Ruthenium(IV)-catalyzed isomerization of the C=C bond of o-allylic substrates: a theoretical and experimental study

A general mechanism to rationalize Ru(IV) -catalyzed isomerization of the C=C bond in O-allylic substrates is proposed. Calculations supporting the proposed mechanism were performed at the MPWB1K/6-311+G(d,p)+SDD level of theory. All experimental observations in different solvents (water and THF) and under different pH conditions (neutral and basic) can be interpreted in terms of the new mechanism. Theoretical analysis of the transformation from precatalyst to catalyst led to structural identification of the active species in different media. The experimentally observed induction period is related to the magnitudes of the energy barriers computed for that process. The theoretical energy profile for the catalytic cycle requires application of relatively high temperatures, as is experimentally observed. Participation of a water molecule in the reaction coordinate is mechanistically essential when the reaction is carried out in aqueous medium. The new mechanistic proposal helped to develop a new experimental procedure for isomerization of allyl ethers to 1-propenyl ethers under neutral aqueous conditions. This process is an unique example of efficient and selective catalytic isomerization of allyl ethers in aqueous medium.     

Origin of diastereoselectivity in the tandem oxy-Cope/Claisen/ene reaction: experimental and theoretical studies of the ring inversion mechanism

We report herein a detailed investigation into the reaction mechanism of the oxy-Cope/Claisen/ene reaction. A series of chiral substrates was prepared, subjected to the tandem sequence, and the enantiomeric excess of the final products was evaluated. The observed conservation of enantiomeric excess was taken as evidence that the ring inversion of the intermediary enol ether does not occur. DFT calculations were used to map out the potential energy surface for the reaction and evaluate the relative energies of the ring inversions relative to those of the Claisen and ene reactions. Transition state energies thus obtained were found to support the presence of a high-energy transition state for the ring inversion of B to D provided R(1) not equal H. In addition, the calculations lent further support to the hypothesis that the selectivity of the transannular ene reaction is under Curtin-Hammett control.     

Synthetic studies toward the construction of the cis-decalin portion of superstolides A and B. Application of a sequential double michael reaction and an anionic oxy-Cope rearrangement

A highly convergent strategy for the asymmetric synthesis of the cis-decalin portion of the antitumor macrolide superstolide A was developed. The key reactions in our approach involve a sequential double Michael reaction and an anionic oxy-Cope rearrangement.     

The aromatic oxy-Cope rearrangement

An aromatic oxy-Cope rearrangement can be achieved under anionic conditions (KH + HMPA) in low yield with a naphthalene ring but not a phenyl.     

Highly efficient transfer of chirality from macrocyclic conformation in the tandem oxy-Cope/Claisen/ene reaction

We report three highly stereoselective pericyclic reactions occurring in cascade leading to the synthesis of Decalins skeletons possessing two contiguous quaternary centers. The tandem reaction is triggered by an oxy-Cope rearrangement to create in situ a 10-membered ring enol ether macrocyle 6, which immediately rearranges via a Claisen [3,3] shift to the corresponding E-cyclodec-6-en-1-one 7. The latter spontaneously cyclizes via a transannular ene reaction to produce Decalin 5. Analysis of the mechanism with respect to the origin of the high diastereoselectivity of the tandem oxy-Cope/Claisen/ene reaction is presented.     

Uridate/pyridyl Pd(II) complexes: Phosphine-free high turnover catalysts for the Heck reaction of deactivated aryl bromides

The synthesis and structure of palladium(II) complexes bearing uridato/pyridyl ligands as an anionic N-donor coordination sites are reported. The complexes have been shown to be highly active catalysts for the Heck reaction of aryl bromides (TON 4.0×10⁴-9.1×10⁴) and moderate activity for the activation of aryl chlorides under phosphine-free conditions.     

Density functional computational studies on the glucose and glycine Maillard reaction: Formation of the Amadori rearrangement products

Theoretical energy changes of various intermediates leading to the formation of the Amadori rearrangement products (ARPs) under different mechanistic assumptions have been calculated, by using open chain glucose (O‐Glu)/closed chain glucose (A‐Glu and B‐Glu) and glycine (Gly) as a model for the Maillard reaction. Density functional theory (DFT) computations have been applied on the proposed mechanisms under different pH conditions. Thus, the possibility of the formation of different compounds and electronic energy changes for different steps in the proposed mechanisms has been evaluated. B‐Glu has been found to be more efficient than A‐Glu, and A‐Glu has been found more efficient than O‐Glu in the reaction. The reaction under basic condition is the most favorable for the formation of ARPs. Other reaction pathways have been computed and discussed in this work. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

Mechanism of a gas-phase dissociation reaction of 4-aminobutyl glycosides under CID MS/MS conditions

The assembly of monosaccharides during the synthetic process of glycan structures is responsible for the diversity of this family of molecules. Because of the complexity of the glycan structure, synthesis of oligosaccharides and structural analysis have been difficult tasks. During efforts to develop glycosides carrying an aglycon that can be used in both functional and structural investigations, we found that 4-aminobutyl glycosides fulfill these criteria. We also observed that the glycosidic linkage underwent an interesting dissociation reaction under collision-induced MS/MS, and that the reaction product is very useful in structural investigation based on mass spectrometry, especially since it provides information regarding anomeric configurations. Despite its importance, the reaction mechanism of the dissociation is not fully understood. For this reason, we studied the mechanism by synthesizing possible products and used them in detailed analyses based on energy-resolved mass spectrometry where the energy dependence of the dissociation reaction was analyzed under collision-induced dissociation conditions. As a result of spectral match with one of synthesized reference compounds, it was suggested that the dissociation reaction to generate a C-ion species and a pyrrolidine took place through a five-membered transition state in two-step reaction sequence.     

