Michał W. Wieczorek

A highly efficient asymmetric synthesis of β-aminophosphonic acids, via addition of α-phosphonate carbanions to chiral, enantiopure sulfinimines

Addition of α-phosphonate carbanions to (S)-sulfinimines 1 affords N-sulfinyl β-aminophosphonates 2 in a diastereoisomeric ratio from 5:1 to 10:1; the major diastereoisomers of 2, after separation, are converted to the corresponding β-aminophosphonates 3 or to (+)-β-amino-β-phenylethane phosphonic acid 4, whose absolute configuration was established as (R) by X-ray crystallography.

Enzyme-promoted kinetic resolution of racemic, P-chiral phosphonyl and phosphorylacetates

Abstract A series of racemic methyl phosphonyl- and phosphorylacetates were hydrolyzed in the presence of porcine liver esterase (PLE) under kinetic resolution conditions to give the corresponding P-chiral phosphonyl- and phosphorylacetic acids and recovered esters in moderate to high enantiomeric purity (up to 95% ee). The Jones PLE active site model was applied to explain the enantioselectivity of this reaction.

Synthesis and conformation of 2-dimethoxyphosphoryl-1,3-diselenanes. The first evidence for SeCP anomeric interactions.

Abstract Analysis of the 1 H and 13 C NMR spectra of conformationally labile 2-dimethoxyphosphoryl-5,5-dimethyl-1,3-diselenane and equilibration of the diastereoisomeric cis - 2 and trans - 2 revealed that the anomeric effect of magnitude about ΔG° A E =10 kJmol −1 is operating in SeC- system. Crystallographic data are in accord with the interplay of the n S e -σ* C − P negative hyperconjugation and repulsive interactions between lone electron pairs on phosphoryl oxygen and lone pairs on the endocyclic selenium atoms in trans - 2 .

Transformation of Carotol into the Hydroindane‐Derived Musk Odorant

Ozonolysis of carotol (1) gives dihydroxy ketone 2 (63% yield), the absolute configuration of which was established by X-ray crystallography. An acidic dehydration of 2 delivers a mixture of isomeric ketones 3 and 4 (3:1) that, catalysed by Pd/C in cyclohexene, yields a 1:1 thermodynamic mixture of 3 and 6. Ketone 6 exhibits an intensive musk odour. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Alkylation of thymine with 1,2-dibromoethane

Abstract Alkylation of thymine with 1,2-dibromoethane depends strongly on the reaction conditions. Various alkyl derivatives may be produced, including N-1- or N-3-monosubstituted alkylthymines and products of their cyclisation, as well higher molecular weight products resulting from intermolecular substitution of N-1- and N-3-mono- and N-1,N-3-dialkylthymines. We have identified two cyclic products 5 and 6 and the dialkylated derivative 7, for which detailed structural analyses have been performed.

The synthesis and X-ray structural studies of 2-cholesteryl-2-thio-1,3,2-oxathiaphospholane and 2-cholesteryl-2-thio-1,3,2-dithiaphospholane

Two “thiophospholane” derivatives of cholesterol: 2-cholesteryl-2-thio-1,3,2-oxathiaphospholane (1) and 2-cholesteryl-2-thio-1,3,2-dithiaphospholane (2) were synthesized as new reagents for introducing a cholesteryl moiety at the 5′-end of oligonucleotidesvia the phosphorothioate or phosphorodithioate bond. Compounds1 and2 were subjected to structural studies by X-ray methods. Both compounds crystallized in the orthorhombic system, space group P212121,1 witha=6.283(1) Å,b=12.067(1) Å,c=38.983(3) Å,2 witha=6.371(1) Å,b=11.971(1) Å andc=39.502(3) Å. The five-membered heterocyclic rings of both compounds attain a half-chair conformation in the solid state. In structures of1 and2 a disorder of some atoms is observed. The absolute configuration at the phosphorus atom in1 of the components of diastereoisomeric mixture has been established.

