document details)
Advisor: RajanBabu, thaliyil
Commitee: Badjic, Jovica, Mattson, Anita
School: The Ohio State University
Department: Chemistry
School Location: United States -- Ohio
Source: DAI-B 78/11(E), Dissertation Abstracts International
Subjects: Chemistry
Keywords: 2, Dibenzocyclooctadiene (dbcod) lignans, Dipropargyl biphenyls, Multicomponent cyclization reactions, Stereoselective acetylide additions
Publication Number: 10630971
ISBN: 9780355012873
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