Thermolyse und photolyse einiger sila- und disilacyclobutane

The thermolysis of some 1,1-di- or 1,1,2-tri-substituted 1-silacyclobutanes leads to 1,3-disilacyclobutanes or to polymeric products. A possible intermediate silaalkene could not be stabilized, even in the presence of bulky substituents at the silicon atom. Photolysis of some di- or tri-substituted silacyclobutanes in methanol results in ring opening or in elimination of an alkene with further reaction of the intermediates with the solvent. Photolysis of the 1,1-diphenyl-2-methyl-l-silacyclobutane in cyclohexane leads to the 1,1,3,3-tetraphenyl-l,3-disilacyclobutane. The influence of the substituents at the silicon or the carbon atom on the reaction pathways is discussed. Photolysis of the 1,1,3,3-tetramethyl-2,4-diphenyl-l,3-disilacyclobutane occurs with ring opening and addition of methanol, whereas the 1,1,3,3-tetraphenyl-l,3-disilacyclobutane does not show any reaction.     

Stereoselective Synthesis of 3-Substituted 4-(Formyloxy)-2-azetidinones by the Unusual Baeyer-Villiger Reaction of beta-Lactam Aldehydes. Scope and Synthetic Applications

The Baeyer-Villiger oxidation of 4-formyl-beta-lactams 1with m-CPBA gave 4-(formyloxy) beta-lactams 2 in a simple, efficient, and totally stereoselective process. This reaction is one of the scarce examples of the preferred migration of a carbon moiety in an aliphatic aldehyde. The influence of the substituents at N1 and C3 of the four-membered ring in the Baeyer-Villiger rearrangement has been studied. Thus, alkyl, alkenyl, aryl, and alkyloxy 3-substituted-1-(p-anisyl)-2-azetidinones 1 form exclusively 4-(formyloxy) beta-lactams 2. Amide or acetoxy substituents at C3 of the four-membered ring produce mixtures of 4-(formyloxy) beta-lactams 2and 4-carboxy beta-lactams 5. The exclusive formation of carboxy derivatives is observed sometimes for 1-alkyl-substituted-2-azetidinones 1. 4-(Formyloxy) beta-lactams 2 are suitable starting materials to prepare different 4-unsubstituted beta-lactams 9 using beta-hydroxy amides 8 as isolable intermediates. The overall transformation 4-formyl-2-azetidinone to 4-unsubstituted beta-lactam is an easy and convenient stereoselective route to these interesting types of compounds.     

Formation of reactive o-quinone methides from the reaction of trimethylsilyl(methyl)-substituted 1,4-benzoquinones with nucleophiles

o-Quinone methides are formed from the reaction of nucleophiles with trimethylsilyl(methyl)-1,4-benzoquinones. These reactive intermediates are trapped by excess nucleophile to form substituted quinones following oxidation. In addition, varying amounts of a symmetrical dimer and a xanthen derivative were observed. The influence of different nucleophiles and ring substituents on the rate of reaction have been studied, and are consistent with rate-limiting formation of a vinylogous enolate initiated by attack of the nucleophile on the silyl group.     

New open-chain tetrapyrroles as chromophores in the plant photoreceptor phytochrome

A series of six open-chain tetrapyrroles has been synthesized and used as chromophores for the plant photoreceptor protein phytochrome. The novel chromophores vary in the size of substituents 17 and 18 at ring D. This ring undergoes maximal conformational change upon light excitation ( Z --> E photoisomerization of the 15,16-double bond). Instead of methyl and vinyl substituents (positions 17, 18) as present in the native chromophore phytochromobilin, dimethyl, methyl and isopropyl, methyl and tert-butyl, ethyl and methyl, vinyl and methyl, and isopropyl and methyl substituents have been generated. All novel chromophores assemble with the apoprotein. The obtained chromoproteins show hypsochromic shifts of the absorbance maxima by 10 nm maximally, compared to the native pigment, except for the 17-isopropyl-18-methyl-substituted compound which showed a 100 nm hypsochromic shift of selectively the P r form. The assembly kinetics were slowed down in correlation to the increasing size of the substituents, with stronger effects for modified substituents at position 17. The thermal stability of the photoinduced P fr form for the 18-isopropyl and the 18- tert butyl substituents was even greater than that of the native pigments. Those chromophores carrying substituents at position 17 larger than the methyl group (ethyl and isopropyl) showed a very low stability of the respective P fr forms. Time-resolved detection of the P r to P fr conversion (laser-induced flash photolysis) revealed a slower formation of the P fr form for those chromophores carrying larger substituents at position 18, whereas the rise and decay kinetics of the early intermediates are only moderately changed. Introduction of larger substituents at position 17 (ethyl, vinyl, and isopropyl) causes drastic changes in the kinetics; in particular the formation of the first thermally stable intermediate, I 700, is significantly slowed, making a detection of its rise possible.     

