o-Iodoxybenzoic acid (IBX): a versatile reagent for the synthesis of N-substituted pyrroles mediated by β-cyclodextrin in water

o-Iodoxybenzoic acid (IBX), a very mild and efficient hypervalent iodine(V) reagent, aromatizes diversely substituted 1-benzylpyrrolidines and N-substituted l-proline analogues to the corresponding substituted pyrroles in good to excellent yields under mild conditions mediated by β-cyclodextrin in water at room temperature. To the best of our knowledge, this is the first report on IBX, promoting complete aromatization leading to N-benzylpyrroles from the corresponding saturated five membered heterocyclic derivatives in water medium.     

Oxidative oxo Diels–Alder Reactions of Baylis–Hillman Adducts with Electron-Rich Alkenes in the Presence of IBX

Baylis–Hillman adducts were oxidized by iodoxybenzoic acid (IBX) to 2-methylene-1,3-dicarbonyl compounds, which can act as oxodiene to react with electron-rich alkenes to generate a variety of oxo Diels–Alder adducts in good yields.     

Facile Deprotection of 1,3‐Oxathiolanes to Carbonyl Compounds with O‐Iodoxy Benzoic Acid (IBX) in the Presence of β‐Cyclodextrin in Water

1,3‐Oxathiolanes are smoothly deprotected to carbonyl compounds by IBX at room temperature with β‐cyclodextrin as a catalyst and water as solvent.     

o-Iodoxybenzoic acid mediated oxidative desulfurization initiated domino reactions for synthesis of azoles

A systematic exploration of thiophilic ability of o-iodoxybenzoic acid (IBX) for oxidative desulfurization to trigger domino reactions leading to new methodologies for synthesis of different azoles is described. A variety of highly substituted oxadiazoles, thiadiazoles, triazoles, and tetrazoles have been successfully synthesized in good to excellent yields, starting from readily accessible thiosemicarbazides, bis-diarylthiourea, 1,3-disubtituted thiourea, and thioamides.     

Stereoselective cyclization reactions of IBX-generated alkoxyamidyl radicals

In this paper, a method for the generation of alkoxyamidyl radicals is presented. These N-centered radicals can efficiently be formed starting from the corresponding acylated alkoxyamines using IBX as an oxidant. Stereoselective 5-exo and 6-exo reactions with these N-heteroatom-centered radicals leading to isoxazolidines and [1,2]oxazinanes are discussed. The N-O bond in the heterocycles can readily be cleaved with SmI(2) to provide N-acylated 1,3-amino alcohols.     

An Oxidation Study of Phthalimide-Derived Hydroxylactams

A systematic study of the oxidation of 3-hydroxy-2-substituted isoindolin-1-ones (hydroxylactams) and their conversion to the corresponding phthalimides was undertaken using three oxidants. Of special interest was the introduction of nickel peroxide (NiO₂) as an oxidation system for hydroxylactams and comparison of its performance with the commonly used pyridinium chlorochromate (PCC) and iodoxybenzoic acid (IBX) reagents. Using a range of hydroxylactams, optimal conversions of these substrates to the corresponding imides was achieved with 50 equivalents of freshly prepared NiO₂ in refluxing toluene over 5–32 h reaction times. By comparison, oxidations of the same substrates using PCC/silica gel (three equivalents) and IBX (three equivalents) required oxidation times of 1–3 h for full conversion but required lengthier purification. While nominal amounts (~25 mg) of substrate hydroxylactams were used to ascertain conversion, scale-up procedures using all three methods gave good to excellent isolated yields of imides.     

Mild One-Pot Deoximation and Conjugate Reduction of α, β-Unsaturated Ketoximes with Hydrosilane and I2O5

The organic chemistry of polyvalent iodine compounds has experienced an unprecedented development during the last decade of 20th century.[1,2] On the other hand, despite its extensive use in industry, I2O5 (iodine pentoxide, IP) has rarely been employed in organic synthesis except as an alternative to iodoxybenzoic acid (IBX) for the dehydrogenation of aldehydes and ketones.[3] Generally, pentavalent iodine reagents, such as IBX and Dess-Martin periodinane (DMP)were used as mild and selective oxidants for oxidation of alcohols[1,2] and dehydrogenation of carbonyl compounds.[3] We wish to report herein that IP can serve as a mild and efficient reagent for the oxidative cleavage of oximes to aldehydes and ketones (Eq. 1). Most interestingly, IP can also activate hydrosilanes for reduction of alkenes. Hence, simultaneous deoximation and conjugate reduction of α,β-unsaturated ketoximes can be achieved by using IP and phenyldimethylsilane (Eq. 2).     

