Application of Hypervalent Iodine Reagents in Chemical Synthesis
Iodine is most commonly in monovalent compounds with an oxidation state of -1, however, because it is the largest, most polarizable, and most electropositive of the group 17 elements, it also forms stable polycoordinate, multivalent compounds. Factors leading to resurgence of interest are, Chemical properties and reactivity is similar to the heavy metal reagents, but without the toxicity & environmental issues; mild reaction conditions and easy handling of hypervalent iodine compounds; commercial availability of key precursors such as PhI(OAc)2. Most hypervalent iodine reagents are solid (amorphous or crystalline) and are stable to atmospheric oxygen and moisture. Certain iodonuim salts are less stable and should be generated in situ. Hypervalent iodine chemistry is based on the strongly electrophilic nature of the iodine making it susceptible to nucleophilic attack, in combination with the leaving group ability of phenyliodonio group. The favorable reduction of the hypervalent iodide to normal valence by reductive elimination of iodobenzene is the key to its reactivity Verities of reactions were developed in our lab, by using the hypervalent iodine reagents, some of them are an efficient aqueous sodium dichloroiodate (NaICl2) mediated protocol for the synthesis of benzofused azoles by the cyclization of 2-amino anilines/thiophenols/phenols with β-diketone compounds. This tandem process involved a C-C bond cleavage and C-N bond formation. Amide is one of the most important functional groups found in polymers, fine chemicals, pharmaceuticals, and natural products. The traditional synthetic approach used for amide formation involves the reaction of an amine with activated carboxylic acid derivatives or coupling with carboxylic acids mediated by coupling reagents, which suffers from several common drawbacks. A facile oxidative coupling of alcohols and amines to construct amides was developed using DIB as a catalyst and aqueous tert-butyl hydroperoxide as an oxidant. The reaction involved operational simplicity, metal free oxidation, and wide functional group tolerance as attractive features. A simple methodology was also developed to synthesize substituted aminothiazoles from the corresponding thiourea and substituted ketones using aqueous NaICl2 at reflux temperature in THF. Aminothiazole have been recently identified as a desired structural element that is screened as part of many drug design processes in medicinal chemistry due to their thiourea like properties and tendency to modulate biological targets.
Index Terms - Hypervalent Iodine, oxidation, C-C cleavage, C-N formation, bioactive compounds.