E. V. Grishkun

Simple route to chiral organophosphorus compounds

Abstract Reaction of chlorides of nonsymmetrically substituted phosphinic and phosphinous acid with (−)-1,2:3,5-disubstituted-α-D-glucofuranose proceeds with very high stereoselectivity to give stereochemically pure phosphinic and phosphinous acid esters, which are starting reagents for preparation of chiral organophosphorus compounds. Stereoselectivity of the reaction depends on the nature of bases, solvent, temperature and excess of chlorophosphine.

Chiral symmetric phosphoric acid esters as sources of optically active organophosphorus compounds

Abstract Chiral symmetric di- and trialkylphosphites, derivatives of (−)-borneol, (−)-menthol and (−)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose, were studied as starting reagents for the preparation of chiral organophosphorus compounds. The reaction occurs by asymmetric induction at the α-carbon atom of substituted α-alkylphosphonates. The stereoselectivity of the reaction depends on the structure of the starting compounds and the reaction conditions. The configuration of the alkylphosphonates was established by NMR spectroscopy, by transformation into α-hydroxyalkylphosphonic acids and by X-ray crystal structure analysis.

ASYMMETRIC INDUCTION IN THE REACTION OF NONSYMMETRICAL PHOSPHINIC AND PHOSPHINOUS ACID CLORIDES WITH DERIVATIVES OF D-GLUCOFURANOSE

Abstract Reaction of nonsymmetrically substituted chlorophosphines (1–3) with (−)-1,2:3,5-di-O-isopropylidene-α-D-glucofuranose (1) or (−)-1,2:5,6-di-O-cyclohexylidene-α-D-glucofuranose (5) proceeds with high stereoselectivity to give stereochemically pure phosphinic acid esters (6–8), which are starting compounds for the preparation of chiral organophosphorus compounds. Reaction of benzyl-phenylphosphinous acid chloride with (1) leads to optically pure phosphinous acid ester (9). The stereochemistry of the reaction is studied in dependence on the nature of the base, solvent, temperature and excess of chlorophosphine.

STEREOSELECTIVE WAY TO DERIVATIVES OF N-PHOSPHORYLATED AMINO ACIDS

Abstract Stereoselective synthesis of the N-phosphor (V) substituted amino acids (2, 3) via the N-phosphor (III) derivatives of amino acids (1) are described. The diastereoisomers of N-phosphor (V) amino acids are separated by crystallization or column chromatography and used as starting compounds for preparation of chiral N-chloroamides. The prepared compounds have been characterized by NMR spectra and HPLC.

Asymmetric synthesis of α-substituted alkylphosphonates based on symmetrical dialkyl phosphites

Chiral C2-symmetrical dialkyl phosphites and C3-symmetrical trialkyl phosphites, derived from (−)-borneol, (−)-menthol, and 1,2∶5,6-di-O-isopropylidene-α-d-glucofuranose, were studied as the starting reagents for the preparation of chiral organophosphorus compounds. The reactions of C2-symmetrical dialkyl phosphites and C3-symmetrical trialkyl phosphites with aldehydes and amines or aldehydes are accompanied by asymmetrical induction at the α-carbon atom to yield optically active α-aminoalkylphosphanates or α-hydroxyalkylphosphonates, respectively. The stereoselectivity of the reaction depends on the structure of the starting compounds and the reaction conditions.

TERT-BUTYLCHLORO- AND BROMOPHOSPHONIC ACIDS AS SOURCES OF DIOXOPHOSPHORANES

Abstract Methods for the synthesis of free halogenophosphonic acids are developed. The first stable chloro- and bromophosphonic acids (4) are synthesized. Flash-vacuum thermolysis (FVT) of trimethylsilyl tert-butylhalogenophosphonates was performed in an attempt to generate tert-butyldioxophosphorane (5). The FVT proceeds with elimination of halogenotrimethylsilane to give unstable tert-butyldioxophos-phorane, readily transforming into trimer (7). Tert-butylhalogenophoshonic acids (9) form with triethylamine rather stable salts, which on heating eliminate triethylamine hydrohalohenide to afford trimer (7).

Halogenophosphonic and Halogenophosphinic Acids

Abstract Methods for the synthesis and preparations of first stable halogenophosphonic acids 1 (X[dbnd]Cl, Br) and halogenophosphinic acids 5 (Y [dbnd] O, S) are developed. The chemical properties of the compounds 1, 4, 5 are studied

Generation of tert-Butyl-λ5-phosphanedione and Its Chemical Properties

Flash vacuum thermolysis of trimethylsilyl tert-butylphosphonohalidates involved elimination of halo(trimethyl)silane with the formation of tert-butyl-λ5-phosphanedione whose structure was confirmed by chemical reactions. tert-Butyl-λ5-phosphanedione readily undergoes trimerization, reacts with 2-phenyloxirane to give cycloaddition product, and takes up alcohols.

Synthesis of chiral phosphonobenzaldehydes and phosphonotyrosine

A method for obtaining of chiral phosphonobenzaldehydes has been developed. The Abramov reaction between dimenthyl phosphite and 4-diethoxymethylbenzaldehyde followed by separation of stereoisomers has yielded enantiomerically pure (1S)- and (1R)-1-hydroxyphosphonates. The resulting phosphonates, after removal of acetal protection, have been converted to (1S)- and (1R)-1-hydroxymethylphosphonobenzaldehydes. By reacting with (diethylamino)trifluorosulfurane, 1-hydroxyphosphonates have been converted to 4-(1-fluoromethyl)phosphonobenzaldehydes. The synthesized chiral phosphonobenzaldehydes are convenient chiral reactants for the preparation of phosphorus analogs of natural compounds, as has been shown with the example of synthesis of the phosphonium analog of phosphotyrosine.