4-ferf-Butylcyclohexanone

This mixture is available from Aldrich Chemical Company, Inc. The checkers used a 7 93 mixture of the cis- and traws isomers, prepared by lithium aluminum hydride [Aluminate(l —), tetrahydro-, lithium, (T-4)-] reduction of 4-ferf-butylcyclohexanone and recrystallization of the crude product. The ketone was purchased from Aldrich Chemical Company, Inc. 

Stable and ordinarily must be used as soon as it is formed, while 60 can be stored several days at room temperature. When diastereomeric epoxides can be formed, 61 usually attacks from the more hindered and 60 from the less-hindered side. Thus, 4-ferf-butylcyclohexanone, treated with 60 gave exclusively 63 while 61 gave mostly 62. Another difference in behavior between the two reagents is that with a,[3-... 

Ashby and coworkers reported in 1974 stereochemical studies on addition of lithium trimethyhnagnesate to several ketones . The reactions of 4-ferf-butylcyclohexanone with methyllithium, with dimethylmagnesium and with lithium trimethyhnagnesate in ether afforded mixtures of the corresponding axial and equatorial alcohols in ratios of 65 35, 70 30 and 69 31, respectively (equation 11). Reaction of 3,3,5-trimethylcyclohexanone with lithium trimethylmagnesate yielded exclusively the axial alcohol (equation 12). Reaction of norcamphor provided 95% of the endo alcohol and 5% of the exo alcohol (equation 13). In contrast, reaction of camphor yielded the exo alcohol with high stereoselectivity (equation 14). Among the methylmetals examined, no difference in the stereoselectivity was virtually observed. 

The ketone functionality in 9 is adjacent to a trans junction, which makes it difficult to flatten. 2-Decalone (10) is slightly more flexible, whereas 4-ferf-butylcyclohexanone is the most easily deformed of the three. In reactions with 2 equiv. of AlMe3, Suzuki et al.65 obtained 60, 82 and 86% axial attack on 9,10 and 11, respectively. 

Rehydrated Mg/Al-OH catalysts have been found to be inactive in the MPV reduction of 4-ferf-butylcyclohexanone by isopropanol, whereas the bifunctional character of the Mg(Al)0 mixed oxides made them highly active in this reaction. The aluminium alkoxidc intermediate of the MPV reaction indeed involves a cooperation between basic and acidic sites. On mixed oxides, the abstraction of a proton from isopropanol on O2 sites gives isopropoxide anions, which are then stabilized on Al3+ and form intermediates with the aldehyde. The high activity of mixed oxide comes from the synergetic effect of strong Lewis basicity and mild acidity. 

The n-BuLi cleavage of the axial C-Se bond of bis(phenylseleno)acetals, derived from 4-ferf-butylcyclohexanone, always occurs under kinetic control at -78°C [14]. In the case of a mixed acetal, having respectively the phenylseleno and methylseleno groups in axial and equatorial positions, the cleavage of the equatorial C-SeMe bond was predominantly observed. The resulting stabilized carbanion rearranges almost instantaneously leading to the a-phenylselanyl-cyclohexyllithium with the C-Li bond in the axial position [14] (Scheme 14). 

Lithium tri-sec-butylborohydride, also known as L-selectride, is a metal hydride reagent that contains three sec-butyl groups bonded to boron. When this reagent is used to reduce cyclic ketones, one stereoisomer often predominates as product. Explain why the reduction of 4-ferf-butylcyclohexanone with L-selectride forms the cis alcohol as the major product. 

Hydroxymethyhtion of ketones. A ketone can be converted into the a-hydroxy-methyl derivative in two. steps acylation with ethyl formate, followed by aluminum hydride reduction. The sequence is illustrated for the conversion of 4-rerr-butylcyclo-hcxanone(l) inlo 2-hydroxymelhyl-4-ferf-butylcyclohexanone(3). 

On p. 1023, it was mentioned that electronic effects can play a part in determining which face of a carbon-carbon double bond is attacked. The same applies to additions to carbonyl groups. For example, in 5-substituted adamantanones (2) electron-withdrawing (-/) groups W cause the attack to come from the syn face, while electron-donating groups cause it to come from the anti face. In 5,6-disubstituted norborn-2-en-7-one systems, the carbonyl appears to tilt away from the 7i-bond, with reduction occurring from the more hindered face. An ab initio study of nucleophilic addition to 4-ferf-butylcyclohexanones attempted to predict 7i-facial selectivity in that system. ... 

