Title

The synthesis and reactivity of 1,5-dioxaspiro[3.2]hexanes

Date of Completion

January 2001

Keywords

Chemistry, Organic

Degree

Ph.D.

Abstract

A general synthesis of 1,5-dioxaspiro[3.2]hexanes is described. This was accomplished via epoxidation of 2-methyleneoxetanes with dry dimethyldioxirane. A study on the chemoselectivity of the epoxidation of the double bond of 2-methyleneoxetanes against that of an isolated alkene was undertaken and resulted in the exclusive epoxidation of the enol ether double bond. ^ The efficient access to 1,5-dioxaspiro[3.2]hexanes afforded us the opportunity of exploring the reactivity of these systems. Studies on their ring opening reactions with nucleophiles revealed an interesting dichotomy in reactivity. Most of the nucleophiles employed provided α-substituted, β-hydroxyketones in good yields. However, those nucleophiles that incorporated a Lewis acid produced 2,2-disubstituted oxetanes. ^ We were intrigued by the potential application of sequences derived from the mode of ring opening leading to α-substituted, β-hydroxyketones. The ease of manipulation of products of this reaction pathway into multifunctionalized compounds was fairly obvious. One class of natural products targeted was the glycosphingolipids, ubiquitous components of cell membranes, involved in virtually all aspects of cellular interactions. Herein, we demonstrate the utility of 3-amino-1,5-dioxaspiro[3.2]hexane in the formal synthesis of an analog of KRN7000, an α-galactosylceramide currently in clinical trials as a chemotherapeutic agent for the treatment of liver tumors. ^