Configurational stability in some 3-coordinate phosphorus compounds

PMR spectra of a variety of 4,4,5,5-tetramethyl-1,3,2-dioxaphospholanes, bearing different substituents at phosphorus, have been determined at different temperatures. There is no inversion at phosphorus detectable. The P-chloro compound undergoes a chemical exchange process the rate of which is concentration dependent.     

Configurational stability of oxymethyllithiums as intermediates in intramolecular rearrangements

Several homochiral oxymethyllithiums, chiral by virtue of the hydrogen isotopes protium and deuterium, were prepared. They were tested for their microscopic configurational stability in intramolecular isomerizations, such as the silyl- and germyl-[1,2]-retro-Brook and the sigmatropic[2,3]-Wittig rearrangement. The influence of temperature, solvent, and migrating group on the stability of the intermediate carbanions was studied. Furthermore, the stereochemical course of these rearrangements was elucidated, resulting in highly enantioenriched alcohols (90-97% ee; ee=enantiomeric excess) up to temperatures of 0 degrees C.     

Configurational stability of 9-hydroxyrisperidone. Kinetics and mechanism of racemization

The configurational stability of 9-hydroxyrisperidone, an atypical antipsychotic, was studied under acidic, basic and physiological conditions. The analysis of 9-hydroxyrisperidone was performed using a recently validated chiral capillary electrophoretic method developed using a dual cyclodextrin mode (hydroxypropylated-β-CD and sulfated-α-CD). The kinetic parameters (rate constants, half-lives, and apparent free energy barriers) of the racemization were calculated through a mathematical model of the first-order reaction. The influences of the pH, the temperature, the nature and the concentration of the buffer, and the presence of an organic co-solvent were investigated. The fastest racemizations were observed under acidic conditions with high phosphate buffer concentrations and high temperatures. Under these conditions, the cyclodextrins (β-CD, methyl- β-CD, or hydroxypropylated-β-CD) added to both enantiomers in various molar ratios were not able to retard the racemization. Finally, the mechanism of racemization was investigated using nuclear magnetic resonance (NMR) and the proton–deuterium exchange of the proton H₉ borne by the chiral carbon has proven the presence of an imine–enamine tautomerism.     

Substitution of 2-phosphaindolizines by bromine and by chlorophosphines

Bromine does not add to phosphorus in a 2-phosphaindolizine 1 but substitutes its 1-position. The 1-bromo derivatives 2 are best prepared with Br₂/NEt₃ or N-bromosuccinimide. Their hydrolysis is remarkable; it involves a debromination of C-1, an oxidation of P and a selective opening of the P/C-3 bond. PCl₃ also causes a substitution of the 1-position. The resulting 1-dichlorophosphino derivatives 5 easily undergo a substituent exchange at the exocyclic phosphorus. More 1-phosphino derivatives are formed in the reaction of 1 with phenyl and diazaphospholyl dichlorophosphine.     

Configurational stability and transfer of stereochemical information in the reactions of enantioenriched organolithium reagents

The conversion of a prochiral methylene group into a stereogenic center by means of a lithiation/substitution sequence has emerged as a powerful synthetic transformation over the past 15 years. This reaction proceeds via a chiral organolithium intermediate, and the stereochemical fidelity of the overall reaction sequence is intimately dependent on the stereochemical behavior of the chiral organolithium as well as on the rate and stereochemical sense of the electrophilic substitution step. Chiral organolithium reagents were first reported by Letsinger, Curtin, and Applequist half a century ago. The lithiated intermediates in these early studies were not highly configurationally stable, and applications in stereoselective synthesis were not immediately forthcoming. The two decades that followed the 1980 report by Still and Sreekumar of a configurationally stable alpha-oxyorganolithium were marked by an increased interest in these reagents. As the synthetic applications of chiral organolithium reagents have grown, so have accompanying mechanistic studies of these intermediates which serve as the basis for this review.     

Effects of chlorophosphines on the radical polymerization of methyl methacrylate

The effect of chlorophosphines (phosphorus trichloride, dichlorophenylphosphine, chlorodiphenylphosphine) on the radical polymerization of methyl methacrylate was investigated in benzene solution. The polymerization was carried out at 50°C by the standard solution method, α,α′-azobisisobutyronitrile being used as an initiator. These chlorophosphines accelerated the polymerization of methyl methacrylate but did not affect the rate of decomposition of α,α′-azobisisobutyronitrile. Ultraviolet and infrared spectral data suggested that the acceleration effect was due to the complex formation of methyl methacrylate with each chlorophosphine. From the result of a copolymerization with styrene, it was found that the reactivity of methyl methacrylate monomer increased in the presence of dichlorophenylphosphine.     

Electrochemical synthesis of tertiary phosphine from organic halides and chlorophosphines

The electrochemical synthesis of a wide range of tertiary mono- and diphosphines has been achieved in very simple and mild conditions, in an undivided electrolytic cell with a sacrificial anode of magnesium.     

