The oxidation of [alpha]-farnesene : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University

Abstract

Autoxidation products of the sesquiterpene α-farnesene 1 increase rapidly in apples during cold storage and are believed to play an important role in the production of the cold storage disorder, superficial scald. The site selectivity of the oxidation of α-farnesene was investigated with a variety of useful reagents for photochemical allylic oxidation, hydroxylation and epoxidation. Oxidation products 33-47 were isolated and characterised. The synthesis of conjugated trienes and related oxidation products of α-farnesene 1, principally from the epoxides of α-farnesene, is described. Base-promoted ring opening of 6,7-epoxide 44 by the mixed base potassium tert-butoxide / lithium disopropylamide afforded the conjugated triene 3 whilst the 3,4-epoxide 45 afforded triene 50. In contrast, 10,11-epoxide 43 failed to undergo epoxide ring opening; rearranging instead to the conjugated triene epoxide 51. Base-promoted ring opening of bis-epoxide 46 afforded trienol epoxide 56 at -30°C, whilst cyclisation to tetrahydrofurans 55a and 55b occurred at room temperature. Photosensitised oxidation of 10,11-epoxide 43 followed by in situ treatment with acid gave the cyclic peroxide 4 and upon reduction, tetrahydrofurans 55a and 55b. Bisallylic alcohol 61 was prepared by alkylation of 3-methylsulpholene 29 with geranial 59 followed by thermolysis. Trienes 3 and 4 have been isolated previously as autoxidation products of α-farnesene 1 and are implicated as the causal agents of the superficial scald of stored apples. The asymmetric dihydroxylation of α-farnesene 1 using the Sharpless ligands (DHQ)2- PHAL and (DHQD)2-PHAL was investigated. The isolation and characterisation of the 3,4-, 6,7- and 10,11-diols 41,42 and 114 as well as the tetraol 115 is described. High enantioselectivity and preferential addition to the 6,7-olefin was observed. The isomeric β-farnesene 2 showed a preference for reaction at the 10,11-position. The enantioselective synthesis of an apple aroma constituent, bicyclicacetal 17, is described. Asymmetric dihydroxylation of 6-methylhept-5-en-2-one 15 was carried out using the ligands (DHQ)2-PHAL and (DHQD)2-PHAL according to the method of Sharpless. Acid-catalysed cyclisation then afforded the required acetal 17 in high enantiomeric excess. Enantiomeric excesses were measured using chiral solvating agent 113 and/or synthesis of the corresponding Mosher ester derivatives, followed by 1H or 19F nmr.