Executive Summary : | The chemistry of Hypervalent iodine I(III) species has drawn much attention because of its wide applications in organic synthesis and potential to deliver a diverse array of synthetic scaffolds and natural products.1 This power has arisen from its electronic and geometrical properties.2 The electronic void on the iodine atom has attracted several types of Lewis bases to coordinate via noncovalent bonding called halogen bonding resulting in a differential mode of reactivity (ionic or radical) and fine-tuning of chemo, regio, and enantioselectivity. Therefore I(III) species can be classified as excellent Lewis acids and X-B doners.3 However, their use as catalytic Lewis acids is very limited until recently few publications have appeared in peer-reviewed journals.4 It is worth mentioning that only groups outside India are developing methodologies on this concept. The proposal disclosed here will utilize the catalytic use of hypervalent iodine (III) species as Lewis acid X-B bond doners. The approach consists of their noncovalent bonding with saturated heterocycles (heteroatom chelation) and enantioselective cascade ring-opening followed by transition metal-free functionalization with various nucleophiles such as indoles, fluoro-trifluoromethyl anion equivalents, etc. Additionally, the unique application of this concept will be extended to a palladium-catalyzed three-component cascade ring-opening reaction. The double chelation of I(III) species with saturated heterocycle and ligand of the Pd-π-allyl complex through Lewis acid-base interaction may speed up the formation of active π-allyl-heterocycle intermediate that may readily undergo ring-opening reactions with various nucleophiles. This will be a three-component variation of the classical Tsuji-Trost allylation reaction. The I(III) species will be generated catalytically by either stoichiometric uses of oxidants or anodic electrochemical oxidation from corresponding iodoarenes. The success of this new concept will allow adding the various type of important nucleophiles to access a functionalized library of scaffolds and further directed toward the synthesis of indomethacin, euroticins, agesamides, and their analogs. The biological assay of all scaffolds/analogs for the anti-inflammatory and cytotoxic activity will be done in collaboration with institutional and industrial partners. |