1 - 2- propen-l-one

In Chapter 2 the Diels-Alder reaction between substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-ones (3.8a-g) and cyclopentadiene (3.9) was described. It was demonstrated that Lewis-acid catalysis of this reaction can lead to impressive accelerations, particularly in aqueous media. In this chapter the effects of ligands attached to the catalyst are described. Ligand effects on the kinetics of the Diels-Alder reaction can be separated into influences on the equilibrium constant for binding of the dienoplule to the catalyst (K ) as well as influences on the rate constant for reaction of the complex with cyclopentadiene (kc-ad (Scheme 3.5). Also the influence of ligands on the endo-exo selectivity are examined. Finally, and perhaps most interestingly, studies aimed at enantioselective catalysis are presented, resulting in the first example of enantioselective Lewis-acid catalysis of an organic transformation in water. 

Finally, in Chapter 5, micellar catalysis of Diels-Alder reactions is discussed. In view of the nonpolar nature of most Diels-Alder reactants, efficient micellar catalysis of this reaction was anticipated However, this has not been observed. The results for the Diels-Alder reaction between cyclopentadiene and substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-one dienophiles, discussed in... 

In summary, the work in this thesis provides an overview of what can be achieved with Lewis-acid and micellar catalysis for Diels-Alder reactions in water as exemplified by the reaction of3-phenyl-l-(2-pyridyl)-2-propene-l-ones with cyclopentadiene. Extension of the observed beneficial effect of water on rates and particularly enantioselectivities to other systems is envisaged. 

Chapter 2 describes the results of the first detailed study of Lewis-acid catalysis of a Diels-Alder reaction in water. Substituted 3-phenyl-l-(2-pyridyl)-2-propen-l-one dienophiles (la-gin Scheme 1) were found to coordinate to Co, Cu" and Zn ions in aqueous solution. This process forms... 

Methylisoxazole (297 R = Me) and its homologs can be synthesized by reaction of hydroxylamine hydrochloride with 1-alkyl-3-dimethylamino-2-propen-l-one (296) (54IZV47), the anilino derivatives of acetoacetaldehyde (47G556), 3-dimethyl-aminomethylene-l-propyne (equation 7) (69ZOR1179) and the /3-ketoaldehyde (293) (66JOC3193). 

Diphenylisoxazole can be synthesized by the reaction of hydroxylamine chloride with 3-anilino-l,2-diphenyl-2-propen-l-one or formyldeoxybenzoin, PhC(CHO)=C(OH)Ph <62HC(17)1, p. 57). 

Isoxazole-3-carbaldehyde has been obtained as a minor product from the reaction of acetylene with a mixture of nitric oxide and nitrogen dioxide (61JOC2976). Although 3-aryl-4-formylisoxazoles have been synthesized in good yields from the reaction of benzonitrile Af-oxides with 3-(dimethylamino)-2-propen-l-one (71S433), the parent member of the series, isoxazole-4-carbaldehyde, has never been reported. It may possibly be obtained by the addition of fulminic acid to 3-(dimethylamino)-2-propen-l-one. 

The mechanisms of the cyclisation of 2 -hydroxychalcone derivatives which can lead to flavanones, flavones and aurones have been reviewed <95MI1> and the formation of 3-hydroxy- chromanones and -flavanones from l-(2-hydroxyphenyl)-2-propen-l-ones via the epoxide has been optimised <96JOC5375>. 

Copper-complexes prepared with other type of N-chelating ligands have been also prepared and evaluated as catalysts for the Diels-Alder reaction. Eng-berts et al. [103] studied enantioselective Diels-Alder reaction of 3-phenyl-l-(2-pyridyl)-2-propen-l-one with cyclopentadiene in water (Scheme 39). By using coordinating chiral, commercially available a-amino-adds and their derivatives with copper salts as catalysts, they obtained the desired product with yields generally exceeding 90%. With L-abrine (72 in Scheme 39) as chiral moiety, an enantiomeric excess of 74% could be achieved. Moreover, the catalyst solution was reused with no loss of enantioselectivity. 

