Tetrakis(triphenylphosphine)nickel(0)1

Ni(PPh3)4

[15133-82-1]  · C72H60NiP4  · Tetrakis(triphenylphosphine)nickel(0)  · (MW 1107.89)

(a source of nickel(0) useful for coupling reactions of organic halides,2 and the cyclooligomerization of cumulenes3)

Physical Data: mp 123-128 °C (N2).

Solubility: sol DMF, DMA, THF, acetonitrile, benzene; slightly sol Et2O; very slightly sol n-heptane, EtOH.

Form Supplied in: widely available as a red powder of greater than 98% purity.

Preparative Methods: the standard preparation involves the reduction of Nickel(II) Acetylacetonate with Triethylaluminum in the presence of Triphenylphosphine. To 21.3 g of anhydrous Ni(acac)2 and 125 g PPh3 in 800 mL of Et2O under N2 at 0 °C is slowly added 28.0 g Et3Al. The reddish-brown precipitate is collected, washed with Et2O, and twice dissolved in benzene and reprecipitated by the addition of n-heptane to give about 50 g (55%) of Ni(PPh3)4.4

Handling, Storage, and Precautions: highly oxygen sensitive. Special inert-atmosphere techniques must be used.5 Should be stored at 0 °C. Cancer suspect agent.

Coupling Reactions of Organic Halides.

The zerovalent nickel complex Ni(PPh3)4 reacts with organic halides by oxidative addition into the carbon-halogen bonds to give organonickel(II) intermediates.6 These intermediates, which are typically not isolated, can react with a variety of nucleophilic reagents to replace the original halide with another group.2 With a catalytic amount of Ni(PPh3)4, aryl halides react with halide salts to give halogen exchange,7 and with MgH2 to give hydrogenation.8 Aryl halides and triflates react with cyanide salts to give nitriles.9 Aryl bromides and iodides both work well as substrates, and many functional groups are tolerated. However, o-substituents tend to slow the reactions down and give lower yields. Oxidative addition to benzylic halides occurs with racemization.6a Insertion of an alkene into the organonickel intermediate leads to overall coupling via a b-hydride elimination pathway.10 This type of reaction has been utilized intramolecularly in the synthesis of indole and oxindole derivatives (eq 1).11 The organonickel intermediate derived from MeI and Ni(PPh3)4 can be used for the regioselective alkylation of epoxides.12

Homocoupling of aryl and alkenyl halides can occur with stoichiometric amounts of nickel(0) (see Bis(1,5-cyclooctadiene)nickel(0)),13 or catalytically in the presence of an added reducing agent such as zinc (see Tris(triphenylphosphine)nickel(0)).14 Ni(PPh3)4 has been used for the homocoupling of 2-halopyridines,15 and a-halo ketones.16 Cross coupling of distinct aryl halides by this method is generally not efficient due to extensive symmetrical coupling. Intramolecular couplings of bis(aryl halides), however, do not suffer from this limitation and give cyclized products.17 These couplings work well for many different tether lengths (eq 2) and this strategy was utilized in the synthesis of the macrocyclic ketone alnusone.18 The mild conditions of this reaction permit a wide variety of functional groups to be present without concern for the formation of byproducts or decomposition. This is in contrast to the copper catalyzed Ullmann reaction, which often requires harsh thermal conditions (>200 °C).19

Coupling Reactions with Organometallic Compounds.

The cross-coupling of aryl and alkenyl halides may be effected by the reaction of organometallic reagents with organic halides in the presence of Ni(PPh3)4. As before, oxidative addition of Ni0 to the organic halide is the initial step in the mechanism. The transiently formed organonickel intermediate can then accept an organic group from the added metal reagent through ligand substitution, which leads, upon reductive elimination, to replacement of the original halide with this new group and regeneration of a catalytic nickel(0) species. While initial studies in this area were confined to highly reactive organomagnesium and -lithium reagents,20 which limited their applicability in synthesis, more recent studies have shown that organic complexes of aluminum, zinc, and zirconium, among others, are all active for the coupling reaction.21

Recent uses of Grignard reagents in the presence of Ni(PPh3)4 include the reaction with trichloroethylene to give 1,1-dichloroalkenes,22 with 1,2-dichloroethylenes to stereoselectively produce vinyl chlorides,23 and with phenolic ethers to give arenes,24 and the reaction of TMSCH2MgCl with vinyl iodides to give allyl silanes.25 In addition, lithium enolates have been coupled with aryl halides inter- and intramolecularly.26

Alkenylalanes readily couple with aryl and alkenyl halides in the presence of Ni(PPh3)4 to give styrene and butadiene derivatives in good yields (eq 3).21 Trans-alkenylalanes, which are readily obtainable by the carboalumination of alkynes, couple with retention of configuration at the double bond to provide an efficient route to trans-alkenes.27 (E)-1,2-Dichloroethene was coupled with an alkenylalane to give a 1-chloro-(E,E)-1,3-diene in 80% yield.28

Alkenylzirconium reagents are similar to alkenylalanes in that they can be easily prepared by carbometalation of alkynes. They may be coupled with aryl, alkenyl, and alkynyl halides (eq 3).21 The coupling is facilitated by the presence of added salts containing Zn or Cd such as Zinc Chloride.29

