Dialkylation Products Research Articles

Visible-Light-Mediated Z-Stereoselective Monoalkylation of β,β-Dichlorostyrenes by Photoredox/Nickel Dual Catalysis

AbstractMetal-catalyzed alkylation of 1,1-dihalovinyl moiety commonly suffers from both a lack of stereoselectivity and the overreaction leading to the dialkylation product. The methodology described herein features a new pathway to alkylate stereoselectively β,β-dichlorostyryl substrates to provide the Z-trisubstituted olefin only with fair to good yields. This cross-coupling reaction bears on the smooth and photoinduced formation of a C-centered radical that engages in a nickel-catalyzed organometallic cycle to form the key Csp2–Csp3 bond.

Method of preparation of alkylated 1,3-diphenylpropan-2-ones, the components for assembly of graphene nanostructures

Long-chain alkylated 1,3-diphenyl-2-propanones are used in the synthesis of graphene nanostructures (graphene nanoribbons and quantum dots). A reliable procedure to obtain mono- or dialkylated diphenyl-2-propanones in 26 and 38% yields has been proposed. The method includes the dioxolane protection of the keto group in 1,3-di-(4-bromophenyl)-2-propanone, then a palladium-catalyzed cross-coupling reaction of the obtained dioxolane with one-and-a-half- or four-fold excess of dodecyl magnesium bromide that leads to a predominant formation of mono- or dialkylation products respectively, followed by hydrolysis of dioxolanes at the last stage to form the desired diphenyl-2-propanones.

Synthesis and Properties of Carbaporphyrin and Carbachlorin Dimethyl Esters Derived from Cyclopentanedialdehydes.

Norbornenes with two ester substituents were prepared by Diels-Alder cycloadditions of cyclopentadiene with dimethyl fumarate and dimethyl 1,1-ethylenedicarboxylate. Oxidation with potassium permanganate gave good yields of related diols that were oxidatively ring-opened to afford cyclopentane dialdehydes. MacDonald-type "3 + 1" condensations with a tripyrrane, followed by oxidation with DDQ in refluxing toluene, gave carbaporphyrin or carbachlorin products in good yields. The macrocyclic products were highly diatropic and produced porphyrin-like UV-vis spectra. The carbaporphyrin was converted into silver(III) and gold(III) organometallic derivatives. Reaction with methyl iodide in the presence of potassium carbonate gave mono- and dialkylation products, and treatment of the former with Ni(OAc)2 or Pd(OAc)2 afforded nickel(II) and palladium(II) complexes. The free base carbaporphyrin and carbachlorin, and the nickel and palladium complexes, were characterized by X-ray crystallography. The carbachlorin also reacted with silver(I) acetate to give a silver(III) derivative. Carbaporphyrins and carbachlorins underwent deuterium exchange at the meso-positions with deuteriated TFA, and this observation indicates that protonation is occurring at the bridging carbons. The new route to carbaporphyrins and carbachlorins has enabled detailed studies on the properties of these systems and provides the foundations for future investigations.

Synthesis and structures of non-cyclic and cyclic mono- and bisphosphonium salts derived from 1,8-bis(diphenylphosphino)naphthalene

A monoalkylated 1,8-bis(diphenylphosphino)naphthalene (dppn) was prepared by treating diphosphine with 1,8-bis(bromomethyl)naphthalene. Unprecedented cyclizations of monophosphonium salts in polar solvents, such as DMF or acetonitrile were elucidated. The mechanistic pathway of the cyclization reaction was postulated and X-ray crystal structure analyses of the resulting 2,2-diphenyl-2,3-dihydro-1H-2-phosphoniaphenalene bromide was performed. 1,8-Bis(diphenylphosphino)naphthalene and α,α′-dibromo-o-xylene afforded—despite unfavorable steric strain—the first dialkylation product of 1,8-bis(phosphino)naphthalene, namely corresponding cyclic bisphosphonium salt. The use of acetonitrile as the solvent was the key for this synthesis. The bromide anions were exchanged in metathesis reaction with hexafluorophosphate anions and the new compound was fully characterized including single crystal X-ray diffraction. The large distance between phosphorus atoms of 3.974 Ǻ clearly demonstrate a strong proximity effect in this hindered bisphosphonium salt.

ChemInform Abstract: Highly Diastereoselective Friedel—Crafts Reaction of Arenes with N‐tert‐Butanesulfinylimino Ester Towards the Efficient Synthesis of α‐Arylglycines.

