Date of Award

2014

Publication Type

Doctoral Thesis

Degree Name

Ph.D.

Department

Chemistry and Biochemistry

Keywords

alkyne, Co2(CO)6, cycloheptyne, Icetexane-diterpene, intramolecular cyclization, Nicholas reaction

Supervisor

Green, James

Rights

info:eu-repo/semantics/openAccess

Abstract

The Nicholas reaction is a Lewis- or Brønsted-acid mediated displacement of dicobalt-hexacarbonyl complexed alcohols, ethers, or acetates, which generates stable cations propargylic to the alkyne-Co2(CO)6 group, that can consequently be trapped by a variety of nucleophiles to form new carbon-carbon or carbon-heteroatom bonds. This reaction features several aspects which makes it especially well-suited for the synthesis of compounds containing cyclic structures by way of annulation reactions. Upon complexation of the alkyne with a Co2(CO)6 unit, the alkyne function bends, and the bond angle is reduced to approximately 140o. This reduced bond angle, coupled with the fact that the generated [(progargylium)Co2(CO)6]+ cations exhibit a relatively high electrophilicity, make participation in ring-formation via electrophilic cyclization by means of Nicholas chemistry a very feasible process. Given the wide occurrence of cycloheptane containing compounds in nature, and the group's ongoing interest in acetylene-Co2(CO)6 chemistry, the following chapters describe a novel approach to cycloheptyne-Co2(CO)6 synthesis via the preparation and reactivity studies of vinylogous propargyl acetate-Co2(CO)6 complexes. Relying on simple (and commercially available) starting materials, a series of 6,7,6-dibenzocycloheptyne-Co2(CO)6 complexes, and 6,7,5-dibenzocycloheptyne-Co2(CO)6 heterocyclic analogue complexes were synthesized in moderate yields. Treatment of their respective complexed precursors with SnCl4 as Lewis acid generated benzylic-Co2(CO)6 cations which were propargylic by vinylogy, and which were subsequently trapped intramolecularly by electron rich arenes. The remainder of the syntheses focused on the generation of a plethora of 6,7,n-tricyclic-Co2(CO)6 model substrates (n = 5, 6, 7), as outlined in the retrosynthesis below. A series of acetate-Co2(CO)6 complexes were exposed to BF3∙OEt2 or SnCl4, which resulted in the formation of their respective allylic/proparyglic cation complexes. Intramolecular nucleophilic attack by electron rich arenes (and in one case, a π-excessive heterocycle) led to ring closure to afford the cycloheptyne-Co2(CO)6 complexed systems in excellent yields. A small number of n,7-bicyclic-Co2(CO)6 systems (n = 6, 7) were synthesized by employing an allylsilane moiety as the nucleophile. These cyclized substrates provided the framework and substitution pattern of a variety of natural products, and hence to establish the broader utility of this process, this procedure was then exemplified by the formal synthesis of some icetexane-diterpenes.

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