It has been found that the combination of Lewis acids and surfactants is particularly effective for catalyzing Diels-Alder reactions in water. The effect of micelles of SDS, CTAB, dodecyl heptaoxyethy-lene ether (Q2E7), and copper and zinc didodecyl sulfate [M(DSb] on the Diels-Alder reaction of 3-(p-substituted phenyl)- l-(2-pyridyl)-2-propen-l-ones (Figure 12.1) with cyclopentadiene was studied. 

The 3-methylimidazolium-3-amino-2-propen-l-one compounds can also be considered as vinylogous azolides, as the following reactions with nucleophiles demonstrate ... 

The cobalt complex 37 was used in combination with quinine as a chiral coordinating base to hydrogenate l,2-diphenyl-2-propene-l-one in 49% ee (Fig. 29.22) [50]. However, no further studies of this type of catalyst were reported. 

Considering that the activity of a Lewis acid depends strongly on the stability of the acid-base complex and that the complexation is notoriously hampered by chemically hard solvents like water, it is clear that reactions of bidentate dienophiles can be catalysed very efficiently36. Prototypical are the derivatives of 3-phenyl-l-(2-pyridyl)-2-propen-l-ones (vide infra). Their Diels-Alder reactions (Table 24) clearly show that the accelerating solvent effect of water is still present in the Lewis acid catalysed reactions, and that the Lewis acid activity is not necessarily hindered by the solvent301. While... 

TABLE 24. Second-order rate constants (M 1 s ) for the Diels-Alder reaction of 3(4-nitro-phenyl)-l-(2-pyridyl)-2-propen-l-one in different media at 25 °C... 

The non-linear optical (NLO) active aromatic chalcone l-(2-furyl)-3-(4-benzamidophenyl)-2-propene-l-one (FAPPO), shown in Fig.l, was found to give a rather big SHG activity of 1-2 order of magnitude higher than crystalline urea [6]. Due to their conjugated system all discussed NLO active molecules are approximately fiat. 

Synonyms Acraldehyde Acrylaldehyde /rans-Acrolein Acrylic aldehyde AI3-24160 Allyl aldehyde Aqualin Aqualine Biocide BRN 1701567 Caswell No. 009 CCRIS 3278 Crolean EINECS 203-453-4 Ethylene aldehyde Magnacide Magnacide H NSC 8819 Papite Propenal 2-Propenal Prop-2-en-l-al 2-Propen-l-one Propylene aldehyde RCRA waste number P003 Slimicide UN 1092. 

Propenol, see Allyl alcohol 2-Propen-l -ol, see Allyl alcohol Propenol-3, see Allyl alcohol 2-Propen-l -one, see Acrolein Propenonitrile, see Acrylonitrile Propenyl alcohol, see Allyl alcohol 2-Propenyl alcohol, see Allyl alcohol... 

Chalcones (l,3-diaryl-2-propen-l-ones) are open-chain fiavonoids that are widely biosynthesized in plants. They are important for the pigmentation of flowers and, hence act as attractants to the pollinators. As fiavonoids, chalcones also play an important role in defending against pathogens and insects. A review of the literature concerning the evaluation of natural chalcones from medicinal plants reveals that many studies into their antimicrobial and antiviral activities have been carried out in recent years. Some of these compounds were isolated by bioassay-guided fractionation, after previously detecting activity on the part of the plants. 

The reduction of a dinitro ketone to an azo ketone is best achieved with glucose. 2,2 -Dinitrobenzophenone treated with glucose in methanolic sodium hydroxide at 60° afforded 82% of dibenzo[c,f [i 2]diazepin-l 1-one whereas lithium aluminum hydride yielded 24% of bis(o-nitrophenyl)methanol [575], Conversion of aromatic nitro ketones with a nitro group in the ring into amino ketones has been achieved by means of stannous chloride, which reduced 4-chloro-3-nitroacetophenone to 3-amino-4-chloroacetophenone in 91% yield [178]. A more dependable reagent for this purpose proved to be iron which, in acidic medium, reduced m-nitroacetophenone to m-aminoacetophenone in 80% yield and o-nitrobenzophenone to o-aminobenzophenone in 89% yield (stannous chloride was unsuccessful in the latter case) [903]. Iron has also been used for the reduction of o-nitrochalcone, 3-(o-nitrophenyl)-l-phenyl-2-propen-l-one, to 3-(o-aminophenyl)-l-phenyl-2-propen-l-one in 80% yield [555]. 

