On the stereochemistry of the Horner—Emmons reaction between 3-functionally substituted 2-methyl-2-propenylphosphonates and aliphatic aldehydes

The reaction of diethyl 3-ethoxycarbonyl-2-methyl-2-propenylphosphonate (1a) with 3-methylbutanal (2) in heterogeneous MOH (solid)-benzene systems in the presence of 5–10 mol.% of benzyltriethylammonium chloride (BTEAC) gives the reaction product (3) with a higher, for M=K, or lower, for M=Li, ratio of 2E,4E and 2Z,4E-stereoisomers than that observed in the absence of BTEAC. Tetrabutylammonium bromide (TBAB) as a catalyst of the reaction1a + 2 3 in the system KOH (solid)-wet benzene leads to a higher [2E,4E-3][2Z,4E-3] ratio than BTEAC; this ratio grows from 4456 without TBAB to 8020 at 100 mol.% of TBAB. In the latter case the stereochemical outcome of the reaction is similar to that obtained when tetrabutylammonium hydroxide in dry benzene is used as the deprotonating agent. The corresponding diisopropyl phosphonate (1b) and 3,7-dimethyloctanal (4a) interact in the system KOH (solid)-wet benzene-TBAB to give hydroprene (5) containing 88 % of the 2E,4E-isomer (5a) while in the case of 1 equiv. of [(n-Bu₄)N]OH in dry benzene the content of5a is 92 %. Diisopropyl 3-isopropoxycarbonyl-2-methyl-2-propenylphosphonate (1c) and 7-methoxy-3,7-dimethyloctanal (4b) under either of these conditions afford methoprene (6) containing 93 % of the 2E,4E-isomer.Part 6, see ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1094–1098, June, 1993.     

Recent topics of the natural product synthesis by Horner–Wadsworth–Emmons reaction

The Horner–Wadsworth–Emmons (HWE) reaction has become well established among existing methodologies for the highly stereoselective olefination of carbonyl compounds. The reliability of this reaction in terms of its robustness, high stereoselectivity, and broad substrate scope permit retrosynthetic disconnection of the olefin bond in α,β-unsaturated carbonyl intermediates in natural product synthesis. This review discusses recent applications of the HWE reaction in natural product synthesis, highlighting its use for carbon chain elongation, coupling reactions of synthetic segments, ring-closing reactions, tandem reactions including HWE olefination, and asymmetric reactions.     

The stereochemistry of the Grignard — Ortho ester reaction revisited: Regioselective endocyclic cleavage in the reaction of Grignard reagents with cis-2-methoxy-4-methyl-1,3-dioxane

The reaction of cis-2-methoxy-4-methyl-1,3-dioxane (4) with Grignard reagents proceeds in a totally regioselective manner via rupture of the less congested C(2)O(1) bond remote from the 4-methyl substituent. The analogous r-2-methoxy-cis-4,cis-6-dimethyl-1,3-dioxane (2) is totally inert to the action of Grignard reagents.     

Synthesis of 2-functionally substituted oxazolines and oxazolidines from methyl bromopropiolate and Β-amino alcohols

The reaction of methyl bromopropiolate with -amino alcohols containing a primary amino group generally results in the formation of 2-(methoxycarbonylmethyl)-²-1,3-oxazolines, while in the reaction with N-methyl- and N,N-dimethyl-substituted -aminoalcohols, 2-(methoxycarbonylmethylene)-1,3-oxazolidines, or their salts are formed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 406–409, March, 1991.     

First mechanosynthesis of piperlotines A,C, and derivatives through solvent-free Horner–Wadsworth–Emmons reaction

Piperlotines are natural products characterized by an α,β-unsaturated amide moiety. These compounds found wide applications in Medicinal Chemistry like antibacterials, cytotoxic agents, anticoagulants, among others. To date, diverse methods of synthesis have been reported for piperlotines, but involving the use of catalysts, hazard reagents, anhydrous media or coupling reagents. Thus, in this work, we developed a greener method of synthesis of piperlotines A, C, and derivatives, through mechanochemical activation under solvent-free conditions. The reaction of a β-amidophosphonate, K₂CO₃, and an aromatic aldehyde afforded target compounds in moderate to good yields (46–77%), in an open atmosphere by grinding. It is worth to mention that this mechanochemical process was under thermodynamic control because just E isomer was isolated for every reaction. Moreover, synthesized piperlotines have been predicted by means of chemoinformatic analysis as potential therapeutic agents for the treatment of arthritis or cancer.     