α-Phosphoryl sulfoxides. VIII: Stereochemistry of α-chlorination of α-phosphoryl sulfoxides

Abstract Chlorination of α-phosphoryl sulfoxides 1 with iodobenzene dichloride and sulfuryl chloride in the presence and in the absence of pyridine and stereochemical investigations of this reaction using (+)-(S)-α-dimethoxyphosphorylmethyl p-tolyl sulfoxide 1a are described. It was found that conversion of 1 to the corresponding α-chloro-α-phosphoryl sulfoxides 2 occurs under the stereochemical control of the sulfinyl group and leads to diastereomeric mixtures. The extent of asymmetric induction at the α-carbon atom and racemization of the chiral sulfinyl centre in 1 depend on the reaction conditions. The structure of the major diastereomer formed in the chlorination of (+)-(S)-1ai.e. (+)-(S)c(S)s-α-chloro-α-dimethoxyphosphorylmethyl p-tolyl sulfoxide 2a was determined by X-ray analysis. The structure was solved by direct methods and refined to R=0.081. The experimental data on chlorination of α-phosphoryl sulfoxides 1 point to retention of the configuration at both chiral centres (C and S) and this stereochemistry can be rationalized assuming addition-elimination mechanism involving the formation of a positively charged ylide as intermediate.

Structure and dynamics of bis(organothiophosphoryl) disulfides in the solid state. X-Ray diffraction and cross-polarization magic angle spinning nuclear magnetic resonance studies

The structure and dynamics of selected bis(organothiophosphoryl) disulfides have been studied by single-crystal X-ray diffraction and high-resolution solid-state NMR spectroscopy. The crystal and molecular structures of bis[tert-butyl(phenyl)thiophosphoryl] disulfide 1, bis-(diphenoxythiophosphoryl) disulfide 2 and bis[tert-butyl(methoxy)thiophosphoryl] disulfide 3 were determined, giving space groups of C2/c, P212121 and P for 1, 2 and 3, respectively. Both phosphorus centres of the disulfide 1 have the same absolute configuration, as have those of the disulfide 3, although their environments were significantly different. It has been unambiguously proved that the S–S disulfide bond length varies as a function of the PSSP torsional angle. Moreover the influence the S–S–PS conformation has on the P–S bond length is discussed. Carbon-13 NMR dipolar-dephasing experiments, using powdered samples, indicated that both the tert-butyl and methoxy groups attached to the phosphorus atom were in a fast regime exchange.

Crystal and molecular structure of the levorotatory (1R,2S)-ephedrinium (S)-t-butylsulfinylacetate: a definitive proof of the absolute configuration of enantiomeric t-butyl methyl sulfoxides

Abstract The levorotatory enantiomer of t-butylsulfinylacetic acid 3 was obtained in the reaction of the α-carbanion of (+)-t-butyl methyl sulfoxide 1 with carbon dioxide. The same enantiopure form of the acid 3 was isolated from its diastereomerically pure levorotatory salt 5 with (−)-(1R,2S)-ephedrine. The structure of this salt was determined by X-ray analysis and the absolute configuration (S) at sulfur was ascribed to the t-butylsulfinylacetate anion. Consequently, the absolute configuration (S) was assigned to the acid (−)-3 and its precursor (+)-t-butyl methyl sulfoxide 1.

Stereochemistry of organophosphorus cylic compounds—XV: Synthesis of tetramethylammonium salt of 2-oxo-2-thio-1,3,2,-oxazaphosphorinan and its crystal and molecular structures

Abstract 2-Hydroxy-1,3,-2-oxazaphosphorinan-2-thione ( 5 ) was prepared by alkaline hydrolysis of 2-chloro-1,3,2-oxazaphosphorinan-2- thione ( 6 ). Treatment of the latter with sodium methoxide afforded the 2-methoxy-derivative 7 from which the tetramethylammonium salt of the thioacid 5 was obtained by the action of trimethylamine. The structure of this salt has been determined by the direct method and refined by least-squares to R = 0.0734, a = 12.303(4), b = 9.041(3), c = 10.419(2) A, space group P2 1 2 1 2 1 . The 2-oxo-2-thio-1,3,2-oxazaphosphorinanyl anion is in the chair form with the exocylic S and O atoms in an axial and equatorial position, respectively. An intermolecular H-bond between S and the endo-cyclic N atom is present in the solid-state structure.