New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

Examining current provision, practice and experience of initial teacher training providers in Ireland preparing pre service teachers for the inclusion of students with special education needs in physical education classes.

Research from an international perspective in relation to the preparation of pre service teachers in physical education and special educational needs indicates that initial teacher training providers are inconsistent in the amount of time spent addressing the issue and the nature of curricular content (Vickerman, 2007). In Ireland, research of Meegan and MacPhail (2005) and Crawford (2011) indicates that physical education teachers do not feel adequately prepared to accommodate students with Special Educational Needs (SEN) in physical education classes. This study examined initial teacher training provision in Ireland in the training of pre service physical education teachers in SEN. The methodology used was qualitative and included questionnaires and interviews (n=4). Findings indicated that time allocation (semester long modules), working with children with disabilities in mainstream settings (school or leisure centre based), lack of collaboration with other PETE providers (n=4) and a need for continued professional development were themes in need of address. Using a combined approach where the recently designed European Inclusive Physical Education Training (Kudlácěk, Jesina, & Flanagan, 2010) model is infused through the undergraduate degree programme is proposed. Further, the accommodation of hands on experience for undergraduates in mainstream settings and the establishment of inter institutional communities of practice, with a national disability research initiative, is essential to ensure quality adapted physical activity training can be accommodated throughout Ireland.