Allyl-2-methylcyclohexanone

Formal Enolate Generation by Flnoride Ion, Increasing the Nucleophilicity of the Silyl Enol Ether 

Kuwajima (15) has provided full details of the regiospecific monoalkylation of carbonyl compounds via their silyl enol ethers, using stoichiometric amounts of fluoride ion. Noyori (16) has given more information on the use of the complex fluoride source (2) (Chapter 18) 

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Using the 3 mm. by 2 m. gas chromatography column described above, a mixture of stereoisomers of 2-allyl-5-methylcyclohexanone [Cyclohexanone, 5-methyl-2-(2-propenyl)-], prepared by allylation of the enamine of 3-methylcyclohexanone,7a showed peaks at retention times of 8.4 minutes (more stable isomer) and 9.6 minutes. A mixture of the two isomeric 2-allyl-3-methylcyclohexanones and the two isomeric 2-allyl-5-methylcyclohexanones clearly exhibited four distinct peaks on gas chromatography. 

The direct conversion of 3-methylcyclohex-2-enone into 2-allyl-3-methylcyclohexanone provides an interesting example of the utility of the reduction-alkylation procedure. Synthesis of this compound from 3-methy I cyclohexanone would be difficult because the latter is converted mainly into 2-alkyl-5-methylcyelohexanones either by direct base-catalyzed alkylation11 or by indirect methods such as alkylation of its enamine (see Note 13) or alkylation of the magnesium salt derived from its cyclohexylimine.12... 

ENONE REDUCTION-ENOLATB ALKYLATION SEQUENCE 2-ALLYL-3-METHYLCYCLOHEXANONE... 

Alternative preparations of 2-allyl-3-methylcyclohexanone include a) lithium-ammonia reduction of 2-allyl-3 methylcyclohex-2-enone (see Note 13), which can be prepared by alkylation of 3-methjdcyclohex-2-enone or by alkjdation of 4-carboethoxy-3-methylcyclohex-2-enone [Hagemann s ester 2-Cyclohexene-l-carboxylic acid, 2-inethyl-4-oxo-, ethyl ester], followed bj hydrolysis and decarboxylation and b) conjugate addition of lithium dimethylcupratc [Cuprate (1-), dimethyl-, lithium] to 2-cyolohexen-l-one followed by trapping of the enolate with allyl iodide or allyl bromidein an appropriate solvent. 

It is interesting that (mw5-2-allyl-3-methylcyclohexanone is by far the major product of this reduction-alkylation sequence, being formed in greater than the equilibrium ratio (see Note 13). The lithium enolate would be expected to exist in the two conformations shown below ... 

The enolate anions, derived from 2-methyl-1-trimethylsilyloxy-l-cyclohexene and 6-methyl-1-trimethylsilyloxy-l-cyclohexene with BuLi, undergo Pd-catalyzed allylation reactions to give allylated methylcyclohexanones (Scheme... 

High-boiling products found in this procedure and in similar experiments involving cyclohex-2-enone derivatives5 probably result from bimolecular reduction processes.15 3-Methylcyclohexanone, which arises by protonation rather than alkylation of the enolate (and which made up ca. 12% of the volatile products), is probably the result of reaction of allyl bromide with liquid ammonia to form the acidic species allyl ammonium bromide.5 10... 

Allenyl Silyl enol ethers, 86 Allyl alcohol trimethylsilyl ether, 84 Allyl carbonates, 114-15 9 Allyl-ay 2 octalone, 34-5 2-Allyl-2 methylcyclohexanone, 106 (Allyldimethylsilyl)methyl chloride, 58, 59 (AUyldimethylsilyl)methylmagnesium chloride, 59... 

The reaction of allylindium sesquibromide with 4 equiv. of bulky lithium alkoxide results in modified reagents 7, which show unusual degrees of chemo- and diastereoselectivity in the reactions with carbonyl compounds for example, allylation of 2-methylcyclohexanone gives a high ratio of axial alcohol 8/equatorial alcohol 9 (Scheme 15).128... 

P-Alkoxy kettmes and y-acetoxy ketones prepared by the oxidation of allyl ethers and homoallyl acetates, respectively, are synthetically useful intermediates. The reaction of (K) in the presence of excess sodium methoxide with 2-methylcyclohexanone afforded methyloctalone (94) in 42% yield (equation... 

Epoxides may undergo rearrangement in the presence of protic or Lewis acids to give carbonyl compounds. However, the nature of the products may depend quite subtly on the reaction conditions. For example, 1-methylcyclohexene oxide has been reported to give the ring-contracted aldehyde as the major product with lithium bromide, but with lithium perchlorate, 2-methylcyclohexanone is the major product (Scheme 2.22a). In the presence of a strong base such as lithium diethylamide, an allylic alcohol may be formed from an epoxide (Scheme 2.22b). 

The configuration of the produced diol is influenced by the relative stabilities of the benzyl- or alkylcarbonium ions formed during the reaction. Similar reactions were investigated earlier. The rate and stereochemistry of the diborane reaction is altered by a small quantity of LiCl. Wide-ranging research has been performed with regard to the mechanism and stereochemistry of the diborane reduction in connection with cyclic and aliphatic a, 3-unsaturated and allylic epoxides, on diterpene models, " and by study of the reduction of epoxy-methylenecyclohexane and 2,3-epoxy-3-methylcyclohexanone. ... 

Palladium(0)-catalyzed a-allylations of TMS enol ethers can be carried out cleanly with allylic carbonates. These reactions are highly regioselective, e.g. the mtne- and less-substituted TMS enol derivative of 2-methylcyclohexanone cf. Scheme 37) gave 2-allyl-2-methylcyclohexanone and 2-methyl-6-allylcyclohexanone, respectively. Allylations of aldehyde silyl enol ers occur similarly. Allylations of enol acetates occur with allyl carbonates in the presence of catalytic amounts of palla-dium(0) complexes and tri-n-butyltin methoxide. ... 

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