Published papers

A stable sulfonylimino-λ3-bromane, CF3SO2N--Br+C6H4-p-CF3, has been synthesized and structurally characterized for the first time. X-ray crystallographic analyses indicated a centrosymmetric dimer structure with little double-bond character for the "ylidic" Br-N bond. The iminobromane serves as an efficient imido group donor and directly undergoes aziridination of olefins stereospecifically with retention of original stereochemistry. Very interestingly, the aziridination proceeds at room temperature using limiting amounts of alkenes under transition-metal-free conditions. The observed rate constants for aziridination of cis-cyclooctene are proportional to concentration of the olefin. The results suggest the involvement of a bimolecular transition state, in which an olefin attacks the σ* N-Br orbital of iminobromane in the nitrenoid transfer process. Copyright © 2007 American Chemical Society.

Reported here for the first time are the developments of an efficient method for oxidative cleavage of carbon-carbon double bonds yielding carbonyl compounds by using aryl-λ3-iodanes, which involve a combination of iodosylbenzene and HBF4 in the presence of water. The method serves as a safety alternative to ozonolysis. The oxidative cleavage of olefins probably involves the hitherto unknown direct vicinal dihydroxylations of double bonds with aryl-λ3-iodanes and the subsequent oxidative glycol fissions. Cyclic (cyclopentenes, cyclohexenes, etc.) and acyclic olefins are cleaved smoothly under our conditions. In the reaction of electron-deficient styrenes such as m-nitrostyrene, intermediate formation of the corresponding epoxide was detected. A variety of aryloxiranes also undergo an oxidative cleavage of the epoxide rings under our conditions, and aromatic aldehydes were obtained in good yields. Copyright © 2007 American Chemical Society.

(Chemical Equation Presented) We report the first example of Hofmann rearrangement of primary arenesulfonamides, which relies on the use of p-trifluoromethylphenyl(difluoro)-λ3-bromane and affords N-arylsulfamoyl fluorides selectively at room temperature. Reaction of aryl-λ3-iodanes with p-toluenesulfonamide affords sulfonylimono-λ3-iodanes, being excellent progenitors for generation of metal-nitrenoid species. In marked contrast, reaction of the difluoro-λ3-bromane with p-toluenesulfonamide in benzene produced unique N-p-tolylsulfamoyl fluoride in a high yield, through Hofmann rearrangement. Arenesulfonamides with electron-donating (p-MeO and o-Me) and -withdrawing substituents (p-F, p-Cl, and p-CF3) efficiently undergoes the λ3-bromane-induced Hofmann rearrangement. The structure of N-p-tolylsulfamoyl fluoride was determined by a single-crystal X-ray analysis. The differences in nucleofugality between aryl- λ3-iodanyl and aryl-λ3-bromanyl groups, the later being greater, probably play a pivotal role in determining the reaction course. The results obtained from the reaction of 2,3,5,6- tetramethylbenzenesulfonamide strongly suggest that generation of sulfonyl nitrene will not be involved in this rearrangement. Copyright © 2009 American Chemical Society.

Exposure of N-heterocycles and aliphatic trialkylamines to trifluoromethanesulfonylimino-lambda(3)-bromane at room temperature results in direct transfer of the sulfonylimino group to the nitrogen atoms and affords a variety of iminoammonium ylides under transition-metal-free conditions. The imino-lambda(3)-bromane probably serves as an active nitrenoid species without any activation and produces the ammonium ylides via a bimolecular nucleophilic substitution process.

(Chemical Equation Presented) 4-tert-Butyl-1-cyclohexenyl(phenyl) (tetrafluoroborato)-λ3-iodane forms a discrete supramolecular complex by the reaction with 18-crown-6. Solvolysis of the cyclohexenyl- λ3-iodane in the presence of 18-crown-6 indicates that the complexation with 18-crown-6 tends to decrease the leaving group ability of hypervalent phenyl-λ3-iodanyl groups. © 2005 American Chemical Society.

Objective: We investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes. Methods: A total of 38 type 2 diabetic patients (22 men and 16 women; mean±S.E.M. age 63.3±1.0 years; duration of diabetes 9.6±0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum N ε-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean±S.E.M. duration of diabetes 8.2±0.7 years) as control (C group). Results: The EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (-0.18±0.13 mU/ml in the EP group vs. +0.22±0.09 mU/ml in the C group, P<.05) after 1 year. Conclusions: Epalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs. © 2010 Elsevier Inc. All rights reserved.

