Eclipsed Isopropyl Conformations of Two Dimeric Hydrazines

The X-ray structures of 4,10-di-tert-butyl-5,9-diisopropyl-4,5,9,10-tetraazatetracyclo[6.2.2.2(3,6)]tetradecane (s4iPr) and its 4,9-di-tert-butyl-5,10-diisopropyl isomer (a4iPr) are reported. Both compounds are in conformations having their in-N-alkyl groups (directed toward the central CH-CH bond of the molecule) anti to each other, as expected from previous work. The principal feature of interest is that one in-isopropyl group in each compound is in an eclipsed conformation, NN,C(alpha)Me twist angle -0.5(5) degrees for s4iPr and -6.4(4) degrees for a4iPr. Low energy (somewhat less) eclipsed in-isopropyl conformations are predicted by both molecular mechanics (MM2) and semiempirical quantum mechanical (AM1) calculations. The asymmetry of the potentially C(2) symmetric a4iPr because the two in-isopropyl groups are in different rotamers is apparently not a result of crystal packing forces, because a conformation with different isopropyl rotamers is the more stable one by at least 1.0 kcal/mol in solution, determined by (13)C-NMR spectroscopy. This result is not predicted by either calculation method. The "monomer", 2-tert-butyl-3-isopropyl-2,3-diazabicyclo[2.2.2]octane (3), proves to be a poor model for the conformations of 4iPr.     

η5-cyclopentadienyl-η5-syn-1-methylpentadienylrhodium and iridium cations - preparation and reactions with nucleophiles

η⁵-cyclopentadienyl-η⁵-syn-1-methylpentadienyliridium(I) hexafluorophosphate, a novel complex containing an open chain pentadienyl ligand, has been prepared $\text{via}$ protonation of η⁵-cyclopentadienyl-η⁴-hexa-2,4-dien-1-ol iridium. It and the corresponding rhodium salt are attacked by methoxide ion at the central 3-position of the dienyl group to give 1,4-diene complexes. This contrasts with nucleophilic attack on pentadienyltricarbonyliron cations which occurs at the terminal positions of the dienyl group.     

Total synthesis of the alkaloids martinelline and martinellic acid via a hetero Diels-Alder multicomponent coupling reaction

[reaction: see text] A concise synthesis of the guanidine alkaloids, (+/-)-martinelline and (+/-)-martinellic acid, using a protic acid catalyzed 2:1 hetero Diels-Alder coupling reaction between N-Cbz 2-pyrroline and methyl 4-aminobenzoate, is described. Protic acid catalysis, rather than Lewis acid catalysis, was necessary to achieve the desired sense of diastereocontrol in the coupling reaction.     

Utilization of 1-oxa-2,2-(dimesityl)silacyclopentane acetals in the stereoselective synthesis of polyols

We have developed a route for the stereoselective synthesis of 1-oxa-2,2-(dimesityl)silacyclopentane acetals, intermediates in the synthesis of highly functionalized 1,3-diols. This route involves a diastereoselective conjugate addition reaction of a hydrosilyl anion, a subsequent diastereoselective enolate alkylation, and a fluoride-catalyzed intramolecular hydrosilylation reaction to afford the oxasilacyclopentane acetal. A highly selective nucleophilic substitution reaction, followed by oxidation of the C-Si bond, leads to the desired polyol.     

Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design

The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.     

Solubility of benzil in binary alkane + dibutyl ether solvent mixtures. Comparison of predictive expressions derived from the nearly ideal binary solvent model

Experimental solubilities are reported for benzil dissolved in six binary mixtures containing dibutyl ether with hexane, heptane, octane, cyclohexane, methylcyclohexane, and 2,2,4-trimethylpentane at 25°C. Results of these measurements are compared to the predictions of equations developed previously for solubility in systems of nonspecific interactions. The most successful equation in terms of goodness of fit involved a volume fraction average of the excess Gibbs energies relative to the Flory-Huggins model, and predicted the experimental solubilities in the six systems studied to within an overall average absolute deviation of 3.4% and with a maximum deviation of 6.0%.     

Antiferromagnetic three-dimensional order induced by carboxylate bridges in a two-dimensional network of [Cu3(dcp)2(H2O)4] trimers

A new Cu(II) complex, [Cu(3)(dcp)(2)(H(2)O)(4)](n), with the ligand 3,5-pyrazoledicarboxylic acid monohydrate (H(3)dcp) has been prepared by hydrothermal synthesis, and it crystallizes in the monoclinic space group P2(1)/c with a = 11.633(2) A, b = 9.6005(14) A, c = 6.9230(17) A, beta = 106.01(2) degrees, and Z = 2. In the solid state structure of [Cu(3)(dcp)(2)(H(2)O)(4)](n), trinuclear [Cu(3)(dcp)(2)(H(2)O)(4)] repeating units in which two dcp(3-) ligands chelate the three Cu(II) ions with the central Cu(II) ion, Cu(1) (on an inversion center), link to form infinite 2D sheets via syn-anti equatorial-equatorial carboxylate bridges between Cu(2) atoms in adjacent trimers. These layers are further linked by syn-anti axial-equatorial carboxylate bridging between Cu(1) atoms in adjacent sheets resulting in the formation of a crystallographic 3D network. A detailed analysis of the magnetic properties of [Cu(3)(dcp)(2)(H(2)O)(4)](n) reveals that the dcp(3-) ligand acts to link Cu(II) centers in three different ways with coupling constants orders of magnitude apart in value. In the high temperature region above 50 K, the dominant interaction is strongly antiferromagnetic (J/k(B) = -32 K) within the trimer units mediated by the pyrazolate bridges. Below 20 K, the trimer motif can be modeled as an S = 1/2 unit. These units are coupled to their neighbors by a ferromagnetic interaction mediated by the syn-anti equatorial-equatorial carboxylate bridge. This interaction has been estimated at J(2D)/k(B) = +2.8 K on the basis of a 2D square lattice Heisenberg model. Finally, below 3.2 K a weak antiferromagnetic coupling (J(3D)/k(B) = -0.1 K) which is mediated by the syn-anti axial-equatorial carboxylate bridges between the 2D layers becomes relevant to describe the magnetic (T, H) phase diagram of this material.     

Charge-transfer hybrids containing covalently bonded polyoxometalates and ferrocenyl units

Two new charge-transfer hybrids with one or two ferrocenyl units covalently attached to a hexamolybdate cluster through an extended pi-conjugated bridge have been prepared using Pd-catalyzed coupling reactions on monoiodo- or diiodo-functionalized cluster substrates in over 60% yields. These hybrids have been characterized by (1)H NMR, FTIR, electrospray ionization mass spectrometry, and X-ray diffraction. The electronic spectra of these hybrids show a broad absorption tail extending beyond 550 nm, indicating the existence of charge-transfer transition from the ferrocenyl donor to the cluster acceptor. The observation of the clear charge-transfer transition indicates the contribution of charge-transfer resonance to the ground state in both 2a and 2b even though the donor-acceptor separation distance of 11.29 A is rather long, signaling a through-bond charge-transfer nature made possible by the organic pi-conjugated bridge. Cyclic voltammetry studies reveal a one-electron oxidation wave and a one-electron reduction wave for the hybrid with one ferrocenyl unit. For the one with two ferrocenyl units, a lower reduction potential and a two-electron oxidation wave are observed, indicating negligible electronic interactions between the two ferrocenyl units.