A novel bornane synthesis by an old idea

Aiming at a synthesis of spiro[2.4]hepta-4,6-dienes with a carbon substituent at C-4, we investigated solvolysis reactions of the thiatricycle 2, obtained from spiro[2.4]hepta-4,6-diene (1) and thiophosgene by [4 + 2] cycloaddition. With methanol or ethanol a mixture of the esters 7 and 8 was formed. Desulfurization of the thionoesters 8 gave methyl and ethyl spiro[2.4]hepta-4,6-diene-4-carboxylate (10a,b). The corresponding alcohol (11) was prepared from 10b by LiAlH(4) reduction. Ethenetetracarbonitrile combined with the 4-substituted spiro[2.4]hepta-4,6-dienes to give the [4 + 2] cycloadducts 12a-c. Diels-Alder reaction between 11 and 2-chloroacrylonitrile afforded the spiro(bicyclo[2.2.1]hept-5-ene-7,1'-cyclopropane) derivative 14a that was transformed in three steps to rac-10-hydroxycamphor (17). This synthesis of a bornane derivative opens opportunity for variations and thus may find further applications.     

Factors Controlling the Addition of Carbon-Centered Radicals to Alkenes-An Experimental and Theoretical Perspective

The successful exploitation of syntheses involving the generation of new carbon-carbon bonds by radical reactions rests on some prior knowledge of the rate constants for the addition of carbon-centered radicals to alkenes and other unsaturated molecules, and of the factors controlling them. Two former classical reviews in Angewandte Chemie by Tedder (1982) and by Giese (1983) provided mechanistic insight and led to various qualitative rules on the complex interplay of enthalpic, polar, and steric effects. In the meantime, the field has experienced very rapid progress: many more experimental absolute rate constants have become available, and there have been major advances in the efficiency and reliability of quantum-chemical methods for the accurate calculation of transition structures, reaction barriers, and reaction enthalpies. Herein we review this progress, recommend suitable experimental and theoretical procedures, and display representative data series for radical additions to alkenes. On this basis, and guided by the pictorial tool of the state-correlation diagram for radical additions, we then offer a new and more stringent quantification of the controlling factors. Our analysis leads to a partial revision of the previous qualitative rules, and it more clearly exhibits the interplay of the reaction enthalpy effects, polar charge-transfer contributions, and steric substituent effects on the reaction energy barrier. The various contributions are cast into the form of new, simple, and physically meaningful but non-linear, predictive equations for the preestimation of rate constants. These equations prove successful in several tests but call for additional theoretical and experimental foundation. The kinetics of related reactions such as polymer propagation, copolymerization, and the addition of radicals to alkynes and aromatic compounds is shown to follow the same principles.     

Oxidative rearrangement processes in the biosynthesis of gilvocarcin V

Gilvocarcin V (GV), an antitumor agent produced by Streptomyces griseoflavus G? 3592 and various other streptomycetes, is the most important representative of the distinct family of benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside antibiotics, which show excellent antitumor activity and a remarkably low toxicity. The most intriguing step of its biosynthesis is an oxidative rearrangement cascade, in which the C-5/C-6 of an angucyclinone precursor bond is broken. Although this oxidative cleavage is essential for the formation of GV's unique chromophore and for GV's biological activity, and is likely to occur similarly in the biosyntheses of other angucyclinone-derived antibiotics, such as the kinamycins and the jadomycins, it is only poorly understood. Herein we report various experiments which shed light onto this intriguing oxidative cleavage reaction. These include incorporation studies with 18O-labeled precursors and the isolation and structure determination of novel intermediates of gilvocarcin biosynthesis accumulated by mutants, in which two genes encoding monooxygenases responsible for the C-C-bond cleavage of the gilvocarcin pathway, gilOI and gilOIV, were deleted through targeted PCR.     