Both stereoisomers of β-(2-phenylethoxy)vinyl-λ3- iodane and (Z)-β-aroyloxyvinyl-λ3-iodane were prepared stereoselectively. These substituted vinyl-λ3-iodanes undergo nucleophilic vinylic substitutions with n-Bu4NX (X=Cl, Br, I) under mild conditions, yielding vinyl halides. The observed inversion of configuration at the ipso vinylic carbon atom is compatible with a concerted vinylic S N2 mechanism. Kinetic measurements indicated that the rates for vinylic SN2 reaction of (Z)-vinyl-λ3-iodane are greater than those of the E-isomer, probably because of the higher ground state energy of the Z-isomer. Electronic effects of β-substituents of vinyl-λ3-iodanes in the vinylic SN2 reaction are also discussed. © 2010 Elsevier Ltd.

Last of the cyclic vinyl cations: The simple solvolysis of cyclopent-1 -enyl-13-bromane efficiently generates the highly strained cyclopent-1 -enyl cation at room temperature (see scheme). The very high nucleofugality of the aryl-13-bromanyl groups are responsible for this unique unimolecular dissociation. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

The synthesis and reactions of N-triflylimino-λ3-bromane are summarized. The hypervalent iminobromane functions as a highly active nitrenoid species at ambient temperature under transition metal-free conditions, probably because of the increased hypernucleofugality of aryl- λ3-bromanyl groups compared to that of aryl- λ3-iodanyl groups. The imino-λ3-bromane undergoes stereospecific aziridination of olefins and transylidation to aromatic nitrogen heterocycles, trialkylamines and iodobenzenes. Difluoro- λ3-bromane-induced Hofmann rearrangement of primary arylsulfonamides is also discussed. © 2010 The Royal Society of Chemistry.

A conceptually distinct, modern strategy for Baeyer-Villiger oxidation (BVO) was developed. Our novel method involves initial hydration of water to carbonyl compounds, followed by ligand exchange of hypervalent aryl-λ3-bromane on bromane(III) with the resulting hydrate, yielding a new type of activated Criegee intermediate. The intermediate undergoes BV rearrangement and produces an ester via facile reductive elimination of an aryl-λ3-bromanyl group, because of the hypernucleofugality. The novel strategy makes it possible to induce selectively the BV rearrangement of straight chain primary aliphatic as well as aromatic aldehydes, which is missing in the classical BVO: for instance, octanal and benzaldehyde afforded rearranged formate esters with high selectivity (>95%) under our conditions, while the attempted classical BVO produced only carboxylic acids. This firmly establishes the powerful nature of new methodology for BVO. © 2010 American Chemical Society.

Sulfonylimino-λ3-bromane functions as a reactive nitrenoid, because of the hyperleaving group ability of aryl- λ3-bromanyl groups, and undergoes transimidations to iodobenzenes at room temperature under metal-free conditions probably via an SN2-type nitrenoid transition state, yielding sulfonylimino- λ3-iodanes. © The Royal Society of Chemistry 2009.

Exposure of sulfides and sulfoxides to trifluoromethanesulfonylimino(aryl)- λ3-bromane in dichloromethane at 0°C results in a facile transfer of the sulfonylimino group to sulfur atoms and affords N-triflylsulfilimines and -sulfoximines in high yields under transition-metal-free conditions. Imination of (R)-methyl p-tolyl sulfoxide proceeded with predominant retention of configuration at the stereogenic sulfur center. The Hammett plot afforded ρ values of -0.58 for para-substituted thioanisoles and -0.49 for their equivalent sulfoxides, which suggests a buildup of positive charge on the sulfur atoms of sulfides and sulfoxides in the transition state. Calculations suggest a bimolecular nucleophilic-substitution mechanism on the negatively charged nitrogen atom of the sulfonylimino- λ3-bromane, which involves the attack of a sulfide from the opposite side to bromine(III). © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reported here for the first time is the iodobenzene-catalyzed α-oxidation of ketones, in which diacyloxy(phenyl)-λ3-iodanes generated in situ act as real oxidants of ketones and m-chloroperbenzoic acid serves as a terminal oxidant. Oxidation of a ketone with m-chloroperbenzoic acid in acetic acid in the presence of a catalytic amount of iodobenzene, BF3·Et2O, and water at room temperature under argon affords an α-acetoxy ketone in good yield. p-Methyl- and p-chloroiodobenzene also serve as efficient catalysts in this direct oxidation. We found that when the reaction was carried out in the absence of a catalytic amount of iodobenzene, Baeyer-Villiger oxidation of a ketone took place. It is noted that use of water and BF3·Et2O is crucial to the success of this α-acetoxylation. Copyright © 2005 American Chemical Society.

