The Mitsunobu Reaction: Origin,Mechanism, Improvements,and Applications

The Mitsunobu reaction is a widely used and versatile method for the dehydrative oxidation–reduction condensation of an acid/pronucleophile usually with a primary or secondary alcohol that requires the combination of a reducing phosphine reagent together with an oxidizing azo reagent. The utility of this reaction stems from the fact that it is generally highly stereoselective and occurs with inversion of the stereochemical configuration of the alcohol starting material. Furthermore, as carboxylic acids, phenols, imides, sulfonamides, and other compounds can be used as the acid/pronucleophile, this reaction is useful for the preparation of a wide variety of functional groups. This Focus Review of the Mitsunobu reaction summarizes its origins, the current understanding of its mechanism, and recent improvements and applications.     

Catalytic asymmetric vinylation of ketones

This communication describes the catalytic asymmetric 1,2-addition of vinylzinc reagents to aromatic, alpha,beta-unsaturated, and dialkyl ketones with enantioselectivities between 79 and 97% and with yields ranging from 84 to 98%. The products of these reactions are tertiary allylic alcohols with chiral quaternary centers that are useful in organic synthesis. The reaction involves hydrozirconation of a terminal alkyne, transmetalation to zinc, and addition to a ketone in the presence of a chiral titanium-based Lewis acid catalyst. The reactions proceed smoothly at room temperature in under 24 h.     

Model complexes for metallated polythiophenes: gold(I) and palladium(II) complexes of bis(diphenylphosphino)oligothiophenes

The preparations of two new phosphinothiophene ligands, 3,3'-bis(diphenylphosphino)-2,2'-bithiophene (dppbt; 1) and 3,3' "-dihexyl-3',3' '-bis(diphenylphosphino)-2,5':2',2' ':5' ',2' "-quaterthiophene (hdppqt; 2) are reported. Oxidation of 1 gives 3,3'-bis(diphenylphosphine oxide)-2,2'-bithiophene (3), and the crystal structure of this compound was determined. Pd(II) and Au(I) complexes of these ligands have been synthesized and characterized. Crystal structures of [(dppbt)PdCl(2)] (1-Pd), [(hdppqt)PdCl(2)] (2-Pd), [(dppbt)(AuCl)(2)] (1-Au), and [(hdppqt)(AuCl)(2)] (2-Au) were obtained. [(dppbt)(AuCl)(2)] crystallized in two solid-state forms; crystals grown from CH(2)Cl(2)/Et(2)O show a gold-gold interaction of 3.3221(4) A, but from CH(2)Cl(2)/toluene, the molecule crystallizes as a toluene adduct (1-Au-tol) and does not show any gold-gold interaction. All the complexes were characterized via UV-vis spectroscopy and cyclic voltammetry, and the effect of the metal on the energy of the pi-pi transition and oxidation potential was determined. These data are correlated to the interannular torsion angles in the oligothienyl groups from the crystal structure studies.     

Quantitation of SR 27417 in human plasma using electrospray liquid chromatography-tandem mass spectrometry: A study of ion suppression

The effect of coeluting matrix compounds on the quantitation of SR 27417 in human plasma using electrospray liquid chromatography-tandem mass spectrometry has been examined. During the method development stage of this assay, plasma samples spiked with the analyte at 100 pg/mL were extracted using three different procedures: a hexane liquid-liquid extraction, an ethyl acetate back-extraction, and a solid phase extraction. Ion intensity of the analyte was found to be related inversely to the percent ionization of coeluting matrix components as evidenced by full scan spectra. The ethyl acetate back-extraction, which contained the fewest coeluting components, resulted in the highest ion intensity for the analyte. An assay comparison was done by using the liquid-liquid hexane and the ethyl acetate back-extractions for sample preparation. Replicate 1-mL samples (n=5) at 11 concentrations from 5 to 2000 pg/mL were extracted and analyzed. The results for the ethyl acetate back-extracted samples were acceptable from 2000 to 5 pg/mL with accuracy ranging from ?11.6 to 2.61% of the nominal concentrations. In contrast, the hexane liquid-liquid method had poor accuracy and precision below 20 pg/mL. The difference is explained by suppression of analyte ion intensity. These results are consistent with the current theory of electrospray ionization.     