6-Membered pseudocyclic IBX acids: syntheses, X-ray structural characterizations, and oxidation reactivities in common organic solvents

We designed and synthesized λ(5)-cyclic periodinanes 1 and 2, which are homologous to IBX (1-hydroxy-1-oxo-1H-1λ(5)-benzo[d][1,2]iodoxol-3-one) by one carbon, to thwart close packing of molecules in the crystal lattice to permit solubility in common organic solvents and to facilitate oxidations with enhanced reactivity. The X-ray crystal structures revealed that both 1 and 2 exist in the solid state as pseudocyclic (PC) acids, i.e., 1PC and 2PC, and that the molecules in the lattice are less weakly associated as compared to those in the parent IBX due to the twisting introduced via the sp(3) benzylic carbon. Both 1PC and 2PC are found to dissolve in palpable amounts in DCM and acetonitrile to allow oxidation of a variety of alcohols and sulfides to carbonyl compounds and sulfoxides in a facile manner. The subtle differences in the sterics due to methyl and ethyl substituents in 1PC and 2PC are found to manifest in contrasting reactivities in that the oxidations of alcohols occur faster with 2PC, while those of sulfides to sulfoxides occur more rapidly with 1PC.     

InCl3/IBX: a novel reagent system for the conversion of glycals into α,β-unsaturated δ-lactones

The combination of indium trichloride with iodoxybenzoic acid (IBX) has been utilized for the first time as a novel reagent system for the one-pot synthesis of 2,3-dideoxy-d-hex-2-enono-1,5-lactones from glycals. The reaction proceeds smoothly in aqueous media and the products are obtained in good yields. This method is suitable for the oxidation of glycals bearing olefin functionality.     

1H-1,3-diazepines, 5H-1,3-diazepines, 1,3-diazepinones, and 2,4-diazabicyclo[3.2.0]heptenes

Tetrazolo[1,5-a]pyridines/2-azidopyridines 1 undergo photochemical nitrogen elimination and ring expansion to 1,3-diazacyclohepta-1,2,4,6-tetraenes 3, which react with alcohols to afford 2-alkoxy-1H-1,3-diazepines 4 (5), with secondary amines to 2-dialkylamino-5H-1,3-diazepines 16, sometimes via isolable 2-dialkylamino-1H-1,3-diazepines 15, and with water to 1,3-diazepin-2-ones 19. The latter are also obtained by elimination of isobutene or propene from 2-tert-butoxy- or 2-isopropoxy-1H-1,3-diazepines 4 or 5. 1,3-Diazepin-2-one 22B and 1,3-diazepin-4-one 24 were obtained from hydrolysis of the corresponding 4-chlorodiazepines. Diazepinones 19 undergo photochemical ring closure to diazabicycloheptenones 25 in high yields. The 2-alkoxy-1H-1,3-diazepines 4 and 5 interconvert by rapid proton exchange between positions N1 and N3. The free energies of activation for the proton exchange were measured by the Forsén-Hoffman method as DeltaG([double dagger])298= 16.2 +/- 0.6 kcal mol(-1) as an average for 4a-c in CD2Cl2, acetone-d6, and methanol-d4, and 14.1 +/- 0.6 kcal mol(-1) for in 4c acetone/D2O. The structures of 2-methoxy-5,6-bis(trifluoromethyl)-1H-1,3-diazepine 4k, 1,2-dihydro-4-diethylamino-5H-1,3-diazepin-2-one 22bB, and diazabicycloheptanone were 26 determined by X-ray crystallography. The former represents the first reported X-ray crystal structure of any monocyclic N-unsubstituted 1H-azepine.     

Total synthesis of wasabidienones B1 and B0 via SIBX-mediated hydroxylative phenol dearomatization

The first total synthesis of the natural nondimerizing o-quinol (+)-wasabidienone B1 was achieved from commercially available 1,3,5-trimethoxybenzene. The key dearomatizing transformation was efficiently accomplished via a hydroxylative phenol dearomatization reaction using the stabilized lambda(5)-iodane reagent IBX (SIBX). (+)-Wasabidienone B1 was then converted into its congener (-)-wasabidienone B0 via an improved thermally induced ring-contracting isomerization reaction.     

IBX in an ionic liquid: eco-friendly oxidation of 17α-methylandrostan-3β,17β-diol, an intermediate in the synthesis of anabolic oxandrolone

An easily available hypervalent iodine(V) reagent, 2-iodoxybenzoic acid (IBX) immobilized in the ionic liquid [bmim][Br] was found to be an efficient and eco-friendly protocol for the oxidation of 17α-methylandrostan-3β,17β-diol (1). At ambient temperature oxidation of 1 with IBX gave mestanolone (2) in good yield and with an increased stoichiometric amount of IBX, oxidation adjacent to the carbonyl functionality (α,β-unsaturation) occurred to give dehydrogenated 17β-hydroxy-17α-methyl-Δ¹-androsten-3-one (3) as the major product in a one-pot reaction. The product is easily obtained by extraction with diethyl ether and evaporation of the solvent.     

Synthesis of N-confused porphyrin derivatives with a substituted 3-C position

Active methylene compounds such as 5,5-dimethylcyclohexane-1,3-dione, cyclohexane-1,3-dione, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, 1,3-dimethyl-1H-pyrazol-5(4H)-one, and 3-methylisoxazol-5(4H)-one react with the 3-C position of N-confused porphyrin in THF for 5 min to afford a novel type of N-confused porphyrin derivatives in good yield without the need of any catalyst.     

