Acetylacetone Michael addition

Scheme 6 Enantioselective Michael-addition of acetylacetone to nitrostyrene catalyzed by a bifunctional thiourea catalyst...

Papai et al. selected as model reaction the addition of 2,4-pentanedione (acetylacetone) to trans-(R)-mtrostyvQnQ, catalyzed by the bifunctional thiourea catalyst shown in Scheme 6 [46]. The analogous Michael-addition involving dimethyl malonate and nitroethylene as substrates, and a simplified catalyst was calculated at the same level of theory by Liu et al. [47]. Himo et al. performed a density functional study on the related cinchona-thiouTQa catalyzed Henry-reaction between nitromethane and benzaldehyde [48]. 

Scheme 7 Two alternative reaction routes for the organocatalytic Michael-addition of acetylacetone to nitrostyrene...

A systematic investigation of the effect of Cl impurity was reported for a metal-catalyzed Michael addition of acetylacetone to methyl vinyl ketone in [BMIM]BF4 (77(5). The time required for the completion of the reaction was used as a measure of the effect of Cl . With a Ni(acac)2.2H20 catalyst, the Michael addition was completed in 2, 5, and 9h when the ionic liquid contained 0, 0.62, and 1.62% CP, respectively. 

Under optimized conditions, the 83-catalyzed (1 mol% loading) Michael addition of acetylacetone to various aryl nitroalkenes as well as alkyl nitroalkenes proceeded in good to excellent yields (80-97%) and enantioselechvities (82-99%) of the desired adducts 1-5 (Scheme 6.93). The authors also reported the successful enantioselective Michael addihon of l,3-diphenylpropane-l,3-dione (adduct in... 

Scheme 6.93 Typical products of the asymmetric Michael addition of acetylacetone to various nitroalkenes catalyzed by 83.

Optically active P-hydroxy /V-methyl sulfoximines have been used as catalysts for the enantioselective transfer of an ethyl group from diethylzinc to aldehydes to give secondary alcohols in enantiomeric excesses of 61-88%.127,135 Related chiral ligands have been used with nickel acetylacetone to promote the enantioselective Michael addition of diethylzinc to chalcones.136... 

Simple tertiary enaminones derived from acetylacetone and benzoylacetone react with acryloyl chloride to yield carbocyclic derivatives. The reaction proceeds via an initial Michael addition of the enaminone / -carbon to the enone107 (equation 76). Analogous behavior of cyclic enaminones leads, according to ring size, to tetrahydroindole, quinoline and benzazepine derivatives108 (equation 77). 

The Michael addition of anions of C-acids, such as acetylacetone or hydrocyanic acid, to phenyl vinyl ketone follows a scheme similar to (7). In the cases studied it was possible to neglect the acid-base properties of the adduct and the reverse elimination reaction (Hrubcova, 1964). Equations analogous to (9) and (10) were used and the pH-dependence of the determined formal rate constant at a given analytical concentration of the C-acid follows a dissociation curve with an inflexion at the pKa value of the C-acid. 

Rann et al. reported the dramatic influence of a new tailor-made, task-specific, and stable ionic liquid, butyl methyl imidazolium hydroxide ([bmim][OH]), in Michael addition. They have discovered that a task-specific ionic liqnid [bmim][OH] efficiently promoted the Michael addition of 1,3-dicarbonyl compounds, cyano esters, and nitro alkanes to a variety of conjugated ketones, carboxylic esters, and nitriles withont reqniring any other catalyst and solvent (Fig. 12.21) [16]. Very interestingly, all open-chain 1,3-dicarbonyl componnds such as acetylacetone, ethyl ace-toacetate, diethyl malonate, and ethyl cyanoacetate reacted with methyl vinyl ketone and chalcone to give the usual monoaddition products, whereas the same reactions with methyl acrylate or acrylonitrile provided exclusively bis-addition products. 

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 second chapter of the book covered the advances in enantioselective nickel(ii)-catalysed conjugate additions. An important breakthrough in the history of the Michael reaction was the achievement of the Michael addition of p-dicarbonyl compounds to a broad variety of electrophiles catalysed by nickel acetylacetonate, described by Nelson in 1979-1980. Since this pioneering contribution, nickel has become one of the preferred metals in catalytic Michael reactions. Later, in 1988, Soai developed the first asymmetric conjugate additions performed under chiral nickel(ii) catalysis. Ever since. 

Scheme 1.55 Michael additions of acetylacetone to nitroalkenes catalysed by bifunctional amine-thioureas.

Michael addition reactions alcohols with maleates, 46 with fumarates, 63 MA with acetylacetone, 235 MA derivatives, 65, 66 in maleamic acid cyclization, 83 with maleates, 63 maleates with thiols, 506 maleic anhydride, 65, 229 maleimides with amines, 512 Mitsubishi process, MA production, 29... 

Phosphorus-based synthons for acetoacetic ester and acetylacetone derivatives are described the phosphonate (78) has been used in the preparation of the /S-ketoester (79), a key intermediate in a synthesis of the fungal sex hormone, trisporic acid B methyl ester (80). Michael addition of an a-methylene ketone to 2,2-diethoxyvinylidenetriphenylphosphorane followed by loss of ethanol gives a valuable reagent (81) for the preparation of 1,3-dioxopent-4-enes by Wittig reaction with aldehydes the intermediate enol ethers (82) can be isolated if desired. 

Scheme 12.1 Two reaction routes envisioned for the Michael addition of acetylacetone (7b) to nitrostyrene (6) [46]. Note that both pathways lead to the formation of the (R) configuration of the Michael adduct 8b in the present arrangement of the substrates.

In the presence of a catalytic amount of triethylamine, a readily enolizable carbonyl compound like acetylacetone (25) can undergo a Michael-type addition onto the triple bond of 23 with C-C bond formation, and subsequent 1,2-addition of the hydroxy group with elimination of an alcohol (MeOH or EtOH) to eventually yield a pyranylidene complex 28 (mode E) [29]. The most versatile access to / -donor-substituted ethenylcarbene complexes 27 is by Michael-type additions of nucleophiles, including alcohols [30-32], primary... 

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