Nickel(II) Chloride1

NiCl2
(NiCl2)

[7718-54-9]  · Cl2Ni  · Nickel(II) Chloride  · (MW 129.59) (NiCl2.6H2O)

[7791-20-0]  · Cl2H12NiO6  · Nickel(II) Chloride  · (MW 237.71)

(mild Lewis acid;2-5 catalyst for coupling reactions,1a,7-12 and in combination with complex hydrides as a selective reducing agent16,33,36-38)

Physical Data: mp 1001 °C; d 3.550 g cm-3.

Solubility: sol H2O, alcohol; insol most organic solvents.

Form Supplied in: yellow solid when anhydrous, green solid for the hydrate; widely available. Drying: for anhydrous nickel chloride, standard procedure for drying metal chlorides can be used by refluxing with Thionyl Chloride followed by removal of excess SOCl2.45

Handling, Storage, and Precautions: nickel(II) is reputed to be toxic and a cancer suspect agent. Use in a fume hood.

Mild Lewis Acid.

Nickel chloride serves as a mild Lewis acid which promotes the regioselective rearrangement of dienols in aqueous t-BuOH at 60 °C in satisfactory yield (eq 1).2 Brønsted acids give dehydration products, whereas other Lewis acids such as Nickel(II) Acetate, Palladium(II) Chloride, and Copper(II) Chloride proved less effective than nickel chloride and yield a mixture of rearranged and dehydration products. When anhydrous alcohol solvent is used, rearranged products bearing terminal alkoxy groups are obtained.

In the presence of a catalytic amount of NiCl2, Cyanotrimethylsilane smoothly reacts with acetals or orthoesters derived from aromatic and a,b-unsaturated carbonyl compounds to give the corresponding a-cyano derivatives under neutral conditions (eq 2).3 NiCl2 can also accelerate the conversion of acrylamide to ethyl acrylate4a and catalyze the amination of 5,8-quinolinediones.4b The ring-opening reaction of epoxides with LiAlR4 is catalyzed by NiCl2 or Nickel(II) Bromide (eq 3).5

Nickel(II) Chloride-Chromium(II) Chloride.

Although the Chromium(II) Chloride-mediated reaction of an aldehyde with a vinylic iodide provides a useful entry for the preparation of allylic alcohol,1a,6 the presence of a catalytic amount of NiCl2 is essential to ensure the completion of the reaction.7-12 Vinyl iodides (eq 4)7 or triflates8a are commonly used. Alkynyl iodides behave similarly (eq 5).9 Silyl enol ethers or enol phosphates are unreactive. The stereochemistry of iodoalkenes is retained in the majority of cases with the exceptions of trisubstituted cis-iodoalkenes and cis-iodoenones, which afford exclusively the trans-alkenes instead of the expected cis-alkenes.7a

Functional groups such as esters, amides, nitriles, ketones, acetals, ethers, silyl ethers (TBDMS or TBDPS), alcohols, alkenes, and triple bonds are stable under the reaction conditions. Substrates containing structural complexity can be employed in this transformation. Thus, the reaction served as the key step for the formation of C(7)-C(8) and C(84)-C(85) bonds in the total synthesis of palytoxin,10 as well as for the synthesis of other natural products and C-saccharides. The reagent has also been proved to be useful in the intramolecular cyclization of the aldehyde (eqs 6 and 7).11,12

A simple and selective method for the conversion of an aldehyde to vinyl iodides, (E)-RCH=CHX, by means of a CHX3/CrCl2 system has been developed (eq 8).13

DMF happens to be the most effective solvent for this coupling reaction. The reaction goes slowly but cleanly in the DMSO solvent.8a The presence of a phosphine ligand in the nickel catalyst gives a diene sideproduct.4a Nevertheless, this later system has been used in the intramolecular cyclization of enynes (eq 9).14

Monosubstituted a,b-unsaturated aldehydes are converted to cyclopropanols in the presence of NiCl2/CrCl2 in moderate yields (eq 10).15

Selective Reductions.