Systematic study for the stereochemistry of the Atherton–Todd reaction

Under the Atherton–Todd reaction conditions, the stereochemistry on the reaction of H-phosphinates with different nucleophiles (e.g., amines, alcohols, phenols) was investigated. All reactions took place stereospecifically with inversion of configurations at the phosphorus centers. The reaction might proceed via a phosphoryl chloride intermediate with retention of configuration at phosphorus, followed by the attack of nucleophiles from the backside of Cl to give the substitution products with inversion of configuration at the phosphorus center. A plausible mechanism was proposed for these reactions.     

Organozinc alkoxide-promoted aldol-Tishchenko reaction of aliphatic aldehydes: an expedient entry to prepare the α-methylene ketones

i-PrOZnEt is an excellent reagent to promote the aldol-Tishchenko reaction of the aliphatic aldehydes tethered with other labile functional groups. The 1,3-diol monoesters 4 were formed as the major products, which could be converted to α-methylene ketones 7 in two steps in good yields.     

A rapid ultrasound-promoted Horner–Wadsworth–Emmons reaction for the preparation of ferrocene derivatives. Application to ferrocene-modified ITO electrodes

The Horner–Wadsworth–Emmons reaction of ferrocenecarboxaldehyde with various phosphonate-stabilized carbanions has been performed under ultrasound irradiation. The reaction time at ambient temperature was considerably shortened (5–15 min) compared to nonsonicated conditions requiring often refluxing for 6–24 h. Control of the reaction time can be achieved by tuning the base strength in different solvents. This method was successfully applied to the preparation of various 2-substituted vinylferrocenes. The as-prepared (E)-2-ferrocenylvinylphosphonic acid was used to modify ITO electrodes to form redox-active functionalized ITO electrodes which have been characterized by means of electrochemical techniques.     

Oxidation of primary aliphatic and aromatic aldehydes with difluoro(aryl)-λ3-bromane

Oxidation of primary aliphatic aldehydes with p-trifluoromethylphenyl(difluoro)-λ(3)-bromane in dichloromethane at 0 °C afforded acid fluorides selectively in good yields, while that of aromatic aldehydes in chloroform at room temperature produced aryl difluoromethyl ethers. A larger migratory aptitude of aryl groups compared to primary alkyl groups during a 1,2-shift from carbon to an electron-deficient oxygen atom in bromane(III) Criegee-type intermediates will result in these differences in the reaction courses.     

The organocatalytic enantioselective [3+2] cycloaddition reaction of α,β-unsaturated aldehydes with azomethine ylides applied to the asymmetric synthesis of densely substituted pyrroloisoquinolines

The synthesis of densely functionalized pyrrolo[2,1-a]isoquinolines was accomplished using the organocatalytic [3+2] cycloaddition between enals and azomethine ylides under iminium catalysis developed in our group some years ago as the key step. The cycloaddition proceeds smoothly yielding the corresponding pyrrolidine as a single endo diastereoisomer with enantiopurity in the range of 94–96% and further manipulations of the obtained cycloadducts using high yielding reaction protocols and a final mesylation/intramolecular N-alkylation sequence allowed the synthesis of target compounds in which the integrity of all stereocenters installed during the first step is maintained.     

On the Mechanism of Condensation between 5—Amino—4,6—dichloro—2—methylpyrimidine and 1—Acetyl—2—imidazolin—2—one

The condensation reaction between 5-amino-4,6-dichloro-2-methylprimidine and 1-acetyl-2-imidazolin-2-one using POCl3 as solvent gave 4,6-dichloro-2-methyl-5-(1-acetyl-tetra-hydro-imidazo-2-ylidene)-aminopyrimidine predominantly and 4,6-dichloro-2-methyl-5-{1-1-(2-oxo-tetrahydro-imidazolyl)]-acetene}-aminopyrimidine as by-product. No 4,6-dichloro-2-methyl-5-(1-acetyl-2-imidazolin-2-yl)-aminopyrimidine was found. The result indicated an esterifi-cation-addition-elimination mechanism.     

Reaction products and kinetics of the reaction of NO2 with γ-Fe2O3

The reaction of NO(2) with Fe(2)O(3) has relevance for both atmospheric chemistry and catalysis. Most studies have focused on hematite, α-Fe(2)O(3), as it is the thermodynamic stable state of iron oxide; however, other forms of Fe(2)O(3) naturally occur and may have different chemistries. In this study, we have investigated the reaction products and kinetics for NO(2) reacting with γ-Fe(2)O(3) powder using diffuse reflectance infrared Fourier transform spectroscopy and compared the results to those of previous studies of NO(2) reacting with α-Fe(2)O(3). Both α- and γ-Fe(2)O(3) produce surface-bound nitrate at the pressures examined in this study (24-212 mTorr); surface-bound nitrite products are observed at all pressures for γ-Fe(2)O(3) whereas nitrite was only observed on α-Fe(2)O(3) at lower pressures. Surface-bound NO(+) and Fe-NO products are observed on γ-Fe(2)O(3), which have not been observed with α-Fe(2)O(3). The reaction kinetics show a first-order dependence on NO(2) pressure and this is used to support the hypothesis of unimolecular reaction of adsorbed NO(2) with the γ-Fe(2)O(3) surface as the slow step in the reaction mechanism. The difference in product formation between NO(2) reacting with γ-Fe(2)O(3) and previous studies of α-Fe(2)O(3) illustrate the fact that care must be taken in generalizing reactivity of different polymorphs.     

