4-Methylpent-3-en-2-one

The cyclohexenone C has been prepared in a one-pot process beginning with 4-methylpent-3-en-2-one. The reagents which are added in succession are 4-methoxy-phenyllithium, Li, and NH3, followed by acidic workup. Show the intermediate steps that are involved in this process. 

It was assumed (59LA(625)74) that the reaction proceeds through acylation of the non-conjugated methylene ketone and the Russian work certainly supports this view. The observation that 4-methylpent-4-en-2-one gives a vastly improved yield of 2,4,6-trimethylpyrylium perchlorate compared with 4-methylpent-3-en-2-one on reaction with acetic anhydride and perchloric acid also favours this suggestion and led to a proposed mechanism (Scheme 249) (61JCS3573). 

By far the most important compounds of this type are the a,/ -unsaturated aldehydes and ketones, of which the simplest general representation is (8) and (9) respectively. Branching may be present at either or both of the a- or p- positions as for example in 2-ethylhex-2-enal (10) and 4-methylpent-3-en-2-one (11). Compounds where the carbon-carbon double bond is terminal are acraldehyde [(8), R=H], and the alkyl (or aryl) vinyl ketones [(9), R = H, R = alkyl, aryl etc.]. 

Trifluoropyruvamide 1040 can react with 4-methylpent-3-en-2-one to afford the tetrahydropyran-4-one 1041 in moderate yield (Equation 404) <2004TL5611>. 

Sequential oxidation and hydrolysis of the enamine derived from the reaction between 4-methylpent-3-en-2-one and pyrrolidinium pyrrolidinedithiocarbamate affords 6,6-dimethylthiopyran-2,4-dione (Scheme 222) <2003RJ0235>. 

Methylpent-3-en-2-one (11) with maiononitrile (10) in the presence of pyrrolidine gave 5-amino-2, 4, 4-trimethyl-7-(pyrrolidin-l-yl)-l,4-dihydro-l,6-naphthyridine-8-carbonitrile (12) [reactants, EtOH, 20°C, HN(CH2)4 dropwise reflux. 7h 32%].170... 

Dimedone has a trivial name because its preparation is so easy that it was discovered early in the history of organic chemistry. The first step is a conjugate addition of diethyl malonate to the unsaturated ketone mesityl oxide (4-methylpent-3-en-2-one given a trivial name for the same reason). Ethoxide ion is the base for the usual reason that nucleophilic substitution at the ester group simply regenerates starting material. 

An especially elegant use of superoxide anion, in combination with dioxygen, is as both an EGB and as an epoxidation reagent [52]. In this way the ROJ species, formed from the carbanion R , reacts in situ with an enone, which is converted into the epoxide (Scheme 15). Specifically, the carrier (PhCHoCN), which has been dubbed an auxiliary carbon acid, is deprotonated by the superoxide anion, and the resulting anion reacts with O2. The Ph2C(CN)OJ species thus formed reacts in situ with an enone, which is converted into the epoxide with elimination of cyanide anion from the carrier and concomitant formation of ketone (Scheme 15). Another possible auxiliary carbon acid is MeCH(C02Et)2 and, apart from the example in Scheme 15, 4,4-dimethyl-2-cyclohexen-l-one, 4-methylpent-3-en-2-one, and trans-cha -cone (PhCH=CHCOPh) may be converted [52] into the corresponding epoxides in >80% yield. 

Thus, dichlorocarbene, generated in a neutral medium by using bromodichloro-methyl(phenyl)mercury, underwent addition to 4-methylpent-3-en-2-one (the product is unstable), and to various 2,2-dichlorovinyl ketones. 

On the other hand, 4-methylpent-3-en-2-one underwent the reaction with chloroform, under phase-transfer catalytic conditions, to give cyclopropane 2. ... 

A stirred suspension of 4-methylpent-3-en-2-one (1.0 g, 10.2 mmol) and amalgamated zinc (5.0 g, 76.5 mmol) in dry EtjO (10 mL) and AcjO (1 mL) was cooled to — 35"C and sat. HCl in EtjO (5mL, 20 mmol) was added dropwise over 5 min. Stirring was continued at — 35°C for 15 min. Then the solution was decanted and poured into sat. aq NaHCOj (50 mL). The mixture was extracted with EtjO. The organic layer was washed with HjO, dried (MgSO. ) and evaporated. The residue was distilled bulb-to-bulb and purified by preparative GC yield 0.94 g (65%). 

The 2,3-dihydro-l//-pyrazole obtained from the reaction of hydrazine with an a-)8-unsaturated carbonyl compound will sometimes give a sufficient proportion of the 4,5-dihydro-3i/-pyrazole tautomer at equilibrium so that it is possible just to heat the 1//-tautomer to eliminate nitrogen and form a cyclopropane. In other cases, it is necessary to reduce the 1//-tautomer and oxidize back to the 3 -form. It is also possible to use the conversion of the H- to the 3//-tautomer to introduce substituents at C3 of the 4,5-dihydro-3//-pyrazole and hence into the cyclopropane. The reaction of 4-methylpent-3-en-2-one with hydrazine gave 2,2,4-trimethyl-2,3-dihydro-lH-pyrazole (1). Treatment with lead tetraacetate gave the 3-acetoxy derivative 2 and on thermolysis, l-acetoxy-l,2,2-trimethylcyclopropane (3). Alternatively, tosylation and reaction with methyllithium gave 3,3,5,5-tetramethyl-4,5-dihydro-3//-pyrazole (4) which on thermolysis or photolysis gave 1,1,2,2-tetramethylcyclopropane route to tetramethylcy-... 

A new synthesis of 2,4,4,6-tetramethyl-4//-l,3-oxazine (155) simply involves a reductive cycloaddition of 4-methylpent-3-en-2-one and acetonitrile in the presence of trimethylsilyl chloride and sodium iodide (Scheme 42) <89TL4741>. Other cycloaddition reactions have been used previously to synthesize 4//-l,3-oxazines and this methodology has been extended to include cycloadditions between alkynes and l-oxa-3-azabuta-1,3-dienes. For example, phenylethyne and the A-benz-oylimine (156) afford 4,4-bis(trifluoromethyl)-2,6-diphenyl-4//-l,3-oxazine (157). The reaction proceeds through a Michael-type addition between the alkyne and the heterodiene giving an adduct which when heated to 80-90°C cyclizes to the oxazine (Scheme 43) <83CC945,89ZN(B)1298>. 

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