New free-radical precursors and pathways
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A method of cataloguing sequential radical reactions according to the individual processes taking place has been described. The system has been used to illustrate the range and power of radical reactions in synthesis, in particular emphasising cascade reactions mediated by reagents that do not contain toxic tin. Of primary consideration were consecutive intramolecular processes, but annulation reactions, in which intermolecular additions precede cyclisations, were also discussed. An EPR and product analysis investigation into the radical reactions of aryl aldoxime esters and ethers is described. O-acyl derivatives of benzaldoxime, 2,4-dimethoxybenzaldoxime and 2,4,6-trimethoxybenzaldoxime underwent direct cleavage of the N-O bond on photolysis, forming an iminyl radical and an alkyl radical via decarboxylation. Synthesis of these precursors from the corresponding carboxylic acid was high yielding, and purification was usually simple. The radicals produced by this method underwent cyclisation when appropriate unsaturation was present. Use of carbon tetrachloride as solvent enabled synthesis of chlorinated products. We have shown that p-methoxyacetophenone acts as a sensitiser in these reactions. The formation of iminyl radicals enabled g-factors of alkyl radicals to be calculated simply in EPR experiments, while not interfering with the main spectrum. Cleavage of the N-O bond in O-alkyl arylaldoximes was much less efficient, and cannot be used as a synthetic method. Radical addition to the iminyl double bond was a more efficient process. The ability of cyclohexadienones to act as radical precursors was investigated. Preparations of suitable precursors were not efficient enough to enable the technique to be synthetically useful. 2-Allyl-2,4,6-trimethylcyclohexa-3,5-dien-l-one, 10a, and 4-allyl-2,4,6-trimethylcyclohexa-2,5-dien-l-one, 11a, expelled the allyl radical on reaction with the trimethylstannyl radical, as evidenced by EPR spectroscopy. 2-Benzyl-2,4,6 trimethylcyclohexa-3,5-dien-l-one 10b acted as a precursor to the benzyl radical, and toluene product was identified by GC/MS analysis. Samarium(II) iodide was shown to be a suitable reagent for performing radical annulation reactions. The cyclopentenol derivatives obtained in this study readily dehydrated, and in at least one case underwent thermal rearrangement. Tin based methods were shown to be much less suitable for annulations, while manganese(III) picolinate based annulations were not investigated due to low yielding precursor preparations. Radicals containing a boronic ester group have been characterised by EPR spectroscopy. The boronic ester group was shown to provide little stabilisation to an adjacent radical centre. The barrier to rotation around the C-B bond in unsymmetric radical 5b was determined as 2.9 ± 0.7 kcal mob1. Hydrogen abstraction from methylboronic ester 8 by the t-butoxyl radical was shown to not be facile, and homolytic substitution was competitive. Addition to vinylboronic ester 12 by nucleophilic radicals was efficient under EPR conditions. P-Bromoboronic esters are susceptible to homolytic substitution at the boron centre under certain conditions. At lower temperatures, bromine abstraction occurs readily.
Thesis, PhD Doctor of Philosopy
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