Tillett, Caroline (1999) Tandem reactions in synthesis: the synthesis of carcocyclic compounds using organocobalt complexes in the key cyclisation step. (PhD thesis), Kingston University, .
Abstract
This programme of work has focused at developing novel cyclisation reactions in order to furnish a variety of carbocyclic ring systems. The formation of these ring systems have all been based around a key cyclisation step, which has involved a novel ‘intra’molecular Nicholas reaction. The use of organcobalt clusters for our work is based around the Nicholas reaction which is the reaction of cobalt complexed propargyl alcohol/ethers with a Lewis acid. This provides an ‘in situ’ cobalt stabilised carbocation that can be reacted with a range of nucleophiles to provide alkylated products. The first chapter reviews tandem cyclisation reactions and their role in organic chemistry. This is followed by a review of the chemistry of organocobalt clusters and the following chapter reports the results of our investigations. The initial investigation followed existing studies, carried out at Kingston University, in an attempted synthesis of bicycle(4:4:0)decanes. These fused carbocycles represent the AB ring system of the steroid nucleus. This work focused upon an investigation into the oxidation of propargyl alcohols to form propargyl aldehydes, using a variety of mild oxidation methods. The cobalt complex of propargyl aldehyde is synthetically useful as it is able to undergo a Nicholas reaction to afford the corresponding propargyl alcohol thus enabling a further Nicholas reaction to be performed. This work was successful in synthesising a cyclisation precursor that contains two centres. When complexed with dicobalt hexacarbonyl it has been possible to separate the diastereomers formed and determine their relative stereochemistry using [sup]1H NMR techniques. These studies then progressed and a novel tandem cyclisation reaction was discovered that provided tricyclic compounds from a monocyclic precursor. The tandem sequence appears to take place ‘via’ an ‘inter’molecular Nicholas reaction followed by an ‘intra’molecular Nicholas reaction. During the sequential decomplexation step of the dicobalt hexacarbonyl complex, an additional cyclisation occurs to afford tricyclic compounds with a further functional group interconversion. For example, applying this one pot synthesis to 3-(4-methyl-3-pentenyl)-1-(trimethyl silyloxy)-1-cyclohex-1-ene, the synthesis of 6,6-dimethyltricyclo(7:4:0:0[sup] 3,7)tridec-4-en-1-one was achieved. It was discovered that some of the cyclisation precursors used, underwent the tandem Nicholas reactions to produce a bicyclic compound, but failed to undergo the additional cyclisation to produce the corresponding tricyclic compounds. For example by applying the methodology to carvone the resulting compound obtained was 3-ethynyl-2-methyl-4-(1-methyl-1-ethenyl)-9-(1-methyl-1-ethenyl)bicyclo(4:4:0)decan-1-one. The final section concludes these investigations by describing the experimental procedures for all the reactions performed.
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