The reduction of 4-ferf-butylcyclohexanone by LiAlH4 in THF at 0 °C affords a mixture of the tram- and ris-alcohols in 88.5 11.5 ratio (Table 1) [9]. The predominant attack takes place obviously from the axial direction as predicted above by the Cieplak model. This selectivity is expected to diminish when the ring carries an equatorial methyl group on C3 because it will (a) not introduce an element of steric interaction during the course of the nucleophilic addition, and (b) raise... 

CH3MgI > CH3CH2MgI —> (CH3)2CHMgI — (CH3)3CMgCl in the reaction with 4-ferf-butylcyclohexanone as shown in Table 2. The steric effect arising from (CH3)3CMgCl is so significant that absolutely no reaction occurs on the axial face and, hence, the civ-alcohol is isolated as the sole product. 

Let us now consider 2-phenyl-1,3-dioxan-5-one and compare its selectivity profile with that of 4-ferf-butylcyclohexanone in reactions with Grignard reagents, see Table 2. In 2-phenyl-1,3-dioxan-5-one, ctC4 o3 —> tt c=o and crC6 (,i > jt c=G... 

Phenylmagnesium bromide reacts with 4-ferf-butylcyclohexanone as shown. 

The Schmidt reaction of a simple cyclic ketone yields lactams with the ring expanded, while the intramolecular Schmidt reaction of cyclic ketone with an azido group at the side chain leads to the formation of bicyclic lactams with nitrogen at the position of fusion. It is interesting that the reaction between a cyclic ketone and 2-azido ethanol can form either a lactam or a lactone by means of the treatment with a different base, in which the lactam is formed when the reaction system is treated with KOH, whereas lactone is generated when NaHCOs is used as the base. Especially, the reaction between 4-ferf-butylcyclohexanone and 3-azido-2-methyl-2-phenylpropanol gives lactam in 19 1 stereoselectivity. ... 

Irradiation of ds-2-propyl-4-terf-butylcyclohexanone in hexane produces 4-ferf-butylcyclohexanone, but irradiation of the trans isomer results in photoisomerization to the cis isomer. Propose a mechanism for the reaction observed for each compound, and explain why the two diastereomers react differently. 

Consult with your instructor before performing this experiment, in which you will determine the stereoselectivity of the reduction of 4-ferf-butylcyclohexanone with sodium borohydride. You might also be asked to use other hydride reducing agents and compare their stereoselectivities with that of sodium borohydride. Follow either... 

Purpose. The reduction of a ketone carbonyl to the corresponding alcohol is carried out using sodium borohydride, a commercially available metal-hydride reducing agent. The alcoholic reaction products are isolated by extraction techniques and purified by preparative gas chromatography. Cis and trans diastereomers are formed in the reduction of the 4-ferf-butylcyclohexanone. These diastereomeric products can be separated during the preparative GC isolation. The stereochemistry of the structures can be deduced, once the mixture is separated into its pure components, using either NMR or IR spectroscopy. 

In the 4-ferf-butylcyclohexanone example, the steric environment is different on either face of the carbonyl group. In this case, the hydride reducing agent attacks more rapidly from the axial direction, and thus the equatorial alcohol (axial H) is the major product. This reaction pathway is preferred with the relatively small sodium borohydride and Uthium aluminum hydride reagents. When one stereoisomeric product is preferentially formed, the reaction is called a stereoselective reaction. 

Scheme 9.18. The results of the reduction of 4-ferf-butylcyclohexanone with lithium aluminum hydride (LiAlH4) in ether showing that the diequatorial product is preferred, although it is unclear if one face of the carbonyl is less encumbered than the other. (See Dauben, W. G. Fonken, G. I Noyce, D. S. J. Am. Chem. Soc. 1956, 78, 2579.)...

Figure 9.4. Space filling and stick representations of 4-ferf-butylcyclohexanone endeavoring to show that both faces are approximately equally encumbered.

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