Nitrile anion cyclization with epoxysilanes followed by Brook rearrangement/ring-opening of cyclopropane nitriles/alkylation

[reactions: see text] The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives 9-12 with a base and an alkylating agent affords (Z)-delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring. Exclusive formation of a (Z)-derivative from trans-epoxides is explained by the reaction pathway that involves a backside displacement of the epoxide by the alpha-nitrile carbanion and the O-Si bond formation followed by concerted processes involving Brook rearrangement and the anti-mode of eliminative ring fission of the cyclopropane from the rotamer 19. The fact that (E)-isomers are exclusively obtained from cis-epoxides and alpha-cyclopropyl-alpha-silylcarbinol derivative 26 provides experimental support for the proposed pathway.     

Torquoselectivity in the cationic cyclopentannelation of (2Z)-hexa-2,4,5-trienal acetals

Inter- and intramolecular trapping experiments and density functional theory ab initio calculations for model systems are consistent with the acid-catalyzed rearrangement of 2-[(1Z)-hexa-1,3,4-trienyl]dioxolanes 1 to tetrahydroalkylidenecyclopenta-1,4-dioxins 4; this involves the electrocyclic ring closure of substituted hydroxypentadienyl carbocations. The reaction, which may be considered a variant of the Nazarov cyclization, occurs much more readily than the standard Nazarov cyclization, proceeding rapidly even at -30 degrees C. B3LYP/6-31G**//HF/6-31G** calculations for models 36, 38 and 40 predict that the two alternative conrotations at the cyclization termini are associated with activation energies differing by 0.55, 0.56 and 1.60 kcalmol(-1), respectively, in favour of the R-outwards rotation. This last value corresponds to an E-41/Z-41 product ratio of >99:1 at -60 degrees C, in consonance with the experimental observation that divinylallene 1a rearranges exclusively to E-4a at temperatures below -30 degrees C. At higher temperatures the torquoselectivity of the reaction 1a-->4a is masked by subsequent isomerization to the Z isomer, the greater stability of which is attributable to steric interaction between the substituent at the exocyclic double bond and the bulky neighbouring tBu group in the E isomer.     

乙酰苯胺和对氨基苯乙酮单分子离子分解机理

从实验和理论两方面对乙酰苯胶和对氨基苯乙酮单分子离子分解反应机理进行研究．在实验方面，采用质谱仪器的磁场／静电场联动扫描检测了两个化合物的亚稳峰，得到化合物在质谱中的分解途径．在理论方面，根据分子轨道理论，用3－21基组从头计算研究分解反应中的能量变化．获得了分解产物的总能量与前体离子的总能量之差△E，按照产物的稳定性和能量有利的原则，在竞争的分解反应中，△E最小的分解反应占优势．计算的结果与质谱实际分析的结果一致．     

Solvent-dependent stereoselectivity in a Still-Wittig rearrangement: an experimental and ab initio study

[see reaction]. The Still-Wittig rearrangement gave opposite selectivities for (Z:E)-alkenes in THF (3:1) vs toluene (1:3) in the synthesis of serine-proline dipeptide amide isosteres. Four transition states leading to (Z)-and (E)-alkenes with THF and without (representing toluene) were identified by ab initio calculations at the 3-21G* level. The calculated (Z:E)-ratios with THF (4.7:1) and without THF (1:3.2) suggested that the transition state geometries and energies were well-represented by the calculations.     

Cyclizative radical carbonylations of azaenynes by TTMSS and hexanethiol leading to alpha-silyl- and thiomethylene lactams. Insights into the E/Z stereoselectivities

Free-radical mediated cyclizative carbonylations of azaenynes were carried out using TTMSS as a radical mediator to compare the efficiency and the stereochemistry with those using tributyltin hydride. Using a substrate concentration of 0.1 M, the reactions gave good yields of alpha-silylmethylene lactams having four to seven-membered rings. The observed E-diastereoselectivity of the resulting vinylsilane moiety is in sharp contrast to the Z-selectivity observed during the analogous carbonylation using tributyltin hydride. When hexanethiol was used as the radical mediator, alpha-thiomethylene lactams were formed with E-favoring stereoselectivity again. Ab initio and DFT molecular orbital calculations on the stability of E and Z products were carried out for a set of five-membered methylene lactams bearing SnH3, SiH3, and SMe groups. The distinct thermodynamic preference for the Z-isomer was only predicted for the Sn-bearing lactam. A steric effect due to the bulky (TMS)3Si group is proposed for the E-selectivity observed in the TTMSS-mediated reaction.     

