Peter Legzdins

Vasodilator effects of organotransition-metal nitrosyl complexes, novel nitric oxide donors.

Nitrovasodilators cause endothelium-independent relaxation of blood vessels by generating nitric oxide (NO). We examined the relaxation and depressor effects of two organotransition-metal nitrosyl complexes, CpCr(NO)2Cl and CpMo(NO)2Cl, relative to those of the prototypal nitrovasodilators, nitroglycerin, and sodium nitroprusside (SNP), in phenylephrine-preconstricted aortic rings and conscious, unrestrained rats. CpCr(NO)2Cl, CpMo(NO)2Cl, nitroglycerin and SNP caused dose-dependent relaxation of aortic rings at maximal responses (Emax) of -118+/-4, -113+/-4, -104+/-1, and -128+/-5% and EC50 of 0.14+/-0.04, 22+/-4, 1.23+/-0.65, and 0.063+/-0.013 microM, respectively. The dose-response curve of CpCr(NO)2Cl was displaced to the right by hemoglobin, as well as methylene blue, showing involvement of the NO/cGMP pathway. Unlike nitroglycerin, preexposure for 1 h to CpCr(NO)2Cl did not alter subsequent relaxation response to the compound. Intravenous bolus injections of CpCr(NO)2Cl, CpMo(NO)2Cl, nitroglycerin, and SNP caused dose-dependent decreases in MAP with Emax of -42+/-2, -51+/-8, -56+/-6, and -58+/-2 mm Hg and EC50 of 0.041+/-0.010, 13+/-4, 1.6+/-0.4, and 0.037+/-0.004 micromol/kg, respectively. These results show that CpCr(NO)2Cl and CpMo(NO)2Cl are efficacious nitrovasodilators in vitro and in vivo.

Facile and Selective Aliphatic C−H Bond Activation at Ambient Temperatures Initiated by Cp*W(NO)(CH2CMe3)(η3-CH2CHCHMe)

Thermolysis of Cp*W(NO)(CH2CMe3)(eta(3)-CH2CHCHMe) (1) at ambient temperatures leads to the loss of neopentane and the formation of the eta(2)-diene intermediate, Cp*W(NO)(eta(2)-CH2=CHCH=CH2) (A), which has been isolated as its 18e PMe3 adduct. In the presence of linear alkanes, A effects C-H activations of the hydrocarbons exclusively at their terminal carbons and forms 18e Cp*W(NO)(n-alkyl)(eta(3)-CH2CHCHMe) complexes. Similarly, treatments of 1 with methylcyclohexane, chloropentane, diethyl ether, and triethylamine all lead to the corresponding terminal C-H activation products. Furthermore, a judicious choice of solvents permits the C-H activation of gaseous hydrocarbons (i.e., propane, ethane, and methane) at ambient temperatures under moderately elevated pressures. However, reactions between intermediate A and cyclohexene, acetone, 3-pentanone, and 2-butyne lead to coupling between the eta(2)-diene ligand and the site of unsaturation on the organic molecule. For example, Cp*W(NO)(eta(3),eta(1)-CH2CHCHCH2C(CH2CH3)2O) is formed exclusively in 3-pentanone. When the site of unsaturation is sufficiently sterically hindered, as in the case of 2,3-dimethyl-2-butene, C-H activation again becomes dominant, and so the C-H activation product, Cp*W(NO)(eta(1)-CH2CMe=CMe2)(eta(3)-CH2CHCHMe), is formed exclusively from the alkene and 1. All new complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them have been established by X-ray crystallographic analyses. Finally, the newly formed alkyl ligands may be liberated from the tungsten centers in the product complexes by treatment with iodine. Thus, exposure of a CDCl3 solution of the n-pentyl allyl complex, Cp*W(NO)(n-C5H11)(eta(3)-CH2CHCHMe), to I2 at -60 degrees C produces n-C5H11I in moderate yields.