One-pot selective syntheses of 5-azaindoles through zirconocene-mediated multicomponent reactions with three different nitrile components and one alkyne component

5-Azaindoles either with three different substituents at their 2-, 4-, and 6-positions or with two identical substituents at their 2- and 6-positions and a different one at the 4-position, were obtained in good to excellent isolated yields by a zirconocene-mediated multicomponent process. Each reaction involved four organic partners, comprising a Si-tethered diyne, one tBuCN component, and two (either different or identical) nitriles. All these four components were combined through the action of a Cp(2)Zr(II) species into a three-ring fused Zr/Si-containing organometallic complex in a perfectly chemo- and regioselective manner. This multicomponent reaction process consisted of three reaction steps, all of which were made clear through the isolation and characterization of their corresponding organometallic intermediates: the zirconacyclopropene-azasilacyclopentadienes 2, the allenyl-aza-zirconacycles 3, and the three-ring fused complexes 6. X-ray single-crystal structural analyses of two three-ring fused Zr/Si-containing intermediates and two 5-azaindoles unambiguously showed the positions of the different substituents and the regioselectivity. Iminopyrrole derivatives could be also highly selectively prepared from a Si-tethered diyne and two different nitriles.     

Theoretical study on intramolecular allene-diene cycloadditions catalyzed by PtCl2 and Au(I) complexes

The intramolecular [4C+3C] cycloaddition reaction of allenedienes catalysed by PtCl(2) and several Au(I) complexes has been studied by means of DFT calculations. Overall, the reaction mechanism comprises three main steps: (i) the formation of a metal allyl cation intermediate, (ii) a [4C(4π)+3C(2π)] cycloaddition that produces a seven-membered ring and (iii) a 1,2-hydrogen migration process on these intermediates. The reaction proceeds with complete diastereochemical control resulting from a favoured exo-like cycloaddition. Allene substituents have a critical influence in the reaction outcome and mechanism. The experimental observation of [4C+2C] cycloadducts in the reaction of substrates lacking substituents at the allene terminus can be explained through a mechanism involving Pt(IV)-metallacycles. With gold catalysts it is also possible to obtain [4C+2C] cycloaddition products, but only with substrates featuring terminally disubstituted allenes, and employing π-acceptor ligands at gold. However the mechanism for the formation of these adducts is completely different to that proposed with PtCl(2), and consists of the formation of a metal allyl cation, subsequent [4C+3C] cycloaddition and a 1,2-alkyl shift (ring contraction). Electronic analysis indicates that the divergent pathways are mainly controlled by the electronic properties of the gold heptacyclic species (L-Au-C(2)), in particular, the backdonation capacity of the metal center to the unoccupied C(2) (pπ-orbital) of the intermediate resulting from the [4C+3C] cycloaddition. The less backdonation, (i.e. using P(OR)(3)Au(+) complexes), the more favoured is the 1,2-alkyl shift.     