Not quite the last word on the Perkin reaction

Microwave irradiation does not accelerate the rate of the Perkin reaction carried out under normal atmospheric pressure. Water is an essential yet catalytic reactant for the Perkin reaction to occur. Containment of the Perkin reaction in a sealed vessel improves the yield. Two pressure increases are observed during a 4 h reaction time. An induction period is seen in the Perkin reaction when sodium acetate is used as a base. A re-appraisal of the reaction mechanism is proposed on the basis of these observations. The use of PFA^® reaction vessels enables the Perkin reaction to occur under aqueous conditions for around 80 reactions/vessel.     

Michael reaction,VI. Effect of carbonyl compounds on the stereochemistry and mechanism of the reaction

Zusammenfassung Die Stereochemie einer zweistufigen Gleichgewichts-Michael-Reaktion zwischen Dialkylamiden der Phenylessigsäure und Methylestern oder Dialkylamiden der Zimtsäure wird von den neutralen Carbonylverbindungen stark beeinflußt. Dieser Effekt kann mit der Zerstörung einer intramolekularen Chelatstruktur des Addukts und der darauffolgenden Bildung einer offenen Metallform mit einem dem neutralen Addukt ähnlichenerythro-threo-Verhältnis erklärt werden. Die Zunahme der elektrischen Leitfähigkeit des Reaktionsgemisches stützt diese Vorstellung.Es wird ein über das Chelat verlaufender Mechanismus im nichtpolaren Medium postuliert. Dieser Mechanismus ist in guter Übereinstimmung sowohl mit der geringen Stereoselektivität (bei kinetischer Kontrolle) als auch mit dem Einfluß der Lösungsmittel auf die Stereochemie.

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Michael reaction, VI. Effect of carbonyl compounds on the stereochemistry and mechanism of the reaction

The equilibrium stereochemical result of the two-stepMichael reaction between phenylacetic acid dialkylamides and methyl cinnamate or cinnamic acid dialkylamides is affected by the neutral carbonyl compounds taking part in the synthesis. This effect is explained by breakdown of the intramolecular chelate structure of the reaction adduct and appearance of an open metal form with isomeric partitioning close to that of the neutral adduct. This is further supported by the increased electroconductivity of the reaction mixtures. A chelate mechanism for the reaction in nonpolar medium is postulated which is in good agreement with the low stereoselectivity under kinetic conditions as well as with the effect of the polarity of the solvent on the kinetic stereochemical result.

     

The palladium-catalyzed cross-coupling reaction of carboxylic anhydrides with arylboronic acids: a DFT study

The mechanism of the cross-coupling of phenylboronic acid with acetic anhydride, a viable model of the widely used Suzuki reaction, has been studied by DFT calculations at the BP86/6-31G level of theory. Two alternative catalytic cycles have been investigated, one starting from a neutral Pd(0)L(2) complex, the other from an anionic "Jutand-type" [Pd(0)L(2)X](-) species. The reaction profiles are in good agreement with the experimental findings, as both pathways require only moderate activation energies. Both pathways are dominated by cis-configured square-planar palladium(II)diphosphine intermediates. Despite careful investigations, we did not find in this model reaction any evidence for five-coordinate palladium(II) intermediates, which are commonly believed to cause the profound effects of counterions in palladium-catalyzed transformations. Instead, our calculations suggest that the higher catalytic activity of anionic complexes, such as [Pd(PMe(3))(2)OAc](-), may arise from their stronger ability to coordinate to carbon electrophiles. The transmetalation sequence is the same for both catalytic cycles, involving the dissociation of one phosphine ligand from the palladium. In the decisive transition state, in which the phenyl group is transferred from boron to palladium, the acetate base is found to be in a bridging coordination between these two atoms.     

Intramolecular proton transfer in the isomerization of hydroxyacetone: Characterization based on reaction force analysis and the bond fragility spectrum

The mechanism of isomerization of hydroxyacetone to 2-hydroxypropanal is studied within the framework of reaction force analysis at the M06-2X/6-311++G(d,p) level of theory. Three unique pathways are considered: (a) a step-wise mechanism that proceeds through the formation of the Z-isomer of their shared enediol intermediate, (b) a step-wise mechanism that forms the E-isomer of the enediol, and (c) a concerted pathway that bypasses the enediol intermediate. Energy calculations show that the concerted pathway has the lowest activation energy barrier at 45.7 kcal mol⁻¹. The reaction force, chemical potential, and reaction electronic flux are calculated for each reaction to characterize electronic changes throughout the mechanism. The reaction force constant is calculated in order to investigate the synchronous/asynchronous nature of the concerted intramolecular proton transfers involved. Additional characterization of synchronicity is provided by calculating the bond fragility spectrum for each mechanism.     

