A Novel Asymmetric [2+2] Cycloaddition and Its Application to the Total Synthesis of 1233A

Dymock, Brian William (1997) A Novel Asymmetric [2+2] Cycloaddition and Its Application to the Total Synthesis of 1233A. PhD thesis, University of Glasgow.

Abstract

The first enantioselective [2+2] cycloaddition of aldehydes with (trimethylsilyl)ketene is discovered and developed using chirally modified Lewis acids. In order to demonstrate the utility of the new methodology, the total synthesis of the cholesterol biosynthesis inhibitor 1233A was undertaken. Background biochemistry on cholesterol biosynthesis and coronary heart disease is discussed followed by previous syntheses of the target molecule. The stereoselective synthesis of 1233A was completed using four key steps: (i) a cobalt semicorrin catalysed enantioselective reduction of an alpha,beta-unsaturated ester; (ii) a copper-mediated coupling of a vinyl iodide with a vinyl stannane; (iii) a novel [2+2] cycloaddition of an aldehyde with (trimethylsilyl)ketene and (iv) a beta-lactone aldol-type reaction quenching with carbon dioxide to install the final carbon of 1233A.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Philip J Kocienski
• Keywords: Organic chemistry
• Date of Award: 1997
• Depositing User: Enlighten Team
• Unique ID: glathesis:1997-75861
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 17:42
• Last Modified: 19 Nov 2019 17:42
• URI: https://theses.gla.ac.uk/id/eprint/75861