IBX oxidation

Figure 4.11. Examples of redox-initiated radical reactions. Samarium diiodide reduction of the bromide gives a radical that cyclizes faster than the second reduction reaction. Manganese triacetate oxidation of the P-keto ester gives an enol radical that is not further oxidized by the manganese reagent. The IBX oxidizes anilides to the corresponding radicals. Hexamethylphosphoramide = HMPA and Tetrahydrofuran = THE.

The closely related o-iodylbenzoic acid (IBX) and Dess-Martin oxidations have proved to be effective methods for the synthesis of peptide aldehydes (Table 7, Scheme 6) 9 38 39] 2-Iodobenzoic acid is oxidized by potassium bromate to form 2-iodylbenzoic acid (IBX), which can be used directly for IBX oxidation. IBX can be further treated with acetic anhydride and TosOH at 100 °C for 40 minutes to form the more stable Dess-Martin periodinane reagent 45 46]... 

The IBX oxidation of protected glutamine derivatives such as Z-Leu-Phe-Gln(Trt)[CH2OH] afford linear Z-Leu-Phe-Gln(Trt)-H in 93% yield. It should be noted that oxidation of nonprotected glutamine derivatives such as Z-Leu-Phe-Gln[CH2OH] typically result in equilibration between Z-Leu-Phe-Gln-H and the predominate cyclic hemiaminal form. The oxidation of protected glutamine derivatives such as Z-Leu-Phe-Gln(Trt)[CH2OH] afford only linear Z-Leu-Phe-Gln(Trt)-H 38]... 

Normally, IBX is dissolved in DMSO for the oxidation of alcohols and the reaction is carried out at room temperature.3 Sometimes, the addition of co-solvents causes the precipitation of IBX, resulting in a slower but still efficient oxidation that nonetheless, normally would need heating.83 In fact, IBX oxidations can be carried out using suspensions of IBX in a solvent other than DMSO, in which IBX is virtually insoluble.83,8811 A substantial acceleration can be achieved by adding a few equivalents of DMSO. 

There is an initial fast equilibrium in which the alcohol interacts with IBX, leading to a small concentration of intermediate 45. This intermediate evolves slowly to IBA and the desired carbonyl compound. As expected, the presence of water displaces the initial equilibrium to the left and produces a decrease on the oxidation speed. Thus, although IBX oxidations can be made in the presence of water, it is better to perform them under dry conditions for maximum velocity. 

An enone obtained by IBX oxidation suffers an in situ intramolecular Diels-Alder reaction. Dess-Martin periodinane produces partial desilylation of the TIPS ether due to its slightly ... 

For the reduction and quantitative removal of iodine species after IBX oxidations by a thiosulfate resin, see J. J. Parlow, B. L. Case, M. S. South, Tetrahedron 1999, 55, 6785-6796. 

Methyldihydroisocoumarin can be obtained via IBX oxidation of the corresponding chroman-2-ol, albeit in poor yield <2004TL309>. 

IBX-oxidations of unsaturated TV-aryl amides and urethanes proceed more efficiently and provide access to a substantial variety of pyrrolidinones and oxazolidinones, examples of which are shown in Scheme 92 (00AGE625, 01AGE202, 02JA2233). 

Dess-Martin- Qxio6xmnQ (DMP, 73) is an oxidizing agent that oxidizes the alcohol at C-7 to the corresponding ketone. The mechanism of this transformation is similar to that of the IBX oxidation shown earlier. 

This chapter concentrates on a novel type of IBX oxidation of silyl enol ethers 8 for the synthesis of a,P-unsaturated carbonyl compounds 9. 

It is important to note that tertiary alcohols do not interfere with IBX oxidations. Furthermore, it has been shown that pyridine and furan rings and double bonds, both conjugated and isolated are not affected with IBX. 

Frigerio and Santagostino6 also demonstrated that 5 smoothly oxidizes 1,2-diols to a-ketols or a-diketones without oxidative cleavage of the glycol bond (12 —> 13 14 —> 15). The IBX oxidations were conducted in DMSO solution at room temperature. 

Oxidation of Alcohols to Aldehydes and Ketones. Hyper-valent iodine compounds have powerful oxidizing capabilities. However, IBX possesses different properties than many similar oxidants, such as the related analogs iodoxybenzene and m-iodoxybenzoic acid. Until recently, the major application of IBX was its use in DMSO for the oxidation of primary alcohols to aldehydes at room temperature, without the danger of over-oxidation to carboxylic acids. The related iodo-oxy reagents oxidize benzyl alcohols to benzaldehydes at elevated temperatures in benzene (80 °C, 5-10 h) or in acetic acid (rt, 24 h), while IBX oxidizes the same compounds in 15 min (or less) at room temperature. IBX is equally effective for the oxidation of secondary alcohols to ketones under analogous conditions. Even sterically hindered alcohols are readily oxidized. Bomeol undergoes smooth oxida-... 

Goddard and Su have investigated theoretically the mechanism of alcohol oxidation with 2-iodoxybenzoic acid (IBX) on the basis of density functional quantum mechanics calculations [134], It has been found that the rearrangement of hypervalent bonds, so-called hypervalent twisting, is the rate-determining step in this reaction. Based on this mechanism, the authors explain why IBX oxidizes large alcohols faster than small ones and propose a modification to the reagent that is predicted to make it more active [134]. 

The IBX oxidation of diol 836 has been utilized in the synthesis of the functionalized hexahydroanthracene dione 837 (Scheme 3.331), a model for the D ring of taxoids [1136]. 

The IBX oxidation of carbohydrate 840 has been employed in synthetic studies of moenomycin A disaccharide analogs (Scheme 3.333) [1138],... 

The synthetic advantages of IBX oxidation procedure were employed in the one-pot synthesis of benzimidazoles 36 (Scheme 6.11), in which in situ generated aldehydes 34 were further reacted with o-phenylenediamine 35. Products were obtained in high yield within 2-3 h of milling. For this procedure, timing of the diamine addition to the reaction mixture was not given (prior to the milling, or after initial aldehyde formation). 

Another procedure involving IBX and ball milling could be effected, namely deprotection of dithianes 46 to prepare aldehydes (Scheme 6.16). Both aromatic and aliphatic aldehydes were prepared by Mai [ 10] employing this reaction protocol in high yield within 45 min to 1.5h, using the oxidation procedure described for IBX oxidation of alcohols to aldehydes (Z1O2 jar and ball, in Retsch MM 200 mill). 

Because the position of carbonyl group of the compound 3.64 deviated from the natural product, selectively hydrogenation was necessary for further conversion. However, compound 3.65 was the only product obtained under the palladium-carbon catalytic hydrogenation condition, whose double bond was hydrogenated (90 % yield). Compound 3.65 was separated to obtain 3.66 in 70 % yield via IBX oxidizing. 

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