The Stereochemistry of Halogenation Reactions

Energy diagram for the exothermic reaction CH3CH2CH3 + Cl- CH3CH2CH2- or (CH3)2CH- + HCI 

Problem 15.13 Why is the reaction of methylcyclohexane with CI2 not a useful method to prepare 1-chloro-1-methylcyclohexane What other constitutional isomers are formed in the reaction mixture  

Problem 15.14 Reaction of (CH3)3CH with CI2 forms two products (CH3)2CHCH2CI (63%) and (CH3)3CCI (37%). Why is the major product formed by cleavage of the stronger 1° C — H bond  

Halogenation is a useful tool because it adds a functional group to a previously unfunctionalized molecule, making an alkyl halide. These alkyl halides can then be converted to alkenes by elimination. and to alcohols and ethers by nucleophilic substitution. 

Sample Problem 1 5.3 Show how cyclohexane can be converted to cyclohexene by a stepwise sequence. 

There Is no one-step method to convert an alkane to an alkene. A two-step method is needed  

Show all steps and reagents needed to convert cyclohexane into each compound (a) the two enantiomers of frans-1,2-dibromocyclohexane and (b) 1,2-epoxycyclohexane. 

The stereochemistry of a reaction product depends on whether the reaction occurs at a stereo-genic center or at another atom, and whether a new stereogenic center is formed. The rules predicting the stereochemistry of reaction products are summarized in Table 15.1. 

Achiral An achiral starting material always gives either an achiral or a racemic product. 

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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... 

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. 

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. 

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. 

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. 

In agreement with the involvement of ionic intermediates for electrophilic halogenation of alkenes, an important role is also exerted by the solvent. Not only the reaction rate is strongly solvent-dependent, but also the stereochemical course of the addition process may be affected by the polarity of the medium. Solvent properties determine the reaction rate the overall kinetic order the nature of the products the stereochemistry of the products... 

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... 

Metal-14 anions react with alkyl halides (RX) mostly by nucleophilic substitution (Sn2), the stereochemistry of which is dependent on the structure of R and X, the solvent and the nature of the counterion. Other reactions were also observed nucleophilic substitution at halogen [also called halogen/metal exchange (HME)] and single electron processes. In some cases steric hindrance around the reactant results in elimination. 

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