First isolation and characterization of 1,2-oxaphosphetanes with three phenyl groups at the phosphorus atom in typical Wittig reaction using cyclopropylidenetriphenylphosphorane

1,2-Oxaphosphetanes bearing three phenyl groups directly bound to the phosphorus atom were successfully isolated for the first time as stable crystals in the typical Wittig reaction of cyclopropylidenetriphenylphosphorane with activated carbonyl compounds. X-ray analysis of the oxaphosphetane showed that the phosphorus atom is at the center of a slightly distorted trigonal bipyramidal structure. Thermal decomposition of these oxaphosphetanes was carried out to give the starting carbonyl compounds and Wittig reaction products, olefins.     

Domino Wittig Diels-Alder reaction: an expeditious entry into the AB ring system of furanosesquiterpenes

A domino Wittig Diels-Alder reaction has been employed in delineating a short and flexible synthetic stratagem for ready access to the AB ring system and the tricyclic framework of furanosesquiterpenes, such as the bioactive natural products, furodysin and furodysinin.     

Characteristic reactions and properties of C-apical O-equatorial (O-cis) spirophosphoranes: effect of the sigma(P)(-)(O) orbital in the equatorial plane and isolation of a hexacoordinate oxaphosphetane as an intermediate of the Wittig type reaction of 10-P-5 phosphoranes

Novel spirophosphoranes (O-cis) that exhibit reversed apicophilicity having an apical carbon-equatorial oxygen array in a five-membered ring showed enhanced reactivity toward nucleophiles such as n-Bu(4)N(+)F(-) or MeLi in comparison with the corresponding stable isomeric spirophosphoranes (O-trans) having an apical oxygen-equatorial carbon configuration. The enhanced reactivity of the O-cis isomer could be explained by the presence of a lower-lying sigma(P)(-)(O(equatorial)) orbital as the reacting orbital in the equatorial plane, whereas the corresponding orbital is a higher-lying sigma(P)(-)(C(equatorial)) in the O-trans isomer. Density functional theory (DFT) calculation on the actual compounds provided theoretical support for this assumption. In addition, we found that the benzylic anion alpha to the phosphorus atom in O-cis benzyl phosphorane is much more stable than that generated from the corresponding O-trans compounds. The experimental results were considered to be due to the n(C) --> sigma(P)(-)(O) interaction in the O-cis anion, and this was confirmed by DFT calculations. Furthermore, the hexacoordinate anionic species derived from the reaction of the benzylic anion from O-cis benzylphosphorane with an aldehyde was also found to be stabilized as compared with analogous species from the corresponding O-trans isomer. The first X-ray structural characterization of a hexacoordinate phosphate intermediate in the Wittig type reaction using pentacoordinate phosphoranes is reported.     

Mechanistic implications in the Morita-Baylis-Hillman alkylation: isolation and characterization of an intermediate

An intermediate phosphonium salt has never been isolated from the Morita-Baylis-Hillman (MBH) reaction. Due to the weakly basic counterion produced in the MBH alkylation and allylation reactions, the reaction can be stopped after electrophilic attack on the zwitterionic enolate and an intermediate isolated. Upon analysis of the crystal structure, a trans geometry is observed, suggesting that there is no electrostatic interaction between phosphorus and oxygen in the zwitterionic enolate that undergoes alkylation, thus giving new mechanistic insight into the MBH reaction.     

The observation of an oxaphosphetane intermediate in the phosphonate modification of the wittig oelfin synthesis

A signal at high field is observed in the ³¹P nmr of the reaction mixtures of some ketones with a five-membered cyclic phosphonate.     

Mechanistic studies on the water-oxidizing reaction of homogeneous manganese-based catalysts: isolation and characterization of a suggested catalytic intermediate

The synthesis, isolation, and characterization of two high-valent manganese dimers with isomeric ligands are reported. The complexes are synthesized and crystallized from solutions of low-valent precursors exposed to tert-butyl hydroperoxide. The crystal structures display centrosymmetric complexes consisting of Mn(2)(IV,IV)(μ-O)(2) cores, with one ligand coordinating to each manganese. The ligands coordinate with the diaminoethane backbone, the carboxylate, and one of the two pyridines, while the second pyridine is noncoordinating. The activity of these complexes, under water oxidation conditions, is discussed in light of a proposed mechanism for water oxidation, in which this type of complexes have been suggested as a key intermediate.     

