Nucleophilic Cyclopropanation Reaction with Bis(iodozincio)methane by 1,4‐Addition to α,β‐Unsaturated Carbonyl Compounds

Treatment of α,β‐unsaturated ketones with an electrophilic site at the γ‐position in the presence of trimethylsilyl cyanide with bis(iodozincio)methane afforded the (Z)‐silyl enol ether of the β‐cyclopropyl substituted ketone in good yields. The reaction proceeds by 1,4‐addition to form an enolate, and its sequential intramolecular nucleophilic attack to an adjacent electrophilic site. The reaction of γ‐ethoxycarbonyl‐α,β‐unsaturated ketone and bis(iodozincio)methane in the presence of trimethylsilyl cyanide afforded 1‐ethoxy‐1‐trimethylsiloxycyclopropane derivatives, which can be regarded as the homoenolate equivalent. Additionally, reaction of the obtained homoenolate equivalents with imines give 1‐(E)‐alkenyl‐2‐(1‐aminoalkyl)alkanols diastereoselectively.     

Multivalency as a Key Factor for High Activity of Selective Supported Organocatalysts for the Baylis–Hillman Reaction

The polystyrene‐supported N‐alkylimidazole‐based dendritic catalysts for the Baylis–Hillman reaction exhibit one of the strongest beneficial effects of multivalent architecture ever reported for an organocatalyst. The yields in the model reaction of methyl vinyl ketone with p‐nitrobenzaldehyde are more than tripled when a non‐dendritic catalyst is replaced by a second‐ or third‐generation analogue. Moreover, the reaction of the less active substrates will not occur with the non‐dendritic catalyst and will proceed to a significant extent only with the analogous catalysts of higher generations. A substantial additional enhancement of the reaction yield could be achieved by increasing the content of water in the reaction solvent. The plausible cause of the dendritic effect is the assistance of the second, nearby imidazole moiety in the presumably rate‐determining proton transfer in the intermediate adduct, after the first imidazole unit induced the formation of the new carbon–carbon bond.     

Non‐Heme‐Type Ruthenium Catalyzed Chemo‐ and Site‐Selective C−H Oxidation

Herein, we developed a Ru(II)(BPGA) complex that could be used to catalyze chemo‐ and site‐selective C?H oxidation. The described ruthenium complex was designed by replacing one pyridyl group on tris(2‐pyridylmethyl)amine with an electron‐donating amide ligand that was critical for promoting this type of reaction. More importantly, higher reactivities and better chemo‐, and site‐selectivities were observed for reactions using the cis‐ruthenium complex rather than the trans‐one. This reaction could be used to convert sterically less hindered methyne and/or methylene C?H bonds of a various organic substrates, including natural products, into valuable alcohol or ketone products.     

Postpolymerization modification of reactive polymers derived from vinylcyclopropane. III. Polymer sequential functionalization using a combination of amines with alkoxyamines,hydrazides, isocyanates,or acyl halides

A new 1,1‐disubstituted‐2‐vinylcyclopropane monomer bearing a ketone and a pentafluorophenyl ester was synthesized and successfully polymerized to yield a polymer with two side chain moieties readily available for post‐polymerization modification. After a quantitative modification of the pentafluorophenyl moiety with amines, a subsequent second functionalization reaction was successfully performed on the ketone moiety leading to a double side‐chain functionalized polymer using two different routes. The first route utilized hydrazide and hydroxylamine derivatives leading to a ketone conversion of 25 to 85%. In the second route, the ketone moiety was first reduced to alcohol (reduction conversion up to 100%) and then converted into the corresponding ester or urethane using acyl halides or isocyanates, respectively, with a conversion ratio of up to 90%. A library of functionalized polymers was synthesized to confirm the effectiveness of this approach. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2841–2849     

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]‐Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3‐siloxy‐1,3,9‐triene‐7‐yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)₅(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl‐substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven‐membered rings were present. The reaction of (Z)‐enol silyl ethers proceeded through Cope rearrangement of cis‐divinylcyclopropane intermediates, and that of (E)‐enol silyl ethers by 1,4‐addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.     

