4-fert-butylcyclohexanone

Hydride reduction of 4-fert-butylcyclohexanone 3 shows a preference for axial addition [axial additioniequatorial addition = 91-88.5 9-11.5 (LiAIH ) [16,17, 50, 51] or 87-86 13-14 (NaBH )] [50, 52]. Addition of acetyhde anion, Na(Li or K) C=CH, also showed a similar axial preference [14, 15, 53]. 

In subsequent smdies, it was shown that, atfer hydrolysis, about 42% of the total radioactive residue in grain may be identified as 4-fert-butylcyclohexanone. Moreover, 34-90% of the TRR was extracted by heating the plant material under reflux with a mixture of methanol and hydrochloric acid. The performance of that method was properly demonstrated by individual fortification experiments with the parent compound and the three primary metabolites (bold in Figure 1). 

Even in the double alkylation of chiral (racemic) 4-fert-butylcyclohexanone imine28, the ster-ically hindered c -l,3-diaxial derivative is formed selectively, followed by epimerization to the more favorable 1,3-trans-product 2. 

Djerassi and coworkers88 showed the extraordinary sensitivity and utility of the chirop-tical methods in detecting subtle conformational changes by CD measurements on chiral 4-fert-butylcyclohexanones. 

In contrast, sterically undemanding hydride donors such as NaBH4 or LiAlH4 reduce 4-fert-butylcyclohexanone preferentially through an axial attack. This produces mainly the cyclohexanol with the equatorial OH group (Figure 8.8, middle and bottom reactions). This difference results from the fact that there is also a stereoelec-tronic effect which influences the diastereoselectivity of the reduction of cyclohexanones. 

In the attack by sterically undemanding reducing agents, this stereoelectronic effect is fully effective (for a completely different but perfectly diastereoselective reduction of 4-fert-butylcyclohexanone to the equatorial alcohol, see Figure 14.46). However, in the attack of such a bulky hydride donor as L-Selectride the stereoelectronic effect is overcompensated by the opposing steric effect discussed above. 

The stereochemical product ratio for the reduction of cyclic ketones by hydrides is affected by the structure of the cyclic ketone and the nature of the hydride used. The reduction of substituted cyclohexanones avoids product interconversion by conformational ring flip because of conformationally locked cyclohexanones. In such cases, axial attack is preferred over equatorial attack. 4-fert-Butylcyclohexanone (6.50) is reduced by NaBH4 and by LiAlH4 to give 86% and 92% of trans-4-fert-butylcyclohexanol (6.51), respectively. Hindered hydrides such as f-BusBHLi show more selectivity. 

The first studies on Lewis acid promotion of allylic stannane additions were conducted with BF3 OEt2 (Table 4) [13]. Aldehydes were found to be more reactive than ketones and methyl ketones were more reactive than internal ketones. Addition to 4-fert-butylcyclohexanone favored equatorial allylation by 85 15. 

Hydrogenation of 4-Cyclohexene-c/s-1,2-dicarboxylic Acid, p. 567 Formation and Reduction of AFCinnamylidene-m-nitroaniline, p. 573 Reduction of 4-fert-Butylcyclohexanone, p. 583 Reduction of Benzoin, p. 584... 

With organolithium and organomagnesium compounds, approach to the carbonyl carbon from the less hindered direction is generally preferred. Assuming this is the case, predict the structure of the major product formed by reaction of methylmagnesium bromide with 4-fert-butylcyclohexanone. 

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

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