Electrons, delocalization regioselectivities

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

The regioselectivities of the reactions of EDG-substituted alkenes are determined by delocalization from R to E via If. The delocalization contains the cychc interactions of orbitals, i.e., the electron-donating orbital (edg) of EDG, electron-accepting orbital (e ) of the electrophile, and the bonding n orbital and the antibonding n orbital. For... 

For the EAG-snbstimted alkenes, the transition states are non-cycUc E-Il-EAG systems. Polarization of Ft, induced by the delocalization from Ft to EAG and E, determines the regioselectivities. The polarization is analogous to that in the TMM dication (Sect. 2.1.4). The cyclic interaction occurs among the electron-accepting orbital eag ) of the substituent, e, n, and n. The a addition is favored by the orbital phase continuity while the P addition is disfavored by the phase discontinuity (Scheme 16). 

When the C—H bonds ortho to the halogen are nonequivalent, two isomeric benzyne structures form. In general, the formation of the benzynes is not regioselective. However, there may be a small preference for formation of the benzyne that results from deprotonation of the more acidic C—H bond. Note that the acidity of these bonds is affected only by the inductive effect of substituents. The electron pair of the anion occupies an sp hybrid orbital. The pair cannot be delocalized in the 71 system because it is perpendicular to the 2p orbitals that form the aromatic system. 

The regioselectivity of Cl ejection following electron transfer to a polychlorobenzene cannot be interpreted simply in terms of the maximal relief of steric strain but is rationalized instead by considering the stabilization of the radical anion QH5 C1 " by the chlorine substituents. Loss of chlorine is fastest from the position where least delocalization of the negative charge is possible. 

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