Year

1994

Degree Name

Doctor of Philosophy

Department

Department of Chemistry

Abstract

This thesis investigates the application of chiral sulfoxides to the asymmetric synthesis of chiral amines and benzazepine alkaloids, the results are presented in four chapters.

In Chapter 1, the addition of the anions of methyl phenyl sulfoxide and the novel methyl 2-methoxy-l-naphthyl sulfoxide to nitrones was shown to be a diastereoselective process under kinetically controlled conditions. The stereochemistry of these adducts was determine by chemical correlation with known p-amino sulfoxides.

Chapter 2 is an extension of this method and describes the addition of lithiated methyl phenyl sulfoxide to oxaziridines. The relative stereochemistry of the major and minor adducts from these reactions was determined by 1H NMR spectroscopic analysis. A new method for the synthesis of oxaziridines by the oxidation of imines with Oxone® is also reported.

In Chapter 3, an attempt was made to extend this methodology to the synthesis of β-amino sulfoxide (7), from the addition of methyl phenyl sulfoxide to nitrile oxides, benzohydroximinoyl chlorides and nitriles, and then reduction of the products by either sodium triacetoxyborohydride or sodium cyanoborohydride. However the diastereoselection of these reductions was poor.

Chapter 4 deals with an attempt to solve the problems encountered with the synthesis of β-amino sulfoxide (2) in Chapters 1, 2, and 3. β-Keto 2- methoxy-1-naphthyl sulfoxides (1) were prepared and converted to β-amino sulfoxide (2) via a number of methods. These methods included reductive alkylation of (1) and the conversion of (1) to its β-sulfinyl enamine followed by diastereoselective reduction. Attempts to use the β-amino sulfoxide (2) for the synthesis of benzazepine alkaloids via a Pummerer type cyclization failed to give the expected product, however a novel rearrangement product was isolated and characterized.

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