Synthesis of macrocycles via cobalt-mediated [2 + 2 + 2] cycloadditions

We investigated the formation of macrocycles from alpha,omega-diynes in cobalt-mediated co-cyclotrimerization reactions. Long-chain alpha,omega-diynes underwent metal-mediated [2 + 2 + 2] cycloadditions with nitriles, cyanamides, or isocyanates in the presence of CpCo(CO)2 (Cp = cyclopentadienide) to yield pyridine-containing macrocycles, i.e., meta- and para-pyridinophanes, such as 5m/5p, 35m/35p, and 41m/41p. The regioselectivity of these reactions was affected by the length and type of linker unit between the alkyne groups, as well as by certain stereoelectronic factors. An analogous alpha,omega-cyano-alkyne, 28, combined with an alkyne to yield two isomeric meta-pyridinophanes, such as 5m and 29m, and an ortho cycloadduct (benzannulation product), such as 29o. We developed a reaction protocol for these cobalt-based [2 + 2 + 2] cycloadditions that involves markedly improved conditions such that this process offers a convenient, flexible synthetic approach to macrocyclic pyridine-containing compounds. For example, diyne 6 reacted with p-tolunitrile in 1,4-dioxane to give 7p and 7m (7:1 ratio) in 87% yield at a moderate temperature of ca. 100 degrees C in 24 h without photoirradiation or syringe-pump addition. Isocyanates were also effective reactants, as exemplified by the formation of 44p almost exclusively (44p:44m > 50:1) in 64% yield from diyne 8 and 2-phenylethylisocyanate. By using this improved protocol we were able to co-cyclotrimerize long-chain alpha,omega-diynes with alkynes in certain cases to demonstrate a successful macrocyclic variant of the Vollhardt reaction. For instance, diyne 6 reacted with dipropylacetylene to give paracyclophane 57p and benzannulene 57o (2:1 ratio) in 29% yield.     

Location of saddle points and minimum energy paths by a constrained simplex optimization procedure

Two methods are proposed, one for the location of saddle points and one for the calculation of steepest-descent paths on multidimensional surfaces. Both methods are based on a constrained simplex optimization technique that avoids the evaluation of gradients or second derivative matrices. Three chemical reactions of increasing structural complexity are studied within the PRDDO SCF approximation. Predicted properties of reaction hypersurfaces are in good overall agreement with those determined by gradient minimization and gradient following algorithms in connection with various ab initio SCF methods. Computational efforts required by the new procedures are discussed.     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

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Synthesis and reactivity of silyl ruthenium complexes: the importance of trans effects in C-H activation,Si-C bond formation,and dehydrogenative coupling of silanes