Thermal isomerization of tricyclo[4.1.0.0(2,7)]heptane and bicyclo[3.2.0]hept-6-ene through the (E,Z)-1,3-cycloheptadiene intermediate

The thermal isomerization of tricyclo[4.1.0.0(2,7)]heptane and bicyclo[3.2.0]hept-6-ene was studied using ab initio methods at the multiconfiguration self-consistent field level. The lowest-energy pathway for thermolysis of both structures proceeds through the (E,Z)-1,3-cycloheptadiene intermediate. Ten transition states were located, which connect these three structures to the final product, (Z,Z)-1,3-cycloheptadiene. Three reaction channels were investigated, which included the conrotatory and disrotatory ring opening of tricyclo[4.1.0.0(2,7)]heptane and bicyclo[3.2.0]hept-6-ene and trans double bond rotation of (E,Z)-1,3-cycloheptadiene. The activation barrier for the conrotatory ring opening of tricyclo[4.1.0.0(2,7)]heptane to (E,Z)-1,3-cycloheptadiene was found to be 40 kcal mol(-1), while the disrotatory pathway to (Z,Z)-1,3-cyclohetpadiene was calculated to be 55 kcal mol(-1). The thermolysis of bicyclo[3.2.0]hept-6-ene via a conrotatory pathway to (E,Z)-1,3-cycloheptadiene had a 35 kcal mol(-1) barrier, while the disrotatory pathway to (Z,Z)-1,3-cyclohetpadiene had a barrier of 48 kcal mol(-1). The barrier for the isomerization of (E,Z)-1,3-cycloheptadiene to bicyclo[3.2.0]hept-6-ene was found to be 12 kcal mol(-1), while that directly to (Z,Z)-1,3-cycloheptadiene was 20 kcal mol(-1).     

Ab initio study of the substituent effects on the relative stability of the E and Z conformers of phenyl esters. Stereoelectronic effects on the reactivity of the carbonyl group

Equilibria between the Z (tau1= 0 degrees) and E (tau1= 180 degrees) conformers of p-substituted phenyl acetates 4 and trifluoroacetates 5 (X = OMe, Me, H, Cl, CN, NO2) were studied by ab initio calculations at the HF/6-31G* and MP2/6-31G* levels of theory. The preference for the Z conformer, DeltaE(HF), was calculated to be 5.36 kcal mol(-1) and 7.50 kcal mol(-1) for phenyl acetate and phenyl trifluoroacetate (i.e., with X = H), respectively. The increasing electron-withdrawing ability of the phenyl substituent X increases the preference of the Z conformer. An excellent correlation with a negative slope was observed for both series between DeltaE of the E-Z equilibrium and the Hammett sigma constant. By using an appropriate isodesmic reaction, it was shown that electron-withdrawing substituents decrease the stability of both conformers, but the effect is higher with the E conformer. Electron-withdrawing phenyl substituents decrease the delocalization of the lone pair of the ether oxygen to the C=O antibonding orbital (nO--> pi*C=O) in both the E and Z forms and in both series studied; this effect is higher in the E conformer than in the Z conformer. The nO --> pi*C=O electron donation has a minimum value with tau1= 90 degrees and a maximum value with tau1= 0 degrees (the Z conformer), the value with tau1= 180 degrees (the E conformer) being between these two values, obviously due to steric hindrance. The effects of the phenyl substituents on the reactivity of the esters studied are discussed in terms of molecular orbital interactions. ED/EW substituents adjust the availability of the pi*C=O antibonding orbital to interact with the lone pair orbital of the attacking nucleophile and therefore affect the reactivity: EW substituents increase and ED substituents decrease it. Excellent correlations were observed between the rate coefficients of nucleophilic acyl substitutions and pi*C=O occupancies of the ester series 4 and 5.     