Synthesis and applications of C2-symmetric guanidine bases

The preparation of the tetracyclic C₂-symmetric guanidinium salts 5 and 11-13 is reported together with their application to enantioselective transformations.     

New details concerning the reactions of nitric oxide with vanadium tetrachloride

The slow addition of NO to a CCl(4) solution of VCl(4) reproducibly forms the known polymer [V(NO)(3)Cl(2)](n)() as a dark brown powder. Treatment of a CH(2)Cl(2) suspension of [V(NO)(3)Cl(2)](n)() with excess THF generates mer-(THF)(3)V(NO)Cl(2) (1) which can be isolated as an orange crystalline material in 55% yield. The reaction of 1 with excess MeCN or 1 equiv of trimpsi (trimpsi = (t)BuSi(CH(2)PMe(2))(3)) provides yellow-orange (MeCN)(3)V(NO)Cl(2)xMeCN (2xMeCN) and yellow (trimpsi)V(NO)Cl(2) (3), respectively. A black, crystalline complex formulated as [NO][VCl(5)] (4) is formed by the slow addition of NO to neat VCl(4) or by the reaction of excess ClNO with neat VCl(4). Complex 4 is extremely air- and moisture-sensitive, and IR spectroscopy suggests that in solutions and in the gas phase it dissociates back into VCl(4) and ClNO. Reaction of 4 with excess [NEt(3)(CH(2)Ph)]Cl generates [NEt(3)(CH(2)Ph)](2)[VCl(6)]x2CH(2)Cl(2) (5x2CH(2)Cl(2)), which can be isolated as deep-red crystals in 51% yield. All new complexes have been characterized by conventional spectroscopic methods, and the solid-state molecular structures of 1, 2xMeCN, and 5x2CH(2)Cl(2) have been established by single-crystal X-ray diffraction analyses.     

Apparent molal volumes of aqueous solutions of bis-tetraalkylammonium salts at 25°C: Methylene-group contribution to the limiting molal volume

Densities of aqueous solutions of a series of polymethonium chloride and bromide salts (CH₃)₃–N–(CH₂)_n–N–(CH₃)₃X₂ have been measured at 25°C. Apparent molal volumes have been calculated, and methylene-group contributions to the limiting apparent molal volumes °_v have been estimated. Constant values of the methylene-group contribution of 16.5 and 17.0 cm³-mole^–1 were obtained for the bromide and chloride salts, respectively. These values are consistent with methylene-group contributions reported for other series of organic electrolytes.     

On the use of two-dimensional potential surface cross sections in the discussion of vibronic spectra of transition metal complexes

For purposes of interpreting broad band electronic spectra of complexes, the 3N-5 dimensional potential energy hypersurface may be reduced substantially. Consideration of the geometry of the orbital transition involved allows selection of an appropriate cross section, depending on which features should be represented. In addition, the orbital transition geometry predicts which vibrational modes will contribute significantly to the width of the spectrum. In the particular case of the first and second spin-allowed bands in d³ and d⁶ complexes, α_1g and ?_g modes are responsible for the band width.     

Rapid computer simulation of ESR spectra. Conventional ESR of axially symmetric 14N-nitroxide spin labels

A computer algorithm is presented for the simulation of the effect of molecular tumbling on ESR spectra, and is applied to simulation of the conventional ESR signal (the absorption signal detected at the first harmonic of the modulation frequency and in-phase with the modulation frequency, in the limit of low microwave and modulation power) of axially symmetric ¹⁴N-nitroxide spin labels. The algorithm is extremely fast and is economical in terms of computer memory requirements.