PALLADIUH-CATALYZED COUPLING OF VINYL TRIFLATES WITH ORGANOSTANNANES 4-tert-BUTYL-l-VINYLCYCLOHEXENE AND 1-(4-tert-BUTYLCYCLOHEXEN-1-YL)-2-PROPEN-l-ONE (Cydohexene. 4-(l,1-dimethyIethyl)-l-ethenyI- and Z-Propen-l-one, l-[4-(l,l-di ethy1ethyl)-l-cycIohexen-l-yl)... 

PALLADIUM-CATALYZED COUPLING OF VINYL TRIFLATES WITH ORGANOSTANNANES 4-tert-BUTYL-l-VINYLCYCLOHEXENE and l-(4-tert-BUTYLCYCLOHEXEN-l-YL)-2-PROPEN-l-ONE... 

The progress of the reaction is conveniently monitored by gas chromatography on a 1/8" x 6 column packed with 6X SP-2100 on Supelcoport, 80-100 mesh, operated at 50°C for 4 min, then heated at 15°C/min to 250°C. The relative retention times are 4.0 min for trimethylvinyltin, 6.5 min for trimethyltin chloride, 13.1 min for 4-tert-butylcyclohexen-l-yl trifluoromethanesulfonate, and 14.7 min for l-(4-tert-butylcyclohexen-l-y1)-2-propen-l-one. Because of the extreme Volatility of trimethylvinyltin, it may be necessary to add additional small amounts of this reagent in order to drive the reaction to completion. 

Di[bis(cyclopentadienyl)iron]-2-propen-l-one, 3840 =K Dicarbonyl- /r-cycloheptatrienyltungsten azide, 3123... 

The zinc(II) chloride promoted intramolecular cycloaddition of l-[6-(3-isopropenyl-4-methyl-3-pentenyl)-2-methoxyphenyl]-2-propen-l-one yields a racemic cycloadduct93 that contains two chiral units a center and a stereogenic axis. On heating, an equilibrium mixture of the two diastereomeric atropisomers 8 and 9 is established94. 

Engberts and co-workers (Otto et al., 1996) reported a detailed study of a Diels-Alder reaction that was catalyzed by Lewis acids in water. They presented the results of the effects of Co Ni, Cu and Zn ions as Lewis acid catalysts on the rate and endo-exo selectivity of the DA reaction between the bidentate dienophiles 3-phenyl-l-(2-pyridyl)-2-propen-l-ones and cyclopentadiene in water (see fig. 6.6). Relative to the uncatalyzed reaction in acetonitrile, catalysis by 0.010 M Cu(N03)2 in water accelerates the Diels-Alder reaction by a factor of 79,300. Water does not induce an enhanced endo-selectivity for this reaction. 

In the reaction of 2-cyclohexenone and of 4-phenylbut-3-en-2-one with chiral organocuprates of type (205), optical yields of only 5% and 15%, respectively, were obtained201 . Methylation of l,3-diphenyl-2-propene-l-one with (205) (R = CH3) produced (S)-l,3-diphenyl- 1-butanone in 68% enantiomeric excess 202>. 

The 12-step synthesis of imatinib mesylate (1) in the manufacturing process was accomplished by Novartis in an astonishingly short time. The synthesis began with a condensation reaction between 6 and ethyl formate. Deprotonation of the methyl group on 3-acetylpyndine (6) using freshly prepared sodium methoxide afforded an enolate. Condensation of the enolate with ethyl formate was followed by exchange with to produce 3-dimethylamino-l-(3-pyridyl)-2-propen-l-one (7). could be prepared from the condensation of 6 and N,N-... 

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