An ab initio study on thermal rearrangement reactions of 1-silylprop-2-en-1-ol H3SiCH(OH)CH=CH2

The thermal rearrangement reactions of 1-silylprop-2-en-1-ol H3SiCH(OH)CH=CH2 were studied by ab initio calculations at the G2(MP2) and G3 levels. The reaction mechanisms were revealed through ab initio molecular orbital theory. On the basis of the MP2(full)/6-31G(d) optimized geometries, harmonic vibrational frequencies of various stationary points were calculated. The reaction paths were investigated and confirmed by intrinsic reaction coordinate (IRC) calculations. The results show that the thermal rearrangements of H3SiCH(OH)CH=CH2 happen in two ways. One is via the Brook rearrangement reactions (reaction A), and the silyl group migrates from carbon atom to oxygen atom passing through a double three-membered ring transition state, forming allyloxysilane CH2=CHCH2OSiH3. In the other, the reactant undergoes a dyotropic rearrangement; the hydroxyl group migrates from carbon atom to silicon atom coupled with a simultaneous migration of a hydrogen atom from silicon atom to carbon atom, forming allylsilanol CH2=CHCH2SiH2OH (reaction B). The barriers for reactions A and B were computed to be 343.5 and 203.7 kJ/mol, respectively, at the G3 level. The changes of the thermodynamic functions, entropy (DeltaS), entropy (DeltaS(doubledagger)) for the transition state, enthalpy (DeltaH), and free energy (DeltaG) were calculated by using the MP2(full)/6-31G(d) optimized geometries, and harmonic vibrational frequencies of reactants, transition states, and products with statistical mechanical methods, and equilibrium constant K(T) and reaction rate constant k(T) in canonical variational transition-state theory (CVT) with centrifugal-dominant small-curvature tunneling approximation (SCT) were calculated over a temperature range 400-1300 K. The conventional transition-state theory (TST) rate constants were also calculated for the purposes of comparison. The influences of the vinyl group attached to the center carbon of the alpha-silyl alcohols on reactions were discussed.     

Hydroboration; An ab initio study of the reaction of BH3 with ethylene

Ab initio molecular orbital calculations indicate the reaction of BH₃ with ethylene to proceed exothermically via an intermediate π-complex, but without an overall activation barrier. The mechanism of the reaction in the gas phase is indicated to proceed in two facile stages: the formation of the π-complex and its rearrangement to ethyl borane product. The progress of the reaction is shown pictorially by drawings of the interacting orbitals at various stages.     

Criteria for pericyclic and pseudopericyclic character of electrocyclization of (Z)-1,2,4,6-heptatetraene and (2Z)-2,4,5-hexatriene-1-imine

The electrocyclic reaction mechanisms of (Z)-1,2,4,6-heptatetraene and (2Z)-2,4,5-hexatriene-1-imine were studied by ab initio MO methods. The activation energy barrier height of the electrocyclic reaction of (Z)-1,2,4,6-heptatetraene is extremely a low energy barrier of 8.58 kcal/mol by a MRMP method. The activation energy barrier height of the electrocyclic ring closure of the trans-type of (2Z)-2,4,5-hexatriene-1-imine is lower by 3.18 kcal/mol than that of (Z)-1,2,4,6-heptatetraene. These low energy barriers come from some orbital interactions relating to allene group. For the reaction of (Z)-1,2,4,6-heptatetraene, the interactions of the vertical and side π orbitals of the allene group with another terminal π orbital are important at the transition state. The interaction of the vertical π orbital of allene group with a lone pair orbital of N atom is dominant at the transition state of the reaction of the trans-type of (2Z)-2,4,5- hexatriene-1-imine. The electrocyclic mechanism of the cis-type of (2Z)-2,4,5-hexatriene-1-imine was also discussed. Contribution of the Mark S. Gordon 65th Birthday Festschrift issue.     

Efficient approach to 3,3-bissilyl carbonyl and enol derivatives via retro-[1,4] brook rearrangement of 3-silyl allyloxysilanes

A facile and highly stereoselective retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes has been discovered. While basic hydrolysis of the formed (Z)-3,3-bissilyl lithium enolates provides 3,3-bissilyl carbonyl compounds efficiently, trapping the species with various electrophiles including alkyl halides leads to the exclusive O-substituted (Z)-3,3-bissilyl enol derivatives that can undergo a Sakurai reaction with aldehyde to produce the synthetically useful 1,2-diol diastereoselectively.     

