Alcohols, reaction with periodinanes

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. 

Alkenes can be transformed into epoxides by reaction with Ac-IBX (44), generated by reaction of Dess-Martin periodinane with water.506 As the oxidation of alcohols is quicker, it is normally possible to oxidize alcohols with no interference from alkenes. 

Like the Swem oxidation, the Dess-Martin periodinane (DMP) reagent oxidizes primary alcohols to aldehydes and secondary alcohols to ketones without using chromium or other heavy-metal compounds. The reaction with DMP takes place under mild conditions (room temperature, neutral pH) and gives excellent yields. The DMP reagent, which owes its oxidizing ability to a high-valence iodine atom, is a commercially available solid that is easily stored. 

The aminocyclitol moiety was synthesized in a stereocontrolled manner from cis-2-butene-l,4-diol (Scheme 40)112 by conversion into epoxide 321 via Sharpless asymmetric epoxidation in 88% yield.111 Oxidation of 321 with IBX, followed by a Wittig reaction with methyl-triphenylphosphonium bromide and KHMDS, produced alkene 322. Dihydroxylation of the double bond of 322 with OSO4 gave the diol 323, which underwent protection of the primary hydroxyl group as the TBDMS ether to furnish 324. The secondary alcohol of 324 was oxidized with Dess-Martin periodinane to... 

Upon deprotection of the benzyl group under hydrogenolysis conditions, and oxidation of the resulting primary alcohol to the corresponding aldehyde with Dess-Martin periodinane [74], compound 137 was obtained. Aldehyde 137 is the coupling partner for the NHK reaction with the vinyl iodide 82. 

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. 

Starting from l-(2-ethynylquinolin-3-yl)ethanone 140, available by subsequent Sonogashira reaction from 2-chloroquinoline, the Grignard reaction with MeMgBr to give a secondary alcohol, and Dess—Martin periodinane oxidation, a method was developed which provided 1-aminoacridines 141 (Scheme 53). On addition of secondary amines, enamines E formed under TiCl4 catalysis (method A), in the presence of molecular sieves... 

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]. 

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]. 

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]. 

Oximes are hydrolyzed to aldehydes and ketones with Dess-Martin periodinane in wet CH2CI2. This reaction competes with the oxidation of alcohols, so that selective oxime hydrolyses can be performed in the presence of alcohols.55 However, O-alkyloximes remain unaffected during the oxidation of alcohols.56... 

Examination by NMR of a solution, resulting from the oxidation of a homopropargylic alcohol with Dess-Martin periodinane, shows a clean reaction leading to an unstable unconjugated inone that isomerizes to an allene on contact with silica. 

The 2-(0-nitrobenzenesulfonamido)alcohol 359 was obtained from 358 through a sequence of reactions, which was then subjected to oxidation with Dess-Martin periodinane to give the 2-(t>-nitrobenzenesulfonamido)ketone 360 in 84% yield (Scheme 74). Upon reductive cyclization with hydrogen and palladium over activated carbon, 360 gave the 1,2,5-benzothiazepine 361 <2004T3349>. 

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