Carbon-13 NMR of fluorocyclopropanes

Carbon-13 and hydrogen NMR data are presented for several cyclopropanes with one to four fluorine atoms attached to the ring. Substituents directly attached to a ring carbon are found to unshield that carbon to an extent increasing with their electronegativity, but remote substituents may have an opposite effect. Relative orientation of the substituent groups, especially if they are bulky, also has a strong influence on the ring-carbon shifts. Chemical shifts of carbons in methyl groups attached to the ring change to an extent which is additive in the effects of gem and cis substituents. One-bond coupling of ring carbons with fluorines is affected both by geminal and vicinal substituents, in a way generally related to their electronegativity. It is tentatively concluded that two-bond coupling between ring carbons and ring-attached fluorines depends in magnitude primarily on what groups are cis to the fluorine. Two-bond coupling between a carbon atom in a ring-attached methyl and the hydrogen gem to the methyl appears to be vanishingly small, but there is appreciable three-bond coupling of the methyl carbons to vicinal hydrogens.     

1H NMR spectra and electronic structure of 3-arylmethyl-idenephthalide and 3-arylthiomethylidenephthalide derivatives

The ¹H NMR spectra of trans-3-phenylmethylidenephthalide and trans-3-phenylthiomethylidenephthalide derivatives were investigated. After applying a correction for the anisotropy of substituents and/or for changes of ring current in the substituted aromatic ring, linear correlations were obtained between the chemical shifts of protons of the substituted phenyl group and the methine group and s? constants of substituents. The influence of the bridge heteroatom on the transfer of electronic effects of substituents through the molecules under study is discussed.     

Unravelling the reaction mechanism of the reductive ring contraction of 1,2-pyridazines

Substituted pyrroles may be synthesized from selected 1,2-pyridazines through a reductive ring contraction involving the addition of four electrons and four protons. Our density functional theory computations of this reaction mechanism show that the first reduction event must be preceded by the uptake of one proton by 1,2-pyridazine and that the reaction proceeds through a 2e(-)/3H(+)-bearing intermediate. In the absence of electron-withdrawing groups able to resonate charge away from the ring, this intermediate lies too high in energy, making the reaction sequence thermodynamically inaccessible. After another two-electron reduction and the addition of two more protons, the original 1,2-pyridazine ring opens. Ring contraction and ammonia elimination then proceed with very small barriers, irrespective of the substituents present in the original 1,2-pyridazine. By establishing the need for electron-withdrawing resonant groups in the 3- and 6-positions to stabilize the critical intermediate in the initial stages of the reaction, this work suggests that the scope of the reductive ring contraction of 1,2-pyridazines may be expanded to pyridazines bearing COCH(3) groups, amides or aryls in these positions. We also explain the lack of reactivity of unsubstituted 1,2-pyridazine and analyze the feasibility of bypassing the high energy 2e(-)/3H(+)-intermediate through disproportionation of earlier 2e(-)/2H(+)-bearing intermediates.     

1H NMR spectra of oxiranes. cis-Arylmethyl oxiranes substituted in the phenyl ring

The ¹H NMR parameters for a number of cis-arylmethyl oxiranes are reported and discussed in comparison with those of trans derivatives and styrene oxides substituted in the phenyl ring. While the macroscopic behaviour of the results is in agreement with a perturbative mechanism through the oxirane ring that is mainly electrostatic in character, a small contribution due to conjugative interaction is not excluded. It seems likely that the effect of substituents in the phenyl ring is mainly transmitted through bonds rather than through space, and that the different polarisation of the C? H bonds in the oxirane ring is mainly responsible for the different behaviour of the protons in cis- and trans- arylmethyl oxiranes towards the effect of substituents.     

Electron-rich heteroaroylphosphonates and their reaction with trimethyl phosphite

Dialkyl heteroaroylphosphonates based on thiophene, pyrrole or furan have been prepared and their reactions with trimethyl phosphite investigated. Deoxygenation of the carbonyl groups in these heteroaroylphosphonates occurs to give carbene intermediates, which then undergo further reaction. In the case of the furan-3-oylphosphonates and those systems containing a thiophene or pyrrole ring, the major reaction pathway involves intermolecular trapping of the carbene intermediates by the trimethyl phosphite, leading to the formation of ylidic phosphonates that can be readily converted into the corresponding 1,1-bisphosphonates. However, in some furan-2-oylphosphonates the carbenes generated undergo ring-opening to initially give acyclic alkynylphosphonates which may react further to give other novel phosphorus compounds. The effects of substituents on the extent to which intermolecular trapping of the initially formed carbene competes with intramolecular rearrangement has been investigated. The latter process appears to be suppressed by a substituent at the 5-position of the furan ring, the resulting ylidic phosphonates being a rare example of an efficient intermolecular trapping of a furan-2-yl carbene.     