Low-valent transition metal complexes generated in situ from metal halides and reducing agents are particularly useful for the selective reduction of various functionalities.16 Nickel chloride and nickel bromide have demonstrated a unique role in these reduction reactions. To illustrate this, in the presence of an equimolar quantity NiCl2, Lithium Aluminum Hydride can reduce alkenes to alkanes in excellent yields.17 Under similar conditions at -40 °C, alkynes are reduced to cis-alkenes in good yield.17 Haloalkanes are also smoothly converted into the corresponding hydrocarbons under these conditions.18a,b Even chlorobenzene and 1-bromoadamantane can be reduced efficiently by this reagent. Sodium Hydride in the presence of NiCl2 or NiBr2 and a sodium alkoxide can also serve a similar purpose.16c,18c

The N-O bond in isoxazolidines is cleaved efficiently by LiAlH4/NiCl2 at -40 °C (eq 11).19 Styrene oxide yields b-phenylethanol in 95% yield by this complex reagent, whereas LiAlH4 alone gives a-phenylethanol.19

Nickel Boride, prepared in situ from the reaction of nickel chloride and Sodium Borohydride, behaves like Raney Nickel.1b In DMF, the dark brown/black solution comprises an efficient system for alkene hydrogenation. The carbon-carbon double bonds of the a,b-unsaturated carbonyl compounds are reduced selectively (eq 12).20 It is noted that carbon-sulfur bonds are selectively reduced under similar conditions (eq 13).16b,21 Thiols, sulfides, disulfides, dithioacetals, as well as sulfoxides can all be hydrodesulfurized smoothly. Sulfones, on the other hand, remain intact under the reaction conditions.21d,e

Reduction of a-halo ketones with nickel boride produces the corresponding ketones.22 The carbon-oxygen bonds in allylic ethers,23a benzylic esters,23b as well as aryl tosylates23c are reduced to the corresponding C-H bonds (eq 14).

Upon treatment with NiCl2/NaBH4, nitro,24a-c azide,24d,e and oxime24f groups are smoothly transformed into amino groups in good yields. Carbon-carbon double bonds are occasionally reduced under these conditions.24a,f Nitro and cyano groups are also reduced to amines by the reagent mixture NiCl2/B2H6.25 Ketones, aldehyde, carboxylic acid, alkene, ester, and amide moieties are unaffected under these conditions.

Addition of TMSCN to an allene is catalyzed by nickel boride generated in situ, although the reaction is nonstereoselective (eq 15).26

Treatment of Diphenylacetylene with excess TMSCN in the presence of the NiCl2/Diisobutylaluminum Hydride or NiCl2/Triethylaluminum catalyst affords a substituted pyrrole in high yield (eq 16).27

Hydrosilylation of conjugated dienes with HSiR3 is catalyzed by NiCl2/Et3Al in excellent yield; 1,4-addition is observed exclusively (eq 17).28

A combination of Aluminum and NiCl2 promotes the selective reduction of a,b-enones to the corresponding saturated carbonyl compounds (eq 18).29 Both nitro groups30 and aryl ketones29 are reduced to amines and benzylic alcohols, respectively.

Nickel(II) Chloride-Zinc.

Finely divided nickel with high catalytic activity is readily obtained by the treatment of NiCl2 with Zinc dust.31 This reagent reduces aldehydes, alkenes, and aromatic nitro compounds in good yields.32a Nitriles as well as aryl ketones give a mixture of reduced products under these conditions. Zn/NiCl2 in the presence Ammonia/NH4+ buffer (pH 6-10)3 has been shown to effect the selective reduction of a,b-enones to the corresponding saturated carbonyl compounds.32b Aryl, allyl, and alkyl halides are reduced by water, zinc, and a catalytic amount of NiCl2, Triphenylphosphine, and iodide ion.32c

Reductive Heck-Like Reactions.

