Di-t-butyl Chromate1

[1189-85-1]  · C8H18CrO4  · Di-t-butyl Chromate  · (MW 230.22)

(selectively oxidizes allylic methylene groups to carbonyl groups; oxidizes alcohols to aldehydes and ketones)

Alternate Name: t-butyl chromate.

Physical Data: red crystals; oil at rt; mp -5 to 0 °C.

Solubility: sol CH2Cl2, C6H6, BuOH, t-BuOH, CCl4, petroleum ether, C6H6 or CCl4 or Cl2C=CCl2/Ac2O/HOAc.

Preparative Method: prepared from t-butanol and Chromium(VI) Oxide or Chromyl Chloride.

Handling, Storage, and Precautions: should be used as prepared. Chromium(VI) compounds are toxic and should be handled with care; the mutagenicity of CrVI compounds is well documented.1f Use in a fume hood.

Oxidation of Allylic Methylene Groups to Carbonyl Groups.

Good to excellent yields of a,b-unsaturated ketones have been obtained from the di-t-butyl chromate oxidation of allylic methylene groups.2-4 The oxidation of cyclohexene affords cyclohexen-3-one and benzoquinone (eq 1).2 Carvomenthene (1) is oxidized to carvotanacetone (2) and piperitone (3) (eq 2).5-7 Similarly, verbenone may be obtained from b-pinene in 40% yield7 and limonene (4) affords carvone (5) and isopiperitenone (6) (eq 3).8

Di-t-butyl chromate, in refluxing t-butanol, oxidizes a-ionone (7) to small amounts of the a,b-unsaturated ketone (8) and 1-hydroxy-4-keto-a-ionone (9) in 23-27% yield (eq 4).9 Allylic methine carbon-hydrogen bonds are more resistant to oxidation than methylene carbon-hydrogen bonds in nonpolar solvents. Ketone (8) is obtained (14%, 14 days) in tetrachloromethane at 0 °C. The hydroxy ketone (9) was converted into abscisic acid, which is a plant hormone involved in flower and leaf abscission. Di-t-butyl chromate is superior to Chromium(VI) Oxide or Potassium Permanganate for oxidation of (+)-car-3-ene (10) to (-)-car-3-en-5-one (11) (eq 5).10 Di-t-butyl chromate does not attack methylene groups adjacent to the cyclopropane ring, as (-)-cis-carane and (+)-caren-3-ol are stable under the experimental conditions.

Di-t-butyl chromate was found superior to Selenium(IV) Oxide or Dipyridine Chromium(VI) Oxide for oxidation of the trienone (14) to (15) (eq 6).11 Compound (16) is used in the synthesis of yomogin. Oxidation of the 1,4-diene (17) affords dienones (18) and (19) in the ratio 1:3 (65% total yield, eq 7).12 Complementary regioselectivity (18/19 = 9:1, 70% yield) is obtained with Pyridinium Chlorochromate (PCC). Chromium(VI) oxide-pyridine gave results similar to di-t-butyl chromate.

The 17b-epimer of D1-5b-pregnen-20-one (20) was converted to progesterone (21) by oxidation with di-t-butyl chromate in tetrachloroethylene/Ac2O/HOAc (eq 8).13 Selective hydrogenation of progesterone (21) afforded 5b-pregnane-3,20-dione. Pregnenolone acetate (22) is oxidized at the C-7 position to afford (23) (eq 9).4 Similarly, 3b,21-diacetoxypregn-5-ene-20-one has been oxidized to 3b,21-diacetoxypregn-5-ene-7,20-dione (71%).4 Di-t-Butyl chromate oxidizes cholesteryl acetate (24) to (25) (eq 10).2,14-16 3b-Substituted (20S)-20-[(benzenesulfonyl)methyl]pregn-5-en-7-ones, which are useful as intermediates for hormones, growth regulators, and calcium metabolism, were prepared by allylic oxidation of the pregn-5-enes with di-t-butyl chromate in acetic anhydride/acetic acid.17

Allylic oxidation of steroidal glycosides by di-t-butyl chromate affords the corresponding carbonyl compounds in high yields.18 Oxidation of a methylene group adjacent to a double bond or aromatic ring to a carbonyl group was effected in a group of diterpenes and triterpenes.19

Oxidation of tetrasubstituted alkenes generally leads to a mixture of products. For example, methyl 13b-abiet-8(9)-en-18-oate is oxidized to five products in tetrachloromethane.20

Di-t-butyl chromate oxidizes the substituted ether (26) to the 2,6-naphthoquinone derivative (27) in low yield (eq 11).6 Presumably the methyl group is oxidized to a carboxyl group which undergoes decarboxylation.

Conjugated homoannular dienes are oxidized to a-diketones. 3b-Benzoyloxy-4,4,9-trimethyl-1,2,3,4,8,9-hexahydronaphthalene (28) is oxidized to the corresponding 6,7-dione (29) in tetrachloromethane containing acetic anhydride and acetic acid (eq 12).21 Similarly, (+)-occidentalol, a sesquiterpene containing a homoannular diene, is oxidized to four products in benzene containing acetic anhydride and glacial acetic acid.22

Oxidation of Alcohols to Aldehydes and Ketones.

