Stereochemistry Of Reaction Research Articles

过渡金属催化高选择性膦氢化反应

In this review, we summarized the literatures in the latest decades, especially those in recent 15 years (from 1996), on the discovery and development of transition metal-catalyzed highly selective hydrophosphorylation reactions of alkynes and alkenes. Scope, mechanism and stereochemistry of the hydrophosphorylation reactions were presented.

Design and Use of Nanostructured Single-Site Heterogeneous Catalysts for the Selective Transformation of Fine Chemicals

Nanostructured single-site heterogeneous catalysts possess the advantages of classical solid catalysts, in terms of easy recovery and recycling, together with a defined tailored chemical and steric environment around the catalytically active metal site. The use of inorganic oxide supports with selected shape and porosity at a nanometric level may have a relevant impact on the regio- and stereochemistry of the catalytic reaction. Analogously, by choosing the optimal preparation techniques to obtain spatially isolated and well-characterised active sites, it is possible to achieve performances that are comparable to (or, in the most favourable cases, better than) those obtained with homogeneous systems. Such catalysts are therefore particularly suitable for the transformation of highly-functionalised fine chemicals and some relevant examples where high chemo-, regio- and stereoselectivity are crucial will be described.

Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450

Cytochromes P450 (CYPs) metabolize polyunsaturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., omega6 in AA or omega3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefin of AA (omega6), EPA (omega3), or DHA (omega3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs.

Cooperative N-Heterocyclic Carbene/Lewis Acid Catalysis for Highly Stereoselective Annulation Reactions with Homoenolates

A new approach that takes advantage of N-heterocyclic carbene/Lewis acid cooperative catalysis provides access to cis-1,3,4-trisubstituted cyclopentenes from enals and chalcone derivatives with high levels of diastereoselectivity and enantioselectivity. The presence of Ti(OiPr)(4) as the Lewis acid allows for efficient substrate preorganization, which translates into high levels of diastereoselectivity. Additionally, we demonstrate the possibility of controlling the absolute stereochemistry of NHC-catalyzed reactions by employing a catalytic amount of a chiral Lewis acid as the unique source of optically active promoter.

The reactions of B-norsteroidal 4- and 5-enes

Aspects of the stereochemistry of addition reactions to B-norsteroidal 4- and 5-alkenes are compared to the corresponding reactions in normal 6:6 A/B series.

Theoretical study of stereodynamics for the O( 1D) + D 2 → OD + D reaction

A quasi-classical trajectory method (QCT) running on the 1A′ and 1A″ potential energy surfaces (PESs) given by Dobbyn and Knowles [A.J. Dobbyn, P.J. Knowles, Mol. Phys. 91 (1997) 1107] has been employed to study the dynamical stereochemistry of the chemical reaction O( 1D) + D 2 → OD + D, especially the vector correlations between products and reagents. The results indicate that product rotational angular momentum j′ is not only aligned, but also oriented along the direction perpendicular to the scattering plane on both PESs, with different rotational polarization behaviors of product OD for the two PESs and for different collision energies. Calculations show that the alignment effect of products become weaker with an increase of the collision energy on the 1A′ PES but is not sensitive to the collision energy on the 1A″ PES. When the collision energy increases, the product OD mainly tends to the forward scattering on the 1A′ PES and displays a switch from the backward scattering to the forward one on the 1A″ PES. These differences are probably attributed to the different characteristics of the two PESs.

Pt−Sn-Based SAPO-34 Supported Novel Catalyst for n-Butane Dehydrogenation

The performance of Pt−Sn/SAPO-34 novel catalyst was investigated for n-butane dehydrogenation. The catalyst was characterized by number of physiochemical techniques X-ray fluorescence (XRF), X-ray diffraction (XRD), ammonia temperature-programmed desorption (NH3-TPD), hydrogen temperature-programmed reduction (H2-TPR), temperature-programmed oxidation (TPO), transmission electron microscopy (TEM), and O2-pulse coke measurement. The metallic contents, structure, acidity, and metallic dispersion were determined in order to explain catalyst superiority and functionality using SAPO-34 as support. Pt−Sn-based SAPO-34 supported catalyst was parametrically characterized in order to obtain superior control of dehydrogenation reaction stereochemistry. Above 91% of total olefins with 80% butene was achieved over Pt−Sn/SAPO-34. The weight hourly space velocity 2.8 h−1 and temperature 585 °C were found to be optimum for the higher dehydrogenation activity. The catalysts also showed very good hydrothermal stability in continuous reaction−regeneration cycles. The coke formation was mainly related to catalyst activity.

