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An intermediate phosphonium salt has never been isolated from the Morita-Baylis-Hillman (MBH) reaction. Due to the weakly basic counterion produced in the MBH alkylation and allylation reactions, the reaction can be stopped after electrophilic attack on t

The stereoselectivities of reactions of allylmagnesium reagents with chiral ketones cannot be easily explained by stereochemical models. Competition experiments indicate that the complexation step is not reversible, so nucleophiles cannot access the widest range of possible encounter complexes and therefore cannot be analyzed easily using available models. Nevertheless, additions of allylmagnesium reagents to a ketone can still be stereoselective provided that the carbonyl group adopts a conformation that leads to one face being completely blocked from the approach of the allylmagnesium reagent.

Friedel-Crafts-type acylation of alkenes with acyl chlorides has been successfully conducted with a wide substrate scope by the combined use of AlCl3 and 2,6-dibromopyridine. Trisubstituted alkenes afford allylketones or vinylketones depending on the presence or absence of hydrogen atom(s) at the β-position to the acylation site, while monosubstituted alkenes exclusively afford vinylketones.

A general and highly chemoselective Pd-catalyzed protocol for the synthesis of α,β-unsaturated ketones by carbonylation of vinyl triflates and nonaflates is presented. Applying the specific monophosphine ligand cataCXium A, the synthesis of various vinyl ketones as well as carbonylated natural product derivatives proceeds in good yields.

A nickel-catalyzed reductive coupling between acid fluorides and vinyl triflates has been described. This method provides an efficient access to various enones and avoids the requirement for acyl or vinyl metallic reagents in the conventional approaches.

Iodohydroxylation of 1-phenyltricyclo[4.1.0.02,7]heptane in aqueous THF at 20°C with N-iodosuccinimide proceeds at the central bicyclobutane bond C1–C7 and results in the formation of two-component mixture of diastereomeric 7-iodo-6-phenyl-6-norpinanols in the ratio 1 : 1.8 in favor of the product of the anti-addition. Treating of iodonorpinanols with trimethylamine in aqueous THF affords 1-benzoylcyclohex-1-ene as a result of 1,4-dehydroiodination accompanied with the Grob fragmentation of the carbon scaffold.

In this work, the relationship between cyclophilin A (CypA) and EV71 prompted us to screen a series of small molecular CypA inhibitors which were previously reported by our group. Among them, compounds 1 and 2 were discovered as non-immunosuppressive anti-EV71 agents with an EC50 values of 1.07 ± 0.17 μM and 3.36 ± 0.45 μM in virus assay, respectively, which were desirably for the further study. The subsequent chemical modifications derived a novel class of molecules, among which compound 11 demonstrated the most potent anti-EV71 activity in virus assay (EC50 = 0.37 ± 0.17 μM), and low cytotoxicity (CC50 > 25 μM). The following CypA enzyme inhibition studies indicated that there was not only the enzyme inhibition activity, undoubtedly important, functioning in the antiviral process, but also some unknown mechanisms worked in combination, and the further study is underway in our laboratory. Nevertheless, to the best of our knowledge, compound 11 was probably the most potent small molecular anti-EV71 agent via CypA inhibitory mechanism to date. Consequently, our study provided a new potential small molecule for curing EV71 infection.

The oxidative conversion of silyl enol ethers to α,β-unsaturated ketones using a less-hindered class of oxoammonium salts (AZADO +BF4-) is described. The reaction proceeds via the ene-like addition of oxoammonium salts to silyl enol ethers.

From the initial development of a homologous Morita-Baylis-Hillman reaction utilizing epoxides as electrophiles, the method was expanded to enable the exclusively organocatalyzed intramolecular allylation of enones and to develop the intramolecular MBH-type alkylation of activated alkenes. We successfully utilized both enones and unsaturated thioesters as the activated alkene component. This work, carried out using stoichiometric amounts of the trialkylphosphine, gave an array of functionalized five- and six-membered carbocycles in high yields. With the cycloalkylation of enones and thioesters, conditions that allowed the use of substoichometric amounts of the phosphine catalyst were developed. As a result both five- and six-membered rings can be formed efficiently with little to no loss in yield upon comparison to yields obtained when stoichiometric amounts of trialkylphosphines were employed. We isolated, for the first time, an MBH-type intermediate exhibiting unprecedented trans geometry of the phosphonium salt and acyl group.

The combined use of a catalytic amount of InX3 (X = OTf and NTf2) and 1-butanol was found to be effective in formal alkynealdehyde metathesis. With this catalytic system, aromatic alkynes reacted with aromatic aldehydes to give chalcones in moderate to good yields. Alkynals were efficiently converted into 5- to 7-membered cyclic compounds by intramolecular alkyne-aldehyde coupling.