Synthesis of polymer microspheres functionalized with chiral ligand by precipitation polymerization and their application to asymmetric transfer hydrogenation

Monodisperse, crosslinked poly(divinylbenzene) and poly(methacrylic acid‐co‐ethylene glycol dimethacrylate) microspheres with (1R,2R)‐N¹‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine ((R,R)‐TsDPEN) moiety were successfully prepared by precipitation polymerization. Introduction site of the (R,R)‐TsDPEN moiety into the polymer microspheres could be controlled by changing the order of addition of the corresponding monomers. The functionalized polymer microspheres were applied to asymmetric transfer hydrogenation of ketone and imine. Polymer microsphere‐supported chiral catalysts showed good reactivity and enantioselectivity in the catalytic asymmetric transfer hydrogenations. Chiral secondary alcohol was quantitatively obtained with 94% ee in the asymmetric transfer hydrogenation of acetophenone in water. We also found that introduction site of the chiral catalyst and hydrophobicity of the microspheres, as well as degree of the crosslinking, affected the yield and enantioselectivity of chiral product in this reaction. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3340–3349, 2010     

Versatile One‐Step One‐Pot Direct Aldol Condensation Promoted by MgI2

A true one‐step one‐pot aldol‐reaction procedure has been developed for the synthesis of β‐hydroxy ketones and esters. The reaction can be run at room temperature by simply mixing four components in CH₂Cl₂, with medium‐to‐high yields of aldol products obtained after regular workup. Mechanistically, the process probably proceeds via Mg‐enolate formation of the ketone or ester component, followed by addition to the electrophilic aldehyde.     

Bifunctionalized Allenes,Part XI: Competitive Electrophilic Cyclization and Addition Reactions of 4‐Phosphorylated Allenecarboxylates

The reaction of the 4‐phosphorylated allenecarboxylates with different electrophilic reagents such as sulfuryl chloride, bromine, benzenesulfanyl, and benzeneselanyl chlorides takes place with a 5‐endo‐trig cyclization or 2,3‐addition reaction depending on the kind of the substituents in the phosphoryl group. Treatment of the 4‐(dimethoxyphosphopyl)‐allenoates with electrophiles gives a mixture of 2,5‐dihydro‐1,2‐oxaphospholes and furan‐2(5H)‐ones in the ratio of about 1.7:1 as a result of the neighboring group participation of phosphonate and carboxylate groups in the cyclization. On the other hand, (3E)‐4‐(diphenylphosphoryl)‐alk‐3‐enoates were prepared, in moderate yields, by chemo‐, regio, and stereoselective electrophilic addition to the C² C³‐double bond in the allenoate moiety. A possible mechanism involving cyclization and addition reactions of the 4‐phosphorylated allenecarboxylates was proposed.     

Mechanistic Studies on the Insertion of Carbonyl Substrates into Cu‐H: Different Rate‐Limiting Steps as a Function of Electrophilicity

We report mechanistic studies on the insertion reactions of [(NHC)Cu(μ‐H)]₂ complexes with carbonyl substrates by UV‐vis and ¹H NMR spectroscopic kinetic studies, H/D isotopic labelling, and X‐ray crystallography. The results of these comprehensive studies show that the insertion of Cu‐H with an aldehyde, ketone, activated ester/amide, and unactivated amide consist of two different rate limiting steps: the formation of Cu‐H monomer from Cu‐H dimer for more electrophilic substrates, and hydride transfer from a transient Cu‐H monomer for less electrophilic substrates. We also report spectroscopic and crystallographic characterization of rare Cu‐hemiacetalate and Cu‐hemiaminalate moieties from the insertion of an ester or amide into the Cu?H bond.     

Synthesis of Some New Nitrogen Bridge‐head Triazolopyridines,Pyridotriazines, and Pyridotriazepines Incorporating 6‐Methylchromone Moiety

Some new triazolo[1,5‐a]pyridines, pyrido[1,2‐b][1,2,4]triazines, and pyrido[1,2‐b][1,2,4]triazepines incorporating 6‐methylchromone moiety were prepared from the reaction of 1,6‐diamino‐4‐(6‐methyl‐4‐oxo‐4H‐chromen‐3‐yl)‐2‐oxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile ( 4 ) with some electrophilic reagents.     

