Ketones Michael addition with

Poly(vinyl alcohol) undergoes Michaels addition with compounds containing activated double bonds, including acrylonitrile (145—150), acrylamide (151—153), A/-methylolacrylamide (154—156), methyl vinyl ketone (157,158), acrolein (157), and sodium 2-acrylamido-2-methylpropanesulfonate (159). The reactions have been carried out under conditions spanning from homogeneous reactions in solvent to heterogeneous reactions occurring in the swollen powder or fiber. 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

Despite a very unfavorable proton transfer using (35) as an EGB, condensation of acetophenone with an aromatic aldehyde took place within a matter of hours. The reaction led to Q , 8-unsaturated ketones, which underwent the Michael addition with a second equivalent of deprotonated ketone. Scheme 30, [80, 81]. The EGB was generated ex situ. 

Scheme 28 Asymmetric enamine-catalyzed Michael additions with ketone donors...

Aldol condensation of the methoxymethyl ether of rn-methoxybenzaldehyde (83) with cyclohexanone affords the conjugated ketone Michael addition of dimethylamine... 

As shown in Scheme 1.2.12, the aldehyde or ketone SAMP hydrazones 50 were metallated using LDA to generate the desired azaenolate, and then TMEDA was added. Subsequent Michael addition with methyl-2-cyclopentenone carboxylate (51) resulted in a clean 1,4-addition leading to the desired adducts 52 in good yields. 

As is to be expected, an alkynic ketone undergoes a Michael addition with a carbanion, leading eventually to a pyranone (50JA1022). Using malonic esters, a 3-alkoxycarbonyl derivative results, which is hydrolyzed to the 2-oxopyran-3-carboxylic acid under alkaline conditions, but to the pyranone by sulfuric acid. Rapid ester exchange is observed with the initial products, the alcohol used as solvent determining the nature of the alkyl group in the 3-carboxylic esters (Scheme 90). 

One problem that may be encountered with this type of reaction is related to the fact that in solid-phase synthesis reagents generally have to be used in excess. This can occasionally lead to side reactions, ff, for instance, a resin-bound aldehyde is condensed under basic conditions with excess ketone, the resulting enone might undergo Michael addition with an additional equivalent of ketone (Figure 5.10). For some of these enones, the Wittig reaction may represent a superior synthetic method [75]. 

Similar changes take place in the acidification of the enol salt of a carbonyl compound, the principal difference being the much longer life of the acf-nitro compound compared to that of an enol of a simple ketone (see Section 17-IB), Primary and secondary nitro compounds undergo aldol additions and Michael additions with suitable carbonyl compounds and basic catalysts ... 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Fig (7) The transformation of cyclohexene-l,3-dione (50) to ketone (52) is described. This involves reduction, terahydropyranilation, methoxy-carbonylation and Michael addition, with methyl vinyl ketone. Treatment of (52) with p-TsOH in methanol, leads the formation of lactone (53) and hydroxy ester (54). The lactone (53) is regarded as an appropiate intermediate for natural o-methyl pisiferic acid (+)(2)and hydroxi ester (54) is intermediate for (-)(55). 

Hindered phenolates have low nucleophilicity and in aprotic solvent may act usefully as EGBs. 2,6-Di-t-butyl-/ -cresol = 16.8) was reduced directly with concomitant hydrogen evolution to give, ex situ, the corresponding tetraethylammonium phenolate [59,60], which was clearly capable of deprotonating aromatic ketones and in the presence of aromatic aldehydes promoted aldol reaction to a, /3-unsaturated ketones which underwent Michael addition. The initial proton transfer from the aromatic ketone ] K = 24.7) is thermodynamically very unfavorable. Even so, aldol reaction took place within a matter of hours upon addition of an aromatic ketone together with an aromatic aldehyde leading to or, /3-unsaturated ketones which subsequently underwent Michael addition with a sec-... 

The enamine 103 of our familiar unsymmetrical ketone 23 gives a clean Michael addition with methyl acrylate on the less substituted side to give the ketoester xyn-104 as the only product providing that the reaction is carried out in MeOH.38... 

Several structurally different diketones (acetylacetone, methyl 2-oxocyclohex-ane carboxylate) and active methylene compounds (diethyl malonate, ethyl aceto-acetate) and thiols (methyl thioglycolate) underwent clean, fast, and efficient Michael addition with methyl vinyl ketone, acrolein, and methyl acrylate over NaY and Na beta zeolites [88] in high yield (70-80%). The reactions were performed in the absence of solvent, at room temperature, with 1 g catalyst per mmol donor. When HY zeolite was used instead of NaY formation of the desired Michael adduct was low and polymerization of Michael acceptor was the main reaction. 

The allenic acid fluoride (254) undergoes Michael addition with KCN to give the 20-cyano-acid (255). Lithium dimethylcopper gives the product (256) of methylation at both C-20 and C-22, but dimethylcadmium reacts selectively at C-22, giving the allenic ketone (257) and a little of its C-21-epimer. ° ... 

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