New reactions of oxetanes

Abstract

This thesis describes the synthesis and new reactions of oxetan-3-ones. Chapter 1 gives an introduction to oxetanes and includes discussion of methods for their synthesis, their reactions, specifically those involving the use of oxetan-3-ones, and their relevance in medicinal chemistry and natural products. Chapter 2 begins with an introduction to multi-component reactions (MCRs) and moves on to describe our efforts in incorporating oxetanes into structurally diverse compounds using Passerini three-component reactions (P-3CRs) and Ugi four-component reactions (U-4CRs). A range of 3,3-disubstituted oxetanes are successfully made in 23-98% yield by reaction of oxetan-3-ones with various carboxylic acids and isocyanides. The synthesis of chiral 2-substituted oxetan-3- ones using the SAMP chiral auxiliary method is also demonstrated, specifically oxetan-3-one is converted into 2-benzyloxetan-3-one in 51% overall yield and 74% ee in three steps. Chapter 3 details our efforts towards the incorporation of the oxetane unit into tetrahydro-β-carbolines using the Pictet-Spengler reaction. Several oxetan-3-ones are demonstrated to take part in Pictet-Spengler reactions with tryptamine and tryptophan ethyl ester derivatives. The chemistry is successfully extended in azetidinones