Unexpected Ring Expansion of the (3aS,6aR)‐γ‐Thiolactone Moiety during the Introduction of the (+)‐Biotin Side Chain

The reaction of vinylmagnesium bromide with the (3aS,6aR)‐γ‐thiolactone 2 in THF afforded, after unexpected ring expansion of the γ‐thiolactone moiety, the seven‐membered‐ring ketone 5 in excellent yield, instead of the expected tertiary alcohol 3 .     

Synthesis of poly(aryl ether ketone)s containing diphenyl moieties by electrophilic Friedel–Crafts solution polycondensation

A new monomer, 4,4′‐bis(4‐phenoxybenzoyl)diphenyl (BPOBDP), was prepared by Friedel–Crafts reaction of 4‐bromobenzoyl chloride and diphenyl, followed by condensation with potassium phenoxide. Novel poly(ether ketone ketone) (PEKK)/poly(ether ketone diphenyl ketone ether ketone ketone) (PEKDKEKK) copolymers were synthesized by electrophilic Friedel–Crafts solution copolycondensation of isophthaloyl chloride (IPC) with a mixture of diphenyl ether (DPE) and BPOBDP, in the presence of anhydrous aluminum chloride and N‐methyl‐pyrrolidone (NMP) in 1,2‐dichloroethane (DCE). The copolymers obtained were characterized by various analytical techniques such as FT‐IR, DSC, TGA, and wide‐angle X‐ray diffraction (WAXD). The results showed that the resulting copolymers exhibited excellent thermal stability due to the existence of diphenyl moieties in the main chain. The glass transition temperatures are above 152°C, the melting temperatures are above 276°C, and the temperatures at a 5% weight loss are above 548°C in nitrogen. The copolymers with 50–70 mol% BPOBDP had tensile strengths of 101.5–102.7 MPa, Young's moduli of 3.23–3.41 GPa, and elongations at break of 12–17%. All these copolymers were semicrystalline and insoluble in organic solvents. Copyright © 2008 John Wiley & Sons, Ltd.     

Direct conversion of tert-beta-bromo alcohols to ketones with zinc sulfide and DMSO

tert-Beta-bromo alcohols, derived from simple monoterpene hydrocarbons, react with zinc sulfide in dimethyl sulfoxide to afford saturated ketones as the major and hydroxy ketones as the minor products. The reaction involves initial nucleophilic attack by DMSO on the carbon attached to the halogen, which is assisted by electrophilic zinc sulfide. Subsequent Kornblum type oxidation yields the alpha-hydroxy ketone. On the other hand, abstraction of proton beta to the hydroxyl group followed by an attack of the neighboring hydroxyl moiety on the sulfur of the dimethylsulfoxonium intermediate and its subsequent collapse yields an enol, which tautomerizes to a saturated ketone. The latter pathway is predominantly followed.     

A Fullerene‐Substituted Pillar[5]arene for the Construction of a Photoactive Rotaxane

Transformation of a methylene group of the pillar[5]arene scaffold into a ketone has been achieved by treatment with N‐bromosuccinimide followed by hydrolysis of the bromide intermediate and oxidation of the resulting secondary benzylic alcohol with BaMnO₄. Condensation of the resulting macrocycle including a ketone function with p‐toluenesulfonyl hydrazide followed by reaction of the corresponding tosylhydrazone with C₆₀ under modified Bamford–Stevens conditions gave a fulleropillar[5]arene derivative. This building block has been used to prepare a rotaxane. The resulting molecule combining the fullerene‐functionalized macrocycle with an axle bearing a porphyrin stopper is a photoactive molecular device in which the porphyrin emission is efficiently quenched by the fullerene moiety.     