Di-t-butyl chromate oxidizes alcohols in nonpolar solvents.23,24 Although aliphatic primary alcohols are oxidized to the corresponding aldehydes in low yields, allylic and benzylic primary alcohols give aldehydes in good to excellent yields. Cyclohexanol affords cyclohexanone (89%), cyclohexane-1,2-diol yields adipic acid, and cyclic vicinal glycols with one secondary and one tertiary hydroxy group are oxidized at the secondary position to give the corresponding hydroxy ketones.25 The ultrasound-mediated di-t-butyl chromate ester oxidation of alcohols in dichloromethane affords aldehydes and ketones in excellent yields.26

The oxidation of alcohols with anhydrous Di-t-butyl Chromate-Pyridine gives high yields of aldehydes and ketones and permits large scale reactions.27,28 The use of excess di-t-butyl chromate in the presence of 3,5-dimethylpyrazole selectively oxidized an allylic methylene position to a carbonyl group in the final step in the synthesis of (-)-solavetivone.29

Other Applications.

In CCl4/Ac2O/HOAc, di-t-butyl chromate is more effective than Ruthenium(VIII) Oxide in converting spiroethers to spirolactones.30

1. (a) Wiberg, K. B. In Oxidation in Organic Chemistry; Wiberg, K. B., Ed.; Academic: New York, 1965; Part A, pp 131-135. (b) Freeman, F. In Organic Synthesis By Oxidation With Metal Compounds; Miijs, W. J.; de Jonge, C. R. H. I., Eds.; Plenum: New York, 1986; Chapter 2. (c) Lee, D. G. The Oxidation of Organic Compounds by Permanganate Ion and Hexavalent Chromium; Presented at Open Court, La Salle, Illinois, 1980. (d) Stewart, R. Oxidation Mechanisms: Applications to Organic Chemistry; Benjamin: New York, 1964. (e) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic Chemistry; Springer: Berlin, 1984. (f) Cupo, D. Y.; Wetterhahn, K. E.; Cancer Res. 1985, 45, 1146 and references therein. (g) Richer, J. C.; Hackey, J. M. CJC 1975, 53, 3087. (h) Behr, W. J.; Fuchs, J. ZN(B) 1973, 28, 597. (i) Muzart, J. CR 1992, 92, 113.
2. Oppenauer, R. V.; Oberrauch, H. An. Asoc. Quim. Argent. 1949, 37, 246 (CA 1950, 44, 3871).
3. Beyler, R. E.; Oberster, E.; Hoffman, F.; Sanett, L. H. JACS 1960, 82, 170.
4. Marshall, C. W.; Ray, R. E.; Laos, I.; Riegel, B. JACS 1957, 79, 6308.
5. Suga, T.; Sugimoto, M.; Fijita, K.; Matsuura, T. BCJ 1966, 39, 2546.
6. Viswanatha, V.; Rao, G. S. K. TL 1973, 4339.
7. Matsuura, T.; Fujita, K. J. Sci. Hiroshima Univ. Ser. A 1952, 16, 173.
8. Fujita, K. Nippon Kagaku Zasshi 1960, 81, 676 (CA 1961, 55, 6516).
9. Roberts, D. L.; Heckman, R. A.; Hege, B. P.; Bellin, S. A. JOC 1968, 33, 3566.
10. Boyle, P. H.; Cocker, W.; Grayson, D. H. JCS(C) 1971, 1073.
11. Yamakawa, K.; Nishitani, K.; Yamamoto, A. CL 1976, 177.
12. Wender, P. A.; Eissenstat, M. A.; Filosa, M. P. JACS 1979, 101, 2196.
13. McCarry, B. E.; Markezich, R. L.; Johnson, W. S. JACS 1973, 95, 4416.
14. Bloch, K. HCA 1953, 36, 1611.
15. Kent, G. J.; Wallis, E. S. JOC 1959, 24, 1235.
16. Heusler, K.; Wettstein, A. HCA 1952, 35, 284.
17. Siemanns, H. J.; Schoenecker, B.; Rau, M. East Ger. Patent 262 431, 1988 (CA 1989, 111, 115 673z).
18. Klemke, R. E. Ger. Patent 4 001 895, 1991 (CA 1991, 115, 183 794x).
19. Pinto, A. C.; Pereira, A. L.; Kelecom, A.; Porreca, L. M.; Ribeiro, N. M.; Barnes, R. A. CPB 1988, 36, 4689.
20. Herz, W.; Schmid, J. J. JOC 1969, 34, 3464.
21. Haynes, N. B.; Redmore, D.; Timmons, C. J. JCS 1963, 2420.
22. Suga, T.; Imamamura, K.; Von Rudloff, E. JCS(P1) 1972, 962.
23. Suga, T.; Kihara, K.; Matsuura, T. BCJ 1965, 38, 893.
24. Suga, T.; Kihara, K.; Matsuura, T. BCJ 1965, 38, 1141.
25. Suga, T.; Matsuura, T. BCJ 1965, 38, 1503.
26. Luzzio, F. A.; Moore, W. J. JOC 1993, 58, 512.
27. Sharpless, K. B.; Akashi, K. JACS 1975, 97, 5927.
28. Leo, A.; Westheimer, F. H. JACS 1952, 74, 4383.
29. Hwu, J. R.; Wetzel, J. JOC 1992, 57, 922.
30. Reynolds, G. F.; Rasmusson, G. H.; Birladeneanu, L.; Arth, G. E. TL 1970, 5057.

Fillmore Freeman

University of California, Irvine, CA, USA

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