Synthesis of 4,8-disubstituted 4H,8H-bis[1,2,5]oxadiazolo[3,4–6:3′,4′-e]pyrazines

The dilithio anion of 3,4-N,N′-disubstituted diamino[1,2,5]oxadiazole ( 4a R = benzyl, 4b R = p-methoxybenzyl, 4c R = isopropyl) and cyanogen oxide gave 4,7-disubstituted 5,6-dioximino[1,2,5]oxadiazolo[3,4-b]-pyrazines 5a,b,c. Ring closure to the title compound 1 was accomplished upon heating 5 with sodium hydroxide in ethylene glycol at 150°.     

ACTION SPECTRUM FOR PHOTOREVERSION OF THE ACTIVE Pfr-FRACTION OF Mougeotia in vivo

Abstract— The dichroic oriented fraction of the far-red light absorbing form of phytochrome (Pfr) in the green alga Mougeotia was characterized by action spectroscopy. Microbeam irradiations had to be used for the induction of chloroplast movement in Pfr-containing cells, because of the special dichroic absorption characteristics of the red light absorbing form of phytochrome (Pr) and Pfr in the alga. Fluence-response curves were elaborated especially in the far-red spectral region by reverting Pfr to Pr at the flanks of the cells and thus generating Pfr-gradients. Linearly polarized light vibrating perpendicularly to the cell axis was used, thus corresponding to the S,-transition moments of Pfr at the flanks of the cells. The action spectrum is characterized by a peak at approximately 715 nm and a very pronounced decrease towards 728 and 734 nm. The data indicate that the spectral absorption of the active Pfr-fraction in green Mougeotia is shifted towards shorter wavelengths as compared to extracted phytochrome from etiolated or even green higher plants. This "blue shift" seems to be typical for Pfr from green lower plants.     

The first stable beta-fluorosilylanion

The reaction of 2 equiv of tris(trimethylsilyl)silylfluoride with potassium tert-butoxide in the presence of donor molecules (THF, DME, 18-crown-6) leads to the clean formation of an adduct of 1-potassio-2-fluorotetrakis(trimethylsilyl)disilane. Attempts to transmetalate this compound effect the elimination of metal fluoride accompanied by the formation of tetrakis(trimethylsilyl)disilene. The latter can either be trapped in a cycloaddition reaction or in the absence of trapping reagents dimerizes to octakis(trimethylsilyl)cyclotetrasilane.     

Nature of long-range correlations of density fluctuations in glass-forming liquids

Based on a concise review of the experimental data, a theory of the structural, kinetic, and dynamic features of the Fischer cluster is put forward. This theory is based on the idea of heterophase fluctuations of glass-forming liquids. According to these ideas in a one-component liquid the solidlike and fluidlike transient associations of molecules (fluctuons) are formed. The fluctuons differ in the short-range order and, consequently, in the free energy. They form a random free energy landscape. The random field free energy functional of the Ginzburg-Landau type, which accounts for the free energy landscape, is deduced. Based on this, the phase equilibrium, critical behavior, and ordering phenomena of the heterophase liquid are considered. It is shown that in the critical region an effective attractive interaction of the fluctuons results in their gravitation and formation of correlated fractal aggregations. The aggregation consists of the fluctuons of similar short-range order. The fractal aggregation formation is a special structural state of the liquid above the glass transition temperature. The condition at which the aggregations are formed is formulated. Thus it is shown that the Fischer cluster is an array of fractal aggregations of fluctuons. The growth kinetics and dynamics of the Fischer cluster are described. The experimental data are analyzed and discussed using the theory that is put forward.     

Reaktionen von Nickel(0)-Komplexen mit p-Chinonen. Bildung phosphinsubstituierter Radikalanionen