Asymmetric synthesis and σ receptor affinity of enantiomerically pure 1,4-disubstituted tetrahydro-1 H-3-benzazepines

A very short (three steps) asymmetric synthesis of enantiomerically pure 1,4-disubstituted tetrahydro-1 H-3-benzazepines 14 has been elaborated upon, starting from the trans- and cis-configured 11a-substituted 3-phenyl-2,3,11,11a-tetrahydro[1,3]oxazolo[2,3- b]-[3]-benzazepin-5(6 H)-ones 6 and 7. The stereoisomerically pure lactams 6 and 7 were benzylated to give 6-benzyl-substituted products 8 and 9. NOE experiments showed a trans-configuration of the benzyl residue and the residue in the 11a-position indicated that the stereochemistry of the benzylation reaction was controlled by the stereocenter at the 11a-position. Reduction of the benzylated tricyclic benzolactams 8 and 9 with AlCl 3/LiAlH 4 (1/3) yielded the 1,3,4-trisubstituted 3-benzazepines 12 and 13, which were formed stereoselectively with the retention of configuration. Finally, removal of the N-(2-hydroxy-1-phenylethyl) residue by hydrogenolytic cleavage resulted in the formation of enantiomerically pure 1,4-disubstituted 3-benzazepines 14. The σ 1, σ 2, and NMDA receptor affinities of the enantiomerically pure 3-benzazepines 14 and ent- 14 were investigated in competitive receptor binding studies. The butyl derivative ent- 14c showed a high affinity towards σ 1 and σ 2 receptors, with K i-values of 26 nM and 41 nM, respectively.

A Short and Efficient Synthesis of (−)-7-Methylomuralide, a Potent Proteasome Inhibitor

Short, practical, and scalable syntheses of (+/-)-7-methylomuralide and (-)-7-methylomuralide have been developed. Three consecutive tandem reaction pairs establish all of the carbons and the stereochemistry of the target molecule, vastly simplifying the synthetic scheme from N-trichloroethoxycarbonyl glycine. The chiral directing group controls the absolute stereochemistry of the key aldol reaction.

A Proposal for a Convenient Notation for P-Chiral Nucleotide Analogues. Part 4. A Relationship Between the D P/L P Notation and Stereochemistry of Reactions

Recently, we have proposed a new DP/LP stereochemical notation for P-chiral dinucleoside monophosphate analogues based on a structural relationship between compounds. As an extension of this work, we present here applications of the DP/LP notation for tracking stereochemistry of reaction pathways involving H-phosphonate, phosphoramidite, phosphorotriester, and other intermediates frequently met in the nucleotide chemistry.

On the Effect of Tether Composition on cis/trans Selectivity in Intramolecular Diels–Alder Reactions

Intramolecular Diels-Alder (IMDA) transition structures (TSs) and energies have been computed at the B3LYP/6-31+G(d) and CBS-QB3 levels of theory for a series of 1,3,8-nonatrienes, H(2)C=CH-CH=CH-CH(2)-X-Z-CH=CH(2) [-X-Z- = -CH(2)-CH(2)- (1); -O-C(=O)- (2); -CH(2)-C(=O)- (3); -O-CH(2)- (4); -NH-C(=O)- (5); -S-C(=O)- (6); -O-C(=S)- (7); -NH-C(=S)- (8); -S-C(=S)- (9)]. For each system studied (1-9), cis- and trans-TS isomers, corresponding, respectively, to endo- and exo-positioning of the -C-X-Z- tether with respect to the diene, have been located and their relative energies (E(rel) (TS)) employed to predict the cis/trans IMDA product ratio. Although the E(rel) (TS) values are modest (typically <3 kJ mol(-1)), they follow a clear and systematic trend. Specifically, as the electronegativity of the tether group X is reduced (X=O --> NH or S), the IMDA cis stereoselectivity diminishes. The predicted stereochemical reaction preferences are explained in terms of two opposing effects operating in the cis-TS, namely (1) unfavorable torsional (eclipsing) strain about the C4-C5 bond, that is caused by the -C-X-C(=Y)- group's strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the endo-(thio)carbonyl group, C=Y, and the diene. The former interaction predominates when X is weakly electronegative (X=N, S), while the latter is dominant when X is more strongly electronegative (X=O), or a methylene group (X=CH(2)) which increases tether flexibility. These predictions hold up to experimental scrutiny, with synthetic IMDA reactions of 1, 2, 3, and 4 (published work) and 5, 6, and 8 (this work) delivering ratios close to those calculated. The reactions of thiolacrylate 5 and thioamide 8 represent the first examples of IMDA reactions with tethers of these types. Our results point to strategies for designing tethers, which lead to improved cis/trans-selectivities in IMDAs that are normally only weakly selective. Experimental verification of the validity of this claim comes in the form of fumaramide 14, which undergoes a more trans-selective IMDA reaction than the corresponding ester tethered precursor 13.