Distinctive Activation and Functionalization of Hydrocarbon C–H Bonds Initiated by Cp*W(NO)(η3-allyl)(CH2CMe3) Complexes

Converting hydrocarbon feedstocks into value-added chemicals continues to offer challenges to contemporary preparative chemists. A particularly important remaining challenge is the selective activation and functionalization of the C(sp(3))-H linkages of alkanes, which are relatively abundant but chemically inert. This Account outlines the discovery and development of C-H bond functionalization mediated by a family of tungsten organometallic nitrosyl complexes. Specifically, it describes how gentle thermolyses of any of four 18-electron Cp*W(NO)(η(3)-allyl)(CH2CMe3) complexes (Cp* = η(5)-C5Me5; η(3)-allyl = η(3)-H2CCHCHMe, η(3)-H2CCHCHSiMe3, η(3)-H2CCHCHPh, or η(3)-H2CCHCMe2) results in the loss of neopentane and the transient formation of a 16-electron intermediate species, Cp*W(NO)(η(2)-allene) and/or Cp*W(NO)(η(2)-diene). We have never detected any of these species spectroscopically, but we infer their existence based on trapping experiments with trimethylphosphine (PMe3) and labeling experiments using deuterated hydrocarbon substrates. This Account first summarizes the syntheses and properties of the four chiral Cp*W(NO)(η(3)-allyl)(CH2CMe3) complexes. It then outlines the various types of C-H activations we have effected with each of the 16-electron (η(2)-allene) or (η(2)-diene) intermediate nitrosyl complexes, and presents the results of mechanistic investigations of some of these processes. It next describes the characteristic chemical properties of the Cp*W(NO)(η(3)-allyl)(η(1)-hydrocarbyl) compounds formed by the single activations of C(sp(3))-H bonds, with particular emphasis on those reactions that result in the selective functionalization of the original hydrocarbon substrate. We are continuing development of methods to release the acyl ligands from the metal centers while keeping the Cp*W(NO)(η(3)-allyl) fragments intact, with the ultimate aim of achieving these distinctive conversions of alkanes into functionalized organics in a catalytic manner.

Organometallic nitrosyl chemistry. 18. Electrophile-induced reduction of coordinated nitrogen monoxide. Sequential conversion of a .mu.3-nitrosyl group to .mu.3-hydroxylimido and .mu.3-imido ligands by protonic acids

The principal impetus for the investigation of the reactivity of coordinated nitrogen monoxide derives from the widespread occurrence of nitrogen oxides as atmospheric pollutants. Initial studies in this regard were focused primarily on the behavior of nucleophiles or electrophiles toward linear or bent M-NO linkages, respectively. More recent research has begun to examine the analogous reactivity patterns of transition-metal complexes containing doubly bridging NO groups. However, maximum reduction of the N-O bond order (and hence optimum activation of the bond NO) should occur in M/sub 3/(..mu../sub 3/-NO) systems. Accordingly, we have investigated the reactions of one such system with strong protonic acids and now report unprecedented, sequential transformations where M = (n/sup 5/C/sub 5/H/sub 4/Me)Mn(NO) which involve an overall formal reduction of the ..mu../sub 3/-NO ligand.The principal impetus for the investigation of the reactivity of coordinated nitrogen monoxide derives from the widespread occurrence of nitrogen oxides as atmospheric pollutants. Initial studies in this regard were focused primarily on the behavior of nucleophiles or electrophiles toward linear or bent M-NO linkages, respectively. More recent research has begun to examine the analogous reactivity patterns of transition-metal complexes containing doubly bridging NO groups. However, maximum reduction of the N-O bond order (and hence optimum activation of the bond NO) should occur in M/sub 3/(..mu../sub 3/-NO) systems. Accordingly, we have investigated the reactions of one such system with strong protonic acids and now report unprecedented, sequential transformations where M = (n/sup 5/C/sub 5/H/sub 4/Me)Mn(NO) which involve an overall formal reduction of the ..mu../sub 3/-NO ligand.

Metal–metal and metal–halogen bond cleavage by lanthanide and related metals

Finely-divided lanthanide and other metals react with substrates such as Mn(CO)5Br, h3–C3H5Fe(CO)3I,[h5–C5H5Mo(CO)3]2, and h5–C5H5Cr(CO)3HgCI in THF to yield reactive solutions which can be utilized as reagents for the synthesis of various organometallic compounds.

