Dicarbonyl compounds Methyl vinyl ketone

Keywords 1,3-dicarbonyl compound, methyl vinyl ketone, chalcone, Michael addition, BiCh, CdCl2, microwave irradiation... 

Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1 and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3 is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl vinyl ketone. This compound generates methyl vinyl ketone in situ by (3-eliminalion. The original conditions developed for the Robinson annulation reaction are such that the ketone enolate composition is under thermodynamic control. This usually results in the formation of product from the more stable enolate, as in Entry 3. The C(l) enolate is preferred because of the conjugation with the aromatic ring. For monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted position in hydroxylic solvents. The alternative regiochemistry can be achieved by using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-substituted enamine is favored, so addition occurs at the less-substituted position. 

The competition between Michael addition of a,(3-unsaturated ketones and Diels-Alder reactions involving furan and 2-methylfuran is affected by the catalyst used. Methyl vinyl ketone gives the alkylation product with furan and 2-methylfuran in the presence of silica gel (88TL175). Bis(alkylated) products have also been obtained in reactions of 2-methylene-1,3-dicarbonyl compounds (90H(31)1699). An intramolecular proton catalyzed alkylation reaction of an a,(3-unsaturated ketone provided a straightforward synthesis of norpinguisone (90TL4343) and in the example shown in Equation (4) the cyclization reaction involved an a,(3-y,8-dienone (94TL4887). 

Dicarbonyl compounds.1 The reaction of enol silyl ethers with methyl vinyl ketone catalyzed by BF3 etherate results in 1,5-dicarbonyl compounds. Almost quantitative yields can be obtained, even from hindered ketones, by addition of an alcohol or even, to a less extent, of water. 

The catalyst RuH2(PPh3)4 itself has no catalytic activity in the C-H activation of carbonyl compounds, and a more basic catalyst such as RuCpH(PPh3)2 and RuCp H(PPh3)2 is required for activation of 1,3-dicarbonyl compounds. The catalytic Michael addition of 3-methyl-2,4-pentanedione to methyl vinyl ketone gave the corresponding adduct in 79% yield [2]. 

Base catalysis is not required for conjugate addition. If the nucleophile is sufficiently enolized under the reaction conditions then the enol form is perfectly able to attack the unsaturated carbonyl compound. Enols are neutral and thus soft nucleophiles favouring conjugate attack, and p-dicarbonyl compounds are enolized to a significant extent (Chapter 21). Under acidic conditions there can be absolutely no base present but conjugate addition proceeds very efficiently. In this way methyl vinyl ketone (butenone) reacts with the cyclic P-diketone promoted by acetic acid to form a quaternary centre. The yield is excellent and the triketone product is an important intermediate in steroid synthesis as you will see later in this chapter. 

Rh-catalyzed 1,4-carbonylative addition to methyl vinyl ketone gives rapid access to the required 1,4-dicarbonyl compounds (Equation 2) <2006T11740>. 

Dicarbonyl compounds.4 Michael addition of a-nitro ketones to methyl vinyl ketone (la) or acrylaldehyde (lb) catalyzed by P(QH5)3 provides the adducts 2, which are reduced by Bu3SnH to 1,5-dicarbonyl compounds (3). Additions to the enal proceed more rapidly than ones to the enone. 

As previously mentioned, 1-alkynyltrialkylborates (18) have become increasingly important in the formation of carbon-carbon bonds via attack of electrophiles. However, such complexes cannot react with simple Qc,P-unsaturated carbonyl compounds such as methyl vinyl ketone, because of their weak electrophilicity. Recently it was ascertained that ,P-unsaturated carbonyl compounds react with 18 via a Michael-type reaction in the presence of titanium tetrachloride, and the usual alkaline hydrogen peroxide oxidation leads to the synthesis of 5-dicarbonyl compounds... 

Hydrolysis of 2-alkoxy-3,4-dihydro-l,2-pytans with dilute hydrochloric acid furnishes a convenient synthesis of glutaraldehyde (R = H) and other l,5 dicarbonyl compounds. The starting materials are obtained by the 1,4-addition of vinyl ethers to a,/3-unsaturated carbonyl compounds. The wide selection of diene systems includes acrolein, crotonaldehyde, meth-acrolein, cinnamaldehyde, /3-furylacrolein, methyl vinyl ketone, benzal-acetone, and benzalacetophenone. Ethyl vinyl ether is preferred as the dienophile. The yields in the cyclization step are in the range of 25 87% and in the subsequent hydrolysis Step, 55 85%. ... 

The mechanism of the Robinson annulation consists of two parts a Michael addition to the a,p-unsaturated carbonyl compound to form a 1,5-dicarbonyl compound, followed by an intramolecular aldol reaction to form the six-membered ring. The mechanism is written out in two parts (Mechanisms 24.7 and 24.8) for Reaction [2] between methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. 

Dicarbonyl compounds are formed by reaction of silyl enol ethers with methyl vinyl ketones in the presence of BF3 Et20 and an alcohol (Eq. 84) [139]. 

BiX mediates the Mukaiyama-Michael addition of a./i-urisaluraled carbonyl compounds (Scheme 14.87) [171, 172 b, c]. The BiCb-catalyzed Michael addition of 1,3-dicarbonyl compounds to methyl vinyl ketone and benzal acetophenone proceeds efficiently under microwave irradiation [179]. The Knovenagel condensation of aldehydes with active methylene compounds can also be promoted by BiCl3 (Scheme 14.88) [180]. 