Formation of γ-Lactones through CAN-Mediated Oxidative Cleavage of Hemiketals

The generation of substituted gamma-lactones can be accomplished through application of a tandem chain extension-aldol reaction, followed by CAN-mediated oxidative cleavage of the aldol product. The oxidative cleavage requires the intermediacy of a hemiketal and the presence of an alpha-heteroatom. Formation of the gamma-lactone through the oxidative cleavage is used to assign stereochemistry of the aldol reaction and as the final step in a short synthesis of members of the phaseolinic acid family of natural products.

Theoretical study of the stereodynamics of the reactions of [formula omitted

The vector correlations between products and reagents for the chemical reactions He + H 2 + / HD + have been calculated by means of the quasi-classical trajectory (QCT) method at a collision energy of 1.0 eV on the AQUILANTI surface [P. Palmieri, C. Puzzarini, V. Aquilanti, G. Capecchi, S. Cavalli, D. De Fazio, A. Aguilar, X. Gimenez, J.M. Lucas, Mol. Phys. 98 (2000) 1835]. The isotope effect on dynamical stereochemistry of the title reactions is discussed in detail. The pronounced isotopic effect may be ascribed to the difference of the mass factor in the two reactions.

Stereochemistry of the carboxylation reaction catalyzed by the ATP-dependent phosphoenolpyruvate carboxykinases from Saccharomyces cerevisiae and Anaerobiospirillum succiniciproducens

The stereochemistry of CO 2 addition to phosphoenolpyruvate (PEP) to yield oxaloacetate catalyzed by ATP-dependent Saccharomyces cerevisiae and Anaerobiospirillum succiniciproducens PEP carboxykinases was determined using (Z)-3-fluorophosphoenolpyruvate ((Z)-F-PEP) as a substrate analog. A. succiniciproducens and S. cerevisiae PEP carboxykinases utilized (Z)-F-PEP with 1/14 and 1/47 the respective K m values for PEP. On the other hand, in the bacterial and yeast enzymes k cat was reduced to 1/67 and 1/48 the value with PEP, respectively. The binding affinity of pyridoxylphosphate-labeled S. cerevisiae and A. succiniciproducens PEP carboxykinases for PEP and (Z)-F-PEP was checked and found to be of similar magnitude for both substrates, suggesting that the lowered K m values for the fluorine-containing PEP analog are due to kinetic effects. The lowered k cat values when using (Z)-F-PEP as substrate suggest that the electron withdrawing effect of fluorine affects the nucleophilic attack of the double bond of (Z)-F-PEP to CO 2. For the stereochemical analyses, the carboxylation of (Z)-F-PEP was coupled to malate dehydrogenase to yield 3-fluoromalate, which was analyzed by 19F NMR. The fluoromalate obtained was identified as (2 R, 3 R)-3-fluoromalate for both the A. succiniciproducens and S. cerevisiae PEP carboxykinases, thus indicating that CO 2 addition to (Z)-F-PEP, and hence PEP, takes place through the 2- si face of the double bond. These results, together with previously published data [Rose, I.A. et al. J. Biol. Chem. 244 (1969) 6130–6133; Hwang, S.H. and Nowak, T. Biochemistry 25 (1986) 5590–5595] indicate that PEP carboxykinases, no matter their nucleotide specificity, catalyze the carboxylation of PEP from the 2- si face of the double bond.

Phosphine-dependent Stereoselective Nucleophilic Reaction to Bicyclic Bis-μ-dichloro-η3-allylpalladium Complexes

Abstract The effects on ligands in nucleophilic reaction of η3-allylpalladium chloride dimers were studied. Reaction of steroid 1 with Na2PdCl4 in concentrated HCl under CO gave the cis,trans-bis-μ-dichloro-η3-allylpalladium complex 2 after recrystallization. Reaction of 2 with malonate anion in the presence of PPh3 afforded trans-3 in 65% yield. When Dppe was used, cis-3 was obtained as the major product. In nucleophilic reactions of bicyclic η3-allylpalladium chloride complex 4a or 4b with PPh3, cis-5 was the major product. However, the reaction with Dppe gave trans-5 predominantly. The stereochemistry in the nucleophilic reaction of η3-allylpalladium chloride dimer is dependent on the added phosphines.

