The development and application of organocatalytic asymmetric epoxidation

Bartlett, Chris (2011) The development and application of organocatalytic asymmetric epoxidation. Doctoral thesis, University of East Anglia.

Download (11MB) | Preview


    Epoxides are widely encountered within organic and biological chemistry, being
    present in many secondary metabolites and pharmaceuticals. In addition, the
    unique functionality of the epoxide has been exploited to facilitate the synthesis of
    many organic molecules. A particularly attractive way to stereoselectively epoxidise
    a substrate is to employ an organocatalytic system. Our group has been actively
    pursuing research in this area for over a decade and we have developed several
    catalytic systems capable of excellent stereocontrol in the epoxidation of alkene
    substrates. In considering possible refinements to catalyst structure, we targeted
    two development paths: i) variation of the dihedral angle Φ within the atropos
    azepinium systems - shown by Lacour to strongly influence the levels of
    stereoinduction,1 and ii) introduction of a substituent α- to the iminium nitrogen,
    which we envisaged would also influence the stereochemical outcome of any
    process occurring at the catalytically active centre.
    The application of the combined optimisations to existing catalyst frameworks
    allowed us to create a second generation of catalyst that was capable of furnishing
    epoxides in ees of up to 97% for tri-substituted unfunctionalised alkenes. We
    observed a tangible improvement upon the previous generation, and, in
    explanation, we offer an in-depth discussion on the influence of α-substitution on
    the ratio of sp2N-sp3C rotamers, and the importance of that ratio on the improved
    enantiocontrol. As part of an extended research program within our group, we also
    report the emergence of atropisomerism of the traditionally tropos sp2C-sp2C axis
    contained within biphenyl systems, presumably caused by efficient stereochemical
    relays mediated by the α-substituent.
    Lastly, we were able to successfully apply our methodology in the
    enantioselective total synthesis of (+)-scuteflorin A.2,3 The key epoxidation step
    proceeded in 99% ee and 99% yield, as part of a 7-step sequence that was
    completed with a 14.3% overall yield.
    1. R. Novikov, G. Bernardinelli, J. Lacour, Adv. Synth. Catal., 2009, 351, 596.
    2. J. Li, Y. Ding, X. –C. Li, D. Ferreira, S. Khan, T. Smillie, I. A. Khan, J. Nat. Prod., 2009, 72, 983
    3. C. J. Bartlett, D. Day, Y. Chan, S. M. Allin, M. J. McKenzie, A. M. Z. Slawin, P. C. B. Page, J. Org. Chem., 2012, 77, 772.

    Item Type: Thesis (Doctoral)
    Faculty \ School: Faculty of Science > School of Chemistry
    Depositing User: Mia Reeves
    Date Deposited: 20 Dec 2012 10:22
    Last Modified: 20 Dec 2012 10:22

    Actions (login required)

    View Item