Formation of Carbon-Carbon and Carbon-Heteroatom Bonds by ET Nucleophilic Substitution of Alkyl Halides

PIERINI, A.B.; PEÑEÑORY, A.B.; BAUMGARTNER, M.T.

Electron Transfer Reactions in Organic Synthesis.

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Año: 2002; p. 63 - 87

Besides unactivated aromatic halides and alkyl halides activated by strong electron withdrawing groups (nitroalkyl, nitroallyl, nitro or cyanobenzyl and their heterocyclic analogues, as well as quinone derivatives), other simple alkyl halides can be substituted by nucleophiles through electron transfer (ET) mechanisms. The main feature of these compounds is their low reactivity toward classical polar nucleophilic substitutions mainly due to steric and strain factors. Among these compounds are neopentyl halides and derivatives, cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl) and bridgehead bicyclo- and policyclo alkyl halides. Perfluoroalkyl halides (RfI) and related compounds are also able to be substituted by this means. Different nucleophiles have been reported to react by ET processes. Among them carbanions from hydrocarbons, ketones, nitroalkanes, thioamides, and anions from nitrogen aromatic heterocycles which afford a new carbon-carbon bond. Carbon-heteroatom bonds are obtained by reaction with anions from tin, phosphorous, arsenic, sulfur, selenium and tellurium. These reactions can take place by the SRN1 mechanism. In some cases a non-chain ET reaction has been proposed. The system constitutes an important approach to achieve the substitution of compounds usually unreactive by other means. The reactions also offer the synthetic possibilities to obtain disubstitution when two leaving groups are present. We will here present the main synthetic scope of nucleophilic substitution reactions by ET for the neopentyl family and derivatives, halocycloalkanes, gem-dihalocyclo-propanes halo- and dihalo policyclo alkanes as well as RfI and derivatives.