Stereochemistry halogenation

The unsymmetrical mechanism is also called the semibenzilic mechanism. Generally, a weakly acidic hydrogen is present a to the carbonyl. When there is no such a -hydrogen, the reaction is called a quasi-Favorskii, and involves the same type of mechanism. The geometry which is necessary for this process to occur is the same in both the acyclic and cyclic series. Obviously in the latter case the reactivity will be directly related to the halogen stereochemistry. Ring strain will also play an important role and will often be the decisive factor in determining which of the semibenzilic and the cyclopropanone mechanisms obtain. 

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. 

Kinetic studies do not allow one to differentiate between the two mechanisms of cyclopropanone formation depending on the halogen stereochemistry. A difference in behavior can be observed, however, between equatorial brominated and chlorinated derivatives. Loftfield s process (Scheme 1), according to which the first step is reversible, is verified in the case of a-bromocyclohexanones. So in 17 and 22 (X = Br) hydrogen-deuterium... 

Although an mechanism cannot be excluded in the case of 18e, the zwitterionic mechanism is the only one which gives a coherent explanation of the reactivity of axial and equatorial halogen derivatives. However, the halogen stereochemistry plays an important role. An axial halogen favors the secondary substitution reactions and the formation of delocalized species these can lead... 

One could actually wonder why the a-halogenated cyclopentanone does not undergo ring contraction by a semibenzilic mechanism. As discussed below, the conditions required for such a mechanism to be operative are very narrowly related to the carbon halogen stereochemistry which must be equatorial. We have just seen that in a-halocyclopentanones, the carbon halogen bond is pseudoaxial, a stereochemistry which is more suitable to zwitterion formation. 

A dihaloalkene is an intermediate and is the isolated product when the alkyne and the halogen are present m equimolar amounts The stereochemistry of addition is anti... 

Enolization is the rate-determining step in the halogenation of normal ketones. Where alternate directions for enolization exist, the preferred direction (and hence the position of kinetic bromination) depends on the substituents and stereochemistry. Furthermore, the orientation of the bromine introduced depends on stereochemical and stereoelectronic factors. 

In spite of these rationali2ations, the stereochemistry of ketone halogenation retains some puzzling features. For example, the effect of a 2-methyl substituent on the direction of bromination at C-2 is unexpected. 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

No completely general and quantitative theory of the stereochemical activity of the lone-pair of electrons in complex halides of tervalent As, Sb and Bi has been developed but certain trends are discernible. The lone-pair becomes less decisive in modifying the stereochemistry (a) with increase in the coordination number of the central atom from 4 through 5 to 6, (b) with increase in the atomic weight of the central atom (As > Sb > Bi), and (c) with increa.se in the atomic weight of the halogen (F > Cl > Br > 1). The relative energies of the various valence-Ievel orbitals may also be an important factor the F(a) orbital of F lies well below both the s and the p valence... 

The stereochemistry of the halogens in their various compounds is summarized in Table 17.8 and will be elucidated in more detail in subsequent sections. 

When the halogenation reaction is carried out on a cycloalkene, such as cyclopentene, only the trews stereoisomer of the dihalide addition product is formed rather than the mixture of cis and trans isomers that might have been expected if a planar carbocation intermediate were involved. We say that the reaction occurs with anti stereochemistry, meaning that the two bromine atoms come from opposite faces of the double bond—one from the top face and one from the bottom face. 

The bromonium ion postulate, made more than 75 years ago to explain the stereochemistry of halogen addition to alkenes, is a remarkable example of deductive logic in chemistry. Arguing from experimental results, chemists were able to make a hypothesis about the intimate mechanistic details of alkene electrophilic reactions. Subsequently, strong evidence supporting the mechanism came from the work of George Olah, who prepared and studied stable... 

HC1, HBr, and HI add to alkenes by a two-step electrophilic addition mechanism. Initial reaction of the nucleophilic double bond with H+ gives a carbo-cation intermediate, which then reacts with halide ion. Bromine and chlorine add to alkenes via three-membered-ring bromonium ion or chloronium ion intermediates to give addition products having anti stereochemistry. If water is present during the halogen addition reaction, a halohydrin is formed. 

One of the most direct routes to vinylsilanes uses vinyl halides as starting materials. Metal-halogen exchange, followed by electrophilic attack by TMSC1, can often provide the vinylsilane quickly and in good yield. As an added bonus, vinyl bromides have been shown (10, II) to proceed through this sequence with retention of double-bond stereochemistry. 

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