Stereochemistry of halogenation reactions

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... 

There are two other mechanistic possibilities, halogen atom abstraction (HAA) and halonium ion abstraction (EL), represented in Schemes 4.4 and 4.5, respectively, so as to display the stereochemistry of the reaction. Both reactions are expected to be faster than outer-sphere electron transfer, owing to stabilizing interactions in the transition state. They are also anticipated to both exhibit antiperiplanar preference, owing to partial delocalization over the C—C—Br framework of the unpaired electron in the HAA case or the electron pair in the EL case. Both mechanisms are compatible with the fact that the activation entropies are about the same as with outer-sphere electron donors (here, aromatic anion radicals). The bromine atom indeed bears three electron pairs located in two orthogonal 4p orbitals, perpendicular to the C—Br bond and in one s orbital. Bonded interactions in the transition... 

The stereochemistry of the reaction is also dependent on the halogen. The reaction of chiral l-halo-2,2-diphenylcyclopropane with 25 xm lithium dispersions containing 1% sodium produced the results shown in Table 16. It should be noted that the optical purity of the acid varies in the same order as the carbon-halogen bond strength Cl > Br > I. 

The following mechanism was proposed by Walborsky and AronofFin 1965 for the lithiation reaction (Scheme 9). The stereochemistry of the reaction may be explained by a single electron transfer (SET) to the carbon-halogen bond which results in either the formation of an ion paired halide radical anion on the metal surface (pathway 1) or what is... 

Two major aspects are involved in the additions of electrophiles to bicyclobutane, namely the product distribution and the stereochemistry of the reaction. In the following. section we will address acid-catalyzed additions to bicyclobutane. This will be followed by a discussion of the addition of other electrophiles such as halogens, and will be concluded by a general discussion of the mechanism of electrophilic additions to bicyclobutanes. 

In addition to the elegant work just described, the stereochemistry of the reaction provides powerful support for a two-step addition of halogen. At the same time, as we shall see in Sec. 7.12, it requires a modification in the mechanism. 

Then we shall examine the stereochemistry of several reactions we have already studied—free-radical halogenation of alkanes, and electrophilic addition of halogens to alkenes- and see how stereochemistry can be used to get information about reaction mechanisms. In doing this, we shall take up ... 

The issue of the role of bridged radicals in the stereochemistry of halogenation has recently been examined computationally and a new interpretation offered. The structure, rotational barriers, and for halogen atom abstraction for P-haloethyl radicals were studied. For the reactions where X=C1 or Br, the halogen atom abstraction reaction shows a preference for a trans TS. 

From the mechanism of catalytic hydrogenation we notice that hydrogen adds to the alkene molecule in such a way that both H-atoms are added to the same side of the molecular plane. The stereochemistry of this reaction is called syn-addition. Addition of halogen follows qnite different stereochemistry two halogen atoms approach the alkene molecular plane from the opposite sides. Such stereochemistry is called anrt-addition. The mechanism is confirmed by the analysis of configurations of products of addition of chlorine to cyclopentene. 

Examples are known, however, in which halogen cleavage of metal-alkyl bonds occurs with retention (Whitesides and Boschetto, 1969 Calderazzo and Noack, 1966 Johnson, 1970 Slack and Baird, 1974, 1976) and others with inversion (Whitesides and Boschetto, 1971 Jensen and Davis, 1971 Jensen et aL, 1971 Anderson et al., 1972). Without firm evidence about the stereochemistry of the cleavage of metal-alkyl bonds, little can be said about the stereochemistry of the reaction between metal nucleophiles with alkyl halides. 

In 1970 two conflicting reports on the stereochemistry of the addition of chiral alkyl halides to square-planar iridium(I) complexes appeared. In one report it was claimed that the reaction of /ra/w-[IrCI(CO)(PPh2Me)2] with optically active CHjCHBrCOjEt occurred with retention of configuration as shown in Scheme 5 (Pearson and Muir, 1970). This result is consistent with a six-coordinate intermediate , as is the lack of incorporation of any free halide into the product (Section 8). However, the conclusions should again be treated with care since the study employs the cleavage of the iridium-carbon bond by halogen, and without knowing the stereochemistry of this reaction little can be said about the stereochemistry of the displacement. 

We have seen that a chemical reaction, such as the halogenation of an alkane, can introduce chirality into a molecule. How exactly does this occur To find the answer, we need to look more closely at the conversion of achiral butane into chiral 2-bromobutane, which gives racemic material. Once we have done so, we shall be able to understand the halogenation of 2-bromobutane and the effect of the chiral environment of a stereocenter already present in a molecule on the stereochemistry of the reaction. 

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. 

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. 

Stereospecificity of this reaction reaches 15 1 for telomer T3. Telomer T3 is a crystalline product, this allowed the authors to use X-ray diffraction analysis for studying stereochemistry. Stereoselectivity observed in the formation of T3 shows that both addition step and the step of halogen transfer to the growing radical proceed stereoselectively in this case. 

Stereochemistry of the halogenation-dehalogenation reaction was studied for 1,2,3,4-tetrabromodibenzodioxin, TBDD (Scheme 4). 

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