Non-aqueous iminium salt mediated catalytic asymmetric epoxidation

Abstract

Citation: PAGE et al, 2006. Non-aqueous iminium salt mediated catalytic asymmetric epoxidation. Tetrahedron 62 (28), pp. [6607][6608][6609][6610][6611][6612][6613] Additional Information: Abstract: A range of substituted dihydroisoquinolinium salts has been tested in the catalytic asymmetric epoxidation of simple alkenes using our newly developed non-aqueous conditions employing tetraphenylphosphonium mono-peroxysulfate (TPPP) as oxidant, giving ees of up to 97%.In 1976 it was established that oxaziridinium salts are extremely reactive reagents for oxygen transfer to nucleophilic substrates. 2 Since then, there has been significant interest in developing effective iminium salt catalysts for epoxidation of olefins. 3 The primary oxidant used is oxone, and the reactions are usually performed at 0 ºC in the presence of a base. In addition to an organic solvent, usually acetonitrile, water is an essential cosolvent, required in order to provide sufficient oxone solubility.We have previously described our approach to new types of cyclic chiral iminium salts, functionalized with chiral units at the nitrogen atom. 4 These enantiomerically pure iminium salts have been successfully employed in the catalytic asymmetric epoxidation of unfunctionalized alkenes, the dioxane-derived catalysts 1-5 giving ees of up to ca 60%, 5 catalyst 6 giving ees of up to 97%, 6 and catalyst 7 ees of up to 95%. The standard conditions employed by ourselves and others in epoxidation reactions catalysed by iminium salts involve the use of oxone as stoicheiometric oxidant, a base (2 mol eq of Na 2 CO 3 per eq of oxone) and water / acetonitrile as solvent mixture.The principal limitation of this system is the restricted range of temperatures at which the epoxidation can be performed (ca -5 °C to ambient). The upper temperature limit results from the relatively fast decomposition of oxone in basic media at room temperature. The lower limit is determined by the requirement for an aqueous solution (the normal ratio of solvents is (CH 3 CN:H 2 O; 1:1); aqueous acetonitrile freezes at -8 °C.An additional drawback arising from the dependency on oxone is the large quantity of inorganic salt byproducts produced in the reaction. We were pleased to find that the use of TPPP in place of oxone induces efficient epoxidation in organic solvents in the absence of water, and furthermore that the presence of base is now not required; indeed, addition of base actually suppresses the epoxidation process. Use of this oxidant also enables greater scope for reaction monitoring and analysis, as water is no longer required. Reactions can be carried out at low temperature, and, when carried out in deuteriated solvent, monitored by NMR spectroscopy. We describe herein the catalytic asymmetric epoxidation of several unfunctionalized alkenes using catalysts 2-6 under the new anhydrous conditions, employing (TPPP) as stoichieometric oxidant. The catalysts were first tested in the asymmetric epoxidation of 1-phenycyclohexene at varying temperatures using TPPP in dichloromet...