Pyridinium dichromate, alcohol oxidation

Pyridine, methyltrioxorhenium hgands, 460-1 Pyridine-2,6-dicarboxylate (dipic), transition metal peroxides, 1060, 1061 Pyridinium dichromate, alcohol oxidation, 787-8... 

When suspended in CHjClj, pyridinium dichromate will oxidize primary alcohols to the corresponding aldehydes and no further ... 

Conditions that do pennit the easy isolation of aldehydes in good yield by oxidation of primaiy alcohols employ vaiious Cr(VI) species as the oxidant in anhydrous media. Two such reagents ar e pyridinium chlorochromate (PCC), C5H5NH ClCi03, and pyridinium dichromate (PDC), (C5H5NH)2 Ci207 both are used in dichloromethane. 

Oxidation of primary alcohols to aldehydes (Section 15.10) Pyridinium dichromate (PDC) or pyridinium chloro-chromate (PCC) in anhydrous media such as dichloromethane oxidizes primary alcohols to aldehydes while avoiding overoxidation to carboxylic acids. 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

A variety of oxidizing agents are available to prepare aldehydes from 1° alcohols such as pyridinium chlorochromate (PCC) and pyridinium dichromate (PDC). 

Adogen has been shown to be an excellent phase-transfer catalyst for the per-carbonate oxidation of alcohols to the corresponding carbonyl compounds [1]. Generally, unsaturated alcohols are oxidized more readily than the saturated alcohols. The reaction is more effective when a catalytic amount of potassium dichromate is also added to the reaction mixture [ 1 ] comparable results have been obtained by the addition of catalytic amounts of pyridinium dichromate [2], The course of the corresponding oxidation of a-substituted benzylic alcohols is controlled by the nature of the a-substituent and the organic solvent. In addition to the expected ketones, cleavage of the a-substituent can occur with the formation of benzaldehyde, benzoic acid and benzoate esters. The cleavage products predominate when acetonitrile is used as the solvent [3]. 

Upon hydrogenation of 24 a 1,2-rearrangement of the epoxide occurred generating aldehyde 25 as a mixture of diastereoisomers. After reaction with methyl lithium, the diastereomeric alcohols 26 and 27 were separated and isolated in yields of 23% and 71%. While alcohol 26 as the minor diastereo-isomer could be oxidized with pyridinium dichromate (PDC) and methyle-nated to give the enantiomer of kelsoene (cnM), its diastereoisomer 27 with the inverse configuration at C-7 required a supplementary epimerization step with sodium methanolate. The enantiomerically pure ent- allowed for the determination of the absolute configuration of natural kelsoene (1) [9, 10]. The previously reported assignment based on NMR-correlation experiments [5] was corrected. 

The BTSP-pyridinium dichromate system has proved to be effective for generation of the oxodiperoxochromium complex 22 in dichloromethane. As the peroxo complex decomposed easily, the oxidant BTSP was added dropwise to the reaction mixture using a syringe drive. The BTSP was stable enough even upon contact with the metallic surface of the syringe needle when it was diluted with dichloromethane. Typical results for the conversion of alcohols into carbonyl compounds are summarized in Table 7. 

One research group has exploited the concept of polymer site-isolation in a multistep/one-chamber solution-phase synthesis in which all the reagents, catalysts, and downstream reactants required for a multistep synthesis were combined in one reaction chamber. For instance, a one-chamber/three-step synthesis of substituted acetophenones has been reported (Scheme 10).84 An a-phenethyl alcohol was introduced into a reaction chamber containing the polymer-supported reagents and reactants necessary to accomplish oxidation by polymer-supported pyridinium dichromate 60 bromination by the A-26 perbromide resin 61 and nucleophilic displacement by the A-26 phenoxide resin 62. Filtration afforded the... 