The reaction of hydrazine derivatives with α,β-unsaturated ketones, such as cyclohexenyl(phenyl)methanone and (E)-2-benzylidenecyclohexanone, were investigated. The reaction between methylhydrazine and e.g., cyclohexenyl(phenyl)methanone was particularly interesting as 3a,4,5,6,7,7a-hexahydro-1-methyl-3-phenyl-1H-indazole was obtained as the major product together with 4,5,6,7-tetrahydro-2-methyl-3-phenyl-2H-indazole as a minor product.

The reductive cyclocondensation of α,α,α-trichlorotoluene to enolisable ketones enables the preparation of (cyclo)alken-1-en-1-yl phenyl ketones via the formation of an intermediate chlorooxirane. Copyright Taylor & Francis Group, LLC.

Using a catalytic amount of trialkylphosphines, alkyl halides undergo efficient intramolecular Morita-Baylis-Hillman cyclization. Georg Thieme Verlag Stuttgart.

sp3 Hybridized electrophiles, never before used in the organo-mediated Morita-Baylis-Hillman reaction, now facilitate the formation of five- and six-membered enone cycloalkylation products. The Royal Society of Chemistry 2005.

We have identified a catalyst capable of effecting the rapid, room-temperature cross-coupling between acid fluorides and diorganozinc reagents. The use of acid fluorides as electrophilic partners allows this reaction to tolerate epimerizable functionality as well as β leaving groups. The same catalyst is also capable of cross-coupling acid chlorides, acyl cyanides, anhydrides, thioesters, and pyridyl esters. Noteworthy is the ability of the reaction to successfully transfer both groups from the organometalic fragment. Copyright

Thermal elimination of the alkoxydiazene oxide group from the derivatives of acyl- and benzoylalkanes (cycloalkanes) afforded the corresponding vinyl ketones. Addition of nitrogen oxide and alkoxides to vinyl ketones followed by removal of the acyl group yielded 1,4-dialkoxy-1,2-diazabut-1-ene 2-oxides.

Cyclic ketone O-trimethylsilylcyanohydrins (2) were prepared and converted to various compounds: α-hydroxyketones (3), dehydroxylated ketones (4), α,β-unsaturated ketones (9), tricyclic ketones (10), 1-ethoxycarbonyl-4- phenyl-1,2,4a,5,6,7,8,8a-octahydro-2-naphthalenone (13), 1- phenylperhydroisocoumarin (18) and 1,2,3,4,4a,10,11,11a-octahydro-5h- benzo[a,d]cyclohepten-10-one (20).

The known reactions of 8,8-dibromotetracyclo2,4.03,5>octane (3a) and homobenzvalene (7) with pyridinium bromide perbromide and iodine, respectively, were carried out in the presence of tetra-n-butylammonium chloride.The formation of the chloro-substituted norpinane derivatives 6a and 9 is evidence for cationic intermediates.The same mechanism is operative in the reaction of pyridinium bromide perbromide with the dichlorotetracyclooctane 3b, which was prepared from 7 and dichlorocarbene.On exposure of tricyclo2,7>heptane (1) to N-bromosuccinimide in acetone/water/triethylamine, the bromonorpinanol 22, the bromonorcaranols 23, and cyclohex-1-ene-1-carboxaldehyde (24) were obtained.On the basis of the steric course and thermodynamic considerations, the cationic intermediates generated in the above reactions by attack of the electrophiles at the bicyclobutane systems are assigned the halonium ion structure 38 and the nonclassical structures 34 and 35, respectively.Elemental bromine and iodine converted the phenyltricycloheptane 10 into the respective diastereomeric norpinanes 11 and 12, which were transformed smoothly into the diastereomeric methyl ethers 13 and 14 treatment with sodium methoxide in methanol.The reactions of 10 with pyridinum bromide perbromide in pyridine, cyanogen bromide in the presence of aluminium trichloride, and N-bromosuccinimide in acetone/water gave rise to norpinane derivatives, i.e. the pyridinium salt 15, the nitrile 16, and the alcohol 18, respectively.In the case of cyanogen iodide in acetonitrile, the solvent participated in the process to yield the 2-(norpinylimino)propionitriles 17.Corresponding to the configurations of the products, the attack of a halogen electrophile at 10 leads to classical 6-phenyl-6-norpinyl cations 41, which may be approached by nucleophiles from the two possible faces.As origin for the low tendency of the cations 33-35 and 41 to rearrange to norcaryl cations, the electronegativity of the halogen atoms is suggested.The reduced migratory aptitude of a CHHal relative to a CH2 group results from its electron deficiency and from the decreased stability of 7-halo-2-norcaryl relative to the parent 2-norcaryl cations.The chlorophenyltricycloheptane 25 was prepared from 10 and treated with aqueous sulfuric acid to give the norpinanol 27.Formed by protonation of the bicyclobutane system of 25, the cationic precursor of 27 shows a behaviour similar to that of cations 41. - Key Words: Norpinanes, preparation / Carbocations, classical and nonclassical / Neighbouring group participation / Halonium ions / Migratory aptitudes in carbocations

Lewis acid-induced reaction of γ-substituted allylstannanes with aldehydes proceeded at the α-, β- or γ-position, depending upon the nature of the substituents.

