Lewis acid catalysed rearrangement of epoxides :a mechanistic study.
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
The Lewis acid catalysed rearrangement of optically active, deuterium labelled styrene oxide derivatives to aldehydes is studied experimentally and the mechanism is further elucidated by ab initio molecular orbital and density functional calculations. The Lewis acid catalysed rearrangement of styrene oxide derivatives is shown to occur via a carbocation intermediate. Opening of the epoxide ring occurs with rotation of the Lewis acid coordinated oxygen either towards or away from the aryl group to form either the cis or trans carbocation. Calculations indicate that conversion between the cis and trans cations will only occur via ring closure back to the epoxide. The selectivity for hydride migration is controlled by the preferred geometry of thc carbocation intemediate, specifically whether the C-O bond prefers to adopt an eclipsed confonnation relative to the adjacent cation substituent or whether the stabilisation of the cation is obtained from hyperconjugation of a terminal hydrogen to the cation centre. Chapter One contains a review of the relevant literature and the results of previous mechanistic studies into the Lewis acid catalysed rearrangement of epoxides are discussed. In Chapter Two, a methodology is developed to measure the relative amounts of hydrogen or deuterium in each position of the aldehyde produced by hydride or deuteride migration in the rearrangement of a styrene oxide derivative. The aldehyde product is reduced to an alcohol and reacted with a chiral acid chloride. The resulting ester can be analysed by III NMR in the presence of Yb(hfC)3 or Eu(hfc)3 chiral shift reagents so that the full stereochemical course of the hydride migration can be determined. Chapter Three describes the BF3.OEt2 and LiC104 catalysed rearrangement of deuterated analogues of optically active p-methylstyrene oxide. It is shown that the rearrangement reaction must proceed at least in part via a carbocation intermediate. The results are analysed by the method of Fujimoto and show that for both the BF3.OEt2 and LiC104 catalysed reactions, the majority of the reaction occurs by epoxide opening with rotation of the Lewis acid coordinated oxygen towards the aromatic group (66% : 34% and 57% : 43% respectively). This is in contrast to previous studies where it was assumed that this reaction pathway would not occur. In the LiC104 catalysed reaction, where epoxide opening occurs with rotation of the oxygen away from the aromatic group, hydride/deuteride migration occurs almost exclusively with inversion of configuration; while in the other reactions hydride migrates to an equal extent with inversion or retention of configuration. In Chapter Four, deuterated fluorohydrin is synthesised from deuterated p-methylstyrene oxide and converted to aldehyde with an excess of BF3.OEh in order to determine whether fluorohydrin is an undetected intermediate in the BF3.OEt2 catalysed rearrangement of p-methyl styrene oxide. It is shown the conversion of fluorohydrin to aldehyde occurs by a nearly concerted mechanism, in contrast to the rearrangement of p-methylstyrene oxide to aldehyde which occurs via a carbocation. The rates of the two reactions are also not compatible and fluorohydrin is shown not to be an intem1ediate in the reaction. Chapter Five describes the LiC104 and BF3.OEt2 catalysed rearrangement of deuterated optically active m-methoxystyrene oxide. The selectivity for hydride migration observed is consistent with the mechanism developed for the rearrangement of p-methylstyrene oxide in chapter 3. More of the reaction goes by epoxide opening with rotation towards the aryl group for the destabilised m-methoxy compared to the p-methyl substituted epoxide. Chapter Six describes a computational investigation into the BF3 and Li+ catalysed rearrangement of various styrene oxide derivatives. Stationary points are calculated on the potential energy surfaces for the reactions and the stationary points are characterised by vibrational frequency calculations. Two confom1ations of carbocation are found on the Li+ catalysed reaction surface. One structure has the C-O bond eclipsed with the adjacent C- aryl bond and both terminal hydrogens equally aligned for migration. The other cation minimum shows one terminal hydrogen already in hyperconjugation with the carbocation p-orbital, making it more likely to migrate. It is also shown that rotation of the oxygen towards and away from the aryl group can be considered separately when analysing the reaction. Chapter Seven describes a computational study into the BF3 catalysed rearrangement of 2,3,3-trimethyl-1-butene oxide. The results are combined with a previous computational and experimental studies and it is shown that the reaction fits with the mechanism developed to explain the results of the rearrangement of styrene oxide derivatives. The synthesis of chiral deuterated, 1-octene oxide and 2,3,3-trimethyl-1-butene oxide and the attempted synthesis of p-methoxystyrene oxide is described in Chapter Eight. Chapter Nine describes an investigation into acetate participation in epoxide rearrangement reactions. In this study epoxide rearranged to ketone and no participation of acetate in a cyclisation reaction was observed. The final chapter details the experimental procedures used in the preceding chapters.