Pyridinium Dichromate1

[20039-37-6]  · C10H12Cr2N2O7  · Pyridinium Dichromate  · (MW 376.24)

(mild and selective oxidizing agent for primary and secondary alcohols;2a can oxidize unsaturated tertiary alcohols,2b silyl ethers,11 the carbon-boron bond,20 and oximes23)

Alternate Name: PDC.

Physical Data: mp 152-153 °C

Solubility: sol DMF, DMSO, acetonitrile; sparingly sol dichloromethane, chloroform, acetone; insol hexane, ether, ethyl acetate.

Form Supplied in: bright orange solid; widely available.

Handling, Storage, and Precautions: the dry solid can be stored in contact with air. Reaction solvents must be anhydrous and free of reducing impurities. Pyridinium dichromate is reported to be a cancer suspect agent. The reagent should be used in a fume hood.

Oxidation of Primary and Secondary Alcohols.

PDC is an oxidizing agent complementary to Pyridinium Chlorochromate (PCC) for alcohols containing acid-sensitive groups. PDC is less acidic than pyridinium chlorochromate, and has more neutral character than the Collins reagent (Dipyridine Chromium(VI) Oxide). PDC is reported to exhibit greater oxidation efficiency than the Collins reagent, especially for large scale preparations. Initially, PDC was used either as a solution in DMF or as a suspension in dichloromethane. In solution in DMF, PDC oxidizes primary and secondary allylic alcohols to the corresponding a,b-unsaturated carbonyl compounds (eqs 1 and 2). Overoxidation of primary allylic alcohols is not observed, and (E)-(Z) isomerization does not take place.2a

Under similar conditions, saturated primary alcohols and aldehydes yield carboxylic acids. The preparation of carboxylic acids from primary alcohols (via the aldehyde intermediate) is usually achieved using 3.5 equiv of PDC at rt for 7-9 h (eqs 3 and 4).2a

An interesting example of the mildness of PDC is the oxidation of citronellol to the corresponding acid in 83% yield. The same oxidation with acidic PCC is complicated by cationic cyclization of the aldehyde intermediate. Aliphatic methyl esters can be directly prepared from aldehydes by oxidation with PDC (6 equiv) in the presence of methanol in yields of 60-80%. This method is not useful for aromatic aldehydes or higher esters.3 Saturated secondary alcohols are rapidly and conveniently converted into ketones, even in the presence of very sensitive groups, such as a thioacetals.

In suspension in dichloromethane, PDC shows considerably different behavior, becoming a milder and selective reagent for the preparation of both saturated and unsaturated aldehydes and ketones (eqs 5-7). Allylic alcohols are oxidized faster than saturated ones, but some (E)-(Z) isomerization is observed.2a

PDC does not attack isolated alkenic and alkynic bonds; in fact, o-alkynyl alcohols are oxidized by PDC in dichloromethane to the corresponding o-alkynyl carbonyl compounds in good yield (eq 8).4

PDC and PCC may show a different chemoselectivity. Thus PDC oxidizes the secondary hydroxyl groups of 5-bromo-2-furylcarbinols to the corresponding ketones in 80% yield, while PCC attacks the furan ring giving g-hydroxy D2-butenolides (eq 9).5

Several modified procedures have been employed to enhance the rate and the efficacy of PDC. Addition of pyridinium trifluoroacetate (0.4 equiv) causes an increase in the reaction rate, and less oxidant is necessary for oxidation (eq 7). Molecular Sieves enhance the oxidation rate with a wide variety of substrates.6 A combination of PDC, molecular sieves, and Acetic Acid has a dramatic effect on the oxidation of carbohydrate alcohols, reducing oxidation time from days to minutes (eq 10).7 Furthermore, the addition of acetic acid has been utilized for the selective oxidation of secondary allylic alcohols in carbohydrates (eq 11).8

