The Stereoselective Synthesis of Functionalised Cyclobutanols via the Samarium(II)-Mediated Cyclisation of Unsaturated Aldehydes

Johnston, Derek (2002) The Stereoselective Synthesis of Functionalised Cyclobutanols via the Samarium(II)-Mediated Cyclisation of Unsaturated Aldehydes. PhD thesis, University of Glasgow.

Abstract

Samarium(II) iodide continues to prove an incredibly versatile reagent in organic synthesis. gamma,delta-Unsaturated aldehydes having a fully substituted centre in the alpha- position, have been prepared from substituted gamma-butyrolactones and undergo efficient 4-exo-trig cyclisation on treatment with samarium(II) iodide to give functionalised cyclobutanols. In all cases when the olefin has E-geometry, cyclisation occurs with complete diastereocontrol to give anti-cyclobutanol products. The importance of olefin geometry on the stereochemical outcome in the cyclisation is discussed. The stereochemistry of the products has been confirmed by NOE and X-ray crystallographic studies. In the cyclisation of substrates having a third substituent on the double bond, alpha- to the ester, significant control is achieved at the third newly formed stereocentre lying outside the ring. The origin of the stereoselectivity at this third centre and its marked dependence on cosolvent are discussed. The application of this novel methodology in an approach to the core of pestalotiopsin A is also discussed. Pestalotiopsin A is a structurally unique caryophyllene-type sesquiterpene which has shown immunosuppressive activity and cytotoxicity in preliminary assays. Our approach is based upon our samarium(II)-mediated 4-exo-trig cyclisation and a trans-lactonisation process triggered by the addition of alkylytterbium reagents to a cyclobutanone intermediate.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: David J Procter
• Keywords: Organic chemistry
• Date of Award: 2002
• Depositing User: Enlighten Team
• Unique ID: glathesis:2002-76265
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 16:12
• Last Modified: 19 Nov 2019 16:12
• URI: https://theses.gla.ac.uk/id/eprint/76265