Stereoelectronic effects cyclohexanones

It has however been suggested by Cieplak (9) that the stereochemistry of nucleophilic addition to cyclohexanone is determined by a combination of steric and stereoelectronic effects. According to this interesting model, steric hindrance favors the equatorial approach while electron donation favors the axial approach. The stereoelectronic effect favors the axial approach because the axial C —H bonds next to the carbonyl group (C — Ha and Cn-Ha) are better electron donors than the Cn-C-j and Cc-Cfi a bonds (cf 7A 7 and 7A-8). J... 

Subsequently, certain authors (126-128) have supported this interpretation, but alternative explanations have also been proposed (129-132). Another early discussion of the stereochemistry of the enolization process was that of Vails and Toromanoff (133). They proposed that if stereoelectronic effects are an important parameter, the cyclohexanone enolate should react by two different pathways, one involving a chair-like transition state (443 444) and the other a boat-like transition state (443 445 446) Thus, both of these reactions proceed by perpendicular attack (134) of the electrophile. Their energy difference results from the difference in strain between the chair (444) and the twist-boat (445) forms. 

In the explanation favored today, the reason for this stereoelectronic effect is as follows The electronically preferred direction of attack of a hydride donor on the 0=0 double bond of cyclohexanone is the direction in which two of the C—H bonds at the neighboring a positions are exactly opposite the trajectory of the approaching nucleophile. Only the axial C—H bonds in the a positions can be in such an antiperiplanar position while the equatorial C—H bonds cannot. Moreover, these axial C—H bonds are antiperiplanar with regard to the trajectory of the H nucleophile only if the nucleophile attacks via a transition state B, that is, axially (what was to be shown). The antiperiplanarity of the two axial C—H bonds in the a positions is reminiscent of the antiperiplanarity of the electron-withdrawing group in the a position relative to the nucleophile in the Felkin-Anh transition state (formula C in Fig. 8.8 cf. Fig. 8.11, middle row). 

Figure 12.51 Stereoelectronic effects on C-C coupling constant in axial and equatorial 2-methyl cyclohexanones.

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. 

The question of the existence of an equilibrium in enamines derived from 3-aIkyl and 3-aryl cyclohexanones has been investigated. The equilibrium ratio (282) (283) is 45 55, whereas (284) dominated the corresponding isomer ratio to the virtual exclusion of (285). However, reaction with 3-nitrostyrene (which reacts quantitatively with some trisubstituted enamines) under conditions of kinetic control gives adducts formed in the first isomeric pair, to the extent of 80% from (283) in the second pair adducts are also formed to the extent of 80 % from (285). This result is rationalized in terms of a rapid equilibrium between the enamine pairs and the high selectivity shown in adduct formation is accounted for in terms of steric and stereoelectronic effects. 

When the carbonyl group is exo to a ring as in cyclohexanone, both the equatorial and the axial approach can lead to a chair intermediate (cf. 7 and 8) with stereoelectronic control because, in each case, the oxygen atom has an electron pair antiperiplanar to the C-Y bond. So, in this case, one process is favored over the other solely on the basis of steric effects and torsional strain due to the presence of the ring (8). ... 

Another very important aspect of enolisation is the "stereo electronic effect , first invoked by Corey [ii2,xx3]. This is revealed in the preferential loss of the axial proton from a conformatiohally rigid cyclohexanone. The stereoelectronic... 

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