C−H Activation of Inert Arenes using a Photochemically Activated Guanidinato-Magnesium(I) Compound

UV irradiation of solutions of a guanidinate coordinated dimagnesium(I) compound, [{(Priso)Mg}₂] 3 (Priso=[(DipN)₂CNPrⁱ₂]⁻, Dip=2,6-diisopropylphenyl), in either benzene, toluene, the three isomers of xylene, or mesitylene, leads to facile activation of an aromatic C−H bond of the solvent in all cases, and formation of aryl/hydride bridged magnesium(II) products, [{(Priso)Mg}₂(μ-H)(μ-Ar)] 4 – 9 . In contrast to similar reactions reported for β-diketiminate coordinated counterparts of 3 , these C−H activations proceed with little regioselectivity, though they are considerably faster. Reaction of 3 with an excess of the pyridine, p-NC₅H₄Bu^t (py^But), gave [(Priso)Mg(py^ButH)(py^But)₂] 10 , presumably via reduction of the pyridine to yield a radical intermediate, [(Priso)Mg(py^But⋅)(py^But)₂] 11 , which then abstracts a proton from the reaction solvent or a reactant. DFT calculations suggest two possible pathways to the observed arene C−H activations. One of these involves photochemical cleavage of the Mg−Mg bond of 3 , generating magnesium(I) doublet radicals, (Priso)Mg⋅. These then doubly reduce the arene substrate to give “Birch-like” products, which subsequently rearrange via C−H activation of the arene. Circumstantial evidence for the photochemical generation of transient magnesium radical species includes the fact that irradiation of a cyclohexane solution of 3 leads to an intramolecular aliphatic C−H activation process and formation of an alkyl-bridged magnesium(II) species, [{Mg(μ-Priso^−H)}₂] 12 . Furthermore, irradiation of a 1 : 1 mixture of 3 and the β-diketiminato dimagnesium(I) compound, [{(^DipNacnac)Mg}₂] (^DipNacnac=[HC(MeCNDip)₂]⁻), effects a “scrambling” reaction, and the near quantitative formation of an unsymmetrical dimagnesium(I) compound, [(Priso)Mg−Mg(^DipNacnac)] 13 . Finally, the EPR spectrum (77 K) of a glassed solution of UV irradiated 3 is dominated by a broad featureless signal, indicating the presence of a doublet radical species.     

Heteroleptic Square Planar Cobalt(I/II) Complexes

Reduction of the cobalt(II) chloride complex, Ph₂B(^tBuIm)₂Co(THF)Cl ( 1 ) in the presence of ^tBuN≡C affords the diamagnetic, square planar cobalt(I) complex Ph₂B(^tBuIm)₂Co(C≡N^tBu)₂ ( 2 ). This is a rare example of a 16-electron cobalt(I) complex that is structurally related to square planar noble metal complexes. Accordingly, the electronic structure of 2 , as calculated by DFT, reveals that the HOMO is largely d_z² in character. Complex 2 is readily oxidized to its cobalt(II) congener [Ph₂B(^tBuIm)₂Co(C=N^tBu)₂]BPh₄ ( 3 -BPh₄), whose EPR spectral parameters are characteristic of low-spin d⁷ with an unpaired electron in an orbital of d_z² parentage. This is also consistent with the results of DFT calculations. Despite its 16-electron configuration and the d_z² parentage of the HOMO, the only tractable reactions of 2 involve one electron oxidation to afford 3 .     

Evaporation of Lennard-Jones fluids

Evaporation and condensation at a liquid/vapor interface are ubiquitous interphase mass and energy transfer phenomena that are still not well understood. We have carried out large scale molecular dynamics simulations of Lennard-Jones (LJ) fluids composed of monomers, dimers, or trimers to investigate these processes with molecular detail. For LJ monomers in contact with a vacuum, the evaporation rate is found to be very high with significant evaporative cooling and an accompanying density gradient in the liquid domain near the liquid/vapor interface. Increasing the chain length to just dimers significantly reduces the evaporation rate. We confirm that mechanical equilibrium plays a key role in determining the evaporation rate and the density and temperature profiles across the liquid/vapor interface. The velocity distributions of evaporated molecules and the evaporation and condensation coefficients are measured and compared to the predictions of an existing model based on kinetic theory of gases. Our results indicate that for both monatomic and polyatomic molecules, the evaporation and condensation coefficients are equal when systems are not far from equilibrium and smaller than one, and decrease with increasing temperature. For the same reduced temperature T/T(c), where T(c) is the critical temperature, these two coefficients are higher for LJ dimers and trimers than for monomers, in contrast to the traditional viewpoint that they are close to unity for monatomic molecules and decrease for polyatomic molecules. Furthermore, data for the two coefficients collapse onto a master curve when plotted against a translational length ratio between the liquid and vapor phase.     

Enantio- and diastereoselective synthesis of (E)-1,5-syn-diols: application to the synthesis of the C(23)-C(40) fragment of tetrafibricin

A highly stereoselective synthesis of (E)-1,5-syn-diols 6 is described. The kinetically controlled hydroboration of allenyltrifluoroborate 8 with Soderquist borane 2 provides the (Z)-allylic trifluoroborate 9, which undergoes sequential allylboration with two different aldehydes to provide (E)-1,5-syn-diols 6 in 72-98% yields with >95% ee and >20:1 dr. Application of this method to the synthesis of the tetrafibricin C(23)-C(40) fragment 19 is described.     

