Butylcyclohexanone, 4-tert

Addition of phenylmagnesium bromide to 4 tert butylcyclohexanone gives two isomeric ter tiary alcohols as products Both alcohols yield the same alkene when subjected to acid catalyzed dehydration Suggest reasonable structures for these two alcohols... 

Iodine fluoride is a more versatile reagent than molecular fluorine in geminal fluorination of other hydrazones and related compounds under milder reaction conditions [55] Substrates fluorinated include hydrazones of simple cyclic or steroidal ketones (e g, 4 tert butylcyclohexanone, 70%, 3 cholestanone, 70%), W methyl and A/N dimethylhydrazones [R2C=NNH(CH3) 70%, R2C=NNC(CH3)2, 50%], semicarbazones (R2C=NNHCONH2, 25-50%), and 2,4-dinitrophenylhy-drazones [R2C==NNH-C6H3-2,4(N02)2, 25-50%]... 

In contrast, the tin(Il) enolates of cyclohexanone undergo addition to (2f)-(2-nitroethenyl)ben-zene to give 2-(2-nitro-l-phenylethyl)cyclohexanones with high anti diastereoselection5. The analogous reactions with cyclopentanone and 4-tert-butylcyclohexanone were less diastereose-lective with anti/syn ratios of 70 30 and 62 38. respectively. Modest to excellent diastereoselec-tivity was observed with acyclic ketones (d.r. 75 25 to 90 10) however the precise stereochemical details were not provided. 

POLYMERIC CARBODIIMIDE. II. MOFFAT OXIDATION 4-tert-BUTYLCYCLOHEXANONE... 

Coleman, Kobylecki, and Utley studied the electrochemical reduction of the conformationally fixed ketones 4-tert-butylcyclohexanone and 3,3,5-tri-methylcyclohexanone 82>. Stereochemically, the cleanest reductions took place at a platinum cathode in a mixture of hexamethylphosphoramide and ethanol containing lithium chloride. Under these conditions the equatorial alcohol predominated heavily (95% from 4-fer/-butylcyclohexane and 91% from 3,3,5-trimethylcyclohexanone).In acidic media roughly equal quantities of axial and equatorial alcohol were produced. It was suggested that organo-lead intermediates are involved in the reductions in aqueous media. This is reasonable, based upon the probable mechanism of reduction in acid 83F Reductions in acid at mercury cathodes in fact do result in the formation of... 

Cyclic hve-membered monothioketals are desulfurized by Raney nickel mainly to their parent ketones (53-55% yields) and several by-products [935]. After stirring for 2 hours at 25° in benzene with W-2 Raney nickel, 4-tert-butylcyclohexanone ethylene monothioketal afforded 53-55% of 4-/err-bu-tylcyclohexanone, 12-14% of cw-4-/ert-butylcyclohexyl ethyl ether, 6-11% of 4-rert-butylcyclohexanone diethyl ketal, 16% of 4-rert-butylcyclohex-l-enyl ethyl ether, and 7-12% of 4-terr-butylcyclohexene [935]. 

Cathodic surfaces of finely divided platinum, palladium and nickel have a low hydrogen overvoltage and the dominant electrochemical reaction is the generation of a layer of hydrogen atoms. The electrocatalytic hydrogenation of aldehydes and ketones can be achieved at these surfaces. Cathodes of platinum or palladium black operate in both acid solution [203] and in methanol containing sodium methoxide [204], The carbonyl compound is converted to the alcohol. Reduction of 4-tert-butylcyclohexanone is not stereoselective, however, 1,2-diphenylpropan-l-one is converted to the / reo-alcohol. 

Stereoselectivity is observed when one face of the enolate is more hindered than the other. This situation is clearly demonstrated by a comparison of the stereospecificity of the alkylation of 4-tert-butylcyclohexanone (6)34 with that of a more rigid and sterically hindered bicyclic ketone 835. 

Few alkylations of chiral azaenolates according to the latter reaction sequence are known. An example is alkylation of the conformationally fixed 4-tert-butylcyclohexanone imine which furnished a single product. As evident from the 13C-NMR spectrum the introduced alkyl group is located exclusively in the axial position. The geometry of the C -N double bond is syn, however, after a period of time, the thermodynamically more stable auF-isomer appears. Upon hydrolysis of the imine partial epimerization to the more stable cquatorial-substituted ketone occurs28. 