Reductive Heck-like reactions (eq 19) can be achieved when alkyl, aryl, and vinyl bromides are treated with zinc/NiCl2.6H2O in the presence of an excess quantity of a,b-unsaturated esters.33 A trace amount of water is essential for this conversion. Similar reactions are observed when alkenes are treated with iodofluoroacetate or iododifluoroacetate under the same conditions (eq 20).34 Tandem reaction can also occur to give cyclic products (eq 21).35

Homocoupling Reactions.

In the absence of a Michael acceptor, aryl and vinyl halides undergo dimerization reaction upon treatment with the NiCl2/Zn reagent.36-38 Under sonication conditions and in the presence of excess Ph3P and Sodium Iodide in DMF, the NiCl2/Zn reagent promotes homocoupling of aryl triflates in good yields.36 Bipyridyls having electron-donating groups, such as methoxy groups, are obtained in satisfactory yields under these conditions (eq 22).37 Thiophene derivatives behave similarly.38 Vinyl bromides dimerize to yield the corresponding butadienes.39 It is interesting that the presence of iodide ion or thiourea can accelerate the reaction.

Cross-Coupling Reactions.

Most cross-coupling reactions using nickel catalysts require phosphine ligands and are therefore discussed in detail under Dichlorobis(triphenylphosphine)nickel(II). The reaction of aryl iodides or bromides with trialkyl phosphites in the presence of NiCl2 is the premier method for preparing dialkyl arylphosphonates (eq 23).40a,b Thermolysis of allyl phosphite in the presence of NiCl2 yields the corresponding allyl phosphonates (eq 24).40c

Miscellaneous Reactions.

Symmetrical alkynes in the presence of NiCl2 or NiBr2 and Magnesium undergo trimerization to give the corresponding hexasubstituted aromatic compounds (eq 25). Terminal alkynes yield a mixture of regioisomers.41

Grignard reagents activated by a catalytic quantity of NiCl2 can substitute the germanium-hydrogen bond with a germanium-carbon bond (eq 26).42 It is noted that the stereochemistry of the original organogermane is retained.

Hydromagnesiation of a styrene with Ethylmagnesium Bromide followed by treatment with Carbon Dioxide gives the 2-arylpropionic acid in good yield (eq 27).43

Thermolysis of 1-phenyl-3,4-dimethylphosphole in the presence of NiCl2 yields the corresponding nickel complex of the dimeric product. The ligand can be liberated upon treatment with Sodium Cyanide (eq 28).44

Related Reagents.

Chromium(II) Chloride-Nickel(II) Chloride; Lithium Aluminum Hydride-Nickel(II) Chloride.