A series of octahedral ruthenium silyl hydride complexes, cis-(PMe(3))(4)Ru(SiR(3))H (SiR(3) = SiMe(3), 1a; SiMe(2)CH(2)SiMe(3), 1b; SiEt(3), 1c; SiMe(2)H, 1d), has been synthesized by the reaction of hydrosilanes with (PMe(3))(3)Ru(eta(2)-CH(2)PMe(2))H (5), cis-(PMe(3))(4)RuMe(2) (6), or (PMe(3))(4)RuH(2) (9). Reaction with 6 proceeds via an intermediate product, cis-(PMe(3))(4)Ru(SiR(3))Me (SiR(3) = SiMe(3), 7a; SiMe(2)CH(2)SiMe(3), 7b). Alternatively, 1 and 7 have been synthesized via a fast hydrosilane exchange with another cis-(PMe(3))(4)Ru(SiR(3))H or cis-(PMe(3))(4)Ru(SiR(3))Me, which occurs at a rate approaching the NMR time scale. Compounds 1a, 1b, 1d, and 7a adopt octahedral geometries in solution and the solid state with mutually cis silyl and hydride (or silyl and methyl) ligands. The longest Ru-P distance within a complex is always trans to Si, reflecting the strong trans influence of silicon. The aptitude of phosphine dissociation in these complexes has been probed in reactions of 1a, 1c, and 7a with PMe(3)-d(9) and CO. The dissociation is regioselective in the position trans to a silyl ligand (trans effect of Si), and the rate approaches the NMR time scale. A slower secondary process introduces PMe(3)-d(9) and CO in the other octahedral positions, most likely via nondissociative isomerization. The trans effect and trans influence in 7a are so strong that an equilibrium concentration of dissociated phosphine is detectable (approximately 5%) in solution of pure 7a. Compounds 1a-c also react with dihydrogen via regioselective dissociation of phosphine from the site trans to Si, but the final product, fac-(PMe(3))(3)Ru(SiR(3))H(3) (SiR(3) = SiMe(3), 4a; SiMe(2)CH(2)SiMe(3), 4b; SiEt(3), 4c), features hydrides cis to Si. Alternatively, 4a-c have been synthesized by photolysis of (PMe(3))(4)RuH(2) in the presence of a hydrosilane or by exchange of fac-(PMe(3))(3)Ru(SiR(3))H(3) with another HSiR(3). The reverse manifold - HH elimination from 4a and trapping with PMe(3) or PMe(3)-d(9) - is also regioselective (1a-d(9)() is predominantly produced with PMe(3)-d(9) trans to Si), but is very unfavorable. At 70 degrees C, a slower but irreversible SiH elimination also occurs and furnishes (PMe(3))(4)RuH(2). The structure of 4a exhibits a tetrahedral P(3)Si environment around the metal with the three hydrides adjacent to silicon and capping the P(2)Si faces. Although strong Si...HRu interactions are not indicated in the structure or by IR, the HSi distances (2.13-2.23(5) A) suggest some degree of nonclassical SiH bonding in the H(3)SiR(3) fragment. Thermolysis of 1a in C(6)D(6) at 45-55 degrees C leads to an intermolecular CD activation of C(6)D(6). Extensive H/D exchange into the hydride, SiMe(3), and PMe(3) ligands is observed, followed by much slower formation of cis-(PMe(3))(4)Ru(D)(Ph-d(5)). In an even slower intramolecular CH activation process, (PMe(3))(3)Ru(eta(2)-CH(2)PMe(2))H (5) is also produced. The structure of intermediates, mechanisms, and aptitudes for PMe(3) dissociation and addition/elimination of H-H, Si-H, C-Si, and C-H bonds in these systems are discussed with a special emphasis on the trans effect and trans influence of silicon and ramifications for SiC coupling catalysis.     

The formation of mixed ligand complexes by metal chelates and some buffer components

A method for the determination of the stability constants of mixed ligand Complexes of metals is described. The influence of the buffer components ammonia (NH₃), imidazole (Im)and hexamethylenetetramine (U) on the murcury (II)-TTHA system was investigated. The binuclear mercury (II)-TTHA chelate has a strong tendancy to coordinate two additional ligands. The following stability constants of mixed ligand chelates were determined:

. Potentiometric titrations were performed to check the effects of the buffers on compleximetric titrations.     

Reactions of charged phenyl radicals with aliphatic amino acids in the gas phase

Gas-phase reactivity of five differently substituted positively charged phenyl radicals was examined toward six amino acids by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR). The reactivity of the radicals studied was determined by the electrophilicity of the radical, which can be characterized by the radical's electron affinity (EA). The larger the electron affinity of the radical, the higher the overall reaction rate. In addition to the expected H-atom abstraction, several unprecedented reaction pathways were observed, including NH2 abstraction, SH abstraction, and SCH3 abstraction. These reaction pathways dominate for the most electrophilic radicals, and they may not follow radical but rather nucleophilic addition-elimination mechanisms. Hydrogen abstraction from glycine was also investigated theoretically. The results indicate that hydrogen abstraction from alphaC of glycine is both kinetically and thermodynamically favored over the NH2 group. The ordering of transition state energies for hydrogen abstraction from the alphaC and NH2 groups was found to reflect the radicals' EA ordering.     