Temporary silicon connection strategies in intramolecular allylation of aldehydes with allylsilanes

Three gamma-(amino)silyl-substituted allylsilanes 14a-c have been prepared in three steps from the corresponding dialkyldichlorosilane. The aminosilyl group has been used to link this allylsilane nucleophile to a series of beta-hydroxy aldehydes through a silyl ether temporary connection. The size of the alkyl substituents at the silyl ether tether governs the outcome of the reaction on exposure to acid. Thus, treatment of aldehyde (E)-9aa, which contains a dimethylsilyl ether connection between the aldehyde and allylsilane, with a range of Lewis and Br?nsted acid activators provides an (E)-diene product. The mechanism of formation of this undesired product is discussed. Systems containing a sterically more bulky diethylsilyl ether connection react differently: thus in the presence of TMSOTf and a Br?nsted acid scavenger, intramolecular allylation proceeds smoothly to provide two out of the possible four diastereoisomeric oxasilacycles, 23 (major) and 21 (minor). A diene product again accounts for the remaining mass balance in the reaction. This side product can be completely suppressed by using a sterically even more bulky diisopropylsilyl ether connection in the cyclization precursor, although this is now at the expense of a slight erosion in the 1,3-stereoinduction in the allylation products. The sense of 1,3-stereoinduction observed in these intramolecular allylations has been rationalized by using an electrostatic argument, which can also explain the stereochemical outcome of a number of related reactions. Levels of 1,4-stereoinduction in the intramolecular allylation are more modest but can be significantly improved in some cases by using a tethered (Z)-allylsilane in place of its (E)-stereoisomer. Oxidation of the major diastereoisomeric allylation product 23 under Tamao-Kumada conditions provides an entry into stereodefined 1,2-anti-2,4-syn triols 28.     

Interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate: a distinctive B(12)-dependent carbon-skeleton rearrangement

The interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate catalyzed by B(12)-dependent glutamate mutase is discussed using results from high-level ab initio molecular orbital calculations. Evidence is presented regarding the possible role of coenzyme-B(12) in substrate activation and product formation via radical generation. Calculated electron paramagnetic resonance parameters support experimental evidence for the involvement of substrate-derived radicals and will hopefully aid the future detection of other important radical intermediates. The height of the rearrangement barrier for a fragmentation-recombination pathway, calculated with a model that includes neutral amino and carboxylic acid substituents in the migrating glycyl group, supports recent experimental evidence for the interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate through such a pathway. Our calculations suggest that the enzyme may facilitate the rearrangement of (S)-glutamate through (partial) proton-transfer processes that control the protonation state of substituents in the migrating group.     

A computational study of the factors controlling triplet-state reactivity in 1,4-pentadiene

The triplet-state reactions of 1,4-pentadiene have been investigated using density functional theory (UB3LYP) and ab initio (CASSCF) calculations with a 6-31G basis set. Intramolecular [2 + 2] photocycloadditions and three different reaction pathways leading to vinylcyclopropane have been examined. The computed results are in good agreement with the experimental observations, predicting the dominant product to be vinylcyclopropane produced by a di-pi-methane rearrangement, and the favored [2 + 2] cycloaddition product to be bicyclo[2.1.0]pentane. Reaction pathways involving initial C-C or C-H bond cleavage were found to be too high in energy to be significant. Both the [2 + 2] cycloadditions and the di-pi-methane rearrangement proceed through cyclic biradical intermediates formed on the triplet surface. The relative rates of formation of these triplet biradicals are found to depend on three factors: biradical stability, the geometry of the transition structure, and orbital interactions through bonds.     

New insight on the origin of the unusual acidity of Meldrum's acid from ab initio and combined QM/MM simulation study.

Ab initio molecular orbital and combined QM/MM Monte Carlo simulations have been carried out to investigate the origin of the unusually high acidity of Meldrum's acid. Traditionally, the high acidity of Meldrum's acid relative to that of methyl malonate has been attributed to an additive effect due to the presence of two E esters in the dilactone system. However, the present study reveals that there is significant nonadditive effect that also makes major contributions. This results from preferential stabilization of the enolate anion over that of Meldrum's acid due to anomeric stereoelectronic interactions. To investigate solvent effects on the acidity in aqueous solution, the relative acidities of Z and E conformers of methyl acetate have been determined in combined ab initio QM/MM simulations. There is significant solvent effect on the conformational equilibria for both the neutral ester and its enolate anion in water, leading to stabilization of the E stereoisomer. However, the computed solvent effect of 4.4 kcal/mol in favor of the E isomer of methyl acetate is largely offset by the favorable solvation of 3.4 kcal/mol for the E conformer of the enolate anion. This leads to an enhanced acidity of 3.4 kcal/mol for the (E)-methyl acetate in water over the Z conformer. In Meldrum's acid, it is the preferential stabilization of the enolate anion due to anomeric effects coupled with the intrinsically higher acidity of the E conformation of ester that is responsible for its high acidity.     