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

AbstractA powerful approach for controlling the stereochemistry of glycosylation reactions involves using a directing group at an adjacent carbon to influence the stereochemistry of nucleophilic attack. The use of substituents such as I, PhS, and PhSe has proven to be especially valuable because it enables the preparation of 2‐deoxysugars after reductive removal of the directing group. The mechanisms of these reactions are generally considered to involve nucleophilic opening of bridged onium ions and to proceed with inversion. Onium ions, however, equilibrate with open cations, and these open forms can be favored when the cation is highly stabilized. Although the selectivities of reactions of carbohydrate‐derived cations are consistent with the intermediacy of onium ions, the reactions of acyclic cations are not. Instead, consideration of the preferred conformations of the oxocarbenium ions and stereoelectronically favored additions to these intermediates provides a predictive model to explain the diastereoselectivities observed in reactions of oxocarbenium ions bearing proximal heteroatoms.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)

Pre-activation protocol leading to highly stereoselectivity-controllable glycosylations of oxazolidinone protected glucosamines

Under pre-activation glycosylation conditions, the 4,6-di-O-acetyl-N-acetyloxazolidinone protected donor afforded either excellent beta- or alpha-stereoselectivity simply by means of the addition of hindered base TTBP or the absence of base, leading to the controllable stereochemistry of coupling reactions.

DFt study of the regioselectivity of addition of sulfenylchloride to ethenes

AbstractThe electrophilic addition reactions of methylsulfenyl chloride to the double bonds of functionalized ethenes have been studied theoretically. Density functional theory (DFT) calculations have been applied for starting species and ethene‐based sulfonium intermediates bearing substitutes at α‐carbon atom to study geometrical parameters and electronic states of plausible intermediate forms. The quantum chemical optimizations of intermediates indicate that the episulfonium ion is the most likely methyl‐ or carboxyl‐substituted ethane‐based intermediate. However, with phenyl substituents the intermediate is more like a carbonium than an episulfonium ion. The role of sulfur appears to be that of directing the stereochemistry of the addition reaction of chloride, forming the trans product upon nucleophilic attack on the C—C bond of the episulfonium ion. The regioselectivity features of the opening of the episulfonium ion by the chloride anion depend on the LUMO and LUMO+1 of the episulfonium ion and the approaching HOMO of chlorine. The results of the theoretical investigations are in agreement with experiment. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:695–703, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20378

Oxygen Donor-Mediated Equilibration of Diastereomeric Alkene−Palladium(II) Intermediates in Enantioselective Desymmetrizing Heck Cyclizations

This investigation examines the origin of enantioselection in the desymmetrization of an acyclic prochiral Heck cyclization precursor. High asymmetric induction (97-98% ee) is attributed to a temporary interaction of a Lewis basic oxygen donor with weakly Lewis acidic palladium(II). A series of control experiments combined with quantum-chemical model calculations provided sound evidence for a mechanism involving oxygen donor-mediated, rapid equilibration of diastereomeric alkene-palladium(II) complexes prior to the selectivity-determining ring-closing event, a Curtin-Hammett scenario. Our study also highlights the importance of the cationic pathway (triflate counter anions versus halido ligand) and alkene stereochemistry (E versus Z) in asymmetric Heck reactions.

A Theoretical Study of Favorskii Reaction Stereochemistry. Lessons in Torquoselectivity

The mechanisms of the chloroenolate-->cyclopropanone step of the "normal" Favorskii rearrangement have been investigated in detail using high-level ab initio calculations. A series of simple alpha-chloroenolates, based on chloroacetone (6), all monomethyl derivatives (7-9), a dimethyl analogue (10), and 1-acetyl-1-chlorocyclohexane (11) was first used to explore and define the basic features of the mechanism, which include the finding of both an "inversion" and a "retention" transition state and that in most cases these arise from separate ground-state conformations of the chloroenolate. These theoretical studies were then extended to an isomeric pair of chloroenolates 1 and 2, the cis- and trans-2-methyl derivatives of 11, which are the reactive intermediates involved in a well-known experimental study carried out by Stork and Borowitz (S-B). Finally, three alpha-chlorocyclohexanone enolate systems 12-14 were studied, since these intermediates have a more restricted enolate geometry. The "inversion" mechanism has been described as an SN2 process but the present results, while supporting a concerted process, is better described as an oxyallyl structure undergoing concerted ring closure. The "retention" mechanism has been described as SN1-like, but the calculations show that this process is also concerted, although much less so, and again involves oxyallyl-like transition-states. The model systems 6-8, 10, and 11 with a potential plane of symmetry have two enantiomeric transition states for inversion and another two for retention of configuration (at the C-Cl center). With 9 and the S-B models 1 and 2, with no symmetry plane, there are a calculated total of four diastereomeric transition states for cyclopropanone ring closure in each case, two for inversion and two for retention. While the transition-state energies calculated for simple chloroenolates favor the inversion process, the S-B models 1 and 2 have almost equal inversion-retention transition-state energies. Solvation simulation calculations of ground states and transition states suggest that the retention mechanism becomes relatively more favored in polar solvents, in agreement with some experimental results. In the chloroenolates 12-14, both inversion and retention mechanisms were also located, these arising from two different ground-state ring conformations of the enolate. In these models, one also finds similar inversion and retention transition-state energies, but again with a small preference for the inversion process.