Toshifumi Dohi

Metal-free oxidative cross-coupling of unfunctionalized aromatic compounds.

A new strategy for mixed biaryl synthesis has been developed using the hypervalent iodine(III) reagents. The unique reactivities of the sigma-heteroaryl iodine(III) intermediates generated in situ are the key element for the unusual metal catalyst-free transformations and strict control of the product selectivities.

Asymmetric Dearomatizing Spirolactonization of Naphthols Catalyzed by Spirobiindane-Based Chiral Hypervalent Iodine Species

This report details the development of a spirobiindane-based chiral hypervalent iodine reagent, especially focusing on its structural elucidation for effective asymmetric induction of the chiral spiro center during the oxidative dearomatizing spirolactonization of naphthols. In this study we synthesized a new series of ortho-functionalized spirobiindane catalysts and demonstrated that the enantioselectivity can be dramatically improved by the presence of the substituents ortho to the iodine atom. The structural elucidation of a spirobiindane-based hypervalent iodine catalyst has led to further improvement in the stereoselective construction of the spiro center during the oxidative dearomatizing spirolactonization of naphthols. Thus, catalytic oxidation with the highest reported level of enantioselectivity in hypervalent iodine chemistry has been achieved with also an excellent level of asymmetric induction (92% ee for substrate 3a). As a result, this study, dealing with a series of modified iodine catalysts, can provide important clues about the transition state and reaction intermediate to help scientists understand the origin of the stereoselectivity. A plausible transition-state model and intermediate in the reaction for the stereoselective formation of spirolactone products are postulated by considering the ortho-substituent effect and the results of X-ray analysis. In this reaction model, the high enantiomeric excess obtained by using the spirobiindane catalysts could be well explained by the occupation of the equatorial site and extension of the surroundings around the hypervalent iodine bonds by the introduced ortho-substituent. Thus, this study would contribute to estimation of the chiral hypervalent iodine compounds in asymmetric reactions.

First hypervalent iodine(III)-catalyzed C–N bond forming reaction: catalytic spirocyclization of amides to N-fused spirolactams

A protic solvent, 2,2,2-trifluoroethanol (CF(3)CH(2)OH), was successfully introduced into hypervalent iodine(III)-involved catalytic cycles as an effective solvent, and the first iodoarene-catalyzed intramolecular carbon-nitrogen bond forming reaction was achieved under strong acid-free and mild conditions.

Unusual ipso Substitution of Diaryliodonium Bromides Initiated by a Single‐Electron‐Transfer Oxidizing Process

The diaryliodonium salts ArIArX , which have two aryl groups bound to an iodine atom as a ligand, represent one of the most popular classes of hypervalent iodine compounds and they have application as important arylating agents in organic synthesis. In general, the arylation of nucleophiles with these iodonium salts is assumed to involve the tricoordinated intermediate A before the final ligand-coupling (LC) steps. Owing to the competition of the two LC pathways of Ar and Nu (LCAr ) or Ar and Nu (LCAr ) at the iodine atoms in the intermediates, a mixture of two types of arylated products, Ar Nu and Nu Ar, are potentially obtained in the unsymmetrical salts (Ar1⁄46 Ar) during the aromatic substitution. Previous studies have revealed that the product produced from these pathways should be effected by both electronic and steric factors exerted by the two differential aryl rings of the initial salts—where the nucleophiles would preferentially react with a relatively electron-deficient aryl ring and/or sterically congested ipso carbon atom (i.e. the so-called “ortho effect”). Therefore, the introduction of nucleophiles to an electron-rich heteroaromatic ring is known to be particularly difficult through typical thermal LC processes, which involve the collapse of the intermediate A. Despite their rich chemistry, the utility of diaryliodonium salts as a heteroaryl transfer agent in LC processes has been somewhat limited. Herein, we report a unique single-electron-transfer (SET) oxidizing strategy using diaryliodonium salts as selective heteroaryl transfer agents during ipso substitution. Recently, our research group has reported a metal-free C H coupling method of thiophenes and aromatic compounds using iodonium salts. The method, using TMSBr in hexafluoroisopropanol (HFIP), is useful for the coupling reaction of the thiophene iodonium salts and introduces aromatic nucleophiles to the g positions of the iodine(III)–carbon bonds [Eq. (1)]. However, this reaction is not suitable for coupling through the ipso substitution of the thiophene iodonium salts 1a-X [X = OTs, Br; Eq. (2)].

