Alcohols, secondary, oxidation with pyridinium chlorochromate

After the known intermediate 79 (contaminated with ca. 6 % < /.v isomer) [39] was prepared from Hajos-Parrish ketone [40] 78, the tert-butyl ether was cleaved (quant.) and the ketone protected as the acetal (96 %). The secondary alcohol was oxidized by pyridinium chlorochromate (PCC) to provide ketone 80 in good yield (71 %) and after fractional crystallization afforded material absent of any m-hydrindane (Scheme 10.6). [NOTE All compounds shown in Schemes 10.6 and 10.7 are shown in the ent-configuration, as published]. The oxidation of protected hydrindane 80 under Saegusa-Ito conditions [41, 42] gave enone 81 (82 %), confirmed by X-ray crystallography. 

The secondary alcohol is readily oxidized with pyridinium chlorochromate (PCC)25 (65) which is commercially available or easily prepared by addition of pyridine to a solution of chromium(VI)-oxide in hydrochloric acid. 

A better reagent for the limited oxidation of primary alcohols to aldehydes is pyridinium chlorochromate (PCC), a complex of chromium trioxide with pyridine and HC1. PCC oxidizes most primary alcohols to aldehydes in excellent yields. Unlike most other oxidants, PCC is soluble in nonpolar solvents such as dichloromethane (CH2C12), which is an excellent solvent for most organic compounds. PCC can also serve as a mild reagent for oxidizing secondary alcohols to ketones. 

Reaction of the C-0 and O-H Bonds Primary alcohols oxidize to carboxylic acids secondary alcohols oxidize to ketones with chromium trioxide or sodium dichromate. Tertiary alcohols do not oxidize under mild conditions. With pyridinium chlorochromate (PCC) the oxidation of primary alcohols can be stopped at aldehydes. 

This section deals with oxidation reactions as an initiative step of the domino process in combination with many other organic transformations. In 2004, Snaith and coworkers [3] demonstrated a simple and efficient method to synthesize 3-substituted 4-piperidinones 4 using a domino oxidation/carbonyl-ene/oxidation reaction (Scheme 9.1). This domino reaction comprises oxidation of unsaturated alcohol 1 using PCC (pyridinium chlorochromate) to give the corresponding aldehyde 2, followed by a carbonyl-ene type reaction to yield the secondary cyclic alcohol 3, which was oxidized under the reaction conditions to give 3-substituted 4-piperidinones 4 in good yields. 

Pyridinium chlorochromate (PCC) Corey and Suggs prepared PCC by mixing CrOs with pyridine in HCl. PCC is used for the oxidation of primary and secondary alcohols in CH2CI2. This reagent is less efficient than Collins reagent for the oxidation of allyl alcohols. 

Pyridinium Chlorochromate. The need for improved oxidation of primary alcohols and greater ease for isolation of products prompted further research into the nature of Cr(VI) reagents. Corey found that addition of pyridine to a solution of chromium trioxide in aqueous HCl allowed crystallization of a solid reagent characterized as 31, pyridinium chlorochromate (PCC). This reagent was superior for the conversion of primary alcohols to aldehydes in dichloromethane but less efficient than the Collins oxidation when applied to allylic alcohols. Oxidation of 1-heptanol with PCC in dichloromethane gave 78% of heptanal, for example. As stated by Corey, PCC is an effective oxidant in dichloromethane although aqueous chlorochromate species are not very effective oxidants. Oxidation of secondary alcohols to ketones is straightforward, as in Banwell s synthesis of y-lycorane, in which 32 was oxidized by PCC to the ketone (33). ... 

A particularly hindered secondary alcohol (an intermediate in the latter stages of the synthesis of tetronolide) resisted oxidation with activated DMSO, Pyridinium Chlorochromate, and ac-tivatedMaji onese Dioxide, yet stoichiometric TPAP afforded the ketone in 81% yield. ... 

The uses of the versatile oxidant pyridinium chlorochromate have been reviewed. Pyridinium chlorochromate has been used for the oxidation of methyl 5-hydroxypentanoate to the aldehyde, an intermediate useful in the synthesis of leukotrienes, and the same reagent oxidatively cleaves secondary vicinal diols to the corresponding aldehydes. The reactivity of the chlorochromate ion as an oxidant can be influenced by the counter-ion. For example, the 4-dimethylaminopyridinium salt is a mild, selective reagent for the oxidation of allylic and benzylic alcohols. Pyridinium fluorochromate oxidizes primary and secondary alcohols to aldehydes and ketones respectively in dichloromethane solution, and shows a less pronounced acidity compared with the chloro-... 

In Summary Reductions of aldehydes and ketones by hydride reagents constitute general syntheses of primary and secondary alcohols, respectively. The reverse reactions, oxidations of primary alcohols to aldehydes and secondary alcohols to ketones, are achieved with chromium(Vl) reagents. Use of pyridinium chlorochromate (PCC) prevents overoxidation of primary alcohols to carboxylic acids. 

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