Reactivity and selectivity in the Wittig reaction: a computational study

The salt-free Wittig reaction of non-, semi-, and stabilized ylides has been investigated on realistic systems using density functional theory (DFT) calculations, including continuum solvation. Our results provide unequivocal support for the generally accepted mechanism and are in very good agreement with experimental selectivities. This study shows that E/Z selectivity of non- and semi-stabilized ylides cannot be fully understood without considering the energy of the elimination TS. The influence of ylide stabilization and the nature of phosphorus substituents on reversibility of oxaphosphetane formation is clarified. Unexpectedly, the puckering ability of addition TSs is shown not to depend on ylide stabilization, but the geometry of the TS is decided by an interplay of 1,2; 1,3; and C-H...O interactions in the case of non- and semi-stabilized ylides, whereas a dipole-dipole interaction governs the addition TS structures for stabilized ylides. The well-known influence of ylide stabilization on selectivity of PPh(3) derivatives is explained as follows: in non- and semi-stabilized ylides reactions, cis and trans addition TSs have, respectively, puckered and planar geometries, and selectivity is governed by an interplay of 1,2 and 1,3 interactions. For stabilized ylides, the high E selectivity is due to a strong dipole-dipole interaction at the addition TS. The influence of the nature of phosphorus substituents on selectivity is also detailed, the different behavior of (MeO)(3)PCHCO(2)Me ylides being explained by their lower dipole. This novel picture of the factors determining TS structures and selectivity provides a sound basis for the design of new ylides.     

Isophosphindole p-oxide : A reactive intermediate and its reaction as a Diels-Alder diene

2-Phenylisophosphindole 2-oxide (3) was generated as a reactive intermediate by the dehydrobromination of r-1-bromo-t-2-phenylisophosphindoline 2-oxide. The existence of 3 was confirmed by trapping with various dienophiles as the Diels-Alder adducts. The stereochemistry of the [4 + 2]π cycloaddition was found to be stereospecific giving endo products with the phosphoryl group syn to the approaching dienophile. When the dienophile was an alkyne, the cycloadduct decomposed under the reaction conditions to give β-substituted naphthalene as the final product.     

Novel ring transfer reaction of furans via intramolecular Diels-Alder reaction of allene intermediate: a new double annulation reaction

A novel ring tansfer reaction of furans to fused furans by tandem intramolecular Diels-Alder reaction and base-catalyzed ring-opening of the adducts has been developed.     

Syntheses of some analogs of a possible intermediate formed in the thymidylate synthetase reaction

The syntheses of a number of analogs of a possible intermediate formed in the thymidylate synthetase reaction are described. These consist of a number of 5-arylaminomethyluracils (X) and N-methyl-N-[1,-(2′-deoxy-β-D-ribofuranosyl)thyminyl]-p-aminobenzoyl glutamic acid (XXb).     

Existence of a new reactive intermediate oxygen species in hypoxanthine and xanthine oxidase reaction

We investigated a hypoxanthine (HPX) and xanthine oxidase (XOD) reaction by using a luminol analog 8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H)dione sodium salt (L-012)-mediated chemiluminescence (CL) response. Addition of a high activity of superoxide dismutase (SOD), a potent O2* scavenger, and of a high concentration of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), a potent spin trapping agent, diminished completely the CL response. Whereas a high concentration of dimethyl sulfoxide (DMSO), as a potent *OH scavenger could not attain to the complete diminishment of the CL response. It has been reported that luminol monoanion reacts with *OH to form luminol radical, and then resultant luminol radical reacts with O2* to elicit CL response. Complete scavenging for *OH is assumed to result in lack of luminol radical, which in turn induces lack of CL response. However, our results did not support the idea. Furthermore, we examined the effect of L-012 on the DMPO-OOH formation in the presence or absence of DMSO in the HPX-XOD system by applying an electron spin resonance (ESR)-spin trapping method. The DMPO-OOH formation was inhibited even in the presence of DMSO, and the rate constant (k2) between L-012 and O2* obtained in the presence of DMSO was 9.77 x 10(2) M(-1) s(-1) and the constant in the absence of DMSO was 2.97 x 10(3) M(-1) s(-1). The data suggests that L-012 is converted to a radical form that reacts with O2* even under the conditions of the absence of *OH. From these, we postulate that the existence of a reactive intermediate oxygen species in the HPX-XOD system.     