Oxidative cyclization of δ,ε- and ε,ζ-unsaturated enol silyl ethers 4a and 4b with cupric triflate and cuprous oxide or ceric ammonium nitrate and sodium bicarbonate in acetonitrile provides the tricyclic ketones 5a and 5b stereoselectively.These cyclizat

Triflic acid catalyzed reaction of 2-hydroxy-2-adamantanecarboxylic acid results via ionizative decarbonylation in the formation of adamantanone.Under carbon monoxide pressure pinacol-type rearrangement gives 4,5-homoadamantanedione.Reactions of a series of α-hydroxy ketones result in fragmentation, deprotonation, and cyclization, respectively.The reactions and their suggested mechanism are discussed.

The reaction of α,α-dichlorobenzyltrimethylsilane with carbonyl compounds in the presence of fluoride ion fails to give reasonable yields of the α,α-dichlorobenzyl adducts except when carried out in the presence of zinc iodide and in HMPA as solvent.Under these conditions moderate yields of the adducts can be obtained with cyclohexanone, cyclohexenone, benzaldehyde and trans cinnamaldehyde.These reactions were compared with those of α,α-dichlorobenzyllithium.

Ring opening of 1,2-epoxycyclohexane by the title aza-allylic anion afforded a mixture of anions, the quenching and subsequent hydrolysis of which gave rise to trans-2-(α-aminobenzyl)cyclohexanol (10) and benzylamine as the basic fraction, and to either 1-benzoylcyclohexene (11) or trans-2-benzoylcyclohexanol (12), cis-2-benzoylcyclohexanol (14), and benzaldehyde as the neutral fraction: the type of ketone obtained depended upon the hydrolytic conditions.The perhydrobenzoxazine (7) was shown to be the precursor of compound (10).Sodium 1,3-diphenyl-2-azapropenide thus behaved both as an α-benzylamine carbanion equivalent and as a benzoyl anion equivalent.

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The palladium-catalyzed cross-coupling reaction of vinyl iodides with trimethyl- or tributylvinylstannanes in the presence of carbon monoxide gives unsymmetrical divinyl ketones in good yields. The reaction conditions are neutral and mild enough (40-50 degree C, 15-50 psig carbon monoxide) that other functional groups in either coupling partner can be brought unaltered into the coupled product. The E geometry in both partners is retained in the coupling product, and the Z geometry in the vinyltin reagent is maintained during the coupling reaction, but the coupled product undergoes slow Z to E isomerization under the usual reaction conditions. Isomerization of the divinyl ketone in the reaction medium is slowed in the dark. The reaction rate is especially sensitive to substituents on the vinyltin reagent, probably as a result of steric hindrance in the transmetalation step of the catalytic cycle.

It was found that acylation of a variety of aliphatic olefins with acid chlorides is efficiently promoted by active zinc compounds, which were prepared from a Zn/Cu couple and alkyl iodides.The crude product mixtures were subsequently treated with 1 M KOH in methanol or were subjected to catalytic hydrogenation to afford the corresponding α,β-unsaturated or saturated ketones in good to moderate yields.It was also shown that the reaction fully follows the Markovnikov rule.

Cyclohex-1-enyl phenyl ketone (Ia) and acetophenone (Ib) on Stobbe condensation with diethyl cyclohex-1-enylsuccinate in the presence of potassium t-butoxide give the corresponding half-esters trans-(Ph/COOC2H5)-2,4-di-(cyclohex-1-enyl)-3-ethoxycarbonyl-4-phenylbut-3-enoic acid (IIa) and trans-(Ph/COOHC2H5)-2-(cyclohex-1-enyl)-3-ethoxycarbonyl-4-methoxy-4-phenylbut-3-enoic acid (IIb).The half-esters (IIa,b) undergo cyclization in the presence CH3COONa/Ac2O to give the acetoxy-esters(IVa,b) which are saponified to give the naphthol derivatives (Va,b).Methylation of Va,b with dimethyl sulphate leads to the formation of the corresponding methoxy esters(VIa,b), which on saponification give the corresponding naphthoic acid derivatives (VIIa,b).Methoxy esters (VIa,b) on heating with Pd/C followed by alkaline hydrolysis afford the fully aromatized 4-methoxy-1,3-diphenyl-2-naphthoic acid (IXa) and 4-methoxy-1-methyl-3-phenyl-2-naphthoic acid (IXb).Also the phenolic acids (Va,b) react with phenyl and methyl isocyanates in boiling benzene in the presence of triethylamine to give the corresponding N-phenyl- and N-methyl-carbamates (VIIIa,b).

An efficient procedure for the conjugate addition of γ-acetoxy-αβ-unsaturated ketones with RCu-AlCl3 is described.