Alcohol periodinane

In contrast, periodinanes (i.e. iodoxo or iodine(V) reagents), preferably as the 1-hydroxy-(li-f)-benzo-l,2-iodoxol-3-one-l-oxide (2-iodoxybenzoic acid, IBX) [20, 21] or its acetylation product, the Dess-Martin reagent [22], have been widely used for oxidation of sensitive and complex alcohols. Periodinanes have not yet been prepared on a polymer support a silica-supported IBX has been reported recently [23]. 

The Dess-Martin periodinane ( DMP ) reagent, U,l-tris(acetyloxy)-l,l-dihydro-l,2-benziodoxol-3(l//)-one, has also been used in several complex syntheses for the oxidation of primary or secondary alcohols to aldehydes or ketones, respectively (e.g., M. Nakatsuka, 1990). It is prepared from 2-iodobenzoic add by oxidation with bromic add and acetylation (D.a Dess, 1983). 

A vanety of secondary alcohols with terminal trifluoromethyl group are oxidized by the Dess-Martin periodinane reagent [52 57] (equation 48)... 

The title compound is produced by treatment of 2-iodylbenzoic acid with acetic anhydride in acetic acid, and has found wide application as a mild oxidant ( Dess-Martin periodinane ) for ly and 2y alcohols. Although it appears not to be sensitive to impact, unlike the precursor acid, both explode violently when heated under confinement. The oxidant, on treatment with water is hydrolysed back to the explosive 2-iodylbenzoic acid. Forethought and caution are advised before using these explosive materials on any scale of working. 

Such reactions are also possible in vitro, as several mild oxidizing agents are at hand nowadays. Thus, the Dess-Martin periodinane (DMP) [50] has been proven to be a versatile and powerful reagent for the mild oxidation of alcohols to the corresponding carbonyl compounds. In this way, a series of new iodine(V)-mediated reactions has been developed which go far beyond simple alcohol oxidation [51], Ni-colaou and coworkers have developed an effective DM P-mediated domino polycy-clization reaction for converting simple aryl amides, urethanes and ureas to complex phenoxazine-containing polycycles. For example, reaction of the o-hydroxy anilide 7-101 with DMP (2 equiv.) in refluxing benzene under exposure to air led to polycycle 7-103 via 7-102 in a yield of 35 % (Scheme 7.28) [52]. 

After successful installation of the first two stereocenters, our attention was focused on elaboration of the terminal alkene in 64 (Scheme 6.9). Treatment with disiamylborane followed by oxidative workup afforded primary alcohol 65 in good yield (70-85 %). A side product containing a mixture of two diastereomers (66) was also observed and resulted from conjugate addition of the alkoxide formed during basic workup onto the unsaturated ester. Maintaining the temperature at 0 °C by a slow, dropwise quench during the oxidative workup was necessary to minimize the amount of the undesired cyclization product (66). Subsequent oxidation of the primary alcohol 65 using Dess-Martin periodinane [28] and a Pinnick oxidation afforded carboxylic acid 67 [29]. 

Several organohypervalent iodine reagents have been used for the oxidation of alcohols and phenols such as iodoxybenzene, o-iodoxybenzoic acid (IBX), bis(trifluoroa-cetoxy)iodobenzene (BTI), and Dess-Martin periodinane etc. But the use of inexpensive iodobenzene diacetate (IBD) as an oxidant, however, has not been fully exploited. Most of these reactions are conducted in high boiling DMSO or toxic acetonitrile media that results in increased burden on the environment. 

Oxidation of trijiuoromethylcarbinols.1 Oxidation of these alcohols to the corresponding ketones with usual oxidants requires rather drastic conditions and an excess of reagent, but can be effected with periodinane (4 equiv.) in CH,C12 at 25° within 3 hours. 

A very unusual Nazarov cyclization of propargyl vinyl ketones has been reported by Hashmi et al. (Eq. 13.16) [18]. Propargyl alcohol 50 was oxidized to ketone 51 with the Dess-Martin periodinane. Attempts to purify 51 by column chromatography on silica gel led to cyclopentenone 53 in 59% isolated yield. This suggests that the solid support catalyzed the isomerization of 51 to allenyl vinyl ketone 52, which was not isolated, but which underwent spontaneous cyclization to 53. This result is consistent with earlier observations of the great ease with which allenyl vinyl ketones undergo the Nazarov reaction (cf. 8, Eq. 13.2). 

