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Title: Ring expansion reaction via homolytic pathways
Author: Robertson, Jeremy
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1990
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The preparation of carbocyclic medium rings by two electron processes is reviewed with particular reference to the synthesis of natural products. The formation of medium rings by oxidative and homolytic methods is also reviewed. The synthesis and behaviour of both cis- and tran- ring expansion precursors is described. The 1,4-addition of tributylstannyl lithium to a range of cyclic α,β-unsaturated ketones was performed and procedures found whereby the so-formed enolates could be alkylated with a variety of electrophiles. Using these procedures a range of trans- ring expansion precursors were obtained in moderate to good yield. By the 1,4-addition of tributylstannyl lithium to 2-(ω-phenylselenoalkyl)-cyclohexenones, followed by enolate quenching with either water or methyl iodide, a range of cis- ring expansion precursors were produced. Homolytic ring expansion by either one, three, or four carbon atoms was shown to be possible, producing, respectively, seven, nine, or ten membered functionalised cycloalkenones in high yield except in cases where intramolecular reductive elimination was also possible. Attempts to extend this methodology to the synthesis of exomethylene cycloalkanones is described. The 3-tributylstannyl-3-(ω-phenylselenoalkyl)-cyclohex-2-enone precursors were found not to be successful substrates for ring expansion. The regiospecific alkylation of 2-(tributylstannylmethyl)-cyclohexanone with l-chloro-4-iodo-butane, followed by conversion of the chloride moiety to iodide led to a precursor which, on exposure to homolysis conditions, fragmented to produce the desired exomethylene cyclodecanone in high yield. Work directed towards the synthesis of medium ring cycloalkynones is described. Procedures were developed whereby 2-alkylated cyclohexan-l,3-dione derivatives could be obtained cleanly and in excellent yield on a large scale. The conversion of these derivatives to potential cycloalkynone precursors is described. It is shown that the products obtained after exposure of these precursors to homolysis conditions could, in principle, be derived from the putative cycloalkynones and mechanisms are suggested to explain the formation of these compounds. The homolytic ring expansion reaction was also performed on a substrate possessing an acyl radical precursor in the hope that a medium ring 1,2-dione would be produced. The synthesis of this substrate and its behaviour towards ring expansion is described. It is shown that, again, radical reaction was successful (to the medium ring dione) however subsequent reactions of this product led to the isolation and characterisation of a number of compounds . Attempts to extend this methodology to the synthesis of the natural products curdione and neocurdione is also described. Model reactions with 2,6-dimethylcyclohex-2-enone as the 1,4-addition precursor and 1,4-di-iodobutane as the electrophile led to a ring expansion substrate which fragmented to two ring contracted isomeric compounds in addition to the ring expanded material. Approaches to the preparation of suitable electrophiles for the natural product synthesis are described and their proposed use in subsequent conversion to curdione and neocurdione given.
Supervisor: Adlington, R. M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Ring formation (Chemistry) Chemistry, Organic Biochemistry