A Beneficial Kinetic Effect of an η5-C5Me4H Ligand

C-H activation of benzene at 26 °C by (η(5)-C(5)Me(5))W(NO)(CH(2)CMe(3))(η(3)-CH(2)CHCHMe) results after 4 h in the production of five new organometallic complexes, only two of which are isomers of the desired (η(5)-C(5)Me(5))W(NO)(C(6)H(5))(η(3)-CH(2)CHCHMe) compound. In contrast, the identical reaction involving the η(5)-C(5)Me(4)H analogue affords only the phenyl complexes during the first 24 h, thereby facilitating their isolation in good yields. This striking difference in reactivity can be attributed to the lesser steric demands of the η(5)-C(5)Me(4)H ligand that result in its complexes reacting at a significantly slower rate.

A Computational Study of Two‐State Conformational Changes in 16‐Electron [CpW(NO) (L)] Complexes (L=PH3, CO, CH2, HCCH, H2CCH2)

High-spinandlow-spin [CpW(NO) (L)] complexes are calculated to be remarkably close in energy. Several critical conformational changes in the singlet compounds are predicted to proceed more readily by spin crossover to the triplet hypersurface. The relationships between spin state, π bonding, ligand orientation, and geometry at W are explored.

Synthesis, Characterization, and Some Properties of Cp*W(NO)(H)(η3-allyl) Complexes

Sequential treatment at low temperatures of Cp*W(NO)Cl2 in THF with 1 equiv of a binary magnesium allyl reagent, followed by an excess of LiBH4, affords three new Cp*W(NO)(H)(η(3)-allyl) complexes, namely, Cp*W(NO)(H)(η(3)-CH2CHCMe2) (1), Cp*W(NO)(H)(η(3)-CH2CHCHPh) (2), and Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3). Complexes 1-3 are isolable as air-stable, analytically pure yellow solids in good to moderate yields by chromatography or fractional crystallization. In solutions, complex 1 exists as two coordination isomers in an 83:17 ratio differing with respect to the endo/exo orientation of the allyl ligand. In contrast, complexes 2 and 3 each exist as four coordination isomers, all differing by the orientation of their allyl ligands which can have either an endo or an exo orientation with the phenyl or methyl groups being either proximal or distal to the nitrosyl ligand. A DFT computational analysis using the major isomer of Cp*W(NO)(H)(η(3)-CH2CHCHMe) (3a) as the model complex has revealed that its lowest-energy thermal-decomposition pathway involves the intramolecular isomerization of 3a to the 16e η(2)-alkene complex, Cp*W(NO)(η(2)-CH2═CHCH2Me). Such η(2)-alkene complexes are isolable as their 18e PMe3 adducts when compounds 1-3 are thermolyzed in neat PMe3, the other organometallic products formed during these thermolyses being Cp*W(NO)(PMe3)2 (5) and, occasionally, Cp*W(NO)(H)(η(1)-allyl)(PMe3). All new complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them have been established by single-crystal X-ray crystallographic analyses.

Thionitrosyl ligand; X-ray molecular structure of dicarbonyl(η5-cyclopentadienyl)thionitrosylchromium

An X-ray crystallographic analysis of (η5–C5H5)Cr(CO)2(NS) shows that the thionitrosyl group co-ordinates essentially linearly to the chromium atom via the nitrogen atom.

Nitrosyl N–O Bond Cleavage During Reactions of Organometallic Nitrosyl Complexes of the Group 6 Elements

Abstract The nitrosyl ligands in organotransition-metal nitrosyl complexes usually stay intact during chemical transformations of these complexes. However, our continuing study of the characteristic reactivity of Group 6 organometallic nitrosyl complexes has recently revealed a number of new product complexes which result from N─O bond cleavage of the nitrosyl groups in the reactants. The various reactions and reaction conditions during which these complexes undergo facile nitrosyl N─O bond dissociation are summarized, and mechanistic ideas as to why these bond cleavages occur are also presented.