Oxidations with IBX

A detailed investigation of IBX reactions with various vicinal diols revealed that, depending on the substrate and the reaction conditions, either oxidation to a-ketols or a-diketones, or oxidative cleavage of the C—C bond can occur (20070BC767). In DMSO solutions, IBX oxidatively cleaves strained and stericaUy hindered syn 1,2-diols, while the non-hin-dered secondary glycols are oxidized to a-ketols or a-diketones. The use of trifluoroacetic acid as a solvent leads to an efficient oxidative fragmentation of 1,2-diols of aU types (20070BC767). 

The IBX-promoted oxygenative dearomatization of phenols leading to cyclohexadienone systems is an especially important synthetic transformation (2010T2235). Representative examples include the use of EBX in key oxidation steps in the total synthesis of the resveratrol-derived polyphenol natural products (—)-hopeanol and (—)-hopeahainol A (2010JA7540), the synthesis of camosic add and camosol (2010CPB27), and the total synthesis of the bissesquiterpene (+)-aquaticol (2007ACE1533). 

Ar= Ph, 3-EtCeH4, 3-BrCeH4, 3-FC6H4, 4-EtC6H4, etc. R - R = H, alkyl, cycloalkyl, etc. 

Additional representative examples of synthetic applications of IBX include the following oxidative transformations (1) aromatization of 

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Functional Group and Protecting Group Sensitivity to Oxidations with IBX... 

Reactions Performed in situ During Oxidation With IBX... 

Sometimes, enones—obtained by oxidation of allylic alcohols—suffer Diels-Alder reactions during oxidations with IBX.106a... 

Martin periodinane to deliver the desired key intermediate, ketone 208. The total synthesis of 181 was finalized in two more steps (49% overall yield) by removal of the acetal and the MEM protective group with simultaneous formation of the desired intramolecular ketal 216, followed by cleavage of the Cl 1 TBDMS ether and in situ oxidation with IBX. The highly complex secondary metabolite 181 was thus accessed in 16 linear steps starting from 210 with an impressive 14% overall yield (Fig. 36). 

The involvement of an aldehyde-enolate as a ligand on IBX has also been postulated in a first oxidative C C bond cleavage reaction using IBX. N-Protected amino alcohols 14 have been oxidized with IBX in DMSO to the corresponding imides 15 [17]. 

The first total synthesis of the marine polycyclic ether toxin (-)-gambierol was accomplished in the laboratory of M. Sasaki. The introduction of the a,(3-unsaturation into the seven-membered H ring of the FGH tricyclic subunit proved to be problematic, because both the conventional selenium-based method and the Nicolaou oxidation with IBX failed. However, when the seven-membered ketone was treated with LiHMDS in the presence of TMSCI and EtsN, the corresponding silyl enol ether was formed, which was oxidized under Saegusa conditions to give the desired cyclic enone in high yield. Because of the small scale of the reaction, a large excess of Pd(OAc)2 was used in acetonitrile so the presence of a co-oxidant was not necessary. 

The following two substrates are subjected to solvolysis in aqueous alcohol and the resultant is subjected to oxidation with IBX. Write the product with full stereo-structure from each. 

Next, we performed the syntheses of cemuane-type alkaloids, cermizine D (90) and cemuine (86), from common key intermediate 91 (Scheme 19). The primary alcohol in 91 was oxidized with IBX to give the aldehyde, which, in turn, was subjected to the Wittig reaction without purification to afford 102. Mild acid... 

Despite the fact that IBX is insoluble in almost all solvents except DMSO, it oxidizes alcohols in other solvent combinations. THF is the preferred cosolvent to facilitate the solubility of alcohols that are insoluble in DMSO, and allow oxidation with IBX. In some cases, the oxidation occurs entirely in the absence of DMSO. Benzoin is oxidized to benzil by treatment with IBX in Thf.io... 

The mild oxidizing properties of IBX enhance its utility for the oxidation of compounds with sensitive functional groups such as thioethers and amines. Oxidation with IBX occurs cleanly in the presence of thioethers and 1,3-dithiolane protecting groups. For exan5)le, oxidation of thiochroman-4-ol, even with 10 equiv of IBX is achieved cleanly to give thiochroman-4-one with no detection of the analogous sulfoxide or sulfone by-products (eq 2). ... 

Similar to the oxidation of alcohols, secondary amines 857 can be oxidized with IBX in DMSO to yield the corresponding imines 858 in good to excellent yields (Scheme 3.342) [1175]. 

Several research groups have used ionic liquids for the oxidation of alcohols with o-iodoxybenzoic acid (IBX) or Dess-Martin periodinane (DMP). Alcohols undergo smooth oxidation with IBX or with DMP in hydrophilic [bmim]BF4 (structure 36, Figure 6.2) and hydrophobic [bmimjPFe (structure 37) ionic liquids at room temperature under mild conditions to afford the corresponding carbonyl compounds in excellent yields with high selectivity [54]. Similar results were obtained for the oxidation of alcohols with IBX and DMP using ionic liquid [bmim]Cl (l-butyl-3-methyUmidazoliumchloride) [55,56]. IBX- and DMP-promoted oxidations are faster in ionic liquids compared to conventional solvents such as DMSO, DMF, ethyl acetate and water. Recovery of the by-product iodosobenzoic acid is especially simple in ionic liquids. The recovered ionic liquids can be recycled in subsequent reactions with consistent activity. 

Porco has reported the gold(III)-catalyzed cydization of o-alkynylbenzaldehydes as a route to azaphilones and related compounds [40]. Toward this goal, treatment of o-alkynylbenzaldehyde 26 with a catalytic amount of Au(OAc)3 in a 10 1 DCE/TFA mixture led to quantitative formation of the benzopyrylium salt 27 within 1 min at room temperature (Scheme 12.7). In a preparative-scale reaction, gold(III)-catalyzed cydization of 26 followed by oxidation with IBX led to isolation of azaphilone 28 in 84% yield (Scheme 12.7). Similarly, the two-step cyclization/oxidation protocol was applied to the synthesis of a number of unnatural azaphilones. 

While the first two macromolecules 34 and 35 are obtained under very mild reaction conditions, heating of the multicomponent mixture was necessary for the last two products 36 and 37, where alcohols were employed instead of unstable aldehydes, which are in situ oxidized with IBX (as described in Section 8.3). The use of the more easily accessible alcohols in the last approach under oxidative conditions increases the possibilities of this reaction giving easy access to difficult frameworks, which would not be available otherwise because of the lack of stability of the aldehydes employed. 

When 90 was heated in toluene, the hydroxylamine added to the alkyne to afford nitrone 91 (after tautomerization of a presumed intermediate N-hydroxyenamine) which was trapped by styrene in an intermolecular 1,3-dipolar cycloaddition to provide 92. An oxidation state adjustment (with removal of the chiral auxiliary) gave 93. The TBDPS protecting group was removed and the resulting primary alcohol was oxidized with IBX (94) (related to the Dess-Martin periodinane) to give aldehyde 95. Application of the Yamamoto variation of the Peterson olefmation gave 96 with decent control over olefin geometry. 

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