(dipy)Ni(COD) react with duroquinone (Dch) or anthraquinone (Ach) to yield the complexes (dipy)Ni(η⁴ -Dch) or (dipy)Ni(η⁴ -Ach). Chloranil (CA), however, reacts as an oxidant and depending on the temperature (dipy)Ni^II(CA^2-) or following an oxidative addition (dipy)Ni^II(Cl)(CAH^-)(THF) are formed.By substitution of (Cy₃P)₂Ni(C₂H₄) the complexes (Cy₃P)Ni(η⁴-Dch) or (Cy₃P)₂Ni(η⁴ -Ach) are obtained, whereas a 1,1-coupling of quinone and the coordinated phosphine proceeds during the reaction between p-benzoquinone of chloranil and (Cy₃P)₂Ni(C₂H₄). By ESR studies it was demonstrated that with Ni(Cy₃P?Ch)₂ or Ni(Cy₃P?CA)₂, resp., complexes are obtained, in which radical anions, which are derived from the product of this 1,1-coupling, are coordinated to low-spin nickel (II). There is a significant difference between (Cy₃P)₂Ni(C₂H₄) and the analogous platinum or palladium complexes, which are substituted by p-benzoquinone while an oxidative addition proceeds with chloranil.     

The reaction of the group-13 alkyls ER3 (E = Al, Ga, In; R = CH2t-Bu, CH2 SiMe3) with the platinum-complex [(dcpe)Pt(H)(CH2t-Bu)]

The reactions of the sterically demanding group-13 alkyls ER₃ (E = Al, Ga, In; R = CH₂t-Bu, CH₂SiMe₃) with the platinum-complex [(dcpe)Pt(H)(CH₂t-Bu)] were re-investigated. The bimetallic compounds [(dcpe)Pt(ER₂)(R)] (3: E = Ga, R = CH₂SiMe₃; 5: E = In, R = CH₂t-Bu; dcpe = bis(dicyclohexylphosphino)ethane) with direct σ(Pt-E) bonds were obtained by oxidative addition of an E-C bond to the coordinatively unsaturated fragment [(dcpe)Pt] produced in situ by thermolysis of the starting complex [(dcpe)Pt(CH₂t-Bu)(H)]. The single crystal structure determination reveals a Pt-Ga bond length of 2.376(2) Å and a Pt-In bond length of 2.608(1) Å. All new compounds were characterised by elemental analysis, ³¹P and ¹⁹⁵Pt NMR spectroscopy. Interestingly, the Pt-Ga compound 3 slowly transforms into the platinum alkyl/hydride isomer {(dcpe)Pt(μ₂-H)[CH₂Si(CH₃)₂ CH₂Ga(CH₂SiMe₃)₂]} (4) during crystallization from solution at room temperature. The X-ray single crystal structure analysis revealed both complexes 3 and 4 coexisting in the unit cell in a 1:1 relation. The inaccessibility of analytically pure samples of the Pt-Al complex {(dcpe)Pt[Al(CH₂t-Bu)₂](CH₂t-Bu)} (6), postulated as intermediate of the reaction of [(dcpe)Pt(H)(CH₂t-Bu)] with Al(CH₂t-Bu) on the basis of ³¹P and ¹⁹⁵Pt NMR data, is attributed to an enhanced tendency to isomerisation into the alkyl/hydride Pt/Al congener of 4. A brief DFT analysis of the bonding situation of the model complex [(dhpe)Pt(GaMe₂)(Me)] (1M) revealed, that the contribution of π(Pt-Ga) back-bonding is negligible.     

Key role of electrostatic interactions in bacteriorhodopsin proton transfer

The first proton transport step following photon absorption in bacteriorhodopsin is from the 13-cis retinal Schiff base to Asp85. Configurational and energetic determinants of this step are investigated here by performing quantum mechanical/molecular mechanical minimum-energy reaction-path calculations. The results suggest that retinal can pump protons when in the 13-cis, 15-anti conformation but not when 13-cis, 15-syn. Decomposition of the proton transfer energy profiles for various possible pathways reveals a conflict between the effect of the intrinsic proton affinities of the Schiff base and Asp85, which favors the neutral, product state (i.e., with Asp85 protonated), with the mainly electrostatic interaction between the protein environment with the reacting partners, which favors the ion pair reactant state (i.e., with retinal protonated). The rate-limiting proton-transfer barrier depends both on the relative orientations of the proton donor and acceptor groups and on the pathway followed by the proton; depending on these factors, the barrier may arise from breaking and forming of hydrogen bonds involving the Schiff base, Asp85, Asp212, and water w402, and from nonbonded interactions involving protein groups that respond to the charge rearrangements in the Schiff base region.