Lewis acid-catalyzed highly diastereoselective asymmetric Friedel–Crafts alkylation of arenes with a chiral N-tert-butanesulfinylimino ester is described. The reaction can be accomplished with ease in the presence of a catalytic amount of In(OTf)3 at room temperature, providing a series of enantiomerically enriched α-arylglycines in good yields and with excellent diastereoselectivities (up to 99% de). Highly stereoselective double Friedel–Crafts alkylation to afford dialkylation product was also investigated.

Highly diastereoselective Friedel–Crafts reaction of arenes with N-tert-butanesulfinylimino ester towards the efficient synthesis of α-arylglycines

Lewis acid-catalyzed highly diastereoselective asymmetric Friedel-Crafts alkylation of arenes with a chiral N-tert-butanesulfinylimino ester is described. The reaction can be accomplished with ease in the presence of a catalytic amount of In(OTf)(3) at room temperature, providing a series of enantiomerically enriched α-arylglycines in good yields and with excellent diastereoselectivities (up to 99% de). Highly stereoselective double Friedel-Crafts alkylation to afford dialkylation product was also investigated.

Nickel(II)-catalyzed carbon–carbon bond formation reaction of functionalized organozinc reagents with aromatic aldehydes

In the presence of a silylating reagent and catalytic amount of Ni(acac) 2, organozinc halides reacted with aromatic aldehydes to give the corresponding dialkylation products in good to excellent yields under mild conditions.

Control of Extremely Fast Competitive Consecutive Reactions using Micromixing. Selective Friedel−Crafts Aminoalkylation

Friedel-Crafts reactions of aromatic and heteroaromatic compounds with an N-acyliminium ion pool were studied. The reaction of 1,3,5-trimethylbenzene in a batch reactor gave rise to the selective formation of a monoalkylation product (69%). Presumably, the second alkylation is slower than the first alkylation because of the protonation of the monoalkylation product that decreases its reactivity. The reaction of 1,3,5-trimethoxybenzene, however, gave rise to the formation of both monoalkylation (37%) and dialkylation (32%) products. Disguised chemical selectivity due to faster reaction than mixing seems to be responsible for the lack of selectivity. The use of micromixing was found to be quite effective to solve this problem to increase the selectivity. The monoalkylation product was obtained in 92% yield together with a small amount of the dialkylation product (4%). The reaction with various aromatic and heteroaromatic compounds revealed that the low mono/dialkylation selectivity was observed only for highly reactive aromatics. In such cases, the use of micromixing was quite effective to improve the selectivity. On the basis of micromixing, the selective sequential dialkylation using two different N-acyliminium ions was achieved. CFD simulations using a laminar flow and finite-rate model are consistent with the experimental observations and clearly indicate the importance of mixing.

A General Procedure to Selectively Prepare N‐Alkylanilines by an Unexpected Reaction of (Z)‐(tert‐Butylsulfanyl)(aryl)diazenes with Alkyllithium Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A General Procedure to Selectively PrepareN-Alkylanilines by an Unexpected Reaction of (Z)-(tert-Butylsulfanyl)(aryl)diazenes with Alkyllithium Reagents

A general procedure has been set up to prepare, selectively, the N-monoalkylanilines 7, reacting (Z)-(tert-butylsulfanyl)(aryl)diazenes 3 with alkyllithium 6 (MeLi, BuLi, s-BuLi, n-C 6 H 1 3 Li). The reactions were carried out in anhydrous diethyl ether at 0 °C or -78 °C, depending on the reagent 6, and then at room temperature. In optimal conditions the yields of the pure products 7 (uncontaminated by dialkylation products) were from good to excellent: for 38 considered examples, 34 were positive with yields varying between 61% and 91% (average yield 78%). Collateral proofs were carried out to support a hypothesized reaction mechanism.

Synthesis and Characterization of New Lithiated Organogermanium Compounds

New (8-methoxy-1-naphthyl)arylgermanes 1a−c are synthesized. The crystal structure of 1b (aryl = mesityl), determined by X-ray diffraction, shows that an intramolecular interaction occurs between the oxygen and germanium atoms, the Ge- - -O distance being 2.75 Å. The corresponding (diarylgermyl)lithiums R2HGeLi are prepared in high yield by hydrogermolysis of tert-butyllithium in THF and are susprisingly stable. Their characterization by 1H, 13C, and 7Li NMR spectroscopy is reported. Dimetalation of the initial arylgermanes depends upon steric hindrance around the germanium atom and the nature of the organolithium compound RLi. The reaction of 1a or 1c with n-BuLi followed by MeI affords the expected dialkylation product, whereas 1b gives the unexpected iodide 5b due to steric hindrance around the germanium atom.