Configurational enthalpy of polystyrene

Recent precision measurements of the heats of combustion of atactic and isotactic polystyrene permit an unequivocal calculation of the enthalpy difference in the bulk amorphous forms of the two isomers of this polymer. Contributions to this quantity arise mainly from the differences in nonbonded interactions in the two configurations but may also contain terms relating to higher energy conformations and to intermolecular interactions. The thermochemical and NMR data of specific polymers and of simple molecules are discussed in a comparison with model compound calculations. The thermochemical method has potentially important applications in studying molecular interactions in stereoregular polymers.     

Configurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides

The bisindolylmaleimides are selective protein kinase inhibitors that can adopt two limiting diastereomeric (syn and anti) conformations. The configurational stability of a range of substituted and macrocyclic bisindolylmaleimides was investigated by using appropriate techniques. With unconstrained bisindolylmaleimides, the size of the 2-indolyl substituents was found to affect configurational stability, though not sufficiently to allow atropisomeric bisindolylmaleimides to be obtained. However, with a tether between the two indole nitrogen atoms in place, the steric effect of 2-indolyl substituents was greatly exaggerated, leading to large differences in configurational stability. The rate of interconversion of the syn and anti conformers varied by over twenty orders of magnitude through substitution of a bisindolylmaleimide ring system, which was constrained within a macrocyclic ring. Indeed, the first examples of configurationally stable atropisomeric bisindolylmaleimides are reported; the half-life for epimerisation of these compounds at room temperature was estimated to be >10(7) years.     

Cyclopropyl carbanions derived from esters of 2-phenylcyclopropylcarboxylic acids: Configurational stability and reaction with electrophiles

The base-catalyzed cis-trans isomerization of cis and trans-alkyl 2-phenylcyclopropylcarboxylates was studied in several aprotic solvents. It was found that contact ion-pain of the derived carbanion lithium salts were configurationally more stable than the solvent-separated ones. Reaction of either the cis or the trans esters with MeI, and the reaction of the cis ester with Ph₂C = O, resulted in the corresponding I-substituted derivatives having cis geometry only. This was explained as due to steric hindrance to elctrophilic attack exerted by the 2-phenyl group in the case of the trans substrate. The trans esters did not react with Ph₂C=O. Inhibition of the trans-to-cis isomerization of the carbanion salt of the trans substrate in presence of Ph₂C=O could lead to this result.     

Configurational Isomerism in Polyoxovanadates

A water‐soluble derivative of the polyoxovanadate {V₁₅E₆O₄₂} (E=semimetal) archetype enables the study of cluster shell rearrangements driven by supramolecular interactions. A reaction unique to E=Sb, induced exclusively by ligand metathesis in peripheral [Ni(ethylenediamine)₃]²⁺ counterions, results in the formation of the metastable α₁* configurational isomer of the {V₁₄Sb₈O₄₂} cluster type. Contrary to all other polyoxovanadate shell architectures, this isomer comprises an inward‐oriented vanadyl group and is ca. 50 and 12 kJ mol^?1 higher in energy than the previously isolated α and β isomers, respectively. We discuss this unexpected reaction in light of supramolecular Sb?O???V and Sb?O???Sb contacts manifested in {V₁₄Sb₈O₄₂}₂ dimers detected in the solid state. ESI MS experiments confirm the stability of these dimers also in solution and in the gas phase. DFT calculations indicate that other, as of yet elusive isomers of {V₁₄Sb₈}, might be accessible as well.     

Configurational statistics of polyamide chains

The statistical mechanical treatment of polymeric chains in terms of the largest eigenvalue of the product of statistical weight matrices for the rotational interactions of skeletal bonds of the repeat unit becomes excessively complicated if the repeat unit spans more than three or four skeletal bonds. Moreover, such treatment is necessarily limited to chains in which the number of repeat units is indefinitely large. Newer methods are readily applicable to chains of any degree of polymerization comprising repeat units of any realizable length. If interdependence of neighboring bond rotations is confined to bond pairs within a given unit, rotations about a pair of bonds belonging to neighboring units being mutually independent, further simplifications may be introduced without sacrifice of rigor. Polyamides, in which rotation about bonds on opposite sides of the amide group are independent, are polymers of this type. Adherence of the amide group to the planar trans conformation favors a more extended configuration of the chain, but this effect is dominated by the smaller steric repulsions affecting rotations about bonds which are first, second, and third neighbors of the amide group. It is for this reason that the characteristic ratio 〈r²〉₀〉/nl² for poly(hexamethylene adipamide), ca. 6.0 according to experimental results of Saunders, is less than the value, 8.0, for polymethylene at 25°C. The characteristic ratios and molecular dipole moments are computed as functions of the degree of polymerization. The poly(εaminocaproamide) chain also is treated.     

Configurational assignment of N-arylsulfonylimines of alpha-polychloroaldehydes

Configurational assignment of seven synthesized N-arylsulfonylimines of alpha-polychloroaldehydes has been carried out by means of experimental measurements and high-level ab initio calculations of their (13)C--(13)C, (13)C--(1)H and (15)N--(1)H spin-spin coupling constants. The title compounds were shown to exist in solution solely in the form of E isomers, in line with thermodynamic reasoning.