Showing papers by "Rita G. Hazell published in 2000"

A Novel Catalytic and Highly Enantioselective Approach for the Synthesis of Optically Active Carbohydrate Derivatives

Abstract: A catalytic enantioselective inverse-electron demand hetero-Diels−Alder reaction of α,β-unsaturated carbonyl compounds with electron-rich alkenes catalyzed by chiral bisoxazolines in combination with Cu(OTf)2 as the Lewis acid is presented. The reaction of γ-substituted β,γ-unsaturated α-keto esters with vinyl ethers and various types of cis-disubstituted alkenes proceeds in good yield, high diastereoselectivity, and excellent enantioselectivity. The potential of the reaction is demonstrated by the synthesis of optically active carbohydrates such as spiro-carbohydrates, an ethyl β-d-mannoside tetraacetate, and acetal-protected C-2-branched carbohydrates. On the basis of X-ray crystallographic data and the absolute configuration of the products, it is proposed that the alkene approaches the si-face of the reacting α,β-unsaturated carbonyl functionality when coordinated to the catalyst.

Catalytic Enantioselective Aza‐Diels‐Alder Reactions of Imines‐An Approach to Optically Active Nonproteinogenic α‐Amino Acids

Abstract: A catalytic enantioselective aza-Diels-Alder reaction of imines has been developed. The reaction of N-tosyl alpha-imino ester with different dienes including activated, non-activated, cyclic, and acyclic dienes has been investigated in the presence of various chiral Lewis acids. A series of phosphino-oxazoline ligands have been synthesized and evaluated for the reaction. It was found that the combination of phosphino-oxazoline ligands with copper(I) salts gives the best results for the activated dienes, while BINAP-copper(I) complexes are good catalysts for all the dienes studied. In the case of activated acyclic dienes the aza-Diels-Alder products can be obtained in higher than 80% isolated yield and 96% ee, while for the unactivated cyclic dienes the exo diastereomer is formed as the major product in up to 95 % ee. For an activated cyclic conjugated diene, 2-trimethylsilyloxy-1,3-cyclohexadiene, the reaction proceeds as a Mannich-type addition reaction giving optically active gamma-oxo alpha-amino acid derivatives in good yields and up to 96% ee. The reaction of an unactivated acyclic diene, 2,3-dimethyl-1,3-butadiene, with the N-tosyl alpha-imino ester gives both the aza-Diels-Alder and aza-ene products, in a ratio of 9:1 favoring the aza-Diels-Alder product. Furthermore, a series of different imines have been synthesized and investigated as possible substrates for the present catalytic enantioselective aza-Diels-Alder reaction in order to obtain mechanistic insight. All imines studied gave moderate to high ee. Particularly, the reaction of the N-phenyl and N-p-methoxyphenyl substituted glyoxylate imines with Danishefsky's diene proceeded well affording the corresponding aza-Diels-Alder product in high yield with up to 91% ee at room temperature. The present catalytic enantioselective reaction of imines provided an effective route to optically active nonproteinogenic alpha-amino acids. The products of the catalytic enantioselective aza-Diels-Alder reaction of the cyclic dienes can be used for the preparation of key compounds such as natural products and compounds of pharmaceutical interest. The absolute configurations of five products have been solved by X-ray structural analysis, and it is found that the absolute configuration of the aza-Diels-Alder adduct is dependent on the substituent on the imine nitrogen atom. It turned out that the N-tosyl glyoxylate imine and N-p-methoxyphenyl glyoxylate imine give the aza-Diels-Alder adduct with opposite absolute configuration using the same enantiomer of the catalyst. On the basis of the results the mechanistic aspects for the reactions are discussed.

Studies on the SmI2-promoted pinacol-type cyclization: synthesis of the hexahydroazepine ring of balanol

Abstract: The efficiency of the samarium(II) iodide induced pinacol-type coupling for the construction of seven-membered cyclic amino alcohols has been investigated. With the acyclic carbonylhydrazones 6 and...

Enantiospecific synthesis of 1-azafagomine.

Abstract: For the first time the two enantiomeric forms of the glycosidase inhibitor 1-azafagomine have been synthesised starting from D- and L-xylose. D-Xylose was converted to the 2,3,5-tribenzylfuranose, which upon reductive amination with tert-butyl carbazate gave the protected 1-hydrazino-1-deoxypentitol in high yield. N-acetylation, mesylation of the 4-OH, removal of the Boc group, cyclisation and deprotection gave (+)-1-azafagomine ((+)-1). By a similar sequence of reactions, L-xylose was converted to (-)-1-azafagomine ((-)-1). Enzymatic and other routes to optically pure 1-azafagomine were also studied. Compound (-)-1 is a potent competitive glycosidase inhibitor, while (+)-1 has no biological activity. The inhibition of almond beta-glucosidase by (-)-1 was found to be slow owing to a slow binding step of inhibitor to enzyme, with no subsequent conformational rearrangement. The rate constants for binding and release were found to be 3.3 x 10(4)M(-1)s(-1) and 0.011 s(-1), respectively, yielding Ki = 0.33 microM.

New layered caesium zinc hydrogen phosphate, CsZn2.5(HPO4)3· 2H2O; synthesis, crystal structure and thermal transformation

Abstract: The synthesis, crystal structure and thermal transformation of a new caesium zinc hydrogen phosphate hydrate, CsZn2.5(HPO4)3·2H2O, is reported. This material crystallised from a gel with molar composition 1 ZnO∶0.48 P2O5∶0.24 Cs2O∶12 H2O∶4.8 MeCO2H, and pH of 1.0, after two months at room temperature. The crystal structure of CsZn2.5(HPO4)3·2H2O has layers built from PO4 and ZnO4 tetrahedra and with other zinc atoms forming octahedra by coordination to water molecules. The zinc octahedra are placed across pseudo 12-rings and caesium ions are placed above and below eight-ring openings. Thermal analysis was performed using thermogravimetric (TG) and differential scanning calorimetric (DSC) measurements. Two weight losses were detected and assigned to expulsion of crystal water and water from condensation of hydrogen phosphate. DSC was used to estimate enthalpy changes from three thermal events.

SmI2-Promoted Pinacol-Type Cyclization: Synthesis of the Hexahydroazepine Ring of Balanol.

Abstract: The efficiency of the samarium(II) iodide induced pinacol-type coupling for the construction of seven-membered cyclic amino alcohols has been investigated. With the acyclic carbonylhydrazones 6 and 16, good yields of the hexahydroazepines 22 and 23 were obtained (56-57%) with high trans-selectivity (= 10:1), which compares well with similar reactions generating the corresponding five- and six-membered carbocycles (Fallis, A. G.; Sturino, C. F. J. Am. Chem. Soc. 1994, 116, 7447). It is essential for ring formation that the strongly electron-donating ligand, hexamethylphosphoramide, be present, as in its absense intermolecular pinacol coupling forming the diols 27-30 is the dominant reaction. Hence, the role for HMPA appears not only to increase the rate of electron transfer but also to modulate rate constants for the subsequent reactions (cyclization and pinacol coupling) of the intermediate ketyl. This ring forming reaction has been applied to the construction of the fully functionalized hexahydroazepine ring of the PKC inhibitor, balanol. Initial attempts to develop an asymmetric version of this reaction indicate the use of chiral ligands based on the structure of HMPA.