Di‐tert‐butyl ketone hydrazone and di‐tert‐butyl ketone triphenyl­phosphoranyl­idene­hydrazone

Reaction of di‐tert‐butyl ketone with hydrazine hydrate gives di‐tert‐butyl ketone hydrazone, C₉H₂₀N₂, which is dimerized by double hydrogen bonding in the solid state. Further reaction of this compound with dibromo­triphenyl­phospho­rane gives di‐tert‐butyl ketone triphenyl­phosphoranyl­idene­hydrazone, C₂₇H₃₃N₂P, in the structure of which double chains parallel to the c axis are formed through weak C—H⋯π and π–π stacking inter­actions. The hydrazone group is nearly planar in both cases. In the second compound, one of the aromatic rings is nearly coplanar with the hydrazone moiety, indicating possible π‐conjugation.     

Photopolymers: Synthesis and Characterization of Poly(3‐methacryloyloxystyryl‐2‐naphthyl ketone)

3‐Methacryloyloxystyryl‐2‐naphthyl ketone containing a photosensitive α,β‐unsaturated ketone moiety was synthesized and polymerized in methyl ethyl ketone using benzoyl peroxide as the initiator. The thermally stable polymer was characterized by means of UV, IR and NMR spectroscopy. The molecular weight data as obtained from gel permeation chromatography suggests a high tendency for chain termination by disproportionation. The photosensitivity of the polymer in the presence and absence of photosensitizers and the effect of solvent on the rate of photocrosslinking (see Figure) was also investigated.     

Diastereo‐ and Enantioselective Hydrogenation of α‐Amino‐β‐Keto Ester Hydrochlorides Catalyzed by an Iridium Complex with MeO‐BIPHEP and NaBArF: Catalytic Cycle and Five‐Membered Chelation Mechanism of Asymmetric Hydrogenation

The development of Ir‐catalyzed asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides is described. This reaction proceeds through a dynamic kinetic resolution to produce anti‐β‐hydroxy‐α‐amino acid esters in a high diastereo‐ and enantioselective manner. Mechanistic studies have revealed that this unique asymmetric hydrogenation proceeds through reduction of the ketone moiety via the five‐membered transition state involving the chelation between the oxygen of the ketone and the nitrogen of the amine function. The relationship studies between the hydrogen pressure and the stereoselectivity have disclosed two mechanisms dependent on hydrogen pressure. Under low hydrogen pressure (<15 atm), the reaction rate proportionally increased with the hydrogen pressure. However, under the high hydrogen conditions, the reaction rate exponentially accelerated along with the increasing hydrogen pressure, which suggests the participation of two or more of hydrogen atoms.     

Carbene‐Catalyzed Enantioselective Aromatic N‐Nucleophilic Addition of Heteroarenes to Ketones

The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi‐functionalized cyclic N,O‐acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza‐fulvene‐type acylazolium intermediate. A broad range of N‐heteroaromatic aldehydes and electron‐deficient ketone substrates works effectively in this transformation. Several of the chiral N,O‐acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection.     

Fe(OTf)3‐Catalyzed α‐Benzylation of Aryl Methyl Ketones with Electrophilic Secondary and Aryl Alcohols

Acid‐catalyzed Friedel–Crafts alkylation of 1,3‐dicarbonyl compounds with electrophilic alcohols, is known to be an effective C? C bond forming reaction. However, until now, this reaction has not been amenable for α‐alkylation of aryl methyl ketones because of the notoriously low nucleophilicities of these compounds. Therefore, α‐alkylation of aryl methyl ketone relies on precious metal catalysts and also, the use of primary alcohols is mandatory. In this study, we found that a system composed of a Fe(OTf)₃ catalyst and chlorobenzene solvent is sufficient to promote the title Friedel–Crafts reaction by using benzhydrols as electrophiles. 3,4‐Dihydro‐9‐(2‐hydroxy‐4,4‐dimethyl‐6‐oxo‐1‐cyclohexen‐1‐yl)‐3,3‐dimethyl‐xanthen‐1(2 H)‐one was also applicable as an electrophile in this type of benzylation reaction. On the basis of this result, a three‐component reaction of salicylaldehyde, dimedone, and aryl methyl ketone was also developed, and this provided an efficient way for the synthesis of densely substituted 4H‐chromene derivatives.