A DFT study on a mutipathways,one product reaction: Initially divergent radical reactions reconverge to form a single product

The mechanism for initially divergent radical reactions reconverging to form a single product is studied using density functional theory calculations. The calculation results suggest that there are six possible pathways from reactants to products. The free energy barriers of the rate‐determining steps of each pathway are almost equal. Thus, different from usual reaction, the selectivity of this reaction is determined by the relative value of free energy barriers of the two competitive reactions, that is, cyclization and bimolecular trapping, rather than that of rate‐determining steps. In all reaction pathways, cyclization reaction is more competitive than bimolecular trapping reaction due to its low free energy barrier. In addition, the free energy barriers of bimolecular trapping reaction between Bu₃SnH and reactants are all lower than that of NC? C₆H₁₁. However, Bu₃SnH is not always suitable due to its large steric repulsion. © 2014 Wiley Periodicals, Inc.     

Synthesis of the complete carbocyclic skeleton of vinigrol

[reaction: see text] An efficient entry to the fully elaborated skeleton of vinigrol is described. The installation of the desired stereochemistry at C(12) and the construction of the eight-membered ring were achieved in one operation by a remarkably facile anionic oxy-Cope rearrangement of Z-isopropenyl isomer 24.     

烯烃在催化裂化催化剂上反应机理的初步研究

在自制的微反-色谱装置上,进行了单体烯烃和催化裂化汽油在不同条件下的催化裂化反应实验。对单体烯烃的裂化反应规律和汽油中的烯烃在半再生催化剂和待生催化剂上的催化裂化反应规律进行对比分析。结果表明,单体烯烃反应中,C6及C6以下的烯烃主要发生骨架异构和双键异构反应,氢转移和直接裂化反应发生的较少。C7以上的烯烃95%以上发生转化,高温下直接裂化生成C3、C4,氢转移和异构化比率较大。汽油中的烯烃转化主要集中在C7以上,烯烃之间存在一定的交互作用,单体烯烃的催化裂化反应规律可以初步预测汽油中烯烃的转化。催化剂上的结焦类型对汽油中的烯烃的转化方式没有影响。     

Conservation of the planar chiral information in the tandem oxy-cope/ene reaction

[reaction: see text] We report the stereoselective synthesis of a Decalin unit using a tandem oxy-Cope/ene reaction. [3,3]-Shift of 1,2-divinylcyclohexenol 18 generates (1E, 3Z, 7E) cyclodecatrien-2-ol 23 which tautomerizes to ketone 21 (Figure 3). The chiral information embedded in 23 is transferred into the newly formed stereogenic carbon C6 in 21. The efficiency of the chirality transfer is a reflection of the difference in the rates of ring inversion versus tautomerization of 23. Ketone 21 undergoes a carbonyl-ene reaction to give Decalin 20. Assuming a rapid equilibrium between macrocyclic diastereomers, the diastereomeric ratio of the transannular ene reaction is governed by the Curtin-Hammett principle. Analysis of the conservation of the planar chiral information in the tandem oxy-Cope/ene reaction is presented.     

On the mechanism of the thermal retrocycloaddition of pyrrolidinofullerenes (retro-Prato reaction)

In contrast to N-methyl or N-unsubstituted pyrrolidinofullerenes, which efficiently undergo the retrocycloaddition reaction to quantitatively afford pristine fullerene, N-benzoyl derivatives do not give this reaction under the same experimental conditions. To unravel the mechanism of the retrocycloaddition process, trapping experiments of the in-situ thermally generated azomethine ylides, with an efficient dipolarophile were conducted. These experiments afforded the respective cycloadducts as an endo/exo isomeric mixture. Theoretical calculations carried out at the DFT level and by using the two-layered ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) approach underpin the experimental findings and predict that the presence of the dienophile is not a basic requirement for the azomethine ylide to be able to leave the fullerene surface under thermal conditions. Once the 1,3-dipole is generated in the reaction medium, it is efficiently trapped by the dipolarophile (maleic anhydride or N-phenylmaleimide). However, for N-unsubstituted pyrrolidinofullerenes, the participation of the dipolarophile in assisting the 1,3-dipole to leave the fullerene surface throughout the whole reaction pathway is also a plausible mechanism that cannot be ruled out.     

Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction

The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.     

Stereoselective synthesis of the cis-decalin subunit of vinigrol via three pericyclic reactions in cascade

Synthesis of the cis-decalin portion of vinigrol using a tandem oxy-Cope/Claisen/ene reaction is described. This three pericyclic reaction cascade proves to be a valuable synthetic tool in the construction of such systems.