Cyclohexanones conformations

When the cyclohexanone conformation deviates from the chair, the substituent contribution changes for the a-methy group the rotatory strength varies in a regular way with the... 

Draw the conformational isomers of cis-1,2-dimethylcyclohexane and cis-3,4-dimetliylcyclohexanone. While the cyclohexane conformers are of equal energy, the cyclohexanone conformers are not. Indicate which con-former is favored and explain why. 

Combined n.m.r., i.r., and u.v. spectroscopic evidence from 2- and 4-methyl-2,3,6-trichloro- and -tribromo-cyclohexanones has shown that the latter have fixed conformations whereas in the former two conformers can exist. In certain solvents one of these is preferred, e.g. triequatorial in MeCN, triaxial in CCl. In a related study of 2,3,6-trichloro-, tribromo-, and mixed trihalogeno-cyclohexanones conformational dependence on solvent was again found. For the 2,3,6-tribromo-cyclohexanone in n-heptane the triaxial conformer is preferred over the triequatorial in the ratio 87 13 in MeCN these proportions are reversed. It was concluded that a 3-halogeno substituent exerts a strong stereoelectronic effect on the conformational behaviour of the 2,3,6-trihalogenocyclohexanones. 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

The conformational energy of an alkyl group at C—3 of cyclohexanone is substantially less than that of an alkyl group in cyclohexane because of reduced... 

There is another aspect to the question of the reactivity of the carbonyl group in r ck)hexanone. This has to do with the preference for approach of reactants from the axial ir equatorial direction. The chair conformation of cyclohexanone places the carbonyl coup in an unsynunetrical environment. It is observed that small nucleophiles prefer to roach the carbonyl group of cyclohexanone from the axial direction even though this is 1 more sterically restricted approach than from the equatorial side." How do the ctfcnaices in the C—C bonds (on the axial side) as opposed to the C—H bonds (on the equatorial side) influence the reactivity of cyclohexanone ... 

Endocyclic cyclohexanone enolates with 2-alkyl groups show a small preference (1 1-5 1) for approach of the electrophile from the direction that permits the chair conformation to be maintained. ... 

Similar to cyclohexanones, substituted cyclopentanones also adopt a conformation with the substituents in a sterically favorable position. In the case of 2-substituted cyclopentanones 1 the substituent occupies a pseudoequatorial position and the diastereoselectivity of nucleophilic addition reactions to 1 is determined by the relative importance of the interactions leading to predominant fra s(equatorial) or cw(axial) attack of the nucleophile. When the nucleophile approaches from the cis side, steric interaction with the substituent at C-2 is encountered. On the other hand, according to Felkin, significant torsional strain between the pseudoaxial C-2—H bond and the incipient bond occurs if the nucleophile approaches the carbonyl group from the trans side. 

Exclusive exo (equatorial) attack is also observed with bicyclo[3.2.1]octan-3-one (5), whereas addition of methylmagnesium iodide to bicyclo[3.2.1]octan-2-one (7) affords the diastereomeric products in almost equal amounts5i. The cyclohexanone moiety of both bicyclic ketones 5 and 7 adopts a chair conformation and therefore the 3,5-diaxialethano bridge in... 

It is interesting that fmws-2-allyl-3-methy]cyclohexanone is by far the major product of this reduction-alkylation sequence, being formed in greater than the equilibrium ratio (see Note 13). The lithium cnolate would be expected to exist in the two conformations shown below ... 

The principles involved in the conformational analysis of six-membered rings containing one or two trigonal atoms, for example, cyclohexanone and cyclohexene are similar. The barrier to interconversion in cyclohexane has been calculated to be 8.4-12.1 kcal mol . Cyclohexanone derivatives also assume a chair conformation. Substituents at C2 can assume an axial or equatorial position depending on steric and electronic influences. The proportion of the conformation with an axial X group is shown in Table 4.4 for a variety of substituents (X) in 2-substituted cyclohexanones. 

TABLE 4.4 Proportion of Axial Conformation in 2-Substituted Cyclohexanones, in CDCI3... 

Bicyclic keto ester (22) was needed for conformational studies. The common atoms are marked ( ) and the obvious disconnections of this symmetrical molecule require double alkylation of cyclohexanone with a reagent such as (23), Double 1,5-diCO disconnection of (22) is impossible as you will discover if you attempt it. 

For cyclic ketones conformational factors also come into play in determining enolate composition. 2-Substituted cyclohexanones are kinetically deprotonated at the C(6) methylene group, whereas the more-substituted C(2) enolate is slightly favored... 

For simple, conformationally biased cyclohexanone enolates such as that from 4-t-butylcyclohexanone, there is little steric differentiation. The alkylation product is a nearly 1 1 mixture of the cis and trans isomers. 

The enamines derived from cyclohexanones are of particular interest. The pyrrolidine enamine is most frequently used for synthetic applications. The enamine mixture formed from pyrrolidine and 2-methylcyclohexanone is predominantly isomer 17.106 A steric effect is responsible for this preference. Conjugation between the nitrogen atom and the tt orbitals of the double bond favors coplanarity of the bonds that are darkened in the structures. In isomer 17 the methyl group adopts a quasi-axial conformation to avoid steric interaction with the amine substituents.107 A serious nonbonded repulsion (A1,3 strain) in 18 destabilizes this isomer. 

Crystalline samples of syndiotactic poly(methyl methacrylate) (st-PMMA) may be obtained from chloroacetone 178). This guest could be completely replaced by a variety of other guest molecules such as acetone, 1,3-dichloroacetone, bromoacetone, pinacolone, cyclohexanone, acetophenone and benzene. The X-ray diffraction patterns for these inclusion compounds were similar. These data indicate that the st-PMMA chains adopt a helical conformation of radius about 8 A and pitch 8.85 A. The guest molecules are located both inside the helical canals and in interhelix interstitial sites. 

Conformationally constrained 2-cyclohexenones which cannot undergo the lumiketone rearrangement (cf. chapter 3.1.5) are efficiently reduced to cyclohexanones (4.18) 420). 

---