Date of Award

2011

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry and Biochemistry

First Advisor

GREEN, JAMES (Chemistry and Biochemistry)

Keywords

Chemistry.

Rights

CC BY-NC-ND 4.0

Abstract

The Nicholas reaction is one of the important organometallic transformations in organic chemistry. The facile synthesis of its precursors, complexation of alkyne with the Co2(CO)6 unit, and straightforward demetallation after the completion of the reaction has made this reaction a tool of first choice for the synthetic chemist. Due to its versatile applications in organic syntheses, Nicholas reaction chemistry was considered to be well suited to the preparation of a cyclohepta[de]naphthalenes. Natural products such as microstegiol, oxomicrostegiol, salvibretol and oxosalvibretol are important examples of compounds possessing cyclohepta[de]naphthalene carbon skeleton, and to date, no synthesis of any of these compounds appears in the literature. In a model study for the synthesis of cyclohepta[de]naphthalenes, the reactivity pattern of propargyldicobalt cations with derivatives of naphthalene-2,7-diol, such as 2,7-dimethoxy- and dibenzyloxynaphthalene, were investigated under conventional Nicholas reaction conditions. Predominantly C-1 monocondensation and 1,6-dicondensation reaction products were formed, while in selected instances C-3 monocondensation or 1,8-dicondensation products were favoured. The mono- and dicondensation Nicholas reaction products were employed to synthesize cyclohepta[de]naphthalenes via ring closing metathesis and Friedel Crafts reactions. The application of Nicholas reaction chemistry of a selectively protected 2,7-naphthalenediol in the synthesis of the natural product (▒)-microstegiol was investigated. The differentially protected 2,7-naphthalenediol allowed the selective replacement of one of oxygen functions by a methyl group, and facile deprotection of other oxygen function allowed tautomerization to a cyclohepta[de]naphthalene-1-one upon seven membered ring closure in most cases. Ultimately the total synthesis of ()-microstegiol was accomplished in 15 steps with 7.2% overall yield from 2,7-dihydroxynaphthalene.

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