Detection of a thermally unstable intermediate in the Wittig reaction using low-temperature liquid secondary ion and atmospheric pressure ionization mass spectrometry

The signal of an extremely air sensitive and thermally unstable intermediate, four-membered ring oxaphosphetane in the Wittig reaction was detected for the first time at subambient temperature using liquid secondary ion mass spectrometry (LSIMS) and atmospheric pressure ionization (API) mass spectrometry. A copper probe and interface were constructed to perform LSIMS analysis at the temperature below ?70 °C. A stable signal from a oxaphosphetane ion [in dry tetrahydrofolate (THF)] was obtained by LSIMS without using a viscous matrix. The signal of the oxaphosphetane was also detected using a low-temperature API source (?40 °C) connected to a reaction vessel.     

Gas-phase conversion of tetrazoles to oxadiazoles: isolation and characterization of the N-acylated intermediate

The 5-substituted tetrazole ring was reacted in the gas phase with an acyl ion generated as the secondary reactive chemical ionization plasma in the mass spectrometer. The product ions obtained, among others, were proposed as the rearranged 2,5-disubstituted-1,3,4-oxadiazole nucleus. Its structure was demonstrated by comparison of the product ion spectrum of the 2,5-disubstituted-1,3,4-oxadiazole derivative obtained by condensed-phase reaction and the product ion spectrum of the oxadiazole derivative generated in situ by reaction of the 5-substituted tetrazole derivative with the acyl plasma. It was proposed that the mechanism of this transformation involved the presence of an acylated tetrazole intermediary, which could not be isolated in the condensed phase, followed by the rearrangement, with nitrogen loss, to afford the oxadiazole derivative. Under our conditions we were able to isolate the intermediate ion in the first field free region and demonstrate its structure by collision induced dissociation-tandem mass spectrometry.     

Diazothenes: evidence for their production by way of a Wittig reaction.

Base-promoted reaction of dimethyl diazomethylphosphonate ($\text{1}$) with dialkyl and cyclic ketones affords species having the chemical properties associated with vinylidenes ($\text{3}$) or their equivalents. Data are presented showing that diazoethenes ($\text{2}$) are unexpectedly unstable, losing nitrogen even at ?78°C to give the corresponding carbenes or carbenoids.     

Mechanism for the direct synthesis of tryptophan from indole and serine: a useful NMR technique for the detection of a reactive intermediate in the reaction mixture

The reaction mechanism for the biomimetic synthesis of tryptophan from indole and serine in the presence of Ac₂O in AcOH was investigated. Although the time‐course ¹H‐NMR spectra of the reaction of 5‐methoxyindole with N‐acetylserine were measured in the presence of (CD₃CO)₂O in CD₃CO₂D, the reactive intermediate could not be detected. This reaction was conducted without 5‐methoxyindole in order to elucidate the reactive intermediate, but the intermediate could not be isolated from the reaction mixture. Since the intermediate would be expected to have a very short life time, and therefore be very difficult to detect by conventional analytical methods, the structure of the intermediate was elucidated using a 2D‐NMR technique, diffusion‐ordered spectroscopy (DOSY). Two intermediates were detected and confirmed to be 2‐methyl‐4‐methyleneoxazol‐5(4H)‐one and 2‐methyl‐4‐hydroxymethyloxazol‐5(4H)‐one. The present results demonstrated that DOSY is a powerful tool for the detection of unstable intermediates. Copyright © 2010 John Wiley & Sons, Ltd.     

Isolation, characterization of an intermediate in an oxygen atom-transfer reaction, and the determination of the bond dissociation energy

The synthesis and structure of a phosphine oxide-bound intermediate molecule originating from a dioxo-molybdenum(VI) complex is described. The loss of phosphine oxide has been followed by surface-induced dissociation mass spectrometry that gave the bond dissociation energy of 29.5 (+/- 3.5) kcal/mol. Considering the bond dissociation energy for a Mo=O bond to be 100 kcal/mol, this value suggests that the primary driving force for the reaction is the formation of the intermediate complex.     

Wittig reaction of formyl-substituted organotrifluoroborates and stabilized phosphonium ylides in an aqueous medium

The synthesis of unsaturated organotrifluoroborates using the Wittig alkenation is described. These transformations to disubstituted alkenes were achieved by using formyl-substituted organotrifluoroborates and stabilized ylides using water as a solvent. The products were isolated in moderate to excellent yields and the reaction gave preferentially the E-isomer.