Raney Nickel1

Ni

[106-51-4]  · Ni  · Raney Nickel  · (MW 58.69)

(useful as a reducing agent for hydrogenation of organic compounds1)

Solubility: insol all organic solvents and water.

Form Supplied in: black solid.

Preparative Methods: there are many types of Raney nickel; they differ based on their methods of preparation. These methods essentially determine the hydrogen content as well as the reactivities of various types of Raney nickel. The most popular W-type Raney nickels can be prepared as the seven different types listed in Table 1.

Handling, Storage, and Precautions: Raney nickel is generally stored in an alcoholic solvent, or occasionally in water, ether, methylcyclohexane, or dioxane. The activity of Raney nickel decreases due to loss of hydrogen over a period of about 6 months. Raney nickel ignites on contact with air and should never be allowed to dry.

Desulfurization.

The most widespread application of Raney nickel is the desulfurization of a wide range of compounds including thioacetals, thiols, sulfides, disulfides, sulfoxides, sulfones, thiones, thiol esters, and sulfur-containing heterocycles.

The well-known desulfurization of dithianes remains one of the most efficient methods for reductive deoxygenation of ketones. Recently, Rubiralta demonstrated an example in his synthesis of the aspidosperma alkaloid framework. Dithiane (1) was reduced to indole derivative (2) in 85% yield without reduction of the alkene (eq 1).2

Raney nickel is frequently used to remove the sulfur atom of thiols,3 sulfides, and disulfides from a carbon skeleton, regardless of whether the sulfur is attached to an alkyl carbon,4 an aryl carbon,5 or a carbon atom in a heterocycle.6 Several examples are shown in eqs 2-5. A solvent effect was observed in the Raney nickel reduction of vinyl sulfide (11), which gave glycoside (12) in methanol, whereas the double bond remained intact to produce alkene (13) in THF (eq 6).7

The sulfur atom can be part of a heterocycle. Högberg8 and Tashiro9 used Raney nickel to remove sulfur from thiophene derivatives (14) and (16) to give compounds (15) and (17), respectively (eqs 7 and 8).

Raney nickel can remove the sulfinyl and sulfonyl groups from sulfoxides and sulfones under neutral conditions (eqs 9 and 10).10,11 Cox demonstrated the cleavage of both sulfur-carbon bonds in sulfoxide (22) and noted that the stereogenic center remained untouched (eq 11).12

Some thioamides are reduced by Raney nickel to the corresponding imines. Two typical examples are shown in eqs 12 and 13.13,14 Thiones have been reported to give alkanes, but only low or unstated yields are reported (eqs 14 and 15).15,16

Liu and Luo17 used Raney nickel to reduce glycidic thioester (32) to the corresponding 1,3-diol (33) in good yield (eq 16). With Sodium Borohydride at ambient temperature or Lithium Aluminum Hydride at -78 °C, glycidic thioester (32) was reduced chemoselectively to furnish 2,3-epoxy alcohol (34) in 82% yield (eq 16).17

Deoxygenation and Deamination.

Besides the widely used desulfurization process, Raney nickel can be used to reduce benzylic nitrogen and oxygen atoms. Behren's report shows the partial deoxygenation of diol (35) to mono alcohol (36) in 75-96% yields (eq 17).18 Ikeda used W-2 Raney nickel to remove the benzyl protecting group from compound (37). However, partial epimerization occurred in this reaction to produce a 3.7:1 mixture of the 6a- and 6b-alcohols (38) (eq 18).19 Azetidine (39) was opened by Raney nickel in refluxing ethanol, to give acyclic amine (40) in 88% yield (eq 19).20

Krafft reported that tertiary alcohols were also deoxygenated to alkanes by Raney nickel (eq 20). On the other hand, primary alcohols were oxidized to aldehydes and then subsequently decarbonylated (eq 21), and secondary alcohols were oxidized to the corresponding ketones (eq 22).21

Recently, Ohta reported Raney nickel would deoxygenate N-oxide (47) to pyrazine (48), while Phosphorus(III) Bromide gave many side products (eq 23).22

Cleavage of Heteroatom-Heteroatom Bonds.