Nonlinear chemical reaction between Na_2S_2O_3 and Peroxide compound

Kinetics of reaction between Na2S2O3 and peroxide compound ( H2O2 or Na2S2O8) in a batch reactor and in a continuous stirring tank reactor (CSTR) were studied.Steady oscillations in uncatalyzed reactions in a CSTR were first discovered.In Na2S2O3-H2O2-H2SO4 reaction system,Pt potential and pH of higher and lower flow rutes beyond oscillation flow rates were in around the same extreme values.The reaction catalyeed by Cu2+ corsist of the catalyzed oscillation process and the uncatalyzed osciliation one.On the basis of experiment,a reaction mechanism consisting of three stages was put forward.The three stages are H positive-feedback reactions,proton negative-feedba k (uncatalyzed negative-feedback and catalyzed negative-feedback) reactions and transitional reactions.The mechanism is able to explain reasonably the nonlinear chemical phenomena appearing in the thiosulfatc oxidation reaction by peroxide-compounds.     

Modes of coordination and stereochemistry of the NO3 − anions in inorganic nitrates

Stereochemical features of 950 nitrate groups in the structures of 365 inorganic nitrates were analyzed using TOPOS software. The types of coordination of nitrate groups are systematized by means of Voronoi-Dirichlet polyhedra and the method of intersecting spheres. Terminal coordination (53% of the total number of nitrate groups), most of all terminal bidentate coordination (47%) was found to prevail. Bridging nitrate groups occur less frequently (20%). A considerable number of nitrate groups are not incorporated in the coordination sphere of the complexing atom but form H-bonds or bonds of mainly ionic nature (27%). A number of metal cations show clear-cut tendency for a certain mode of coordination of the NO₃ group. Criteria for classification of nitrate groups into four types (slightly distorted groups and groups with monodentate, bidentate and asymmetric type distortion) are proposed. Structural features of nitrate groups depending on the mode of coordination are considered. The geometry of mono- or bidentate nitrate groups can differ appreciably from the typical one because of participation of terminal oxygen atoms in ionic or hydrogen bonds. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 429–440, March, 2008.     

PBu3-mediated vinylogous Wittig reaction of α-methyl allenoates with aldehydes and mechanistic investigations

A highly stereoselective PBu(3)-mediated vinylogous Wittig olefination between α-methyl allenoates and a variety of aldehydes is presented as the first example of a practical and synthetically useful vinylogous Wittig reaction. Mechanistic experiments including deuterium-labeling, intermediate entrapment, and NMR monitoring have been deliberately conducted. On the basis of mechanistic investigations, a reliable mechanism for the vinylogous Wittig reaction is proposed, which features a water/phosphine-coassisted allylic phosphorus ylide 1,3-rearrangement pathway, rather than previous retro-Diels-Alder ones. It is noteworthy that mechanistic findings in this work also provide supportive evidence for typical mechanisms of important phosphine-mediated reactions of allenoates.     

Synthesis and stereochemistry of chiral azetidin-2-ones and azetidine-2-thiones. 3. Stereodirected construction of theβ-lactam fragment of the thienamycin molecule

It has been shown possible to introduce an -hydroxyethyl group trans-stereospecifically into position 3 of 4-methyl-1-(-methyl-benzl)azetidin-2-one. The stereochemistry of the asymmetric centers C₍₃₎, C₍₃₎, and C₍₄₎ of the diastereoisomers of the 3--hydroxyethyl derivative obtained in larger amount and of the corresponding three adjacent chiral centers C₍₈₎, C₍₆₎, and C₍₅₎ in thienamycin are the same.For part 2 see [1].M. V. Lomonosov Moscow State University, Moscow, 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 254–257, February, 1995. Original article submitted December 14, 1994.     

Study on the “Tin-Ene” reaction of α-bromoacetophenone and metallic tin with aldehydes

β-hydroxy ketones were obtained in good yields by the “tin-ene” reactions of α-bromoacetophenone and metallic tin with aldehydes.     

On the extent of racemization of allylic esters during palladium—mediated alkylation with homochiral 3-methyl-δ-butyrolactone derivatives

The allylic phosphate 4e has been shown to racemize 4̃–6% upon alkylation with the sodium lactone enolates of 1c and ent-1c in the presence of Pd(Ph₃P)₄. The acetate 4d racemizes 11%.