Synthesis vinyl ketone

Methyl vinyl ketone can be produced by the reactions of acetone and formaldehyde to form 4-hydroxy-2-butanone, followed by dehydration to the product (267,268). Methyl vinyl ketone can also be produced by the Mannich reaction of acetone, formaldehyde, and diethylamine (269). Preparation via the oxidation of saturated alcohols or ketones such as 2-butanol and methyl ethyl ketone is also known (270), and older patents report the synthesis of methyl vinyl ketone by the hydration of vinylacetylene (271,272). 

Methyl vinyl ketone is used as a comonomer in photodegradable plastics, and is an intermediate in the synthesis of steroids and vitamin A. It is highly toxic and faciUties handling over a threshold of 100 lbs (45.5 kg) are subject to special OSHA documentation regulations (273). 

The synthesis and condensation reactions of 2,2,2-trifluoroethyl vinyl ketone with enamines and ketones were investigated [57J (equation 38) (Table 13). These reactions lead to the formation of 2-trifluoromethylcyclohexenones. 

Reactions of 3- and 4-piperidone-derived enamines with a dienester gave intermediates which could be dehydrogenated to tetrahydroquinolines and tetrahydroisoquinolines (678). The methyl vinyl ketone annelation of pyrrolines was extended to an erythrinan synthesis (679). Perhydrophenan-threnones were obtained from 1-acetylcyclohexene and pyrrolidinocyclo-hexene (680) or alternatively from Birch reduction and cyclization of a 2-pyridyl ethyl ketone intermediate, which was formed by alkylation of an enamine with a 2-vinylpyridine (681). 

The side-chain cyanoethylation of alkyl thienyl ketones with acrylonitrile has been studied " and used for the preparation of 8-oxonitriles and S-oxoacids. Aminomethylation (Mannich reaction) of 2-acetylthiophene followed by steam distillation yielded 50% of 2-thienyl vinyl ketone, and has also been used for the synthesis of compounds of biological interest. ... 

The ability of 1,2 (or l,6)-dihydropyridines to undergo a Diels-Alder reaction with dienophiles such as methyl vinyl ketone, methyl acrylate, and acrylonitrile has been utilized in the synthesis of polyfunctional isoquinuclidine as a key intermediate in the synthesis of aspidosperma- and iboga-type alkaloids (66JA3099). 

The reaction of a cyclic ketone—e.g. cyclohexanone 1—with methyl vinyl ketone 2 resulting in a ring closure to yield a bicyclic a ,/3-unsaturated ketone 4, is called the Robinson annulation This reaction has found wide application in the synthesis of terpenes, and especially of steroids. Mechanistically the Robinson annulation consists of two consecutive reactions, a Michael addition followed by an Aldol reaction. Initially, upon treatment with a base, the cyclic ketone 1 is deprotonated to give an enolate, which undergoes a conjugate addition to the methyl vinyl ketone, i.e. a Michael addition, to give a 1,5-diketone 3 ... 

A. number of rutro compounds used m ndturdl product synthesis have been prepared by the n of alkyl halides Some recent examples are summarized m Table 2 4 fi-Nitro carbonyl compounds are important for synthesis of natural products The reaction of alkyl vinyl ketones with sodium nitrite and acetic acid in THF gives thecorrespondmgfi-nitro carbonyl compounds in42-82% ""rhis method is better for the preparation of fi-nitro carbonyl compounds than the nitration of the corresponclmg halides... 

For the synthesis of quinolines and isoquinolines the classical approaches are the Skraup and the Bischler-Napieralski reactions. The reaction of substituted anilines with different carbonyl compounds in acid medium has been reported to be accelerated under microwave irradiation to give differently substituted quinolines and dihydro quinolines [137]. Although the yields are much better and the conditions are milder than under conventional heating, the acidity of the medium may prevent the preparation of acid-sensitive compounds. Thus, alternative approaches have been investigated. Substituted anilines and alkyl vinyl ketones reacted under microwave irradiation on the surface of sihca gel doped with InCU without solvent [137] to furnish good yields of quinohnes 213 (Scheme 77). 

Faced with the problem of making simple vinyl ketones (15) and (16) as intermediates in a longer synthesis, chemistsfound they needed both strategies outlined here ... 

Organic synthesis [OS 55) Addition of2,4-pentanedione enolate to methyl vinyl ketone [8]... 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

Reaction of /V,/V-unsubstituted selenoureas 332 with methyl vinyl ketone in the presence of ferric chloride in refluxing ethanol gives 2-amino-5-(l -ethoxy)-1,3-selenazoles 335 <06H(68)2145>. This approach obviates the use of lachrymatory halo carbonyl compounds frequently utilized in the synthesis of 1,3-selenazoles. 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

Simple synthesis of ( )-17-epiyohimbol (73) has been reported by Mori et al. (214). yV-Benzyloctahydroindolo[2,3-a]quinolizinone (126), prepared according to the procedure of Novdk and Szdntay (97) was coverted to the corresponding pyrrolidine enamine, which was treated with methyl vinyl ketone to give N-benzylyohimbenone (379). Reduction of 379 with sodium in liquid ammonia... 

For the synthesis of Diels-Alder adducts a morphinan-6,8-diene system, as present in thebaine, is indispensable. Older publications started from thebaine and methyl vinyl ketone (but-3-en-2-one), yielding, after a Grignard reaction with propylmagnesium bromide, etorphine (13), a 6,14-endoethenomorphinan that is over 1000x as active as morphine and is used in veterinary medicine (Scheme 5.10). 

An alternative solution to blocking groups, is the introduction of an activating group at the less reactive position in order to favour the attack of the reagent at this site of the molecule. Such is the case, for instance, in the synthesis of helminthosporal by Corey [24]. In the first step of the synthesis, which involves a Michael condensation of carvomenthone (36) with methyl vinyl ketone to give the... 

In the partial synthesis shown, there are two reagents, the a,P-unsaturated ketone methyl vinyl ketone and the 1,3-diketone 2-methylcyclohexa-1,3-dione. 

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

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