Development and Application of the One-Pot Julia Olefination

Blakemore, Paul Richard (1999) Development and Application of the One-Pot Julia Olefination. PhD thesis, University of Glasgow.

Abstract

The influence of heterocycle, base and solvent on the recently reported one-pot Julia olefination was investigated. 1-Phenyl-1H-tetrazol-5-y1 (PT) sulfones emerged as a promising alternative to the previously reported benzothiazol-2-yl (BT) sulfones for use in the olefin synthesis. For both BT and PT systems an increase in solvent polarity resulted in a heightened trans selectivity for the synthesis of simple 1,2-disubstituted monoenes. However, only for the new PT variant was the stereochemical outcome also dependent on base counter cation. Potassium derivatives of PT sulfones react with saturated aldehydes in 1,2-dimethoxyethane (DME) to produce trans-1,2-disubstituted alkenes with excellent selectivity. A partial synthesis of vitamin D2 was achieved employing fragments derived from a new improved degradation procedure. Condensation of the sodium derivative of BT sulfone 230 with aldehyde 198 yielded 70% of vitamin D2 (163, 7E:Z = 72:28) after deprotection. The first total synthesis of the polyketide herboxidiene (233) was completed in 22 linear steps from cyclohexanone. Both BT and PT one-pot Julia methodologies were used at pivotal junctures in the synthesis. The new PT variant was employed to access a simple trans-1,2-disubstituted olefin (327) prior to subsequent Sharpless asymmetric dihydroxylation. The established BT technology was used to conjoin two late stage intermediates, 332 and 238, to yield 81% of the protected herboxidiene derivative 394 with 10E:Z = 91:9.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Philip Kocienski
• Keywords: Organic chemistry, Polymer chemistry, Chemical engineering
• Date of Award: 1999
• Depositing User: Enlighten Team
• Unique ID: glathesis:1999-74684
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 17:11
• Last Modified: 27 Sep 2019 17:11
• URI: https://theses.gla.ac.uk/id/eprint/74684