Conformations haloketones

Dipole-dipole interactions have been used to assess the conformational populations of 2-haloketones (Eliel et al., 1965). With respect to SS, however, there are few applications in which these and related effects are considered. It is interesting that dipole induction and London dispersion effects were used some thirty years ago to account for the high endo over exo preference in the Diels-Alder reaction (Wassermann, 1965). Although effects are small for any pair of atoms, there are many closely packed atoms in a Diels-Alder transition state. At a carbon-carbon distance of 2-0 a between the atoms to be bonded, the energy favoring endo addition is 2-7 for dipole induction and 3-4 kcal/mole for dispersion in the reaction of cyclopentadiene with p-benzoquinone (Wassermann, 1965). These nonbonding attractive energies cooperate with the secondary HMO effects discussed earlier to lead to an endo product. 

Table 13.6. Carbonyl Band Positions and Probable Conformations of Haloketones in C 2 Solution (Kasturi. 1963)...

Corey, E. J. (1953). The Stereochemistry of a-Haloketones. I. The Molecular Configurations of Some Monocyclic a-Halocyclanones. Journal of the American Chemical Society, 75(10), 2301-2304. See also Allinger, N. L., Allinger, J. (1958). Conformational Analysis. II. The 2-Bromo-4-t-butylcyclohexanonesl,2. Journal of the American Chemical Society, 80(20), 5476-5480. 

The a-haloketone effect, as this phenomenon is known, is believed to be a result of dipolar interactions between the carbonyl group and the carbon-halogen bond dipole. The conformation with the smaller dipole moment is the one with the halogen axial, and is favored in solvents of low dielectric constant. 

The above discussion shows that cyclopropanone formation is a consequence of the halogen orientation and the nature of the solvent. Therefore the reaction mechanisms can be predicted and verified by conformational analysis of the stereochemistry of the rearranged products experimentally obtained. These ideas were at the origin of a great deal of research using cyclic a-haloketones where the halogen stereochemistry was known. The results are discussed in the following sections. 

In cyclohexanyl haloketones 21, 22, 23, and 24 the very bulky equatorial substituents 1,3 to the halogen prohibit the existence of any chair-chair equilibration. However, these derivatives can adopt a boat conformation in which the axial halogen is not sterically hindered, except in the case of derivative 24, which does not ring contract in the presence of sodium methoxide in methanol.When zwitterion formation is favored under such conditions, its disrotatory in or out cyclization can give rise to both a- and cyclopropanones. Ring opening of the latter will lead to esters with configurations opposite to those of the initial carbon-bromine bond. Such a hypothesis is in accord with the reactivity observed in the case of 23. ... 

The equatorial a-haloketones undergo ring contraction by an S 2 or by a zwitterionic mechanism in the latter case, it is likely that the molecule reacts in a boat conformation where the halogen has become axial. However, one can wonder about the reasons why the equatorial halogen derivatives— which react via a zwitterion similarly to their axial halogen epimers—do not give mainly secondary products. 

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