1. (a) Cintas, P. S 1992, 248. (b) Ganem, B.; Osby, J. O. CR 1986, 86, 763.
2. (a) Kyler, K. S.; Watt, D. S. JACS 1983, 105, 619. (b) Kyler, K. S.; Bashir-Hashemi, A.; Watt, D. S. JOC 1984, 49, 1084.
3. Mukaiyama, T.; Soga, T.; Takenoshita, H. CL 1989, 997.
4. (a) Czarnik, A. W. TL 1984, 25, 4875. (b) Yoshida, K.; Yamamoto, M.; Ishiguro, M. CL 1986, 1059.
5. Boireau, G.; Abenhaim, D.; Bernardon, C.; Henry-Basch, E.; Sabourault, B. TL 1975, 2521. Boireau, G.; Abenhaim, D.; Henry-Basch, E. T 1980, 36, 3061.
6. Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H. TL 1983, 24, 5281.
7. (a) Jin, H.; Uenishi, J.-i.; Christ, W. J.; Kishi, Y. JACS 1986, 108, 5644. (b) Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Matelich, M. C.; Scola, P. M.; Spero, D. M.; Yeon, S. K. JACS 1992, 114, 3162. (c) Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Scola, P. M. TL 1992, 33, 1549. (d) Dyer, U. C.; Kishi, Y. JOC 1988, 53, 3383. (e) Goekjian, P. G.; Wu, T.-C.; Kang, H.-Y.; Kishi, Y. JOC 1987, 52, 4823. (f) Chen, S. H.; Horvath, R. F.; Joglar, J.; Fisher, M. J.; Danishefsky, S. J. JOC 1991, 56, 5834.
8. (a) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. JACS 1986, 108, 6048. (b) Angell, R.; Parsons, P. J.; Naylor, A.; Tyrrell, E. SL 1992, 599.
9. (a) Wang, Y.; Babirad, S. A.; Kishi, Y. JOC 1992, 57, 468. (b) Aicher, T. D.; Kishi, Y. TL 1987, 28, 3463.
10. Armstrong, R. W.; Beau, J. M.; Cheon, S. H.; Christ, W. J.; Fujioka, H.; Ham, W.-H.; Hawkins, L. D.; Jin, H.; Kang, S. H.; Kishi, Y.; Martinelli, M. J.; McWhorter, W. W., Jr.; Mizuno, M. Nakata, M.; Stutz, A. E.; Talamas, F. X.; Taniguchi, M.; Tino, J. A.; Ueda, K.; Uenishi, J. I.; White, J. B.; Yonaga, M. JACS 1989, 111, 7525. (b) Kishi, Y. PAC 1989, 61, 313.
11. (a) Rowley, M.; Tsukamoto, M.; Kishi, Y. JACS 1989, 111, 2735. (b) Rowley, M.; Kishi, Y. TL 1988, 29, 4909.
12. (a) Crévisy, C.; Beau, J. M. TL 1991, 32, 3171. (b) Lu, Y.-F.; Harwig, C. W.; Fallis, A. G. JOC 1993, 58, 4204.
13. Takai, K.; Nitta, K.; Utimoto, K. JACS 1986, 108, 7408.
14. Trost, B. M.; Tour, J. M. JACS 1987, 109, 5268.
15. Montgomery, D.; Reynolds, K.; Stevenson, P. CC 1993, 363.
16. (a) Pons, J.-M.; Santelli, M. T 1988, 44, 4295. (b) Luh, T.-Y.; Ni, Z.-J. S 1990, 89. (c) Caubère, P. AG(E) 1983, 22, 599.
17. Ashby, E. C.; Lin, J. J. JOC 1978, 43, 2567.
18. (a) Ashby, E. C.; Lin, J. J. TL 1977, 4481. (b) Ashby E. C.; Lin, J. J. JOC 1978, 43, 1263. (c) Brunet, J. J.; Vanderesse, R.; Caubere, P. JOM 1978, 157, 125.
19. Tufariello, J. J.; Meckler, H.; Pushpananda, K.; Senaratne, A. T 1985, 41, 3447.
20. (a) Dhawan, D.; Grover, S. K. SC 1992, 22, 2405. (b) Abe, N.; Fujisaki, F.; Sumoto, K.; Miyano, S. CPB 1991, 39, 1167.