The PDC-Acetic Anhydride combination gives rise to a strong and neutral oxidant. This system (0.6-0.7 equiv of PDC and 3 equiv of Ac2O) can be used for the selective oxidation of primary and secondary alcohols of carbohydrates to the corresponding carbonyl compounds in high yields. The addition of DMF as cosolvent to the reaction mixture prevents overoxidation (eq 12).9 Interestingly, the PDC-Ac2O combination is able to perform an oxidative fragmentation of 5-hydroxymethyl groups in 2,3-O-isopropylidene nucleosides to form the corresponding g-lactone nucleosides, albeit in moderate yield (eq 13).10

Oxidation of primary and secondary alcohols to carbonyl compounds can be carried out with PDC-Chlorotrimethylsilane, which is a rapid and selective oxidant.11 This combined reagent system can effect the deprotection-oxidation of silyl ethers and enol silyl ethers. Primary and secondary trimethylsilyl and t-butyldimethylsilyl ethers, usually stable to PDC, may be converted by the above combination directly into the corresponding carbonyl groups in high yields (eq 14). The method can be applied to the preparation of quinones from hydroquinone silyl ethers (eq 15) with higher efficiency than that using PCC and this reagent is applicable to substrates both with electron-donating and electron-withdrawing groups.11

Catalytic PDC Oxidation of Alcohols.

PDC can be utilized as a catalytic oxidant when coupled with Bis(trimethylsilyl) Peroxide as cooxidant. The method has proven to be mild and useful not only for the oxidation of a wide range of primary and secondary alcohols, saturated and unsaturated, but also for the conversion of homoallylic alcohols to the corresponding b,g-enones (eq 16).12

Oxidation of Cyanohydrins.

Cyanohydrins of nonconjugated aldehydes are oxidized to carboxylic acids by PDC-N,N-Dimethylformamide in excellent yields. Cyanohydrins from a,b-enals (as the O-trimethylsilyl derivatives) behave differently, being converted by PDC-DMF into a,b-unsaturated g-lactones (D2-butenolides), in cases in which the b-carbon is disubstituted and the g-carbon possesses at least one hydrogen. This reaction is performed with PDC (3 equiv) in DMF at rt for 12 h, and provides a mixture of two isomeric D2-butenolides, whose ratio (4:1) indicates that oxidative attack at the g-methyl is favored over the g-methylene (eq 17).13

Oxidation of Activated Methylene Groups.

PDC can perform allylic oxidation of methylene groups, but a large excess of oxidant is required. D5-Steroids are selectively transformed into D5-7-keto steroids by treatment with PDC (25 equiv) and molecular sieves in pyridine at 100 °C for 24 h; yields range from 63-86% (eq 18).14

A PDC-t-Butyl Hydroperoxide mixture (1:1) has proven to be useful for the mild oxidation of cyclic 1,4-dienes to the corresponding cyclic 2,5-dienones (eq 19).15 The use of the combination of PDC, t-butyl hydroperoxide, and Celite is particularly suitable for the oxidation of benzylic methylenes into aryl ketones (eq 20)16 and for the highly regioselective conversion of D5-steroids into the corresponding D5-7-keto steroids (eq 18).16 The method is rather poor for allylic oxidation of linear and cyclic alkenes, furnishing a,b-enones in 23-44% yield (eq 21).16

Oxidative Rearrangement of Unsaturated Alcohols.

Linear and cyclic secondary homoallylic alcohols are oxidized by PDC-DMF to trans-enediones in 53-75% yield. The one-pot procedure seems to be particularly convenient for the oxidation of steroidal substrates, which contain a rigid and sterically congested structure. Thus 3b-hydroxy D5-steroids afford the corresponding 3,6-diketo-D4-steroids (eq 22).17 The method is rather unsatisfactory for linear homoallylic alcohols and fails with alcohols possessing a terminal allylic group.

