Wongtap, Hathaichanuk (1999) A radical approach to nitrogen heterocycles. PhD thesis, University of Warwick.

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Abstract

The generation of amidyl radical and carbon centred radicals using both tin hydride and non-tin hydride methods are described.
The effect of the nitrogen substituent upon the stereoselectivity of amidyl radical cyclisations onto the alkyl side chain using the tin hydride method was investigated The O-benzoyl hydroxamic acid derivatives were chosen as precursors for these radicals. The results indicated that the tram isomers were the major isomers from the cyclisation reaction. The greatest diastereoselectivity was found when the nitrogen substituent was a methoxy group. However, the cyclisations afforded low yields of the desired sample products due to the difficulty in removing the tin residues from the crude.
Amidyl radicals were also generated from cyclohexadienyl functionalised hydroxamide acid derivatives using peroxides as initiators. Due to the rapid reduction of the amidyl radical by hydrogen abstraction from the initial cyclohexadienyl system under these conditions, the cyclisations were not successful.
The atom transfer radical cyclisation of allyl trichloroacetate was investigated N- pentyl-2-pyridylmethanimine [164] was reported as an effective ligand in copper mediated cyclisation using Cu(I)Cl The reaction was optimised in order to investigate the effect of ligand concentration, of catalyst concentration, of substrate concentration, and of solvent It was found that two equivalents of ligand with CuCI provided the most effective catalyst while the use of 30mol% of catalyst was essential for the success of the cyclisation A lower yield of product was obtained if the amount of catalyst was lowered and this may be due to its gradual decomposition The reaction was best carried out at a concentration between 0.065 to 0.13M solution in order to suppress telomerisation processes and intermolecular addition and reduction processes due to hydrogen abstraction reactions At higher concentrations more telomers were obtained. In toluene solution, the CuCl-[164] catalyst system provided faster reactions when compared with the same reaction in acetonitrile solution.
The Cu(I)Cl-[164] was also used as an effective catalyst system for the atom transfer radical cyclisations of N-allyl trichloroacetamides. Intermolecular capture of cyclised radicals by a highly radicophilic reagent such as diphenyl diselenide was possible whereas the transfer of a cyano group by ethyl cyanoformate not. The cyclisation of tribromoacetamide derivatives using Cu(I)Br-[164] was also investigated. In addition, the effect of the structure of the ligand on the rate and diastereoselectivity of the cyclisation of N-allyl-N-tosyl dichloromethylacetamide was also studied The cyclisation afforded the trans isomer as the major product. Ligands with more bulky N-substituents gave slower cyclisations and smaller diastereomer excesses.
Finally, the synthesis of medium-size lactams was investigated. Unexpectedly, attempts to synthesis the bigger ring lactams failed completely. The precursors underwent [1,5] aromatic rearrangement instead of cyclisation. In addition, the intramolecular 1,5 hydrogen abstraction of the starting amide radicals afforded significant amounts of reduced products.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH):	Chemistry, Organic, Chemistry, Heterocyclic chemistry, Radicals (Chemistry), Heterocyclic compounds -- Synthesis, Organonitrogen compounds -- Synthesis
Official Date:	June 1999
Dates:	Date Event June 1999 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Clark, Andrew J.(Professor)
Sponsors:	Thailand.‏‎Krom Phatthanā læ Songsœ̄m Phalangngān
Extent:	viii, 246 leaves
Language:	eng

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