Heterogeneous enantioselective epoxidation catalyzed by Mn(salen) complexes grafted onto mesoporous materials by phenoxy group

Three chiral Mn(salen) complexes were immobilized into different mesoporous material via phenoxy group by a simplified method and they show high activity and enantioselectivity for asymmetric epoxidation of various substituted unfunctional olefins. The heterogeneous Mn(salen) catalysts show comparable ee values for asymmetric epoxidation of styrene and 6-cyano-2,2-dimethylchromene and much higher ee values for epoxidation of a-methylstyrene (heterogeneous 79.7% ee versus homogeneous 26.4% ee) and cis-beta-methylstyrene (heterogeneous 94.9% ee versus homogeneous 25.3% ee for cis-epoxide) than the homogeneous catalysts. These heterogeneous catalysts also remarkably alter the cis/trans ratio of epoxides for asymmetric epoxidation of cis-beta-methylstyrene (heterogeneous 21 versus homogeneous 0.38). The axial tether group does not make a big effect on ee values and the increase in ee value and change in cis/trans ratio are mainly attributed to the axial immobilization mode and the support effect of heterogeneous catalysts. The catalysts keep constant ee values for the recycle tests of eight times for asymmetric epoxidation of a-methylstyrene. And several possibilities were proposed to elucidate the difference in ee values of heterogeneous catalysts from homogeneous catalysts. (c) 2005 Elsevier B.V. All rights reserved.

Towards the enantioselective synthesis of Plakortide P and its application to the development of drugs for the treatment of Chagas disease

The primary focus of this thesis was the asymmetric peroxidation of α,β-unsaturated aldehydes and the development of this methodology to include the synthesis of bioactive chiral 1,2-dioxane and 1,2-dioxalane rings. In Chapter 1 a review detailing the new and improved methods for the acyclic introduction of peroxide functionality to substrates over the last decade was discussed. These include a detailed examination of metal-mediated transformations, chiral peroxidation using organocatalytic means and the improvements in methodology of well-established peroxidation pathways. The second chapter discusses the method by which peroxidation of our various substrates was attempted and the optimisation studies associated with these reactions. The method by which the enantioselectivity of our β-peroxyaldehydes was determined is also reviewed. Chapters 3 and 4 focus on improving the enantioselectivity associated with our asymmetric peroxidation reaction. A comprehensive analysis exploring the effect of solvent, concentration and temperature on enantioselectivity was examined. The effect that different catalytic systems have on enantioselectivity and reactivity was also investigated in depth. Chapter 5 details the various transformations that β-peroxyaldehydes can undergo and the manipulation of these transformations towards the establishment of several routes for the formation of chiral 1,2-dioxane and 1,2-dioxalane rings. Chapter 6 details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.

Assembly intermediates in polyketide biosynthesis; enantioselective syntheses of beta-hydroxycarbonyl compounds

A versatile approach for the enantioselective synthesis of functionalised beta-hydroxy N-acetylcysteamine thiol esters has been developed which allows the facile incorporation of isotopic labels. It has been shown that a remarkable reversal of selectivity occurs in the titanium mediated aldol reaction of the acyloxazolidone intermediate using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The aldol products are valuable intermediates in the synthesis of 4-hydroxy-6-substituted gamma-lactones.

Isolation and characterisation of bacterial strains containing enantioselective DMSO reductase activity: application to the kinetic resolution of racemic sulfoxides

The kinetic resolution of racemic sulfoxides by dimethyl sulfoxide (DMSO) reductases was investigated with a range of microorganisms. Three bacterial isolates (provisionally identified as Citrobacter braakii, Klebsiella sp. and Serratia sp.) expressing DMSO reductase activity were isolated from environmental samples by anaerobic enrichment with DMSO as terminal electron acceptor. The organisms reduced a diverse range of racemic sulfoxides to yield either residual enantiomer depending upon the strain used. C. braakii DMSO-11 exhibited wide substrate specificity that included dialkyl, diaryl and alkylaryl sulfoxides, and was unique in its ability to reduce the thiosulfinate 1,4-dihydrobenzo-2, 3-dithian-2-oxide. DMSO reductase was purified from the periplasmic fraction of C. braakii DMSO-11 and was used to demonstrate unequivocally that the DMSO reductase was responsible for enantiospecific reductive resolution of racemic sulfoxides.

