2,6-Dimethylcyclohexanones

Tlie bifunctional sulfenyl chloride 213 was obtained by chlorination of 144 in good yield, although excessive chlorination led to the saturated compound 214 (94CB533). A series of compounds 215-220 were obtained from 213 by reactions with secondary amines ferf-butyl methyl ketone hexane-2,4-dione 2,6-dimethylcyclohexanone diethyl malonate and acetylacetone, respectively. 

It is also possible to achieve enantioselective enolate formation by using chiral bases. Enantioselective deprotonation requires discrimination between two enantiotopic hydrogens, such as in d.v-2,6-dimethylcyclohexanone or 4-(/-butyl)cyclohcxanonc. Among the bases that have been studied are chiral lithium amides such as A to D.22... 

The two-phase reduction of cyclohexanones by sodium dithionite in the presence of a stoichiometric amount of Adogen gave higher yields of the cyclohexanols than those obtained by the standard procedure using sodium dithionite in a water dioxane system (Table 11.9). A marked improvement in yield was also observed with the reduction of sterically hindered 2,6-dimethylcyclohexanone and there was a greater degree of stereoselectivity, which was comparable to that noted for the corresponding reduction with the borohydride ion [4]. 

The anion of cyclohexanone A, A -dimethyI hydrazonc shows a strong preference for axial alkylation.82 2-Methylcyclohexanone A, A - d i m c th y I h yd razo n c is alkylated by methyl iodide to give cfr-2,6-dimethylcyclohexanone. The methyl group in the hydrazone occupies a pseudoaxial orientation. Alkylation apparently is preferred anti to the lithium cation, which is on the face opposite the 2-methyl substituent. 

Reaction of the chiral lithium enolate of meso-2,6-dimethylcyclohexanone (6), generated by deprotonation with (R)-l-phenylethylamine and (/ )-camphor/(R)-l-phenylethylaniine derived chiral lithium amides (Table 1, entries 17 and 64) with 3-bromopropene, leads to homoallyl ketones of opposite absolute configuration in acceptable yield with poor to modest enantiomeric excess14, which can be determined directly by H-NMR spectroscopy in the presence of tris [3-(heptafluorohydroxymethylene)-D-camphorato]europium(III) [Eu(hfc)3]. 

It was originally reported that irradiation of 2-methylcyclohexa-none gave solely franj-5-heptenal,321 in accord with the then-postulated concerted singlet mechanism. Now, however, it has been reported that 2,6-dimethylcyclohexanone yields both cis- and /rstep process.328 The reaction seems to resemble type I cleavage very closely, with the difference that disproportionation in the biradical primary product is much faster than decarbonylation, except in high vibrational levels of the excited singlet state, or when both ends of the biradical so produced are resonance stabilized.329... 

Examples of the use of platinum and nickel catalysts are seen in the hydrogenation of 2-allyl-2,6-dimethylcyclohexanone to 2-propyl-2,6-dimethylcyclohexanone over platinum oxide (eq. 3.48)207 and 2-allylcyclohexanone to 2-propylcyclohexanone over Raney Ni (eq. 3.49).208... 

B. (1a,2a,6 )-2,6-Oimethylcyclohexanecarbonithle and (1a,2, 6a)-2,6-Dimeth-ylcyclohexanecarbonitrile (2). The apparatus depicted in Figure 1 lacking the HCI trap and with a glass stopper in place of the thermometer is used for this procedure. The 1-L reaction flask is charged with mesitylenesulfonylhydrazine (56.0 g, 0.262 mol) (Note 1) and 175 mL of acetonitrile. The mixture is stirred at room temperature until solution is attained (Note 14). 2,6-Dimethylcyclohexanone (Note 3) (32.2 g, 0.255 mol) is added in one portion and the reactants are stirred an additional 10 min. A 10-drop portion of concentrated sulfuric acid is added and the mixture is stirred at room temperature for 12 to 18 hr to facilitate complete hydrazone formation (Note 15). Water is circulated through the reflux condenser that is already attached to the flask, and potassium cyanide (27.2 g, 0.418 mol) is added (Note 3). The reaction mixture is... 

Mesitylene (1,3,5-trimethylben2ene), chlorosulfonic acid, hydrazine monohydrate, 2,6-dimethylcyclohexanone and potassium cyanide were purchased from Aldrich Chemical Company, Inc., and used without further purification. 

A valuable feature of the enamine reaction is that it is regioselective. Thus, in the alkylation of an unsymmetrical ketone, e.g. 3.4, the substitution takes place at the less substituted a-carbon atom. However, direct base-catalyzed alkylation of unsymmetrical ketones usually gives a mixture of products. Also in the enamine reactions, since no alkali is used, there is no possibility of side products, which are normally obtained from carbonyl compounds. For example, the reaction of enamine 3.42 with methyl iodide followed by hydrolysis gives almost exclusively 2,6-dimethylcyclohexanone (3.43) (Scheme 3.20). 

For example, 2-methylcyclohexanone can be converted to either 2,6-dimethylcyclohexanone (A) or 2,2-dimethylcyclohexanone (B) by proper choice of reaction conditions. 

Yamamoto and Saito reported that the kinetically controlled generation of the more substituted enolate of unsyimnetrical dialkyl ketones can be realized by the combined use of ATPH and LDA [175]. Precomplexation of ATPH with 2-methyl-cyclohexanone (175) at -78 °C in toluene was followed by treatment with LDA in THF, and the mixture was stirred for 1 h. Subsequent treatment with methyl trifluoro-methanesulfonate (MeOTf) furnished 2,2-dimethylcyclohexanone (177) and 2,6-dimethylcyclohexanone (176) in the ratio 32 1 (53 % isolated yield). Use of ter/-butyl-dimethylsilyl triflate (TBSOTf) in place of alkyl triflates in this alkylation system produced siloxybutylated product 178 as a result of THF ring-opening alkylation occurred similarly at the more hindered a-carbon of the unsymmetrical ketone 175 (Sch. 136) [176]. 

Ultramicroscale Reduction of 2,6-Dimethylcyclohexanones with Sodium Borohydride... 

Dimethylchromanes, 317 (2S,6S)-2,6-Dimethylcyclohexanone, 11 Dimethyl diazomethylphosphonates, 157 o,o -Dimethyldibenzylamide, 245 Dimethylformamide diethyl acetal, 157 Dimethylformamide dimethyl acetal, 158 Dimethyl fumarate, 302... 

Chiral lithium amide bases have been used successfully in the asymmetric deprotonation of prochiral ketones [55, 56]. WUliard prepared polymer-supported chiral amines from amino acid derivatives and Merrifield resin [57]. The treatment of cis-2,6-dimethylcyclohexanone with the polymer-supported chiral lithium amide base, followed by the reaction with TMSCl, gave the chiral silyl enol ether. By using polymeric base 96, asymmetric deprotonation occurred smoothly in tetrahydrofuran to give the chiral sUyl enol ether (, S )-102 in 94% with 82% ee (Scheme 3.28). 

Simpkins examined the deprotonation of 2,6-dimethylcyclohexanone using a series of chiral amide bases. Enantioselectivity up to 74% was achieved using the bicyclicbase 13,Eq. (17) [57]. 

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