Year

1997

Degree Name

Doctor of Philosophy

Department

Department of Chemistry

Abstract

This thesis presents a number of new applications of racemic and optically active sulfoximines to diastereoselective and asymmetric synthesis. In the first Chapter a review is made of the preparation of racemic and optically active sulfoximines and their applications to organic synthesis. The general aims of this project are presented.

In Chapter two, our attempts to develop an asymmetric synthesis of the insect pheromone, Lardolure are presented. In the first step, the Michael addition reaction of lithiated N-tosyl S-allyl S-phenyl sulfoximine with 3-penten-2-one was undertaken. This reaction gave the 1,4-α adduct with good diastereoselectivity (85 : 15). In the second step, the diastereoselective reduction of γ-keto allylic sulfoximines with DIBAL-H was explored. The stereochemistry of both the Michael adduct and the reduction products were determined by a combination of single crystal X-ray structural analysis and NMR spectroscopy. Further synthetic studies towards the preparation of Lardolure were not pursued since the desired Michael addition of the O -protected γ-alcohol allylic sulfoximines with 3-penten-2-one did not occur.

A novel palladium(O) catalysed rearrangement of primary and secondary allylic sulfoximines to their isomeric allylic sulfinamides, which upon subsequent base hydrolysis gave the corresponding N-protected allylic amines, is reported in Chapter three. This facile rearrangement was shown to be highly efficient and regioselective. When optically active secondary allylic sulfoximines were employed, these rearrangements resulted in the formation of chiral N-protected allylic amines in high enantiomeric purities. The mechanism and the stereochemical outcomes of these rearrangement reactions are also discussed.

In Chapter four, the stereochemistry and diastereoselectivity of the Michael additions of α-lithiated sulfoximines with enones under kinetically controlled conditions are reported. The initially formed anionic Michael adducts were found to undergo intramolecular displacement of the sulfonimidoyl group at rt to give cyclopropanes. The reactions of α-lithiated sulfoximines with acyclic enones gave cyclopropanes in a highly efficient and diastereoselective manner. Optically active versions of these sulfoximines gave cyclopropanes in high enantiomeric purities. The absolute stereochemistries of the Michael adducts were determined from single crystal X-ray analysis and the stereochemistry of the cyclopropanes were determined by ID and 2D NMR spectroscopy.

An one-pot method of preparation of bicyclo[2.2.1]heptanones and bicyclo[2.2.2]octanones via the Michael addition of five and six membered cyclic enones with lithiated S-allyl S-phenyl sulfone at rt was developed in Chapter five. When acyclic enones were employed then novel 3-cyclohexen-1-ols were obtained. The stereochemistry of these annulation products was determined by single crystal X-ray structural analysis and NMR spectroscopy.

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