When the same reaction is performed with adamantanone dinitrophenylhydrazone (DNP) or adamantanone O-mcthyloxime (OMO), the yields of 2,2-difluoroadamantanc are 65 and 50%, respectively. 4-tert-Butylcyclohexanone is converted via its azine, DNP or OMO into 4-tert-butyl-l.l-difluorocyclohexanc in 65, 75 or 50% yield, respectively. Similar results are obtained with aliphatic straight-chain ketones. Decan-2-one azine and decan-2-one DNP can be transformed into 2,2-difluorodecane in 60 and 80% yield. Deactivated aromatic rings, e.g. in 3-nitroacetophenone, do not undergo bromination with bromine trifluoride and the action of 2 equivalents of bromine trifluoride on 3-nitroacetophenone O-methyloxime results in 90% yield of 1-(1. l-difluorocthylj-S-nitrobenzene.122... 

The aryl and enol triflates 306 and 307 couple with Me3Al, Et3Al and BU3AI [136], The enol phosphate 309, derived from ketone 308, is displaced with methyl group of Me3Al using Pd catalyst in dichloroethane. Based on this reaction, 4-tert-butylcyclohexanone (308) is converted to 2-methyl-5-tert-butylcyclohexanone (311) via 310 [137],... 

Scheme 13.1 4-tert-butylcyclohexanone reduction under hydrogen transfer conditions with heterogeneous copper catalysts. 

A deep study of the 4-tert-butylcyclohexanone reduction aimed at understanding the effect of the donor alcohol structure revealed the existence of a two-step mechanism based on donor alcohol dehydrogenation and ketone hydrogenation. In particular, when the reaction was carried out in the presence of Cu/Si02, in order to exclude a contribution from the support, all the alcohols used as donors were capable of transferring H2, and in the case of (iPr)2CHOH and 3-octanol, not only was the formation of the corresponding ketone observed but it continued after complete conversion of the substrate. 

Fig. 10.11. Addition of various hydride donors to 4-tert-butylcyclohexanone. With L-Selectride the equatorial approach (Formula A) is preferred, with sterically (less) demanding hydride donors the reaction proceeds axially via transition state B (cf. text and, particularly. Side Note 10.1). For comparison see the Felkin-Anh transition state C (in Figure 10.16 EWG = electron-withdrawing group).

Fig. 8.8. Addition of different hydride donors to 4-tert-butylcyclohexanone. For L-Selectride the equatorial attack is preferred (formula A), whereas for sterically undemanding hydride donors the axial attack via transition state B is preferred. For easier comparison the Felkin-Anh transition state C (from Fig. 8.11 EWG, electron-withdrawing group).

A very high stereoselectivity was observed in the reduction of 4-tert-butylcyclohexanone to the m-alcohol (> 95%), which is the industrially relevant product. The observed high selectivity to the thermodynamically unfavorable cis-alcohol was explained by a restricted transition-state for the formation of the trans-alcohol within the pores of the zeolites (Scheme 5). This reaction was found not only to be catalysed by Al-Beta, van der Waal et al. reported the catalytic activity of aluminum-free zeolite titanium beta (Ti-Beta) in the same reaction.74 Again, a very high selectivity to the cis-alcohol was observed indicating similar steric restrictions on the mechanism. Kinetically restricted product distributions were also reported for the 2-,3- and 4-methylcyclohexanone the cis, trans- and ds-isomers being the major products, respectively. In this case the tetrahedrally coordinated Ti-atom was assumed to behave as the Lewis acid metal center. Recent quantum-chemical calculations on zeolite TS-1 and Ti-Beta confirm the higher Lewis acidic nature of the latter one.75... 

The important fragrance intermediate 4-tert-butylcyclohexanol 27 (Eq. 15.3.1) is available commercially as an isomer mixture containing about 70% of the preferred c/s-form 27. H. van Bekkum et al.(32) reported on the first stereoselective Meerwein-Ponndorf-Verley reduction (MPV) of 4-tert-butylcyclohexanone to the desired czs-4-tert-butylcyclohexanol catalyzed by zeolite BEA. 

Equation 15.3.1 Meerwein-Pondorf-Verley reduction of 4-tert-butylcyclohexanone 27... 

Table 15.4 MPV reduction of 4-tert-butylcyclohexanone with isopropanol to 4-tert- butylcyclohexanol over various heterogeneous catalysts ...

The MPV reduction of 4-tert-butylcyclohexanone provides an excellent example of stereoselectivity by zeolite BEA, and also an example of unequivocal distinction between external-surface and internal micropore activity. 

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