A similar dramatic influence of ionic liquid was also reported by Ranu s group in the Michael reaction of active methylene compounds with methyl vinyl ketone and methyl acrylate in the presence of an ionic liquid, 1-butyl-3-methylimidazolium hydroxide ([bmImjOH). Interestingly, open-chain 1,3-dicarbonyl compounds 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 (Scheme 5.55). 

Takei utilized a furan as the synthetic equivalent of a 1,4 dicarbonyl compound in his synthesis of pyrenophorin as described in Scheme 4.6. ° Thus butenolide 28, obtained by Michael addition of butenolide 27 to methyl vinyl ketone, was silylated to provide the silyloxyfuran. Treatment with lead tetraacetate followed by aqueous hydrolysis gave 29 in 55% yield. Protection of the ketones as dimethyl ketals followed by selective removal of the C-7 ketal and reduction gave seco acid 30. Dimerization and hydrolysis gave a mixture of 9 and 18 (17% from 29). 

These compounds, exemplified by acrolein, crotonaldehyde, and methyl vinyl ketone, are known to react with ozone and with OH radicals. Photolysis and N03 radical reaction are of minor importance. Under atmospheric conditions the 03 reactions are also of minor significance (Atkinson and Carter, 1984), leaving the OH radical reaction as the major loss process. For the aldehydes, OH radical reaction can proceed via two reaction pathways OH radical addition to the double bond and H-atom abstraction from the -CHO group (Atkinson, 1989). For crotonaldehyde, for example, the OH reaction mechanism is given in Fig. 3. As can be noted from Fig. 3, these a,/3-unsaturated aldehydes are expected to ultimately give rise to a-dicarbonyls such as glyoxal and methylglyoxal. For the a,/3-unsaturated ketones such as methyl vinyl ketone, the major... 

Indole-3-carboxylate esters and 3-acetylindoles can be prepared by palladium-catalyzed cycli-zation of enamines (14). These can be prepared from the corresponding anilines by condensation with j8-dicarbonyl compounds or by palladium-catalyzed substitution reactions with ethyl acrylate or methyl vinyl ketone <86BCJ927, 90S215>. Overall yields for the two-step process are 60-80% (Scheme 33). 

Dicarbonyl compounds are formed from the reaction of silyl enol ethers with methyl vinyl ketones in the presence of BF3 OEt2 and an alcohol (eq 9). a-Methoxy ketones are formed from a-diazo ketones with BF3-OEt2 and methanol, or directly from silyl enol ethers using iodobenzene/BF3-OEt2 in methanol. ... 

Very high enantioselectivities in the PTC Michael addition of 1,3-dicarbonyl compounds to enones have been achieved by Maruoka et al. [189,233] As shown in Scheme 2.86, just a 2 mol% of the binaphthyl-derived phase-transfer catalyst 124b [Scheme 2.70, 124, Ar=3,5-((CFj)jC H3)] in the presence of 10 mol% of solid KjC03, is able to achieved a highly efQdent and enantioselective addition of 2-(9-fluorenoxycarbonyl)cyclopentanone to methyl vinyl ketone [189]. 

In 2007, Ramachary et al. reported an asymmetric Knoevenagel/hydrogenation/Robinson annulation sequence to obtain Wieland-Miescher ketone 189 [88] (Scheme 2.62). The reaction of 5 equiv of aldehyde 9 with the 1,3-dicarbonyl compounds 186 (with CH acid) and Hantzsch ester 187 under proline catalysis furnished the expected cyclo-hexane-1,3-dione B in good yields. Once the solvent was removed by vacuum pump, the crude reaction mixture was diluted with DMF and treated with methyl vinyl ketone 188 in the presence of (S)-proline (1) furnishing the expected... 

The Michael reaction of a,p-unsaturated ketones, such as methyl vinyl ketone and 3-penten-2-one, with P-dicarbonyl compounds has been investigated in aqueous solution in the presence of CTABr and other cationic surfactants [39]. The reaction yield depends on the temperature, concentration, nucleophile precursor, surfactant and structure of the substrate. 

Organocopper )V)V-dimethylhydrazone (DMH) derivatives have been used for the synthesis of a variety of 1,5-dicarbonyl compounds. In contrast to the normal Robinson annelation of 2-methylcyclohexanone, which leads to attachment of methyl vinyl ketone analogues at C-(2) and eventual formation of (56), the organocopper DMH derivative of 2-methylcyclohexanone reacts with methyl vinyl ketone to give the 1,5-diketone (57), which undergoes base cyclization to the octalones (58). 

Now let s consider 1,4-dicarbonyl compound 39. One polar disconnection leads to charged fragments A -I- B or C -l- D (Case 1). The C -I- D pair can easily be related to an acyl anion equivalent and methyl vinyl ketone (by apph-cation of the principle of vinylogy). The acyl anion equivalent can be generalized by structure 40 in which an A-fimction behaves as a N-fiinction. 

The addition of 11 to methyl vinyl ketone or acrylaldehyde proceeds in the presence of triphenylphosphine with good to excellent yields in THF at room temperature. The subsequent denitration of 36 is accomplished with tin hydride and free radical initiator AIBN in refluxing bezene with good yields to form 1,5-dicarbonyl compounds 37. ... 

In the Michael reaction, an enolate acts as a nucleophile and adds 1,4 to an a,P-unsaturated carbonyl compound (Section 22.12). 1,3-Dicarbonyl compounds firequently provide the enolate, called the Michael donor. Three a,p-unsaturated carbonyl compounds are commonly used as Michael acceptors 3-buten-2-one (methyl vinyl ketone), 2-propenal (acrolein), and methyl 2-propenoate (methyl acrylate). For example, dimethyl malonate reacts with 3-buten-2-one in a base-catalyzed reaction. 

---