Efficient access to orthoquinols and their [4 + 2] cyclodimers via SIBX-mediated hydroxylative phenol dearomatization

SIBX, the nonexplosive formulation of the lambda5-iodane 2-iodoxybenzioc acid (IBX), safely and efficiently mediates the hydroxylative dearomatization of various 2-alkylphenols and napthols into orthoquinols or their [4 + 2] cyclodimers. Reactions are typically run at room temperature using SIBX as a suspension in THF. Using these conditions, natural products such as the cyclodimer of the terpene carvacrol and, for the first time, the shikimate-derived (+/-)-grandifloracin were prepared in one step from their respective phenolic precursor.     

Safe oxidation of sulfides into sulfoxides using SIBX

SIBX is a stabilized (i.e., nonexplosive) formulation of the λ⁵-iodane 2-iodoxybenzoic acid IBX that can be used as a suspension in various organic solvents to oxidize safely sulfides into sulfoxides. Most yields are comparable to those obtained using IBX or other iodanes such as PhIO and PhIO₂. An asymmetric version of this SIBX-mediated sulfoxidation was performed in high chemical yield and moderate enantioselectivity by simple addition of an external chiral source.     

Pyridinium o-iodoxybenzoate as a Safe form of a Famous Oxidant

The stable pyridinium salt of o-iodoxybenzoic acid (PIBX) that is easy to obtain can serve as a convenient substitute of IBX as an oxidant. PIBX is safer, has neutral properties behaves as an equivalent to IBX in the oxidation of alcohols to ketones or aldehydes in polar solvents (DMF, DMSO), and provides higher oxidation rate in THF due to better solubility.     

Hypervalent iodine-mediated oxygenative phenol dearomatization reactions

Both λ³- and λ⁵-iodanes have proven to be useful reagents in the oxygenative dearomatization of phenols, and exploitations of their chemistry in the conception of both substrate- and reagent-controlled asymmetric variants of such a transformation of great value for natural product synthesis have shown evident signs of success. Moreover, the use of stabilized IBX (i.e., SIBX) in our methodology for O-demethylation of 2-methoxyphenols, which relies on the same key oxygenating dearomatization event, is reported here to be much more efficacious than that of IBX itself in the chemoselective one-step conversion of homovanillyl alcohol into hydroxytyrosol, and bergenin into norbergenin.     

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.     

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.     

Enhancing 2-iodoxybenzoic acid reactivity by exploiting a hypervalent twist

A rearrangement of hypervalent bonds, or twisting, proves to be the rate-determining step in the 2-iodoxybenzoic acid (IBX) oxidation of alcohols. From this insight, derived from density functional theory calculations, we explain why IBX oxidizes large alcohols faster than small ones and propose a modification to the reagent predicted to make it more active.     

2-Methyl-2-propanol as solvent for o-iodoxybenzoic acid (IBX) oxidation of 1? alcohols to aldehydes

2-Methyl-2-propanol has been demonstrated to be an effective solvent for IBX oxidation of 1? alcohols to the corresponding aldehydes. IBX has a measurable, but low, solubility in 2-methyl-2-propanol and thus partially avoids the drawbacks inherent in the solubility problems associated with IBX without resorting to less desirable solvents. This may be particularly useful where solubility of the alcohol is also at issue.     

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.     

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).     

A new method for the synthesis of Z-enediones via IBX-mediated oxidative rearrangement of 2-alkynyl alcohol systems

o-Iodoxybenzoic acid (IBX) was found to mediate the conversion of alpha-alkynyl alcohols into Z-enediones under notably mild conditions via a novel rearrangement mechanism (33-65% yield, 13 examples).     

A facile route to a polymer-supported IBX reagent

A three-step preparation of a polymer-supported IBX reagent from poly(p-methylstyrene) is reported. This reagent has been used successfully for the efficient oxidation of a series of alcohols to the corresponding aldehydes.     

IBX-mediated one-pot synthesis of benzimidazoles from primary alcohols and arylmethyl bromides

A variety of primary alcohols are shown to be converted to the corresponding benzimidazoles in one pot by employing IBX and o-phenylenediamine in DMSO at room temperature. o-Iodobenzoic acid is the end product of IBX, which is employed in 1.0 equiv. Arylmethyl bromides are also shown to be converted likewise to benzimidazoles in moderate yields in one pot, albeit at slightly elevated temperatures.     

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.     

Macroporous polystyrene-supported IBX amide: the improved oxidative properties in various solvents

In this study, macroporous polystyrene-supported IBX (MPS-IBX) amides were prepared in two simple steps, and the polymeric reagent was then evaluated for its efficiency in converting a range of alcohols to the corresponding carbonyl compounds in various solvents. The results indicated that the MPS-IBX amides were compatible with a variety of solvents, and had a more efficient oxidation activity toward alkyl alcohols than the gel type polystyrene-supported IBX amides. Finally, the resin that was consumed in the oxidation reaction was regenerated to give a restored loading level of 0.44-0.54 mmol/g.     

A new route to optically pure highly functionalized tetrahydro-isoquinolines with a quaternary carbon stereocenter

A facile synthesis of highly substituted, optically pure tetrahydro-isoquinolines with a quaternary carbon stereocenter is described. Glycolic cleavage of 1,2-dihydroxy-hexahydro-pyrrolo-isoquinolines 1 affords a mixture of cyclic hemiacetals, which can be converted via intramolecular chemoselective Cannizzaro reaction into respective β-amino alcohols, whereas the IBX oxidation gives N-formyl aldehydes. We have demonstrated the utility of such synthons by the synthesis of (+)-6,7-dimethoxy-salsoline-1-carboxylic acid and its new 1-phenyl analogue.     

Simple preparation of polymer supported IBX esters and amides and their oxidative properties

Novel polymer supported IBX esters and amides were prepared in two steps, which were the coupling of 2-iodobenzoic acid to a hydroxy or amino polystyrene followed by activation of the intermediate product. These polymer supported reagents were tested as oxidants by the conversion of a series of alcohols to the corresponding aldehydes or ketones. We found that the polymer supported IBX amides displayed excellent oxidative activity, in that they oxidized benzyl alcohol to benzaldehyde completely within 1 h at an oxidant to alcohol ratio of 2 to 1.     

A simple and advantageous protocol for the oxidation of alcohols with O-iodoxybenzoic acid (IBX)

[reaction: see text] An efficient, user-friendly procedure for the oxidation of alcohols using IBX is described. Simply heating a solution of the alcohol in the presence of suspended IBX followed by filtration and removal of the solvent gives excellent yields of the corresponding carbonyl compounds. We illustrate this procedure with a panel of primary and secondary alcohol substrates and note that it allows recycling and reuse of the oxidant.     

Mild oxidation of alcohols with o-iodoxybenzoic acid (IBX) in water/acetone mixture in the presence of beta-cyclodextrin

A mild and efficient oxidation of alcohols with o-iodoxybenzoic acid (IBX) catalyzed by beta-cyclodextrin in a water/acetone mixture (86:14) has been developed. A series of alcohols were oxidized at room temperature in excellent yields.