Cyclisation desymmetrisation reactions of cyclohexa-1,4-dienes

• Main Author: El-Sayed, Nahed Nasser Eid
• Published: Cardiff University 2006
• Subjects: 547.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.583900

This thesis describes different strategies to desymmetrise 1,4-cyclohexadiene derivatives with concomitant formation of a quaternary stereogenic centre. Chapter 1 gives a brief overview of the previous desymmetrisation and diastereotopic group selection processes of 1,4-cyclohexadiene derivatives. Chapter 2 describes the initial model studies for the formation of the quaternary stereogenic centre using achiral cyclohexa-1,4-dienone derivatives. This was developed to permit stereoselective formation of a quaternary stereogenic centre using a chiral sulfinyl group as the stereodirecting influence during the cyclisation step. This proceeded with acceptable levels of discrimination between the two diastereotopic double bonds. Chapter 3 outlines attempts to improve the level of diastereoselectivity obtained under the influence of the sulfinyl group by synthesising a range of different compounds having only carbon atoms in the tether. Chapter 4 describes the desymmetrisation of the two diastereotopic double bonds of derivatives of cyclohexa-1,4-diene using free-radical methodology. The sense and level of the diastereoselectivity is dependent on the protecting group used. Application of this methodology toward natural product synthesis has been described. Chapters 5 describes the desymmetrisation of the two diastereotopic double bonds of 1,4-cyclohexadiene derivatives using the Prins cyclisation reaction. This approach afforded an easy and stereocontrolled access to fused tetrahydropyrans and tetrahydrofurans depending on the reaction conditions employed. The stereochemical outcome of all of these reactions can be rationalised by a single transition state model.