The preparation, structure, and chemistry of hypervalent iodine compounds are reviewed with emphasis on their synthetic application. Compounds of iodine possess reactivity similar to that of transition metals, but have the advantage of environmental sustainability and efficient utilization of natural resources. These compounds are widely used in organic synthesis as selective oxidants and environmentally friendly reagents. Synthetic uses of hypervalent iodine reagents in halogenation reactions, various oxidations, rearrangements, aminations, C–C bond-forming reactions, and transition metal-catalyzed reactions are summarized and discussed. Recent discovery of hypervalent catalytic systems and recyclable reagents, and the development of new enantioselective reactions using chiral hypervalent iodine compounds represent a particularly important achievement in the field of hypervalent iodine chemistry. One of the goals of this Review is to attract the attention of the scientific community as to the benefits of...

Advances in Synthetic Applications of Hypervalent Iodine Compounds

A palladium-catalyzed intramolecular oxidative aryltrifluoromethylation reaction of activated alkenes has been explored. The reaction allows for an efficient synthesis of a variety of CF(3)-containing oxindoles. Preliminary mechanistic study indicated that the reaction involves a C(sp(3))-Pd(IV)(CF(3)) intermediate, which undergoes reductive elimination to afford a C(sp(3))-CF(3) bond.

Palladium-catalyzed oxidative aryltrifluoromethylation of activated alkenes at room temperature.

Iodine reagents have been identified as economically and ecologically benign alternatives to transition metals, although their application as molecular catalysts in challenging C-H oxidation reactions has remained elusive. An attractive iodine oxidation catalysis is now shown to promote the convenient conversion of carbon-hydrogen bonds into carbon-nitrogen bonds with unprecedented complete selectivity. The reaction proceeds by two interlocked catalytic cycles comprising a radical chain reaction, which is initiated by visible light as energy source. This unorthodox synthetic strategy for the direct oxidative amination of alkyl groups has no biosynthetic precedence and provides an efficient and straightforward access to a general class of saturated nitrogenated heterocycles.

An Iodine-Catalyzed Hofmann–Löffler Reaction†

Metal‐Free Oxidative Carbon‐Heteroatom Bond Formation Through C–H Bond Functionalization

Hypervalent iodine(III) reagents have been known for over a century, and their reaction profile is still actively investigated. Recent years have seen impressive improvements in the area of alkene difunctionalization reactions, where new methodologies have become available. Especially chiral non-racemic hypervalent iodine(III) reagents and catalysts have emerged as versatile tools for the realization of important enantioselective transformations.

Vicinal difunctionalization of alkenes with iodine(III) reagents and catalysts.

Enantioselective Metal‐Free Diamination of Styrenes

A new approach to direct intermolecular allylic amination has been developed using metal-free conditions at room temperature. The reaction employs a hypervalent iodine(III) reagent as an oxidant and bistosylimide as a nitrogen source. A series of different allylic aminations are presented with up to a 99% yield. Mechanistic studies including isotope labeling and Hammett correlation suggest that depending on the substrate structure two different mechanisms can be operating.

Iodine(III)-Mediated Intermolecular Allylic Amination under Metal-Free Conditions

New bisimido iodine(III) reagents with unprecedented reactivity are presented and applied in direct metal-free amination reactions.

Defined hypervalent iodine(III) reagents incorporating transferable nitrogen groups: nucleophilic amination through electrophilic activation.

A direct metal-free amination of arylalkynes has been developed, which proceeds by reaction of the terminal alkyne with the hypervalent iodine reagent PhI(OAc)NTs2 within a single-step operation. This unprecedented intermolecular C–H to C–N bond conversion provides rapid access to the important class of ynamides. In addition to the title reaction, the related transformation between alkylated alkynes and the iodine(III) reagent is also discussed.

Metal-free iodine(III)-promoted direct intermolecular C-H amination reactions of acetylenes.

A new metal-free method for the rapid and productive preparation of indoles has been developed. This process is based on sterically congested hypervalent iodine compounds of the family of Koser reagents, and iodosobenzene in combination with 2,4,5-tris-isopropylbenzene sulfonic acid provides the highest yields and fastest reaction times. This reagent alone promotes the chemoselective oxidative cyclization of 2-amino styrenes to indoles in high yields under mild conditions.

José A. Souto

Papers

Enantioselective Metal‐Free Diamination of Styrenes

Iodine(III)-Mediated Intermolecular Allylic Amination under Metal-Free Conditions

Defined hypervalent iodine(III) reagents incorporating transferable nitrogen groups: nucleophilic amination through electrophilic activation.

Metal-free iodine(III)-promoted direct intermolecular C-H amination reactions of acetylenes.

Indole Synthesis Based On A Modified Koser Reagent