Halogen scrambling

Allcock, H. R., and Connolly, M. S., Polymerization and halogen scrambling behavior of phenyl-substituted cyclotriphosphazenes. Macromolecules. 18, 1330, 1985. 

Reactions of powerful alkyllithiums with halo pyridines, quinolines, and diazines may lead to nucleophilic substitution (by addition-elimination or hetaryne mechanisms), ring opening, halogen-scrambling, and coupling reactions, which compete with the desired DoM process. 

When adopting the dehydrohalogenation method in syntheses it is well to remember that halogen migration of the type discussed in connection with SnAt substitution may be a problem. Halogen scrambling is especially common with bromo compounds.83 84>... 

One clear tendency is apparent from the equilibrium product distribution of Letvis acid-induced transfluorination and halogen scrambling if fluorine can migrate it vill al vays tend to concentrate at one carbon atom. Most preferred reaction products are trifluoromethyl derivatives, followed by geminal difluoromethy] derivatives. This thermodynamic product control is often referred to as the general fluorine effect (Scheme 2.19). 

Scheme 2.19 The general" fluorine effect in Lewis acid-induced halogen scrambling.

During their extensive studies on the reaction and structural chemistry of palladium complexes of bisdiphenylphosphinomethane [bisfdppm)], Hunt and Batch examined the halogen scrambling reactions shown in Eqs. (22)— (23) in detail (31). 

The mild chlorination of 2,4,6-tris(dibromomethylene)-l,3,5-trithiane 159 yields not the expected addition product but, due to extensive halogen scrambling, 2-(bromodichloromethyl)-4,6-. r(trichloromethyl)-l,3,5-trithiane 160 (Scheme 42) <1990SUL63>. The stereochemistry was not determined and only the gross structure was ascertained by mass spectrometry. 

Alternatively, the directed ortho metalation strategy has been applied to the regioselective fluorination with NFSi. 4-Fluoro-7-azaindoles were functionalized at C-5 without any halogen scrambling or competitive lithiation at C-2 (eq 37). The orf/io-fluoro derivative of [(/ )-(l-phenyl)ethyldimethylamine]chromium tricarbonyl was prepared diastereoselectively by electrophilic fluorination employing NFSi (eq 38). ... 

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