The remaining three steps are accomplished without purification of the intermediate products. The secondary hydroxy group is protected by acetylation and the benzyl ether is removed by hydrogenolysis to provide a primary alcohol. The alcohol is oxidized to a carboxylic acid by ruthenium(III) chloride or pyridinium dichromate. This method has been applied to the synthesis of various enzyme inhibitors containing the 1-hydroxyethylene isostere. 

Popular oxidation reactions of peptide alcohols such as the Parikh-Doering or Dess-Martin in addition to older oxidation reactions such as Collins, pyridinium chlorochromate, or Swern oxidation afford racemization free productsJ9121415 37-39 Oxidations using pyridinium dichromate results in racemization and low yields of product.[l3 Oxidation reactions have also been utilized in semisynthetic pathways of peptide aldehydes (1) peptide aldehydes are obtained through the enzymatic acylation of a peptide ester to an amino alcohol with subsequent oxidation of the peptide alcohol to afford the aldehyde, and (2) peptide aldehydes can also be obtained by direct enzymatic oxidation of the peptide alcohol by alcohol de-hydrogenaseJ40 41 ... 

This oxidant is a bright-orange solid that is soluble in organic solvents, and very convenient to store and manipulate, because of its lack of hydro-philicity. Pyridinium dichromate (PDC), which is normally used in dichlor-omethane at room temperature, is a very efficient oxidant able to transform alcohols in aldehydes and ketones in high yield. The absence of water in the reaction media prevents the over-oxidation of aldehydes into carboxylic acids. 

General Procedure for Oxidation of Alcohols to Aldehydes and Ketones with Pyridinium Dichromate (PDC)... 

A compound prepared and first described as nicotinium dichromate (NDC) by Palomo et al.,379 was later shown by X-ray-crystal analysis380 to be a betainic mixed anhydride of nicotinic and chromic acid (NACAA). Because of its unique structure, it deserves a close scrutiny of its oxidative properties.381 Replacement of the chloride anion in the quaternary ammonium resin, Dowex 1-X8, for the dichromate anion, leads to a polymer supported dichromate, which is able to make selective benzylic oxidations.382 Finally, poly[vinyl(pyridinium dichromate)] (PVPDC), a polymeric analogue of PDC, must be mentioned whose use in the oxidation of alcohols allows for a very easy work-up.383... 

Chromium-based oxidants tend to react quicker with unsaturated alcohols, although the difference of oxidation speed with saturated alcohols is normally not sufficient for synthetic purposes. Nevertheless, the chromium-based reagent pyridinium dichromate (PDC) possesses a mildness and, therefore, a relative greater selectivity that allows its occasional employment for selective oxidations of allylic and benzylic alcohols.134... 

Note. (1) These reaction conditions are used for the oxidation of decan-l-ol, hexane-1, 6-diol and oct-2-yn-l-ol. In the case of alcohols where acid-sensitive groups are also present (e.g. tetrahydropyranyl ethers), sodium acetate is added to buffer the reaction mixture alternatively pyridinium dichromate may be used.99... 

In an alternative route,2 Boc-protected amino acids are reduced to the protected amino alcohol with borane-THF (45-95% yield) and pyridinium dichromate is used for oxidation to the aldehyde (75-90% yield). The optical rotations of the aldehydes obtained by these two procedures differ considerably, presumably owing to racemization encountered in the PDC oxidation. 

The initial a-addition adduct from the reaction of methyl (S)-2-isocyano-4-methylpentanoate 232 and protected (S)-alaninal 233 further reacted with benzoic acid to furnish 234 as a diastereomeric mixture. The stereochemistry of the resulting benzoyl-protected alcohol was inconsequent since the latter functionality is oxidized during the course of the synthesis using pyridinium dichromate to afford the a-oxoamide in the final target. In general, however, in isocyanide MCRs the control of the newly created stereogenic center is problematic and separation of diastereomeric mixtures cannot be avoided. A recent report by Denmark and Fan on a catalytic asymmetric variant of this reaction therefore represents an interesting development [119]. 

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