Ionic Liquid Effect on the Reversal of Configuration for the Magnesium(II) and Copper(II) Bis(oxazoline)-Catalysed Enantioselective Diels-Alder Reaction

Ionic liquids have been used to support a range of magnesium-and copper-based bis(oxazoline) complexes for the enantioselective Diels-Alder reaction between N-acryloyloxazolidinone and cyclopentadiene. Compared with reaction performed in dichloromethane or diethyl ether, an enhancement in ee is observed with a large increase in reaction rate. In addition, for non-sterically hindered bis(oxazoline) ligands, that is, phenyl functionalised ligands, a reversal in configuration is found in the ionic liquid, 1-ethyl-3-methylimidazolium bis[(trifluoromethanesulfonyl)imide], compared with molecular solvents. Supported ionic liquid phase catalysts have also been developed using surface-modified silica which show good reactivity and enantioselectivity for the case of the magnesium-based bis(oxazoline) complexes. Poor ees and conversion were observed for the analogous copper-based systems. Some drop in ee was found on supporting the catalyst due a drop in the rate of reaction and, therefore, an increase in the contribution from the uncatalysed a chiral reaction.

Azaarene cis-dihydrodiol-derived 2,2 '-bipyridine ligands for asymmetric allylic oxidation and cyclopropanation

Biphenyl dioxygenase-catalysed cis-dihydroxylation of 2-chloroquinoline, 2-chloro-3-methylquinoline and 2-chloro-6-phenylpyridine substrates yielded the corresponding enantiopure cis-dihydrodiols; enantiopure 2,2'-bipyridines, synthesised in four steps from 2-chloroquinoline, proved to be efficient chiral ligands in catalytic asymmetric allylic oxidation and cyclopropanation reactions of alkenes.

Ligand differentiated complementary Rh-catalyst systems for the enantioselective desymmetrization of meso-cyclic anhydrides

Two distinct systems for the rhodium-catalyzed enantioselective desymmetrization of meso-cyclic anhydrides have been developed. Each system has been optimized and are compatible with the use of in situ prepared organozinc reagents. Rhodium/PHOX species efficiently catalyze the addition of alkyl nucleophiles to glutaric anhydrides, while a rhodium/phosphoramidite system is effective in the enantioselective arylation of succinic and glutaric anhydrides.

Enantioselective Rhodium-Catalyzed Alkylative Desymmetrization of 3,5-Dimethylglutaric Anhydride

A rhodium-catalyzed enantioselective cross-coupling of sp³ organozinc reagents and 3,5-dimethylglutaric anhydride has been developed to afford the corresponding products, syn-deoxypolypropionates, in excellent yields and enantioselectivities. This reaction has been developed so that both commercially available and in situ prepared organozinc reagents are competent coupling partners.

Enantioselective formal total synthesis of the Dendrobatidae frog toxin, (+)-pumiliotoxin B, via O-directed alkyne free radical hydrostannation

Herein we describe our application of the O-directed free radical hydrostannation of disubstituted alkyl-acetylenes (with Ph3SnH and Et3B) to the (+)-pumiliotoxin B total synthesis problem. Specifically, we report on the use of this method in the synthesis of the Overman alkyne 8, and thereby demonstrate the great utility of this process in a complex natural product total synthesis setting for the very first time. We also report here on a new, stereocontrolled, and highly practical enantioselective pathway to Overman's pyrrolidine epoxide partner 9 for 8, which overcomes the previous requirement for use of preparative HPLC to separate the 1:1 mixture of diastereomeric epoxides that was obtained in the original synthesis of 9.