Racemic-2-methylcyclohexanone

Chiral 2,2-disubstituted cycloalkanones.1 The imine 2 prepared from racemic 2-methylcyclohexanone and (S)-( - )-l, reacts with methyl vinyl ketone to form an adduct that is hydrolyzed to the (R)-( + )-diketone 3 in 91% ee with recovery of 1 in almost quantitative yield. The reaction is described as a deracemizing alkylation. ... 

Asymmetric protonations. Deprotonation (LDA) of the imine (2b) obtained from racemic 2-methylcyclohexanone and lb followed by protonation with ethanol and hydrolysis gives (S)-2-methylcyclohexane (3) in 90% ee. The enantioselectivity depends in part on the R group when R = H (2a), (R)-3 is formed in 22% ee. When (-butyl alcohol is used as the proton source, completely inactive 3 is obtained by the same sequence. No enantioselectivity is observed in protonation of the lithioenamine of 2-methylcyclohexanone and nonsupported la.2... 

A sample of racemic 2-methylcyclohexanone-1- 3 was prepared by methylation of the lithium cyclohexanolate-l-13 , with methyl iodide (VI ) The enolate was prepared from the cyclohexanone-1-13c by way of the trimethyl silyl derivative following the pro-" cedure of House and coworkers (12). A sample of trans-D,l-2-methylcyclohexanol-l -13C was then obtained by reduction of the ketone with lithium aluminum hydride in the presence of aluminum chloride as prescribed by Eliel and coworkers (13). 

When optically active (fl)-2-methylcyclohexanone is treated with either aqueous base or acid, racemization occurs. Explain. 

CHMO is known to catalyze a number of enantioselective BV reactions, including the kinetic resolution of certain racemic ketones and desymmetrization of prochiral substrates [84—87]. An example is the desymmetrization of 4-methylcyclohexanone, which affords the (S)-configurated seven-membered lactone with 98% ee [84,87]. Of course, many ketones fail to react with acceptable levels of enantioselectivity, or are not even accepted by the enzyme. 

In contrast, 2-methylcyclohexanone and 2-methylindanone were racemized during imine hydrolysis with sodium acetate/acetic acid/pentanc/water8. In the preparation of 2-isopropyIcy-clohexanone and 2-isopropyl-6-methylcyclohexanone enantiomeric excess of the final products was low due to racemization8. 

S)-3-Methylcyclohexanone isn t racemized by base because its chirality center is not involved in the enolization reaction. 

Would you expect optically active (S)-3-methylcyclohexanone to be racemized on acid or base treatment in the same way as 2-methylcyclohexanonc (Problem 22.32) Explain. 

Fig. 4.8 FT-IRAS spectra of racemic 3-methylcyclohexanone and R-3-methylcyclohexanone adsorbed at the kink sites on the Cu(643) surfaces. The peak intensities in the spectra of the racemic mixture are identical indicating the same net orientation on the two surfaces. The spectral intensities from the R-3-methylcyclohexanone on the two surfaces differ, indicating different average orientations of molecules adsorbed at the R- and the S-kinks. Reprinted with permission from [21]. Copyright 2008 American Chemical Society...

The D,L-2-methylcyclohexanone-l.- 3C was also the precursor to the trans,trans-2,6-dimeth.ylc.yclohexanoT-1-13c required to prepare the 6-glucoside 9 from which the a-anomer 8 was obtained by ano-merization. The ketone was converted to racemic 2-hydroxymethyl ene-6-methylcyclohexanone-1-13 in 30% yield following the procedure described by Johnson and Posvic (14). This product was in turn converted, except for the 13C-label, to the known (15) 2-n-butylthiomethylene-6-methylcyclohexanone- -13C. Reduction and... 

In Figure 10.3, we illustrate nonselective and aselective morpholytic processes. The reductions of ( )-3,3,5-trimethylcyclohexanone, ( )-37, with triisobutylaluminum, and of ( )-2-methylcyclohexanone, ( )-40, with Alpine-borane are morpholytononselective processes in each reaction, the two enantiomers are consumed at equal rates. Thus, the two enanhomers in racemate ( )-37 react with achiral triisobutylaluminum (36), at expectedly-equal rates, to give racemic cis-38 plus racemic trans-39 (cis/trans = 4.8 1). In contradistinction, the two enantiomers in racemate ( )-40 react at accidentally-equal rates to give nonracemic ds-41 (68% ee) and nonracemic trans-M (68% ee) cis/trans = 1 1). No kinetic resolution of either ( )-37 or ( )-40 takes place. 

Allylation of simple ketone is not possible under usual conditions, but the reaction can be carried out under selected conditions. Asymmetric allylation of the chiral racemic o -methylcyclohexanone 161 with allyl carbonate proceeded in the presence of LDA as a base with or without MesSnCl as a Lewis acid at room temperature to provide the allylated ketone 162 in very high yield with 82 % ee when (5,5)-Trost L-1 was used. The choice of base is crucial, and it was claimed that no reaction took place when Na or K bases were used in this reaction [57]. Asymmetric allylation of a-aryl and heteroaryl ketones has been carried out. Asymmetric allylation of 2-indolylcyclohexanone 163 took place at 0 C to give the the allyl ketone in 82 % yield with 84 % ee. In this reaction, NaHMDS was used as a base and Trost L-2 as chiral ligand [58]. Asymmetric allylation of the tetralone 164 with allyl acetate was carried out using Trost L-6 in the presence of CS2CO3 to provide the allylated ketone with 91 % ee in 90% yield [59]. 

A thermophilic alcohol dehydrogenase (TADH) was applied in a segmented flow capillary microreactor to perform the enzyme-catalyzed reduction of racemic 3-methylcyclohexanone 5 to (lS,3S)-6 in a hquid-hquid two-phase system [76]. This study demonstrated the excellent mass transfer rates accomphshed by the enhanced surface area to volume ratio as the true benefit of microreactor systems in multiphase enzymatic catalysis. 

Explain why R-2-methylcyclohexanone is racemized in aqueous base, but l -3-methylcyclohexanone is not. 

If we consider the same process for 3-methylcyclohexanone, again, enolization may occur at either site, but in this case, the chiral carbon atom is unaffected, and hence no racemization occurs ... 

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