PDC is the oxidant of choice for the oxidation of tertiary allylic dienols. These alcohols, easily prepared by addition of Vinyllithium to conjugated cyclohexenones or cyclopentenones, undergo a 1,3-oxidative rearrangement to afford the corresponding conjugated dienones in moderate to good yield (eq 23). The rearrangement is completely regiospecific, leading to the formation of the more stable isomers. The reaction does not suffer from the presence of withdrawing substituents on the alkene system, but linear a-dienols give lower yields of rearranged isomeric products (eq 24).18

In a similar fashion, tertiary a-enynols are converted by reaction with PDC in dichloromethane to the corresponding conjugated enynones; yields are good to excellent. These rearrangements are completely regioselective, involving only the alkene. The procedure is limited to cyclic allylic alcohols and shows wide applicability only with enynols containing (Z) double bonds (eq 25).19

Oxidation of Carbon-Boron Bonds.

A synthetically useful procedure has been developed for the conversion of terminal alkenes into carboxylic acids via oxidation of organoboranes obtained by hydroboration of terminal alkenes. The oxidation works well with organoboranes derived from Dibromoborane-Dimethyl Sulfide, but other reagents may be utilized such as monobromoborane-dimethyl sulfide, Monochloroborane-Dimethyl Sulfide, Thexylborane, and Dicyclohexylborane. Alkyldibromoboranes are hydrolyzed to alkylboronic acids, which undergo a facile oxidation with PDC-DMF (5 equiv) at rt for 24 h to provide carboxylic acids in 62-78% yield (eq 26).20 In some cases PCC may effect the same reaction in higher yields; however, carboxylic acids are often best obtained with Chromium(VI) Oxide as oxidant in 90% aqueous acetic acid.20

Oxidation of Enol Ethers.

PCC is a selective reagent for the oxidative cleavage of enol ethers and PDC shows a similar but modest reactivity. PDC can effect oxidative double bond fragmentation of cyclic enol ethers to esters and keto lactones (eq 27).21

Interestingly, the PDC-t-BuOOH combination can achieve the one-step conversion of 3,4-dihydro-2H-pyrans into 5,6-dihydro-2H-pyran-2-ones under very mild conditions; yields are moderate. The reaction is performed at 0 °C in dichloromethane with PDC-t-BuOOH for 2-4 h. t-Butylperoxy derivatives are obtained as byproducts (eq 28).22 This reagent system can chemoselectively oxidize 3,4-dihydro-2H-pyrans to the corresponding a,b-unsaturated lactones without affecting pendant hydroxyl groups (eq 29).

Oxidative Cleavage of Oximes.

PDC can perform oxidative cleavage of oximes to ketones and aldehydes in excellent yield (eq 30). The reagent seems to be superior to PCC for this transformation. The rate of deoximation is increased by adding 3 Å molecular sieves, but the yields of carbonyl compounds are lowered.23

Oxidation with Iodine and PDC.

PDC has been utilized for oxidation of cyclic alkene-iodine complexes to a-iodo ketones (eq 31). The yields range from 50 to 70%.24 The reaction shows a wide applicability; D2-cholestene is selectively converted, by the same procedure, into 3a-iodocholestan-2-one in 70% yield (eq 32). The reaction fails with linear alkenes; however, it seems to be characteristic of PDC. In contrast, PCC converts the cyclohexene-iodine complex into trans-1-chloro-2-iodocyclohexane (66%), while the a-iodo ketone is a byproduct (8%).24

Cyclic trisubstituted alkenes, activated with Iodine, are easily converted into iodohydrins and epoxides by PDC, which acts as nucleophilic and iodide removing agent. Iodohydrins can be isolated in 48-65% yield when the starting alkenes have a mobile conformation. The reaction is performed in dichloromethane with PDC (2.5 equiv) and 4 Å molecular sieves at rt for 3 h. More prolonged reaction times (16 h) lead to epoxides in 50% yield (eq 33).25 Conformationally rigid alkenes are directly converted into epoxides in 51-86% yield, since the iodohydrin intermediates undergo a fast elimination of iodide by the oxidant (eq 34).

