Alcohols oxidation with pyridinium dichromate

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. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

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 ... 

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

The secondary alcohol was smoothly oxidized to a ketone in high yield with pyridinium dichromate in dimethylformamide (cf 36). The IR spectrum indicated the presence of a ketone group bonded to the a-carbon of a thiophene (absorption at 1660 cm 1). The 200 MHz XH NMR spectrum showed all the features expected of this structure (cf Figure 12) as did the mass spectrum (cf. 1). 

The first issue confronted by Myers was preparation of homochiral epoxide 7, the key intermediate needed for his intended nucleophilic addition reaction to enone 6. Its synthesis began with the addition of lithium trimethylsilylacetylide to (R)-glyceraldehyde acetonide (Scheme 8.6).8 This afforded a mixture of propargylic alcohols that underwent oxidation to alkynone 10 with pyridinium dichromate (PDC). A Wittig reaction next ensued to complete installation of the enediyne unit within 11. A 3 1 level of selectivity was observed in favour of the desired olefin isomer. After selective desilylation of the more labile trimethylsilyl group from the product mixture, deacetalation with IN HC1 in tetrahydrofuran (THF) enabled both alkene components to be separated, and compound 12 isolated pure. 

Primary alcohol groups can be exclusively oxidized to aldehyde groups with pyridinium dichromate [149,150] and to carboxyl groups with the 2,2,6,6-tetramethyl-1-piperidine oxoammonium ion (TEMPO) [151]. The aldehydes can then be reduced to primary alcohols by reaction with NaB H4 [150,152], giving radiolabeled H-starch and the carboxyl group can be inverted by the action of Azotobacter vinlandii poly- 8-D-marmuronic acid C-5-epimerase to give L-iduronic acid [153]. 

Sharpless also found that this reaction works with only a catalytic amount of titanium-tartrate complex because the reaction products can be displaced from the metal centre by more of the two reagents. The catalytic version of the asymmetric epoxidation is well suited to industrial exploitation, and the American company J. T. Baker has employed it to make synthetic disparlure, the pheromone of the gypsy moth, by oxidation of the epoxy alcohol to an aldehyde with pyridinium dichromate (PDC) (p. 543), Wittig reaction (p. 689), and hydrogenation. 

Corey has reported the oxidation of allylic alcohols to a,/3-unsaturated aldehydes with pyridinium dichromate in DMF, DMAc, and DMSO. ... 

Enones can be converted into their 2-halo derivatives by reaction of their a-seleno derivatives (generated in situ) with further selenating agent [equation (40)]. Complexes of a-acetylenic alcohols and iodine are oxidized by pyridinium dichromate to a-iodo-enones [equation (41)]. ... 

Primary and secondary hydroxyl groups can be mildly oxidized to carbonyl groups (aldehydes or ketones) by reaction with pyridinium dichromate. Primary tosyl groups can also be oxidized to aldehydes by reaction with DMSO in collidine. Primary hydroxyl groups can be mildly and selectively oxidized, in the presence of secondary alcohols, to carboxyl groups by reaction with 2,2,6,6-tetram-ethyl-1-piperidine oxoammonium ion (TEMPO) to form uronic acids. Uronic acid carboxyl groups can be reduced to primary alcohols by reaction with car-bodiimide and sodium borohydride. 

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. 

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]. 

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. 

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