Practical azidation of 1,3-dicarbonyls

An operationally simple, direct azidation of 1,3-dicarbonyl compounds has been developed. The reaction proceeds readily under ambient conditions using sodium azide and an iodine-based oxidant such as I(2) or 2-iodoxybenzoic acid (IBX)-SO(3)K/NaI. In particular, the latter method, as a new and well-balanced oxidizing agent, shows excellent functional group tolerance and substrate scope and thus allows access to a variety of tertiary 2-azido and 2,2-bisazido 1,3-dicarbonyl compounds that would be more difficult to access by using traditional methods. Because the azide-containing products easily undergo 1,3-dipolar cycloaddition with alkynes, our report represents a novel route to analogues of sensitive complex molecules.     

Structure-activity relationships of 1,3-benzoxazole-4-carbonitriles as novel antifungal agents with potent in vivo efficacy

A series of 1,3-benzoxazole-4-carbonitriles was synthesized and evaluated for its antifungal activity, solubility, and metabolic stability. Among those compounds, 4-cyano-N,N,5-trimethyl-7-[(3S)-3-methyl-3-(methylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamide (16b) exhibited potent in vitro activity against Candida species, higher water solubility, and improved metabolic stability compared to lead compound 1. Compound 16b showed potent in vivo efficacy against mice Candida infection models and good bioavailability in rats.     

Nitromethane with IBX/TBAF as a nitrosating agent: synthesis of nitrosamines from secondary or tertiary amines under mild conditions

Aliphatic or aromatic N,N-disubstituted nitrosamine was generated in fair to excellent yield from the reaction of a secondary or tertiary amine with o-iodoxybenzoic acid (IBX) or o-iodosylbenzoic acid (IBA)/R(4)NX (X = halide) and nitromethane. The product yield was strongly influenced by both the halide of R(4)NX and iodanes. IBX gave a higher yield than IBA, while the halides follow F(-) > Cl(-) > Br(-) ～ I(-). Nitrous acid formed in situ from nitromethane and IBX (or IBA)/halides is likely responsible for the observed reaction.     

Pd-catalyzed ring opening of oxa- and azabicyclic alkenes with aryl and vinyl halides: efficient entry to 2-substituted 1,2-dihydro-1-naphthols and 2-substituted 1-naphthols

An efficient syntheses of 2-substituted 1,2-dihydro-1-naphthols and 2-substituted 1-naphthols has been developed that involves the sequential palladium-catalyzed ring opening of oxabicyclic alkenes with aryl and vinyl halides followed by oxidation of with IBX. In the first step of the sequence, a combination of Pd(OAc)2, PPh3, Zn, and PMP in dry DMF was employed to catalyze the ring opening of 7-oxabenzonorbornadienes with aryl and vinyl halides to afford the corresponding cis-2-substituted 1,2-dihydronaphthols in good to excellent yields. These reactions occurred under very mild conditions with a variety of aryl halides bearing electron-withdrawing or -donating groups. Similarly, a 7-azabenzonorbornadiene substituted with an electron-withdrawing group on the nitrogen atom underwent facile ring-opening reaction with aryl halides to provide cis-2-substituted (1,2-dihydro-1-naphthyl)carbamates in excellent yields. Oxidation of the intermediate 1,2-dihydro-1-naphthols using IBX yielded the corresponding 2-substituted 1-naphthols in good to excellent yields.     

An effective and catalytic oxidation using recyclable fluorous IBX

Oxidation of alcohols in the presence of a catalytic amount of fluorous IBX and Oxone as a co-oxidant resulted in the corresponding carbonyl compounds in good to high yields. The fluorous IBX is readily recovered as insoluble fluorous IBA from the reaction mixture by simple filtration, and can be reused without significant loss of the catalytic activity.     

In situ generation of o-iodoxybenzoic acid (IBX) and the catalytic use of it in oxidation reactions in the presence of Oxone as a co-oxidant

[structure: see text] Catalytic use of o-iodoxybenzoic acid (IBX) in the presence of Oxone as a co-oxidant is demonstrated for the oxidation of primary and secondary alcohols in user- and eco-friendly solvent mixtures. Also demonstrated is the in situ (re)oxidation of 2-iodosobenzoic acid (IBA) and even commercially available 2-iodobenzoic acid (2IBAcid) by Oxone to IBX allowing one to use these less hazardous reagents, in place of potentially explosive IBX, as catalytic oxidants.     

2-Iodoxybenzoic acid--a simple oxidant with a dazzling array of potential applications

Since its discovery by Christoph Hartmann and Victor Meyer in 1893, 2-iodoxybenzoic acid (IBX) has emerged as a rather ubiquitous oxidant for organic synthesis. The past decade has seen the development of a large variety of applications that go far beyond the simple oxidation of alcohols. This Review is concerned with the synthetic potential of IBX, with particular emphasis on uncommon reactivity patterns and novel fields of application.