The number of possible structures of conformationally fixed O-alkylation products of calix[4]arenes

Abstract O-Alkylation of calix[4]arenes leads to conformationally fixed derivatives provided the groups attached to the oxygen are large enough. In principle 34 different tetra-, 13 tri-, 8 dialkylation products may be obtained starting with a calix[4]arene consisting of four identical phenolic units. 17,9 and 3 of these derivatives are inherently chiral.

Alkylation of toluene with methanol over AlPO 4, AlPO 4Al 2O 3, AlPO 4TiO 2, and AlPO 4ZrO 2 catalysts

The catalytic activity and selectivity of a series of AlPO 4 and AlPO 4-metal oxide systems (Al 2O 3, TiO 2, and ZrO 2 with an AlPO 4/metal oxide weight ratio of 3) were investigated at temperatures ranging from 673 to 873 K for the gas-phase microcatalytic alkylation of toluene with methanol. The results show that AlPO 4's catalyst exhibits surface acid sites accessible to toluene molecules that are strong enough to alkylate in the presence of methanol. The methylation of toluene produces a mixture of xylenes (XY) as principal products, although 1,2,4-and 1,2,3-trimethylbenzenes (TMB) were also found to be dialkylation products for AlPO 4-Al 2O 3 catalysts. The formation of TMB is associated with a parallel decline in o-XY and p-XY selectivity. Furthermore, in all cases, scarcely any side-chain-methylation of toluene to ethylbenzene (ETB) is found. The alkylation reaction follows the Bassett-Habgood kinetic equation for first-order reaction processes in which the surface reaction is the controlling step. The influence of the reaction temperature, pulse number, and toluene/methanol molarity upon the conversion of toluene and the selectivities of the products were investigated. The activity of AlPO 4 and AlPO 4-metal oxide catalysts in the ring-methylation of toluene decreases in the order AlPO 4Al 2O 3 > AlPO 4 > AlPO 4TiO 2 > AlPO 4ZrO 2. This order is relatively well interpreted in basis to the surface acid properties studied gas-chromatographically through the irreversible adsorption of pyridine at temperatures in the range 473 to 673 K. This indicates that Brønsted acidity decreases when Al 2O 3 is substituted by TiO 2 or ZrO 2 in the AlPO 4-metal oxide system. OPE (Optimum Performance Envelope) curves on product selectivity plots show that ETB and XY are competitive primary reaction products, while TMB are stable secondary reaction products. In all cases, the selectivity decreases in the order S XY > S TMB > S ETB.

Hydrophilic recognition by polymer-supported phase transfer catalysts and its effect on reaction activity and selectivity

Cross-linked polystyrene latexes with surface-bound quaternary ammonium groups have been prepared by a two-step method. First the functional monomer vinylbenzyl chloride (VBC) was introduced into a partially polymerized concentrated emulsion of styrene and divinylbenzene (ST/DVB) in water and complete polymerization was carried out. Second the poly(ST/DVB) particles with surface-bound benzyl chloride groups were quaternized. The dual-surface characteristics due to the hydrophilic bound cations and hydrophobic polystyrene can be varied by controlling the partial polymerization time of ST/DVB and the amount of VBC introduced. The phase transfer catalysts thus obtained were employed in the alkylation reaction of isopropylidene malonate (Meldrum acid). The ratio of mono- to dialkylation products was observed to increase with decreasing accessible hydrophilicity of the supported catalysts. When the partial polymerization time is short, a part of VBC copolymerizes with styrene and another part homopolymerizes and is grafted to the surface of the particles. When the partial polymerization time is long, only homopolymers of VBC, which are grafted to the particles, form. The ammonium groups to which the benzyl chloride units are converted via quaternization are more accessible, for steric reasons, to the Meldrum acid and to the monosubstituted Meldrum acid when they are part of the grafted chains than when they are part of the copolymer. As a result, the activity for the conversion of the Meldrum acid increases as the partial polymerization time increases. However, the selectivity for the monosubstituted Meldrum acid increases with decreasing partial polymerization time of the concentrated emulsion, because the fraction of hydrophilic groups that are accessible decreases and the monosubstituted compound has more difficulty, for steric reasons, binding to the onium cations than the unsubstituted compound.