Following a similar strategy, an ingenious mixed resin bed quench and purification strategy was devised for the Dess-Martin periodinane mediated conversion of alcohols to carbonyls. This hypervalent iodine oxidant was viewed as containing an inherent masked carboxylic acid functionality that was revealed at the end of the reaction (Species (11) Scheme 2.30). Therefore purification was easily achieved by treatment of the reaction mixture with a mixed-resin bed containing both a thiosulfate resin and a polymeric base. The thiosulfate polymer was used to reduce excess hypervalent iodine lodine(V) and (III) oxidation states species to 2-iodoben-zoic acid (11), which was in turn scavenged by the polymeric base [51]. 

To estimate the relative reactivity of allylic, benzylic, and nonconjugative aliphatic alcohols toward the Ar3BiCl2/DBU system, intermolecular competitive oxidations were examined. As summarized in Scheme 20, cinnamyl and benzylic alcohols were preferentially oxidized in the presence of ethyl alcohol. The chemos-electivities observed for the Ar3BiCl2/DBU oxidant (Ar = o-tolyl) are considerably higher than those achieved by Dess-Martin periodinane [83, 84]. 

Three equivalents each of alcohols were used. b Dess-Martin periodinane. 

Scheme 20 Chemoselective oxidation of alcohols with (o-TolbBiC -DBU and Dess-Martin periodinane [82]...

Efficient new methods for oxidation are always welcome. The Dess-Martin periodinane has become the workhorse for alcohol to aldehyde or ketone conversion in organic research labs around the world. Viktor V. Zhdankin of the University of Minnesota, Duluth has described (Chem. Commun. 2004, 106) a complementary family of reagents. Oxidation of an ester I of o-iodobenzoic acid with NaOCl delivers 2. Depending on the ester, the reagent 2 is soluble and an effective oxidant, with KBr catalysis, in a wide range of organic solvents. Presumably, the spent oxidant can be recovered and recycled. 

The purity of the Dess-Martin periodinane (2) was assayed by treatment of 2 (1 equiv) with an excess of benzyl alcohol (2 equiv) in methylene chloride (CH2CI2) followed by analysis of the reaction mixture for benzaldehyde by capillary vapor phase chromatography (15-m fused silica capillary column, Durawax DX3 stationary phase, 120°C). After correction for response factors, the purity was established to be >95%. 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

A vanety of secondary alcohols with terminal trifluoromethyl group are oxidized by the Dess-Martin periodinane reagent [52 53] (equation 48) Conversion of l,6-anhydro-4-0-benzyl-2 deoxy 2-fluoro-p-D-glucopyranose to the corresponding oxo derivative is earned out by ruthenium tetroxide generated in situ from ruthenium dioxide [54] (equation 49)... 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

A few years later,3 it was shown that o-iodoxybenzoic acid (36)—itself a precursor in the preparation of Dess-Martin periodinane—is able to oxidize very effectively alcohols in DMSO solution. o-Iodoxybenzoic acid—normally referred to as IBX—exists mainly as a cyclic form 37, which crystallizes as a polymer with very low solubility in most solvents with the exception of DMSO. Although, IBX (36) was already known in 1893,4 this ultracentenial reagent found very little use till very recently, when awareness about its solubility in DMSO was raised. 

In the foundational paper of Dess-Martin periodinane,2 it was shown that this compound is very efficient in the oxidation of alcohols in dichloro-methane solution at room temperature. While the alcohols are oxidized to the corresponding aldehydes and ketones, Dess-Martin periodinane is transformed into the organic iodinane 38 and acetic acid. 

Thus, impure samples of Dess-Martin periodinane containing 44 because of partial hydrolysis of Dess-Martin reagent or incomplete acetylation during its preparation can in fact perform much better during the oxidation of alcohols than very pure samples of Dess-Martin periodinane. Likewise, performing the oxidation in the air or using wet solvents may result in better yields because of the in situ generation of periodinane 44. 

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