Reduction of 2-methylcyclohexanone

Reduction of 2-methylcyclohexanone gave the following percentage proportions of the less stable m-2-methylcyclohexanol (with axial hydroxyl) with lithium aluminum hydride 25%, with diborane in tetrahydrofuran 26%, with di-sec-amylborane in tetrahydrofuran 79%, with dicyclohexylborane in diglyme 94%, and with diisopinocampheylborane in diglyme 94% (the balance to 100% being the trans isomer) [837. ... 

The fluoride ion-catalyzed reduction of 2-methylcyclohexanone by various hydrosilanes gives the corresponding silyl ethers in 40-99% yields (equation 27)41. The reactivity, markedly influenced by the steric bulk of hydrosilanes (see entry 30 of Table 1), decreases in the order of Ph2SiH2 >>PhMe2SiH > Ph2MeSiH > Ph3SiII. 

This new reagent is an active reducing agent and reduces cyclic and bicyclic ketones with superstereoselectivity.1 Thus reduction of 2-methylcyclohexanone (1) gives m-2-methylcyclohexano) in 99.3 % purity. Note that reduction with lithium trimethoxy-aluminum hydride alone yields (2) in 69 % yield. Thus increasing the size of the alkyl substituents on boron enhances the stereoselectivity of the borohydride anion. Even... 

The reduction of 2-methylcyclohexanone and 2-isopropylcyclohexanone by LiAlH was subjected to DFT analysis (B3LYP/6-31G(d,p)) to optimize the TSS. Four TSSs were located for each ketone for the axial and equatorial attacks by LiAlH4. Electronic potential maps were used to investigate the electronic effect of the substituents on TSS stabilization. The lowest unoccupied molecular orbital (LUMO) maps and natural bond orbital (NBO) analysis helped in elucidating the uneven distribution of molecular orbital around the carbonyl tt-plane, and the preference for the hydride attack in terms of tensional and electronic properties. ... 

Carbonyl Reactivity.—A new reagent, lithium tri-s-butylborohydride, is claimed to exhibit enzyme-like stereoselectivity in reduction of cyclic (and bicyclic) ketones. Reduction of 2-methylcyclohexanone at 0°C in THF for 30 min occurred quantitatively to give the less stable cis-alcohol with an epimeric purity of 99.3%. 3,3,5-Trimethylcyclohexanone was reduced to the trans-alcohol with 99.8% stereoselectivity and 3-methylcyclohexanone likewise with 85% stereoselectivity. Reduction of 4-methylcyclohexanone to the cis-alcohol occurs with 80.5% stereoselectivity correspondingly cis-4-t-butyl-cyclohexanol is produced with 93% isomeric purity, much higher than in previous cited procedures, and this figure rises to 96.5% when reaction is... 

Methylcyclohexanone is reduced to give 65 % of the tmns-2L cdho. However, the larger reagents, disiamylborane and diisopinocamphenylborane, give respectively 77 % and over 90 % of the cw-alcohol. Later work confirmed that reductions of 2-alkylcycloalkanones with dialkyl boranes give predominantly the less stable alcohol/ ... 

Further evidence for surface effects upon the stereochemistry of electrochemical reduction of ketones comes from the discovery that the nature of the cathode material may effect stereochemistry. Reduction of 2-methylcyclo-hexanone affords pure trans-2-methylcyclohexanone at mercury or lead cathodes, a mixture of cis and trans alcohols (mostly trans) at nickel, and pure cis alcohol at copper 81 >. Reduction could not be effected at platinum presumably hydrogen evolution takes place before the potential necessary for reduction of the ketone can be reached. 

Reduction of cyclic and bicyclic ketones. This hydride reduces 4-r-butyl- and 3-methylcyclohexanone with some bias favoring formation of the more stable isomer. In contrast, 2-methylcyclohexanone is reduced preferentially to the less stable cis-isomer (72%). Essentially, only the ra-isomer is formed on reduction of 2-f-butylcyclohexanone (98% stereoselectivity). Norcamphor is reduced to the endo-alcohol in > 99% stereoselectivity, whereas the more hindered camphor is reduced to the exo-alcohol with 98% stereoselectivity. 

Meerwein-Ponndorf reduction (I, 35-36), A recent study of the Mcerwein-Ponndorf reduction of mono- and bicyclic ketones shows that, contrary to commonly held views, the reduction of such ketones proceeds at a relatively high rate. The reduction of cyclohexanone and of 2-methylcyclohexanone is immeasurably rapid. Even... 

Sodium hydridotrimethoxyborate reacts more stereospecifically with cyclic ketones than does NaBH4 On reduction of 2- and 4-methylcyclohexanone the /m -isomers are obtained in, respectively, 99 and 88% yield.388... 

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. 

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. 

Expoxidation of alkenes. In the presence of this complex, alkenes undergo epoxidation with oxygen (oxidant) and cyclic ketones as reductant. The most useful reductant is 2-methylcyclohexanone. Yields are 80% for trisubstituted or exo-terminal alkenes. 

Axial alcohols. A soln. of 2-methylcyclohexanone in 2-propanol containing chloroiridic acid and trimethyl phosphite refluxed a few days — cis-2-methyl-cyclohexanol. Y 95-97%.—Equatorial alcohols are the major products of the reduction of unhindered cyclohexanones by most reagents. F. e. s. Y. M. Y. Haddad et al., Proc. Chem. Soc. 1964, 361. 

Biochemical reduction of a,/3-unsaturated ketones using microorganisms (best Beauveria sulfurescens) takes place only if there is at least one hydrogen in the /3-position and the substituents on a-carbons are not too bulky. The main product is the saturated ketone, while only a small amount of the saturated alcohol is formed, especially in slightly acidic medium (pH 5-5.5). The carbonyl is attacked from the equatorial side. Results of biochemical reduction of 5-methylcyclohex-2-en-l-one are illustrative of the biochemical reduction by incubation with Beauveria sulfurescens after 24 hours 74% of the enone was reduced to 3-methylcyclohexanone and 26% to 3-methylcy-clohexanol containing 55% of cis and 45% of trans isomer. After 48 hours the respective numbers were 70% and 30%, and 78% and 22%, respectively [878]. 

Different stereoisomeric cyclohexanols resulted also from reduction of ethyl 4-/ r/-butyl-2-methylcyclohexanone-2-carboxylate with sodium borohydride (equatorial hydroxyl) or with aluminum isopropoxide (axial hydroxyl) [1088]. 

Bhattacharyya et al. reported the first total synthesis of clausenalene (90) to establish its structure (99). This total synthesis uses Japp-Klingemann and Fischer-Borsche reactions as key steps. The phenyl hydrazone 1000 required for the transformation to 1-0x0-tetrahydrocarbazole 1001 under Fischer-Borsche conditions was obtained by condensation of 2-hydroxymethylene-5-methylcyclohexanone (999) with diazotized 3,4-methylenedioxyaniline (998) using Japp-Klingemann conditions. Wolff-Kishner reduction of 1001 furnished 3-methyl-6,7-methylenedioxy-l,2,3,4-tetrahydrocarbazole (1002), which, on aromatization wifh 10% Pd/C in decalin, afforded clausenalene (90) (99) (Scheme 5.143). 

The fused tetrahydropyran-2-one (566) is obtained from 2-methylcyclohexanone by Michael addition to methyl prop-2-enoate and reduction of the resulting keto ester (565 Scheme 216) (63JOC34). When the enamine derived from the cyclohexanone reacts with the unsaturated ester, a mixture of keto esters (565) and (567) is formed. The pyranone (568) is formed by reduction of the latter. 

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