This thesis details investigations into two modes of organocatalytic enolate generation and reactivity. The first is the addition of chiral NHCs to a ketene to form an azolium enolate. Investigations into three different electrophiles within this system will be discussed. The second catalytic system investigated is the formation of a C1-ammonium enolate through the addition of chiral isothioureas to activated carboxylic acids. Studies on one electrophile within this system will be discussed. Chapter 2 investigates the use of bespoke C2-symmetric NHCs in the asymmetric Staudinger reaction: the formal [2+2] cycloaddition between ketenes and imines. A chiral relay mechanism was proposed and experimentally validated with β-lactams prepared in good yields (up to 85%) and moderate enantioselectivity (up to 61% ee). Chapter 3 describes the asymmetric formal [4+2] cycloaddition between alkylarylketenes and γ-substituted-β,γ-unsaturated α-ketocarboxylates. A substrate dependant switch in diastereoselectivity was observed with γ-aryl α-ketocarboxylates giving preferentially the syn-dihydropyranones (up to 70:30 dr syn:anti, up to 98% ee syn) and γ-alkyl α-ketocarboxylates giving preferentially the anti-dihydropyranones (up to 18:82 dr syn:anti, up to 75% ee anti, 97% ee syn). Chapter 4 illustrates the extension of the methodology described in Chapter 3 to include γ-substituted-β,γ-unsaturated α-ketophosphonates. Once more, a substrate dependant switch in diastereoselectivity was observed with γ-aryl α-ketophosphonates giving preferentially the syn-dihydropyranone-phosphonates (up to 72:28 dr syn:anti, up to 98% ee syn) and γ-methyl α-ketophosphonate giving preferentially the anti-dihydropyranone-phosphonates (20:80 dr syn:anti, 71% ee anti, 90% ee syn). Within this system it is also possible to generate the alkylarylketenes in situ with no loss in stereoselectivity but with typically improved yield when compared with the corresponding two-step procedure. Chapter 5 describes the activation of arylacetic acids via the formation of a mixed anhydride followed by C1-ammonium enolate generation with a chiral isothiourea. Asymmetric Michael addition and lactonisation with γ-substituted-β,γ-unsaturated α-ketophosphonates gave the corresponding anti-dihydropyranone-phosphonates (up to 89:11 dr anti:syn, up to 97% ee anti). More conveniently however, in situ ring opening with MeOH gave di-esters with excellent stereocontrol (up to >98:<2 dr anti:syn, up to 99% ee anti) and which can be readily derivatised.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:574825 |
| Date | January 2013 |
| Creators | Leckie, Stuart M. |
| Contributors | Smith, Andrew D. |
| Publisher | University of St Andrews |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10023/3622 |
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