Abstract

Reaction of diethyl 2,2-difluoro-3-(α-methylbenzyl)imino-4,4,4-trifluoropropanephosphonate (3) with triethyl- amine afforded a mixture of normal [1,3]-proton shift reaction product 5 and its HF-eliminated compound 6Z in 1:1 ratio. Upon hydrolysis, this reaction mixture gave solely 1,3,3,3-tetrafluoro-2-dioxypropanephosphonate (9). Reaction of 3 with DBU provided only 6, in which the ratio of E/Z forms was dependent on the reaction conditions. Aqueous hydrolysis of 6 led to 9. Catalytic hydrogenation and hydrogenolysis of 6 gave geometric isomers of 11 as expected. The reaction mechanism involved was discussed.

An improved procedure for the asymmetric synthesis of α-aminoalkylphosphonic acids using S-2-anilino-methylpyrrolidine as the chiral auxiliary was described. The chemical transformations involved in this protocol could proceed under mild reaction condition to provide good chemical and enantiomeric yields.

The two enantiomers of 4-hydroxy-2-oxo-4-alkyl/-arylalkylphosphonates were prepared chemoenzymatically and converted to chiral 2-phosphoryl-3-oxo-5-alkyl/-aryl tetrahydrofurans using an intramolecular O−H insertion reaction catalyzed by rhodium(II) acetate. The potential biological activity of the resulting tetrahydrofurans is of much interest. The presence of the β-ketophosphonate skeleton in these heterocycles allowed their use as substrate in the cyclic Horner−Wadsworth−Emmons reaction with aldehydes or ketones furnishing chiral α,β-unsaturated ketones − a new class of building block in organic synthesis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

We describe a convenient and simple synthesis of optically active β-amino-β-arylethylphosphonates based on Mitsunobu reactions of chiral β-aryl-β-hydroxyethylphosphonates, prepared in turn by Candida rugosa lipase catalyzed kinetic resolution of the corresponding racemates. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A new and facile method based on an intermolecular cycloaddition was described for the synthesis of wedelolactone derivatives.

A chemoenzymatic approach was applied to the preparation of chiral 3-hydroxy-3-arylpropionates and 3-hydroxy-4,4,4-trifluorobutanoate that are potential precursors for certain chiral pharmaceuticals including chiral tomoxetines and fluoxetines.

An efficient lipase-catalyzed enantioselective hydrolysis of butyryloxyalkanephosphonates in water-equilibrated diisopropyl ether was developed. The relationship between the substrates'structure and the reactivity, as well as the enantioselectivity of this enzymatic transformation was studied. The catalytic preference of crude Candida rugosa lipase toward such molecules was assigned according to modified Mosher's method and X-ray crystallographic analysis. Optically pure 2-hydroxy-2-arylethanephosphonates, 3-hydroxy-3-phenylpropanephosphonate, and 3,3, 3-trifluoro-2-hydroxypropanephosphonates were conveniently prepared in this manner.