Discovery of linear receptors for multiple dihydrogen phosphate ions using dynamic combinatorial chemistry

We describe the use of dynamic combinatorial chemistry to discover a new series of linear hydrazone-based receptors that bind multiple dihydrogen phosphate ions. Through the use of a template-driven, selection-based approach to receptor synthesis, dynamic combinatorial chemistry allows for the identification of unexpected host structures and binding motifs. Notably, we observed the unprecedented selection of these linear receptors in preference to competing macrocyclic hosts. Furthermore, linear receptors containing up to nine building blocks and three different building blocks were amplified in the dynamic combinatorial library. The receptors were formed using a dihydrazide building block based on an amino acid-disubstituted ferrocene scaffold. A detailed study of the linear pentamer revealed that it forms a helical ditopic receptor that employs four acylhydrazone hydrogen-bond donor motifs to cooperatively bind two dihydrogen phosphate ions.     

Synthesis of the 4-methyl-1,2-oxazetidine-4-carboxylic acid moiety of the originally proposed halipeptin A and B structures

O-Alkylation of N-hydroxycarbamate 6 with iodo ester 5 affords 15, which was elaborated to mesylate 4. Intramolecular N-alkylation affords methyl N-Boc-4-methyl-1,2-oxazetidine-4-carboxylate (3). The geminal coupling constant of the methylene protons is 8.5 Hz, which is much smaller than the 12.0 Hz reported for halipeptins A and B. This confirms that the halipeptins do not contain an oxazetidinecarboxylic acid as originally proposed in structure 1, but a thiazoline as in the revised structure 2. The unusual O-alkylation of 5 probably proceeds by an electron transfer mechanism.     

Investigation of the metabolic fate of 2-, 3- and 4-bromobenzoic acids in bile-duct-cannulated rats by inductively coupled plasma mass spectrometry and high-performance liquid chromatography/inductively coupled plasma mass spectrometry/electrospray mass spectrometry

Inductively coupled plasma mass spectrometry (ICPMS) has been used to determine the rate and routes of excretion of bromine following the intraperitoneal administration (50 mg kg(-1)) of 2-, 3- and 4-bromobenzoic acids to male bile-duct-cannulated rats. Analysis of urine and bile for (79/81)Br using ICPMS showed that all three bromobenzoic acids were rapidly excreted (82-98%) within 48 h of dosing, primarily via the urine. High-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS) was then used to obtain metabolite profiles for bile and urine. These profiles revealed that extensive metabolism had taken place, with the unchanged bromobenzoic acids forming a minor part of the total of compound-related material detected. Concomitant MS studies, supplemented by alkaline hydrolysis, enabled the identification of the major metabolite of all three of the bromobenzoic acids as a glycine conjugate. Ester glucuronide conjugates were also identified, but formed only a small proportion of total.     

Action of HCl on 3-hydroxypyrazolo(iso)quinolines to give 1-chloropyrazoles: evidence for an addition–elimination mechanism by ab initio calculations in gas phase and water

 Addition–elimination reactions involving a nucleophile and a remote leaving group [S^H _N(AE)^tele] are well-known under basic conditions, especially amongst electron-poor six-membered heterocycles, but are less commonly encountered for five-membered heterocycles and are rare under acidic conditions. Concentrated HCl converts 1-hydroxy-1H-pyrazolo[3,4-c] isoquinoline and 1-hydroxy-1H-pyrazolo[3,4-c]quinoline into 3-chloro-1H-pyrazolo[3,4-c]isoquinoline and 3-chloro-1H-pyrazolo[3,4-c]quinoline, respectively. However, apparently neither the isomeric 1-hydroxy-1H-pyrazolo[4,3-c](iso)-quinolines nor the parent 1-hydroxypyrazole undergo this reaction. Additionally, all these systems are refractory under basic conditions. We present a plausible mechanism for the reaction, involving the 3-addition of Cl^- to the diprotonated heterocycle, followed by the elimination of water. Calculations of the initial transition states and intermediates, using optimisation at B3LYP/6-311+G(d,p), including thermochemistry [HF/6-31+G(d)], and single-point Poisson–Boltzmann self-consistent reaction field determination of the free energy of solvation (Jaguar Poisson–Boltzmann self-consistent reaction field), support this mechanism and reproduce the observed order of reactivity, the addition step being 2–4 kcal less favourable for the isomeric 1-hydroxy-1H-pyrazolo[4,3-c](iso)quinolines and provide a rationalisation for the role of strong acid. Received: 27 June 2002 / Accepted: 6 September 2002 / Published online: 14 February 2003     

Aspects of stereocontrol in the L-Selectride reduction of 4-acyl-1,3-dioxolane derivatives

The application of L-Selectride, either alone or in combination with ZnCl₂, to aryl ketones 1, 8 and 11 resulted in highly anti-stereoselective reduction. In contrast, lactols 22 and 23 gave a moderate syn-preference using L-Selectride alone and a high syn-preference in the presence of ZnCl₂. Uniquely, high anti- stereoselectivity was observed in the reduction of o-anisyl lactol 37 with L-Selectride alone, which was switched to a high syn-preference when ZnCl₂ was present.     

Tripyrrolidinophosphoric acid triamide as an activator in samarium diiodide reductions

The electrochemical and spectrophotometric characterization of the complex formed from samarium diiodide and 4 equiv of tripyrrolidinophosphoric acid triamide (TPPA) is presented. Kinetic studies indicate that the SmI(2)/TPPA complex possesses reactivity greater than the complex formed between samarium diiodide and 4 equiv of HMPA. Examples of the use of SmI(2)/TPPA in synthesis are presented.