Revised structure of a purported 1,2-dioxin: a combined experimental and theoretical study

3,6-Bis(p-tolyl)-1,2-dioxin (1g) was suggested by Shine and Zhao as a product in an electron-transfer (ET) photochemical reaction. This photoproduct is instead shown to be (E)-1,4-di-p-tolylbut-2-ene-1,4-dione ((E)-4a). Ab initio and DFT calculations indicate that ring-closed 1,2-dioxin is thermodynamically far less stable than open-chain but-2-ene-1,3-dione. These calculations indicate that (E)-4a is formed via the cation radical of 1g, which sequentially isomerizes to a novel sigma-radical with an O,O 3e bond [(Z)-4a](+)(*), undergoes ET to give (Z)-4a, and then photoisomerizes to (E)-4a.     

Retro‐Brook Rearrangement of Ferrocene‐Derived Silyl Ethers

An intramolecular Li–Si exchange was observed on various lithiated ferrocenylbenzyl silyl ethers. The thermodynamically more stable C‐silylated isomers were isolated in good yields and fully characterized. The reaction mechanism of the [1,4] retro‐Brook rearrangement was investigated by DFT calculations. Two distinct reaction routes were proposed and a possible stabilization effect of the ferrocenyl fragment on the C‐silylated isomers was described. The diastereoselective rearrangement of the trimethylsilyl group to the ortho position of the ferrocenyl cyclopentadienyl ring was also accomplished and the absolute configuration of the product was determined.     

Enzyme catalysis of 1,2-amino shifts: the cooperative action of B6, B12, and aminomutases

Ab initio molecular orbital theory is used to investigate 1,2-amino shifts catalyzed by aminomutases, coenzyme B12, and vitamin B6 (in the form of pyridoxal 5'-phosphate or PLP). Our calculations suggest essential catalytic roles for each of B12, B6, and the enzyme in aminomutase-catalyzed reactions. In the first place, coenzyme B12 provides a source of abstracting radicals, allowing the rearrangement reaction to take place on the radical surface. The involvement of radicals is supported by comparison of experimental and theoretical electron paramagnetic resonance parameters. Next, B6 allows the enzyme to lower the barrier height by introducing a double bond (allowing a low-energy intramolecular rearrangement pathway) and by providing a suitable site for partial protonation (preventing overstabilization of the reaction intermediate which could lead to enzyme inactivation). The PLP hydroxyl group is also identified as an important participant in these reactions. Finally, the enzyme holds the various reaction components in place and is the source of acidic functional groups that can provide partial protonation.     

A pericyclic cascade to the stereocontrolled synthesis of 9-cis-retinoids

A domino reaction that is pericyclic in nature is thought to be triggered upon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl sulfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiating [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrence of the C7 to C11 hydrogen migration has been demonstrated by labeling experiments. The double diastereoselection of the [1,5]-sigmatropic hydrogen shift to afford a single isomer of the final polyene 13 is thought to arise from a combination of the electronic effect of the sulfoxide at one terminus, and the steric effect imparted by the bulky trimethylcyclohexenyl substituent at the other terminus. The overall process thus constitutes a stereoselective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in particular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoids, including labeled analogues, is straightforward.     

乙叉到乙炔重排反应的反应途径的理论研究

本文用Morokuma提出的数值方案, 基于SCF MO ab initio(STO-3G), 求得了乙叉到乙炔重排反应的内禀反应坐标IRC(Fukui提出的与坐标系无关的反应途径), 并对反应过程中几何构型的改变进行了讨论, 在用MINDD/3方法对诚反应进行研究时, 发现反应过程中有其它中间体存在, 本文也对这种不正确的结果进行了讨论。
本文优化得到的反应物、产物和过渡态几何构型与更精确的理论方法所得的结果定性相符, 用单行列式和CID(考虑所有双激发组态的组态相互作用)所得该反应的位垒分别为123.85和95.81 kJ mol~(-1), 也与更精确方法得到的值相符; 本文还得到了该反应的过渡态的振动频率和正则振动模式。