Both N-N and N-O bonds can be cleaved by Raney nickel in the presence of hydrogen. Alexakis reported that hydrazine (49) was easily cleaved to the free amine by Raney nickel under hydrogen atmosphere, then protected to give carbamate (52) (eq 24).23 In addition, he found even hindered hydrazines (50) and (51) were successfully deaminated to free amines (56) and (57), respectively, without racemization if the reactions were assisted by ultrasound.24

The N-O bonds in 1,2-oxazine (58) and isooxazolidine (60) were cleaved by Raney nickel via a radical mechanism to produce 1,4-diketone (59) and b-lactam (61), respectively (eqs 25 and 26).25,26

Hydrogenation of Multiple Bonds.

Applications in this area are not very popular for Raney nickel. Raney nickel in dilute base is, however, an effective reagent for reduction of pyridines to the corresponding piperidines. The reaction is accelerated by substituents in the 2-position and by electron-withdrawing groups in the 3- and 4-positions, while electron-donating groups in the 3- and 4-positions retard the reaction (eq 27).27 Occasionally, Raney nickel is used to reduce acyclic multiple bonds. An example for selective reduction of triple bonds to cis double bonds is shown in eq 28.28

Deselenation.

Similar to the desulfurization process, Raney nickel can be used to remove selenium from selenoketones, diselenides, selenides, and selenooxides. Typical examples are shown in eqs 29-33.29-31 Moreover, Raney nickel has been used for a hydrodetelluration of chiral compound (76) without any racemization (eq 34).32

Reductive Amination of Carbonyl Groups.

Reactions of this type can be accomplished by reduction of intermediate imines or oximes.33-35 Recently, Chan and co-workers found that Raney nickel can be an efficient catalyst in the preparation of phenylalanine. Treatment of sodium phenylpyruvate with either Ammonia gas or aqueous ammonia solution in the presence of Raney nickel under 200 psi pressure gave >98% of phenylalanine (eq 36). Other a-keto esters such as 4-hydroxyphenylpyruvic acid, pyruvic acid, and benzoyl acid also gave the corresponding amino acids in excellent yield.36

Asymmetric Reduction.

Recently, asymmetric synthesis has become a center of attention for synthetic chemists. The use of Raney nickel and tartaric acid was recently reported by Bartok. Reduction of ketone (82) gave alcohols (83) and (84) as a 92:8 mixture in 70% chemical yield.37 Takeshita et al.9 also reported an asymmetric reduction of b-keto ester (85) to give the corresponding b-hydroxy ester (86) in 80% ee (eq 38). In addition, it was found that enantioselectivities were improved by treatment of the Raney nickel with ultrasound prior to use.38 Blacklock et al. reported an asymmetric reductive amination of a-keto ester (88) in which they used the chiral amine (87) instead of a chiral catalyst. The result, shown in eq 39, indicates that the amino ester (89) was produced in 80% yield with 74% de.39