Sequential Norrish Type II Photoelimination and Intramolecular Aldol Cyclization of α‐Diketones: Synthesis of Polyhydroxylated Cyclopentitols by Ring Contraction of Hexopyranose Carbohydrate Derivatives

The excitation of the innermost carbonyl of nono‐2,3‐diulose derivatives by irradiation with visible‐light initiates a sequential Norrish type II photoelimination and aldol cyclization process that finally gives polyfunctionalized cyclopentitols. The rearrangement has been confirmed by the isolation of stable acyclic photoenol intermediates that can be independently cyclized by a thermal 5‐(enolexo)‐exo‐trig uncatalyzed aldol reaction with high diastereoselectivity. In this last step, the large deuterium kinetic isotope effect found for the 1,5‐hydrogen atom transfer seems to indicate that the aldol reaction runs through a concerted pericyclic mechanism. Owing to the ready availability of pyranose sugars of various configurations, this protocol has been used to study the influence of pyranose ring‐substituents on the diastereoselectivity of the aldol cyclization reaction. In contrast with other pyranose ring contraction methodologies no transition‐metal reagents are needed and the sequential rearrangement occurs simply by using visible light and moderate heating (0 to 60 °C).     

On the interaction between supercritical CO2 and epoxides combining infrared absorption spectroscopy and quantum chemistry calculations

The nature and strength of the interactions occurring between epoxides and CO(2) have been investigated by combining infrared spectroscopy with quantum chemistry calculations. A series of infrared absorption experiments on four model epoxide molecules highly diluted in supercritical CO(2) have been performed at constant temperature T = 40 °C for various CO(2) pressures varying from 1 to 30 MPa. Then, we carried out a theoretical analysis based on quantum chemistry calculations using Density Functional Theory (B3PW91 and CAM-B3LYP) and ab initio (MP2) computational methods. A very good agreement between experimental and calculated vibrational frequency shifts of the epoxide ring vibrations group was obtained using the CAM-B3LYP functional, hence validating the calculated optimized geometries of the epoxide-CO(2) complexes. Whatever the epoxide considered, CO(2) is found to be on average above the oxygen atom of the epoxy ring and interacts with the carbon atom of CO(2) through a Lewis acid-Lewis base type of interaction. The substituents on the epoxide ring are found to influence the stability of the epoxide-CO(2) complexes mainly because of the partial charge on the oxygen atom that is sensitive to the nature of the substituent.     

Stereoselective control in the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents: experimental investigation and theoretical rationalization

The stereoselectivity of the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents was investigated experimentally by determination of the product stereochemistry and theoretically via DFT calculations. The results indicate that imines preferentially attack the less sterically hindered exo-side of the ketenes to generate zwitterionic intermediates. Subsequently, for cyclic imines, the intermediates undergo a conrotatory ring closure directly to produce β-lactams, while for linear imines, the imine moiety of the intermediates isomerizes to more stable intermediates, which further undergo a conrotatory ring closure to afford trans-β-lactams. The steric hindrance and the isomerization, rather than the torquoelectronic effect, play crucial roles in controlling the stereoselectivity in the practical Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents, although the unaccessible borylketene with a powerful electron acceptor group controls the stereoselectivity torquoelectronically, in theory.     

