Abstract
The first project described in this thesis is the investigation of the rductive alkylation of γ-cyano-α,β-unsaturated enones 58 and 59 by sequential treatment with lithium naphthalenide and an alkylating agent. The reduction precursors 58 and 59 were individually synthesized starting with the Thorpe-Ziegler condensation of pimelonitrile and suberonitrile followed by acid hydrolysis of the ensuing cyano enamines. α-Cyano ketones 52 and 53 thus obtained separately were alkylated with allyl bromide in the presence of lithium hydride to give ketones 54 and 55 which were subsequently subjected to oxidation under Wacker conditions to give 1,4-diketones 56 and 57 respectively. Aldol condensation of diketones 56 and 57, under basic conditions with azeotropic removal of water, then gave enones 58 and 59 respectively. The reductive alkylation of γ-cyano-α,β-unsaturated enones 58 and 59 using an excess of benzyl bromide gave α,α,α‘-trialkylated ketones 60 and 61 in synthetically useful yields. Slight modification of reaction conditions also allowed the synthesis of mono-methylated ketone 62 in excellent yields after accounting for recovered starting material. In essence, we have developed a facile entry into highly functionalized bicyclic ketones which are otherwide difficult to access by convetional means. The latter part of this thesis describes our investigation into developing a more stereoselective entry into the known amino sulfide 90. Amino sulfide 90 was also converted to selenide 104 and spectroscopic analysis of a variety of its two-dimensional NMR spectra allowed the unequivocal assignment of the stereochemistry of selenide 104 and, by extension, amino sulfide 90. This result allowed us to predict the transition state of the amino-Cope reaarangement reacion with a certain degree of confidence.The details of our investigations are described in this thesis.