1. (a) Hauptmann, H.; Walter, W. F. CRV 1962, 62, 347. (b) Caubere, P.; Coutrot, P. COS 1991, 8, 835. (c) Billica, H. R.; Adkins, H. OSC 1955, 3, 176.
2. Troin, Y.; Diez, A.; Bettiol, J. L.; Rubiralta, M. Grierson, D. S.; Husson, H.-P. H 1991, 32, 663.
3. Graham, A. R.; Millidge, A. F.; Young, D. P. JCS 1954, 2180.
4. Fujisawa, T.; Mobele, B. I.; Shimizu, M. TL 1992, 33, 5567.
5. Lottaz, P. A.; Edward, T. R. G.; Mentha, Y. G.; Burger, U. TL 1993, 34, 639.
6. Ohta, S.; Yamamoto, T.; Kawasaki, I.; Yamashita, M.; Katsuma, H.; Nasako, R.; Kobayashi, K. Ogawa, K. CPB 1992, 40, 2681.
7. Tietze, L. F.; Hartfiel, U.; Hubsch, T.; Voss, E.; Bogdanowicz-Szwod, K.; Wichmann, J. LA 1991, 275.
8. Högberg, H. E.; Hedenström, E.; Fägerhag, J.; Servi, S. JOC 1992, 57, 2052.
9. Takeshita, M.; Tsuge, A.; Tashiro, M. CB 1991, 124, 411.
10. Kast, J.; Hoch, M.; Schmidt, R. R. LA 1991, 481.
11. Sadanandan, E. V.; Srinivasan, P. C. S 1992, 648.
12. Cox, P. J.; Persad, A.; Simpkins, N. S. SL 1992, 197.
13. Carrington, H. C.; Vasey, C. H.; Waring, W. S. JCS 1953, 3105.
14. Kung, P. P.; Jones, R. A. TL 1991, 32, 3919.
15. Coscia, A. T.; Dickerman, S. C. JACS 1959, 81, 3098.
16. Bourdon, R. BSF 1958, 722.
17. Liu, H.-J.; Luo, W. CJC 1992, 70, 128.
18. Behren, C.; Egholm, M.; Buchardt, O. S 1992, 1235.
19. Ishibashi, H; So, T. S.; Okochi, K.; Sato, T.; Nakamura, N.; Nakatani, H.; Ikeda, M. JOC 1991, 56, 95.
20. Ojima, I.; Zhao, M.; Yamato, T.; Nakahashi, K. JOC 1991, 56, 5263.
21. Krafft, M. E.; Crooks, W. J., III; Zorc, B.; Milczanowski, S. E. JOC 1988, 53, 3158.
22. Aoyagi, Y.; Maeda, A.; Inoue, M.; Shiraishi, M.; Sakakibara, Y.; Fukui, Y.; Ohta, A.; Kajii, K.; Kodama, Y. H 1991, 32, 735.
23. Alexakis, A.; Lensen, N.; Mangeney, P. TL 1991, 32, 1171.
24. Alexakis, A.; Lensen, N.; Mangeney, P. SL 1992, 3, 625.
25. Zimmer, R.; Collas, M.; Roth, M.; Reissig, H. U. LA 1992, 709.
26. Purrington, S. T.; Sheu, K.-W. TL 1992, 33, 3289.
27. Lunn, G.; Sansone, E. B. JOC 1986, 51, 513.
28. Soukup, M.; Widmer, E. TL 1991, 32, 4117.
29. Florey, K.; Restivo, A. R. JOC 1957, 22, 406.
30. Wiseman, G. E.; Gould, E. S. JACS 1954, 76, 1706.
31. Wiseman, G. E.; Gould, E. S. JACS 1955, 77, 1061.
32. Backvall, J. E.; Bergman, J.; Engman, L. JOC 1983, 48, 3918.
33. Freifelder, M.; Smart, W. D.; Stone, G. R. JOC 1962, 27, 2209.
34. Botta, M.; De Angelis, F.; Gambacorta, A.; Labbiento, L.; Nicoletti, R. JOC 1985, 50, 1916.
35. Graham, S. H.; Williams, A. J. S. JCS(C) 1966, 655.
36. Chan, A. S. C.; Lin, Y.-C.; Chen, C.-C. Personal communication.
37. Wittmann, G.; Gondos, G.; Bartok, M. HCA 1990, 73, 635.
38. Tai, A.; Kikukawa, T.; Sugimura, T.; Inone, Y. D.; Osawa, T.; Fujii, S. JCS(C) 1991, 795.
39. Blacklock, T. J.; Shuman, R. F.; Butcher, J. W.; Shearin, W. E. Jr. Budavari, J.; Grenda, V. J. JOC 1988, 53, 836.

Teng-Kuei Yang & Dong-Sheng Lee

National Chung-Hsing University, Taichung, Taiwan



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