21. (a) Myrboh, B.; Singh, L. W.; Ila, H.; Junjappa, H. S 1982, 307. (b) Euerby, M. R.; Waigh, R. D. SC 1986, 16, 779. (c) Nishio, T.; Omote, Y. CL 1979, 1223. (d) Truce, W. E.; Perry, F. M. JOC 1965, 30, 1316. (e) Back, T. G. CC 1984, 1417.
22. Sarma, J. C.; Borbaruah, M.; Sharma, R. P. TL 1985, 26, 4657.
23. (a) He, Y.; Pan, X.; Zhao, H.; Wang, S. SC 1989, 19, 3051. (b) Sharma, D. N.; Sarma, R. P. TL 1985, 26, 371. (c) Wang, F.; Chiba, K.; Tada, M. JCS(P1) 1992, 1897.
24. (a) Nose, A.; Kudo, T. CPB 1988, 36, 1529. (b) Hanaya, K., Fujita, N.; Kudo, H. CI(L) 1973, 794. (c) Osby, J. O.; Ganem, B. TL 1985, 26, 6413. (d) Sarma, J. C.; Sharma, R. P. CI(L) 1987, 764. (e) Rao, H. S. P.; Reddy, K. S.; Turnbull, K.; Borchers, V. SC 1992, 22, 1339. (f) Ipaktschi, J. CB 1984, 117, 856.
25. (a) Nose, A., Kudo, T. CPB 1986, 34, 3905. (b) Satoh, T.; Suzuki, S.; Suzuki, Y.; Miyaji, Y.; Imai, Z. TL 1969, 4555.
26. Chatani, N.; Takeyasu, T.; Hanafusa, T. TL 1986, 27, 1841.
27. Chatani, N.; Hanafusa, T. TL 1986, 27, 4201.
28. Lappert, M. F.; Nile, T. A.; Takahashi, S. JOM 1974, 72, 425.
29. Hazarika, M. J.; Barua, N. C. TL 1989, 30, 6567.
30. Sarmah, P.; Barua, N. C. TL 1990, 31, 4065.
31. (a) Sakai, K.; Watanabe, K. BCJ 1967, 40, 1548. (b) Rieke, R. D.; Kavaliunas, A. V.; Rhyne, L. D.; Fraser, D. J. J. JACS 1979, 101, 246.
32. (a) Nose, A.; Kudo, T. CPB 1990, 38, 2097. (b) Petrier, C.; Luche, J.-L. TL 1987, 28, 2351. (c) Colon, I. JOC 1982, 47, 2622.
33. Sustmann, R.; Hopp, P.; Holl, P. TL 1989, 30, 689.
34. (a) Wang, Y.; Yang, Z.-Y.; Burton, D. J. TL 1992, 33, 2137. (b) Yang, Z.-Y.; Burton, D. J. JOC 1992, 57, 5144.
35. Yang, Z.-Y.; Burton, D. J. TL 1991, 32, 1019.
36. Yamashita, J.; Inoue, Y.; Kondo, T.; Hashimoto, H. CL 1986, 407.
37. (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Montanucci, M. S 1984, 736. (b) Tiecco, M.; Tingoli, M.; Testaferri, L.; Chianelli, D.; Wenkert, E. T 1986, 42, 1475. (c) Tiecco, M.; Tingoli, M.; Testaferri, L.; Bartoli, D.; Chianelli, D. T 1989, 45, 2857.
38. Sone, T.; Umetsu, Y.; Sato, K. BCJ 1991, 64, 864.
39. Takagi, K.; Hayama, N. CL 1983, 637.
40. (a) Tavs, P. CB 1970, 103, 2428. (b) Balthazor, T. M.; Grabiak, R. C. JOC 1980, 45, 5425. (c) Lu, X.; Zhu, J. JOM 1986, 304, 239.
41. (a) Mauret, P.; Alphonse, P. JOM 1984, 276, 249. (b) Mauret, P.; Alphonse, P. JOC 1982, 47, 3322. (c) Alphonse, P.; Moyen, F.; Mazerolles, P. JOM 1988, 345, 209.
42. Carre, F. H.; Corriu, R. J. P. JOM 1974, 74, 49.
43. Amano, T.; Ota, T.; Yoshikawa, K.; Sano, T.; Ohuchi, Y.; Sato, F.; Shiono, M.; Fujita, Y. BCJ 1986, 59, 1656.
44. (a) Mercier, F.; Mathey, F.; Fischer, J.; Nelson, J. H. JACS 1984, 106, 425. (b) Mercier, F.; Mathey, F.; Fischer, J.; Nelson, J. H. IC 1985, 24, 4141.
45. Pray, A. R. Inorg. Synth. 1957, 5, 153.

Tien-Yau Luh & Yu-Tsai Hsieh

National Taiwan University, Taipei, Taiwan



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