Some naturally-occurring polyenes such as (E,Z)-geranyl acetate undergo a regioselective conversion to terminal epoxides by a two-step sequence, which includes the formation of the corresponding terminal iodohydrins by reaction with PDC-iodine and subsequent conversion to the epoxides by adsorption on neutral alumina (30-65% yield) (eq 35).25

The nucleophilic and oxidizing properties of PDC can be utilized for a one-pot conversion of a-ynol-iodine complexes to a,b-unsaturated a-iodo aldehydes in 30-66% yield. This reaction is performed by adding PDC (2.2 equiv) to a solution of a-ynol and iodine (1:1), in the presence of 4 Å molecular sieves at rt for 24 h (eq 36). The conversion is regio- and stereospecific, yielding only one of two possible geometrical isomers and shows wide applicability.26

1. (a) Cainelli, G.; Cardillo, G. Chromium Oxidation in Organic Chemistry; Springer: Berlin, 1984. (b) Haines, A. H. Methods for the Oxidation of Organic Compounds, Alcohols, Alcohol Derivatives, Alkyl Halides, Nitroalkanes, Alkyl Azides, Carbonyl Compounds, Hydroxyarenes and Aminoarenes; Academic: London, 1988. (c) COS 1991, 7, Chapters 2.1, 2.7, and 3.7.
2. (a) Corey, E. J.; Schmidt, G. TL 1979, 399. (b) Luzzio, F. A.; Guziec, F. S., Jr. OPP 1988, 20, 533.
3. O'Connor, B.; Just, G. TL 1987, 28, 3235.
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6. Herscovici, J.; Antonakis, K. CC 1980, 561.
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8. Czernecki, S.; Vijayakumaran, K.; Ville, G. JOC 1986, 51, 5472.
9. Andersson, F.; Samuelsson, P. Carbohydr. Res. 1981, 129, C1.
10. Kim, J. N.; Ryu, E. K. TL 1992, 33, 3141.
11. Cossio, F. P.; Aizpurua, J. M.; Palomo, C. CJC 1986, 64, 225.
12. (a) Kanemoto, S.; Oshima, K.; Matsubara, S.; Takai, K.; Nozaki, H. TL 1983, 24, 2185. (b) Kanemoto, S.; Matsubara, S.; Takai, K.; Oshima, K.; Utimoto, K.; Nozaki, H. BCJ 1988, 61, 3607.
13. Corey, E. J.; Schmidt, G. TL 1980, 21, 731.
14. Parish, E. J.; Wei, T.-Y. SC 1987, 17, 1227.
15. Schultz, A. G.; Taveras, A. G.; Harrington, R. E. TL 1988, 29, 3907.
16. Chidambaran, N.; Chandrasekaran, S. JOC 1987, 52, 5048.
17. D'Auria, M.; De Mico, A.; D'Onofrio, F.; Scettri, A. S 1985, 988.
18. Majetich, G.; Condon, S.; Hull, K.; Ahmad, S. TL 1989, 30, 1033.
19. Liotta, D.; Brown, D.; Hoekstra, W.; Monahan, R., III TL 1987, 28, 1069.
20. Brown, H. C.; Kulkarni, S. V.; Khanna, V. V.; Patil, V. D.; Racherla, U. S. JOC 1992, 57, 6173.
21. Baskaran, S.; Islam, I.; Raghavan, M.; Chandrasekaran, S. CL 1987, 1175.
22. Chidambaram, N.; Satyanarayana, K.; Chandrasekaran, S. TL 1989, 30, 2429.
23. Satish, S.; Kalyanam, N. CI(L) 1981, 809.
24. D'Ascoli, R.; D'Auria, M.; Nucciarelli, L.; Piancatelli, G.; Scettri, A. TL 1980, 21, 4521.
25. Antonioletti, R.; D'Auria, M.; De Mico, A.; Piancatelli, G.; Scettri, A. T 1983, 39, 1765.
26. Antonioletti, R.; D'Auria, M.; Piancatelli, G.; Scettri, A. TL 1981, 22, 1041.

Giovanni Piancatelli

University of Rome La Sapienza and CNR, Rome, Italy

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