Alkylation of ethyl 4,4,4-trifluoroacetoacetate. First example of a reversible O-alkylation process leading to C-alkylation

In aprotic polar solvents the ratio of O vs. C alkylation products of ethyl 4,4,4-trifluoroacetoacetate (ETFAA)can be dependent on reaction time; in hexamethylphosphoric triamide (HMPA) or acetone, the SN2 cleavage of enol ethers of ETFAA with sodium iodide was observed with concomitant formation of the sodium enolate and the corresponding iodides, and in the case of an activated iodide the mono- and di-alkylation products resulted quantitatively.

Characteristic features of reactions of phenolate ions with polyfluorocarbonyl compounds

1. Phenolates containing electron-acceptor substituents in the aromatic ring are regiospecifically C-alkylated by hexafluoroacetone and methyl trifluoropyruvate to form monoalkylation products, and in the presence of an excess of hexafluoroacetone form dialkylation products. 2. In Freon-113, Li and Na phenolates are alkylated by hexafluoroacetone in the o-position, and K phenolates in the p-position; in DMF, irrespective of the counterion, the phenolates form p-alkylation products with hexafluoroacetone. The regiospecific o-alkylation of Li and Na phenolates in nonpolar media, is possibly explained by chelate formation.

ChemInform Abstract: Synthesis of β‐Substituted Furans by Alkylation of β‐Dicarbonylic Compounds with 1,2,3‐Trihalopropanes.

AbstractThe β‐dicarbonyl compounds (I) react with the trihalopropanes (II) or with propargyl bromide (VI) to give the monoalkylation products (III) or (VII) and the dialkylation products (IV) or (VIII), or the cyclization products (V) and (IX), depending on the reaction conditions.

Crystal structure and tautomerism in 4‐phenylisoxazoles with two potential hydroxyl groups at positions 3 and 5

AbstractThe crystal structure of 4‐phenyl‐3‐hydroxyisoxazol‐5‐one semihydrate exhibits an exceptional hydrogen bonded polymeric structure with a unit cell of 8 molecules. The hydrogen bonds stretch out, using the oxohydroxy groups in positions 3 and 5 in the direction of one axis and along a perpendicular direction the layers are stitched together by water molecules. The layers are stitched by using four hydrogen bridges of water molecules, the heterocyclic ring nitrogen as well as the oxygen at position 5. Tautomerism of this moiety in solution is discussed, in light of some new dialkylation products. The state in which these products exist in solution depends on the solvent. A zwitterionic tautomer is present in ether. In some alkylation conditions, the predominant dialkylation product is the N,N‐disubstituted betaine (Anhydro‐2,2‐dialkyl‐3(5)‐oxo‐5(3)hydroxy‐4‐phenylisoxazolonium hydroxide). Study of tautomerism in polar and protic solvent is unreliable owing to associations and dissociation phenomena.

Alkylation of ?-dicarbonyl compounds by 1,2,3-trihalopropanes as a method for the preparation of ?-substituted furans

Alkylation of Β-dicarbonyl compounds by 1,2,3-trihalides leads to a readily separable mixture of mono- and dialkylation products, and under more rigorous conditions, to 3-substituted 2,4-dimethylfurans. A similar reaction with propargyl bromide leads to furans with a “normal” structure, namely, 2,5-dimethylfurans.

Use of 1-arylthio-2-acetoxy-2-methyl-but-3-ene as a substituted C5-synthon in the synthesis of isoprenoids

1. Alkylation of 1-arylthio-2-acetoxy-2-methylbut-3-enes with lithium or magnesium cuprates is either an SN2 or SN2′ reaction, depending on the carbanionic component. 2. The reaction of 2-acetoxy-2-methyl-1-phenylsulfinylbut-3-ene with the same reagents involves successive selective 8N2′ and SN2 steps, the dialkylation product being obtained with a high degree of stereoselectivity. 3. The possibility of using these adducts for the synthesis of isoprenoids has been demonstrated by the synthesis of the Komstok scale insect pheromone and the preparation of a C10-intermediate in the synthesis of the juvenoid echinolone.