The isolation, characterization, and reaction of the active species hydroxy(phenyl)iodonium ion with hypervalent bonding are reported. Reaction of iodosylbenzene with HBF4-Me2O in the presence of equimolar 18-crown-6 in dichloromethane afforded the hydroxy-λ3-iodane complex PhI(OH)BF4·18-crown-6 as stable yellow prisms. X-ray structure analysis indicated that both the close contacts between the iodine(III) and the three adjacent oxygen atoms of 18-crown-6, and the hydrogen bonding OH⋯O(crown ether) will be responsible for the increased stability of the complex as compared to the uncomplexed PhI(OH)BF4. The crown ether complex is highly reactive and serves as a versatile oxidant even in water: thus, the complex undergoes oxidative transformations of a variety of functional groups such as olefins, alkynes, enones, silyl enol ethers, sulfides, and phenols under mild conditions. Copyright © 2003 American Chemical Society.

Transition metal-catalyzed oxidative cleavage of carbon-carbon multiple bonds has emerged as a powerful tool in organic synthesis. High-valent oxometals, mostly of Ru, Os, Mn, Mo, W, and Re, were used catalytically as reactive oxygen transfer agents to the multiple bonds. Reported here for the first time are the organocatalytic versions of the oxidative cleavage reactions. Our method involves use of iodomesitylene as an effective organocatalyst, which generates an active aryl(hydroxy)-B3-iodane 5 in situ, and m-chloroperbenzoic acid (m-CPBA) as a terminal oxidant under metal-free conditions. Cyclic and acyclic olefins as well as aliphatic and aromatic alkynes were smoothly cleaved to carboxylic acids under the organocatalytic conditions. Copyright © 2009 American Chemical Society.

Reaction of 3-phenylpropanol with an activated iodosylbenzene - 18-crown-6 complex [Phl(OH)BF4-18C6] in dichloromethane in the presence of BF3-Et2O afforded directly the 6-chromanyl(phenyl)- λ3-iodane-18C6 complex through tandem oxidative intramolecular cyclization yielding chroman and its regioselectlve phenyl- λ3-iodanation. © 2007 American Chemical Society.

Oxidative cleavage of carbon–carbon double bonds to carbonyl compounds is an essential operation in organic synthesis. Ozonolysis is generally accepted as the standard method for this direct transformation. However, its utility is often limited by safety concerns. Use of high–valent oxometals such as RuO4, OsO4, and MeReO3 in combination with a number of oxygen donors as stoichiometric oxidants is suitable for the oxidative catalytic cleavage of olefins, but they are expensive and/or toxic. Therefore, the development of a safe and environmentally friendly procedure for the cleavage of carbon–carbon double bonds is highly desirable. In this review, we report a safe, environment–friendly, and heavy metal–free ozonolysis of olefins, which involves activated iodosylbenzene monomers, hydroxy–λ3–iodanes, as active species. Organocatalytic version of the oxidative cleavage of olefins that involves in situ generation of hypervalent aryl–λ3–iodanes as effective organocatalysts and the use of m–chloroperbenzoic acid as a stoichiometric terminal oxidant under metal–free conditions is described. Cyclic and acyclic olefins as well as aliphatic and aromatic alkynes were cleaved to carboxylic acids under the organocatalytic conditions.

Oxidation of 3-hydroxypiperidine with iodosylbenzene in water afforded 2-pyrrolidinone directly in good yields. The reaction probably involves oxidative Grob fragmentation yielding imino aldehyde, which upon hydrolysis produces 2-pyrrolidinone via a cyclization-oxidation sequence.

Oxidative rearrangement of benzyl alcohols with difluoro(p-trifluoromethylphenyl)-λ3-bromane (5 × 10-2 M) in chloroform at room temperature afforded aryl fluoromethyl ethers selectively in good yields, probably via 1,2-shift of aryl groups from benzylic carbon to oxygen atoms. © 2009 Elsevier Ltd. All rights reserved.

Reported here for the first time are the synthesis and characterization of supramolecular complexes between diaryl -lambda(3)-iodanes and 18-crown-6 (18C6). Slow evaporation of solvents afforded 1:1 and 2:1 complexes between Ph2IBF4 and 18C6 as stable crystals, depending on the conditions. X-ray crystal structures of these complexes indicated that each iodine atom contacts with the three adjacent oxygen atoms of 18C6 through two hypervalent secondary bonding and a weak interaction. H-1 NMR analyses and CSI-MS spectra showed that, in dichloromethane solution, Ph2IBF4 exclusively forms the 1:1 complex with 18C6 (binding constant K-a, 1.02 x 10(3) M-1). The binding constants decrease with the increased solvent donor ability (Gutmann's DN). Changing the heteroatom ligand from BF4 to the less nucleophilic PF6 and AsF6 increased the binding constant by about six times. Substitution of an electron-withdrawing group onto the para position of Ph2IBF4 tends to increase in the complex stability. A linear Hammett relationship (rho = 0.59) between log K-a and sigma(P)(+) values of substituents indicates that the diaryl-lambda(3)-iodanes with electropositive iodine(III) interact more efficiently with 18C6. Decreased binding magnitude was measured with 15C5, dibenzo-18C6, dibenzo-21C7, and dibenzo-30C10.