A new H2O2/acid anhydride system for the iodoarene-catalyzed C-C bond-forming reactions of phenols.

We have succeeded in the first versatile iodoarene-catalyzed C-C bond-forming reactions by development of a new reoxidation system at low temperatures using stoichiometric bis(trifluoroacetyl) peroxide A in 2,2,2-trifluoroethanol (TFE). The catalytic system supplies a wide range of substrates and functional availabilities sufficient to be used in the key synthetic process of producing biologically important Amaryllidaceae alkaloids.

Clean and efficient benzylic C-H oxidation in water using a hypervalent iodine reagent: activation of polymeric iodosobenzene with KBr in the presence of montmorillonite-K10.

We have found that unreactive and insoluble polymeric iodosobenzene [PhIO] n induced aqueous benzylic C-H oxidation to effectively give arylketones, in the presence of KBr and montmorillonite-K10 (M-K10) clay. Water-soluble and reactive species 1 having the unique I(III)-Br bond, in situ generated from [PhIO]n and KBr, was considered to be the key radical initiator during the reactions.

Metal-Free C–H Cross-Coupling toward Oxygenated Naphthalene-Benzene Linked Biaryls

The intermolecular C-H cross-coupling between aromatic ethers has been achieved for the first time using perfluorinated hypervalent iodine(III) compounds as extreme single-electron-transfer (SET) oxidants. The demonstrations of this specific coupling could provide a direct route to valuable oxygenated mixed naphthalene-benzene biaryls 3 only, without formation of other biaryl-derived byproducts.

Discovery of Stabilized Bisiodonium Salts as Intermediates in the Carbon–Carbon Bond Formation of Alkynes

The oxidation of carbon–carbon triple bonds with hypervalent iodine reagents is an expedient strategy for the synthesis of 1,2-difunctionalized alkenes or their tautomers from alkynes through successive carbon–heteroatom bondforming events [Eq. (1), Nu = heteroatom]. The postulated iodonium species, which have two carbon groups bound to an iodine atom, are putative reaction intermediates, but would sometimes be isolable as the salt forms, depending on the reaction conditions. However, the possibility that similar iodonium-intermediate formation could accompany the installation of a new carbon–carbon bond has never been thoroughly confirmed. Such a transformation, to the best of our knowledge, has not appeared as a general method for alkyne functionalization in the long history of the chemistry of hypervalent iodine compounds.

Metal-Free Regioselective Oxidative Biaryl Coupling Leading to Head-to-Tail Bithiophenes: Reactivity Switching, a Concept Based on the Iodonium(III) Intermediate

A new synthetic concept for obtaining unsymmetrical biaryl coupling products by an oxidative method is reported. Our synthetic strategy casts light on the reaction intermediate for switching the reactivity of 3-substituted thiophenes. On the basis of this strategy, a novel direct method for the synthesis of head-to-tail bithiophenes using hypervalent iodine(III) reagents has been developed.

New synthesis of spirocycles by utilizing in situ forming hypervalent iodine species

A very effective spirocyclization procedure for installing nucleophiles (Nu = N(3), NO(2), SCN, SO(2)Tol, and halogens) via iodonium(III) salts has been developed using the combination of iodoarene and mCPBA. The high-yielding syntheses of the cyclohexadienone-type spirocyclic compounds 2 having varied functionalities in the skeletons have been achieved from the aryl alkynes 1 with the optimized bis(iodoarene) 3h.