Poly(ethylene glycol)--oligolactates with monodisperse hydrophobic blocks: preparation, characterization, and behavior in water

Methoxypoly(ethylene glycol)-b-oligo-L-lactate (mPEG-b-OLA) diblock oligomers with monodisperse OLA blocks were obtained by fractionation of polydisperse block oligomers using preparative HPLC. The fractionated oligomers were composed of an mPEG block with a molecular weight of 350, 550, or 750 and an OLA block with a degree of polymerization of 4, 6, 8, or 10. The diblock oligomers with a low PEG content were fully amorphous, with glass transition temperatures ranging from -60 to -20 degrees C, indicating that the blocks were miscible. Upon heating aqueous dispersions of the block oligomers, cloud points, depending on the PEG/OLA ratio of the block oligomer, were observed at temperatures above 40 degrees C. The monodispersity of the hydrophobic block enabled the amphiphilic molecules to form nanoparticles in water with a hydrodynamic radius of 130-300 nm, at concentrations above the critical aggregation concentration (0.4-1 mg/mL), whereas polydisperse mPEG-b-OLAs gave formation of large aggregates. Static light scattering measurements showed that the nanoparticles have a low density (0.6-25 mg/mL), indicating that the particles are highly hydrated. In agreement herewith, the (1)H NMR spectra of nanoparticles in D2O closely resembled spectra in a good solvent for both blocks (CDCl3). It is therefore suggested that the nanoparticles contain a hydrated core of mPEG-b-OLA block oligomers, stabilized by a thin outer PEG layer. The particles were stable for two weeks, except for the mPEG350 series and mPEG750-b-OLA4, indicating that both the PEG block size and the PEG weight fraction of the oligomers determine their stability. The evident self-emulsifying properties of mPEG-b-oligo-l-lactates with monodisperse hydrophobic blocks as demonstrated in this study, together with their expected biocompatibility and biodegradability, make these systems well suitable for pharmaceutical applications.     

The molecular structure of trans- and cis-bicyclo-[4.3.0]nonane in the gas phase,studied by electron diffraction and molecular mechanics

The structure and conformations of trans- and of cis-bicyclo[4.3.0]nonane have been studied in the gas phase. Molecular mechanics calculations applying the force field of Ermer and Lifson were used to obtain geometrical constraints, vibrational amplitudes and perpendicular vibrational corrections. The vibrational parameters were corrected for the large amplitude motion of the five-membered ring. The refinement for the trans-isomer confirms completely the predictions of the force field calculations. Although a stable solution could not be obtained for the cis-compound there is no contradiction between experiment and model calculations. The cyclohexane ring in both isomers is found to have a distorted chair conformation. In the cis-isomer it is flattened along the junction and more twisted in the other part. For the trans-compound the reverse is true.The following structural parameters r_g, r_α-structure) are put forward, (a) trans-compound: C₂-symmetry, _r(C-C)_av = 1.536 Å. Average bond angle and average torsion angle in the cyclohexane ring are 110.2° and 58.1°, respectively. The connection angle, defined as the angle between the planes bisecting C6-C1-C5-C9 and C2-C1-C5-C4, is 180°. (b) cis-compound: no symmetry, r(C-C)_av = 1.536 Å. Average bond and torsion angles in the cyclohexane ring are 112.2° and 52.3°, respectively. The connection angle is 124.8°.A comparison is made with structures of related compounds.     

Structures and stabilities of [C3H2]+ ˙ and [C3H2]2+ ions

Ab initio molecular orbital theory using basis sets up to 6-311G^{* *}, with electron correlation incorporated via configuration interaction calculations with single and double substitutions, has been used to study the structures and energies of the C₃H₂ monocation and dication. In agreement with recent experimental observations, we find evidence for stable cyclic and linear isomers of [C₃H₂]^{+ ˙}. The cyclic structure (, a) represents the global minimum on the [C₃H₂]^{+ ˙} potential energy surface. The linear isomer (, b) lies somewhat higher in energy, 53 kJ mol^?1 above a. The calculated heat of formation for [HCCCH]^{+ ˙} (1369 kJ mol^?1) is in good agreement with a recent experimental value (1377 kJ mol^?1). For the [C₃H₂]²⁺ dication, the lowest energy isomer corresponds to the linear [HCCCH]²⁺ singlet (h). Other singlet and triplet isomers are found not to be competitive in energy. The [HCCCH]²⁺ dication (h) is calculated to be thermodynamically stable with respect to deprotonation and with respect to C? C cleavage into CCH⁺ + CH⁺. The predicted stability is consistent with the frequent observation of [C₃H₂]²⁺ in mass spectrometric experiments. Comparison of our calculated ionization energies for the process [C₃H₂]^{+ ˙} → [C₃H₂]²⁺ with the Q_min values derived from charge-stripping experiments suggests that the ionization is accompanied by a significant change in structure.