3- f-Butylcyclohexanone

Red phosphorus in bromination of 7 butj rolactone 46, 22 Reduction, of 3/3 acetoxy 5 pregnene 20-one with lithium aluminum tn t butoxyhydnde, 46, 57 of 4-f butylcyclohexanone with lithium aluminum hydride aluminum chloride, 47,16... 

This stereoelectronic effect also explains the contrasting regioselectivity of cis- and fra x-2-fluoro-4-f-butylcyclohexanone.235 As a result of a balance between its polar effect and hyperconjugation, the net effect of a fluoro substituent in acyclic systems is small. However, in 2-fluorocyclohexanones an unfavorable dipole-dipole interaction comes into play for the cis isomer and preferential migration of the fluoro-substituted carbon is observed. 

Propyl-4-f-butylcyclohexanone, type II cleavage of cis and trans isomers, 121 Pryor, W. A., 487... 

A further example of the importance of stereoelectronic effects results from the behavior of cis- and m w-2-ii-propyl-4-f-butylcyclohexanone,<9B)... 

The (V-lithio-n-butylpyridine- 1,2-dihydro adduct (212) has found use as a reducing agent, for example in the conversion of 4-f-butylcyclohexanone to a mixture (cis trans, 10 1) of 4-f-butylcyclohexanols (equation 136) (65CJC2631). 

Methylaluminum bis(2,6-di-t-butyl-4-methylphenoxide) (MAD, 1) methylal-uminum bis(2,4,6-tri-Ubutylphenoxide) (MAT, 2). The complexes formed from 4-f-butylcyclohexanone and 1 or 2 (3 equiv.) react with methyllithium or CH3MgBr... 

Alkylations of enolates, enamines, and silyl enol ethers of cyclohexanone usually show substantial preference for axial attack. The enamine of 4-f-butylcyclohexanone, which has a fixed conformation because of the i-butyl group, gives 90% axial alkylation and only 10% equatorial alkylation with n-Prl. 

Cholestan-3-one was also stereoselectively hydrogenated to the axial alcohol in 98.5% yield (GC) over a palladium black in isopropyl alcohol at 25°C and atmospheric pressure (see Fig. 5.1 and Section 5.4.2).153d Accompanying formation of the isopropyl ether was not observed in the case of the steroid ketone, whereas a large amount (55%) of the ether and an almost 1 1 mixture of cis and trans alcohols were produced in the hydrogenation of 4-f-butylcyclohexanone under the same conditions. 

TABLE 6.3 Reductive Alkylation of Ammonia with 4-f-Butylcyclohexanone over Platinum Metals ... 

New bases have also been proposed to extend the arsenal presented in Scheme 16. In particular, conformational constraints have been introduced on the amide. It was shown, for instance, that e.e. values up to 81% can be returned for the deprotonation of 4-f-butylcyclohexanone in a THF/HMPA mixture by a lithium amide derived from a tetrahydroquinoline bearing a heterocycle at C3102. Note that the same ketone can be converted in its (S)-enolate in 90% e.e. resorting to the bulky lithium A-trityl-A-(/ )-l-phenethylamide79. Interestingly, chiral lithium amides on polymeric solid support have also been successfully employed to deprotonate bridged cycloheptanones103. 

In the pyrrolidine enamine of 2-methyl-4-f-butylcyclohexanone the methyl group is largely axial15. The morpholine enamine of 2-methyl-4-f-butylcyclohexanone exists as an isomeric equilibrium mixture of 54% trisubstituted enamines 55 and 56 and 46% tetrasubstituted enamine 57. The distribution between quasiequatorial and quasiaxial trisubstituted isomers is 1 1 (i.e. the mixture contains 27% of each)15. 

The stereoselectivity of bromination of 4-f-butylcyclohexanone enamines has been studied and the ratio of axial. equatorial bromine incorporation shown to vary with the amine moiety (pyrrolidine 51 49 piperidine 66 34 morpholine 74 26 Af-methylaniline 52 48, di-isobutylamine 52 48)237. This variation in the axial equatorial selectivity has been rationalized in terms of the nature of the transition state. C-Bromination of the pyrrolidine, Af-methylaniline and di-isobutylamine enamines must occur via an early reactant-like transition state thus resulting in low stereoselectivity (Scheme 99). The... 

Under these conditions the stereoselectivity is higher, as the attack of the reagent occurs equatorially, leading to axial amines (72-92%). A comparison with the results of reduction of 4-f-butylcyclohexanone shows a complete inversion of stereoselectivity (16-27% of equatorial attack). Reductions of 2-alkylcyclohexanone enamines also proceed with high stereoselectivity, leading predominantly to the cis amines in the six-membered ring derivatives (66-96%), and almost exclusively in the case of the five-membered enamines (95-98%) (Scheme 84). The A1,3 strain112 in fact would shift the conformational equilibrium towards the axial (or pseudo xial) orientation of the substituent. 

Highly selective reduction of aldehydes rather than ketones, even 4-f-butylcyclohexanone, has been achieved by a binuclear hydrido molybdenum anion (Et4N[ JL-HMo2(CO)io]) and acetic acid in refluxing THF," The stable complex is readily prepared from molybdenum hexacarbonyl, which can be recovered after reduction. The full value of this reagent in synthesis remains to be established. Tributyltin hydride has been shown to be effective for the selective reduction of aldehydes in the presence of dried silica gel which acts as a mild acid catalyst," The reaction proceeded at room temperature in cyclohexane, many common functional groups were inert under these conditions. 

Table 2 Diastereoselectivity in Reductions of the Dimethyl Ketal of 4-f-Butylcyclohexanone OMe H OMe...

Carboxyl-labeled dicarboxylic acid 68 has been prepared from l,5-di(bromomagnesio) pentane and labeled carbon dioxide [Eq. (27) 51]. However, when the di-Grignard reagent 67 was heated with isotopically labeled barium carbonate, labeled 4-f-butylcyclohexanone 69 was isolated [52]. 

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