Evidence of substituent-induced electronic interplay. Effect of the remote aromatic ring substituent of phenyl benzoates on the sensitivity of the carbonyl unit to electronic effects of phenyl or benzoyl ring substituents

Carbonyl carbon (13)C NMR chemical shifts delta(C)(C[double bond]O) measured in this work for a wide set of substituted phenyl benzoates p-Y-C(6)H(4)CO(2)C(6)H(4)-p-X (X = NO(2), CN, Cl, Br, H, Me, or MeO; Y = NO(2), Cl, H, Me, MeO, or NMe(2) ) have been used as a tool to study substituent effects on the carbonyl unit. The goal of the work was to study the cross-interaction between X and Y in that respect. Both the phenyl substituents X and the benzoyl substituents Y have a reverse effect on delta(C)(C[double bond]O). Electron-withdrawing substituents cause shielding while electron-donating ones have an opposite influence, with both inductive and resonance effects being significant. The presence of cross-interaction between X and Y could be clearly verified. Electronic effects of the remote aromatic ring substituents systematically modify the sensitivity of the C[double bond]O group to the electronic effects of the phenyl or benzoyl ring substituents. Electron-withdrawing substituents in one ring decrease the sensitivity of delta(C)(C[double bond]O) to the substitution of another ring, while electron-donating substituents inversely affect the sensitivity. It is suggested that the results can be explained by substituent-sensitive balance of the contributions of different resonance structures (electron delocalization, Scheme 1).     

Investigation of benzimidazoles. III—transmission of the substituent effects in 2-substituted 1-methylbenzimidazoles studied by 13C nuclear magnetic resonance

The influence of substituents on the ¹³C NMR chemical shifts of 2-substituted 1-methylbenzimidazoles has been investigated. The electronic effects of the substituents are transmitted to C-4 and C-7 mainly by the resonance mechanism, and to C-5, C-6 and N-CH₃, by approximately equal contributions of the resonance and inductive components. A critical analysis of the share in the transmission of substituent effects through the ‘pyridine-type’ and ‘pyrrole-type’ nitrogen atoms is given.     

Bulky Substituent Effect on Reactivity of Localized Singlet Cyclopentane‐1,3‐diyls with π‐Single Bonding (C‐π‐C) Character

Thorough investigation of key intermediates, such as long‐lived singlet diradicals, is essential to understand the homolytic bond cleavage reactions. In this study, we evaluate the effect of bulky substituents at the meta‐position of the phenyl ring on the bond formation process in singlet 2,2‐diethoxy‐1,3‐diarylcyclopentane‐1,3‐diyls. The bulky groups have significant influence on the diradical lifetime, as such, when the triisopropylphenyl group was used, the lifetime was 45 times longer than that of the parent diradical in benzene at 293 K.     

New lipophilic crown ethers with intraannular carboxylic acid groups: Synthesis and alkali metal cation extraction

A six‐step synthetic route to four lipophilic crown ethers with intraannular carboxylic acid groups and ring sizes of 15‐crown‐4, 18‐crown‐5, 21‐crown‐6 and 24‐crown‐7 is described. Eight new polyether compounds that bear inward‐facing bromo and formate ester substituents are prepared as synthetic intermediates. Selectivities and efficiencies of the four new lipophilic crown ether carboxylic acids in competitive alkali metal cation extraction from aqueous solutions into chloroform are evaluated.     

A General Strategy for the Catalytic,Highly Enantio‐ and Diastereoselective Synthesis of Indolizidine‐Based Alkaloids

Sixteen indolizidine‐based alkaloids (IBAs) that were isolated as poison constituents of the skin of frogs were synthesized in a highly flexible and stereoselective manner. As a key step, a three‐component, organocatalytic, highly enantio‐ and diastereoselective vinylogous Mukaiyama–Mannich reaction was employed furnishing optically highly enriched butyrolactams as central intermediates on a multigram scale. The attached six‐membered ring was constructed through cyclization of the pendant enoate moiety onto the pyrrolidine ring. The absolute configuration of the bridgehead chiral center and the adjacent 8‐position was established in the initial vinylogous Mannich reaction, whereas the 3‐ and 5‐substituents were introduced through organometallic addition at a late stage of the synthesis with full stereochemical control from the substrate. With this strategy, simple as well as even more complex alkaloids were accessible in good overall yields as single stereoisomers. These syntheses also served to establish the absolute and relative configuration of those IBAs that had never been synthesized before.