FeCl₂‐mediated Nucleophilic Chlorination of Iodoalkanes Accelerated by Phenanthroline Ligand

Abstract

Alkyl halides have been considered not only important building blocks but also useful intermediates in synthetic methods of nucleophilic substitution, metal-halogen exchange, and cross-coupling reactions. As the practical synthesis of various alkyl halides, the halogen exchange is one of the fundamental and efficient reactions, which is mainly used for preparing alkyl bromides or iodides. Finkelstein-type reactions 1 have been well studied for the conversion of alkyl chlorides to the corresponding bromides or iodides and alkyl bromides to iodides, which reaction is an equilibrium shifted by taking advantage of the different solubility of the resulting sodium salt in acetone. However, the reverse processes, the replacement of iodide by bromide or chloride, or of bromide by chloride, were not simple.The early investigation on the chlorination of alkyl iodides were involved with the reaction of molecular chlorine or iodine monochloride, 2 which afforded the alkyl iodide-halogen intermediate (RIÁClX, X = Cl or I). The resulting trihalide ion could act as an electronegative leaving group and promote the chloride substitution, showing the preferred reactivity of tertiary and secondary iodides over primary iodides. Metal chlorides such as MoCl 5 3 and BiCl 3 4 were also discovered as the role of providing the chloride source as well as activating the carbon-halogen bond by Lewis acidic coordination to halogen leaving group. This strategy showed the 1,2-migration phenomena in the reaction with 1-iodooctane, supporting the intermediacy of carbocations. Another approach was the oxidativelyassisted substitution, where alkyl iodides were oxidized to iodoso compounds (RI O) by mCPBA 5 or hypervalent iodine 6 compounds for consecutive nucleophilic chlorination. In a similar way, oxidative ligand transfers between alkyl iodides and aryliodine(III) reagents produced the requisite hypervalent alkyliodine intermediates for substitution. The methods described above make the iodide a good leaving group and the modified iodine functional group cannot act as a nucleophile again. On the other hand, a process of separating the generated alkyl chlorides by boiling point difference 7 or separating the leaving iodide into fluorous phase using fluorous phosphonium salt has been developed. 8