Catalytic phosphorus(V)-mediated nucleophilic substitution reactions: development of a catalytic Appel reaction.

Catalytic phosphorus(V)-mediated chlorination and bromination reactions of alcohols have been developed. The new reactions constitute a catalytic version of the classical Appel halogenation reaction. In these new reactions oxalyl chloride is used as a consumable stoichiometric reagent to generate the halophosphonium salts responsible for halogenation from catalytic phosphine oxides. Thus, phosphine oxides have been transformed from stoichiometric waste products into catalysts and a new concept for catalytic phosphorus-based activation and nucleophilic substitution of alcohols has been validated. The present study has focused on a full exploration of the scope and limitations of phosphine oxide catalyzed chlorination reactions as well as the development of the analogous bromination reactions. Further mechanistic studies, including density functional theory calculations on proposed intermediates of the catalytic cycle, are consistent with a catalytic cycle involving halo- and alkoxyphosphonium salts as intermediates.

Phosphine oxide-catalysed chlorination reactions of alcohols under Appel conditions.

A phosphine oxide-catalysed chlorination reaction of primary and secondary alcohols has been developed. This process represents the first triphenylphosphine oxide-catalysed alcohol chlorination under Appel conditions.