Phase-tag assisted synthesis of N-heterocycles using the Pummerer cyclisation

McAllister, Laura A (2004) Phase-tag assisted synthesis of N-heterocycles using the Pummerer cyclisation. PhD thesis, University of Glasgow.

Abstract

Linker strategies lie at the heart of solid phase organic synthesis and combinatorial chemistry. A new class of traceless linker cleaved using SmI2 has been developed previously within the group. This linker system was based on an oxygen link to resin. A novel multi-functional sulfur based linker which not only links the substrate to resin and allows traceless cleavage but also enables Pummerer cyclisation chemistry to be carried out at the point of attachment has been developed. Pummerer cyclisations are a powerful method for constructing carbocycles and heterocycles. The first Pummerer cyclisations on solid phase have been carried out in a convenient route to oxindoles which utilises a traceless sulfur link to resin. Bromoacetamides are immobilised using a benzyl thiol resin. Oxidation of the linking sulfur atom followed by Pummerer cyclisation and traceless cleavage using SmI2 gives the desired oxindole products in good yield and high purity. A variety of oxindoles bearing neutral, electron rich and electron deficient aromatic systems have been synthesised using our approach. Crucially, the sulfur link to resin remains intact throughout the cyclisation leaving the heterocyclic products immobilised. The link can therefore be used again to assist further on-resin modification of the product heterocyclic framework prior to cleavage. Fluorous thiols can be applied in a similar manner to solid supported thiols. Fluorous thiols can be used to introduce fluorous phase-tags, which when incorporated allow easy, convenient purification of the tagged compound using fluorous solid phase extraction (FSPE). Fluorous thiols have been applied in a new strategy for the fluorous phase synthesis of N-heterocycles. The sequence involves a fluorous phase, Pummerer cyclative capture strategy for rapid, one-pot construction of tagged, heterocyclic frameworks. The fluorous tagged heterocyclic frameworks can be modified using a variety of approaches including palladium catalysed cross-coupling reactions. Traceless removal of the phase tag with SmI2 leads to the desired heterocycle in high purity. FSPE is applied throughout the synthetic sequence to assist purification.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: David J Procer
• Keywords: Organic chemistry
• Date of Award: 2004
• Depositing User: Enlighten Team
• Unique ID: glathesis:2004-74052
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Sep 2019 15:33
• Last Modified: 23 Sep 2019 15:33
• URI: https://theses.gla.ac.uk/id/eprint/74052