Studies Of The Mechanism Of Ring-opening Of Epoxides Promoted By Hot Water And The Cationic-π Cyclization Of2,3-oxidosqualene

The thesis contains two sections.In chapter one, we studied the mechanism of ring-opening of epoxides in hot water. Since Breslow et al observed an exceptional acceleration of the Diels-Alder reaction in water in1980, the use of water as a catalyst in organic reactions has attracted great attention from chemists. Rate-enhancing effects were widely observed in organic reactions operated in pure water and these reactions can be summarized into four types:(1) the in-water hydrogen bond catalysis:one or more water molecules activate reactants by forming hydrogen bonds with them;(2) the on-water hydrogen bond catalysis:one or more water molecules form hydrogen bonds with reactants at the interface between water and organic reactants and activate the reactants (it was proposed that there are more free dangling OH groups capable of forming hydrogen bonds at the interface than in bulk water);(3) the Brφnsted acid/base catalysis in high-temperature water (temperature between200-370℃):water can act as an acid, base, or dual acid/base catalyst as the self-ionization of water enhances at high temperatures;(4) the hydrophobic interaction between water and nonpolar organic reactants:the nonpolar segments of reactants are brought together in the transition state by the hydrophobic interaction between water and organic reactants. In2008we reported hot water promoted ring-opening of epoxides and aziridines and hot water was proposed as a Bransted acid catalyst within. In chapter one, we studied hydrolysis of (-)-a-pinene oxide in hot water and also the mechanism of racemization of the initially formed major product trans-(-)-sobvevol.Then we studied the effects of HCl’s concentration, the reaction temperature, the addition of organic co-solvent, and the concentration of the solute to the racemization of trans-(-)-sobrerol and proposed that several roles of water played in the reaction:(1) water participates in the elementary reaction as a reactant and as a product;(2) water is the source of H3O+which catalyzes the SN1solvolysis reaction of trans-(-)-sobrerol;(3) water acts as a very polar solvent stabilizing the carbocation intermediate formed in the reaction. Further investigation of the application of the reaction showed that the racemization or1,3-rearrangement of other allylic alcohols could efficiently proceed in hot water. Then we reported an efficient hydrolytic kinetic separation of trans/cis-(R)-(+)-limonene oxides in1:1mixed solvent of water and1,4-dioxane without additional catalyst. trans-(R)-(+)-Limonene oxide was recovered in high yield (77%) and high purity (de>98%). This method was superior to the existing methods for not using additional catalysts, high yield and high purity of trans-(R)-(+)-limonene oxide recovered and relatively fast reaction rate. This discovery again suggested that hot water can act as a mild acid catalyst to promote organic reactions. In depth1H NMR studies of hydrolysis of6,7-epoxygeranyl acetate in D2O and kinetic studies of hydrolysis of epoxides with different aqueous solubilities were done and we proposed that the ring-opening of epoxides in hot water was not "On Water"-catalyzed but was actually a "In Water"-catalyzed reaction. Then we reported an efficient methodology for ring-opening of extremely hydrophobic epoxides in mixture solvent of water and1,4-dioxane without the use of additional acid or base catalyst. Other nucleophiles such as amines, sodium azide and thiophenol could also effectively open1-dodecene oxide in the same system, yielding the corresponding products.In chapter two we studied the cationic-π cyclization of2,3-oxidosqualene. Cationic-π cyclization provides an efficient method for constructing polycyclic compounds. We tried cyclization of2,3-oxidosqualene in water or1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The cyclization raction could not take place in pure water while squalene1,2-diol was obtained when equal volumn of1,4-dioxane was added. Tricyclic product14-epithalinaol was obtained with15%yield when SDS (20mol%) and PTSA (20mol%) were added to hot water. In HFIP, the cyclization of2,3-oxidosqualene reacted at room temperature and formed major products14-epithalinaol and camelliol. The yield of14-epithalinaol was increased to39%in the optimized reaction condition which was higher than Lewis acid catalyzed the same transformation.