Arylzinc compounds have also been reacted with aryl halides in good yields with very little homocoupling.30 This mild coupling method was used with great success in the synthesis of a bisbenzocyclooctadiene lignan, steganone (eq 4).31 Alkylzincs formed from the Reformatsky reagent also react with aryl halides to give arylacetic acid esters.32 Benzylzinc compounds react with alkenyl halides in a similar fashion; however, palladium catalysts were found to be more suitable for this reaction due to extensive isomerization to the conjugated isomers in the presence of nickel.33 Knochel's (dialkoxyboryl)methylzinc reagents have also been coupled with greater success using palladium catalysts.34

In general, the coupling reactions of aryl halides may be catalyzed with similar efficiency by palladium catalysts such as Tetrakis(triphenylphosphine)palladium(0) or Cl2Pd(PPh3)2-Diisobutylaluminum Hydride. The nickel catalysts tend to be slightly more reactive, however, easily entering into reactions with both organic iodides and bromides, while the palladium catalysts sometimes require activated bromides to react.30a In the case of alkenyl halides, the nickel catalysts have shown slight (<=10%) stereochemical scrambling when coupled with alkenylalanes, whereas with the palladium catalysts the stereochemical integrity is &egt;97%.27b Palladium catalysts also have the added advantage that they are compatible with the nitro group, which nullifies the catalytic activity of the nickel(0) complexes,30a and coupling with boranes is possible.35

Cyclooligomerization of Cumulenes.

Ni(PPh3)4 reacts catalytically with cumulenes via a [2 + 2] cycloaddition to give [4]radialenes36 and in a [2 + 2 + 2] fashion to give [6]radialenes. The choice of solvent affects the selectivity of some reactions, with benzene providing dimers and DMF leading primarily to the trimeric products.37 Several extremely strained cyclobutanes have been prepared by this method.38 Interestingly, the cumulene starting materials (3) can be prepared by the Ni0 mediated coupling of 1,1-dihaloalkenes (1) and the subsequent Ni0 catalyzed elimination of the 2,3-dihalo-1,3-butadiene products (2). Thus [4]radialenes (4) may be prepared in one step from 1,1-dihaloalkenes (1) (eq 5).39

Other Uses.

Terminal alkenes may be prepared by the oxidative addition of primary halides to Ni(PPh3)4 followed by b-hydride elimination.40 Cyclopropanation of electron-deficient alkenes is possible by the reaction of the complex with gem-dibromides or diazoalkanes.41 Methylenecyclopropane is linearly trimerized selectively in the presence of this catalyst.42 Tethered diynes react inter- and intramolecularly with alkynes in [2 + 2 + 2] cycloadditions to give tetralins (eq 6).43


1. Jolly, P. W.; Wilke, G. The Organic Chemistry of Nickel; Academic: New York, 1974; Vols. 1 and 2.
2. Jolly, P. W. In Comprehensive Organometallic Chemistry; Wilkinson, G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon: New York 1982; Chapter 56.5, p 713.
3. Iyoda, M.; Kuwatani, Y.; Oda, M. JACS 1989, 111, 3761.
4. Schunn, R. A. Inorg. Synth. 1972, 13, 124.
5. Shriver, D. F. The Manipulation of Air-Sensitive Compounds, McGraw-Hill: New York, 1969.
6. (a) Stille, J. K.; Cowell, A. B. JOM 1977, 124, 253. (b) Tsou, T. T.; Kochi, J. K. JACS 1979, 101, 6319.
7. Tsou, T. T.; Kochi, J. K. JOC 1980, 45, 1930.
8. Carfagna, C.; Musco, A.; Pontellini, R. J. Mol. Catal. 1989, 54, L23.
9. (a) Cassar, L. JOM 1973, 54, C57. (b) Chambers, M. R. I.; Widdowson, D. A. JCS(P1) 1989, 1365.
10. Kron, T. E.; Lopatina, V. S.; Morozova, L. N.; Lebedev, S. A.; Isaeva, L. S.; Kravtsov, D. N.; Petrov, É. S. BAU 1989, 703.
11. (a) Mori, M.; Ban, Y. TL 1976, 1803. (b) Mori, M.; Ban, Y. TL 1976, 1807. (c) Canoira, L.; Rodriguez, J. G. JHC 1985, 22, 1511. (d) Canoira, L.; Rodriguez, J. G. JCR(S) 1988, 68.
12. Hase, T.; Miyashita, A.; Nohira, H. CL 1988, 219.
13. Semmelhack, M. F.; Helquist, P.; Jones, J. D.; Keller, L.; Mendelson, L.; Ryono, L. S.; Smith, J. G.; Stauffer, R. D. JACS 1981, 103, 6460.
14. Zembayashi, M.; Tamao, K.; Yoshida, J-I.; Kumada, M. TL 1977, 4089.
15. Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D; Montanucci, M. S 1984, 736.
16. Iyoda, M.; Sakaitani, M.; Kojima, A.; Oda, M. TL 1985, 26, 3719.
17. (a) Whiting, D. A.; Wood, A. F. JCS(P1) 1980, 623. (b) Colquhoun, H. M.; Dudman, C. C.; Thomas, M.; O'Mahoney, C. A.; Williams, D. J. JCS(C) 1990, 336.
18. Semmelhack, M. F.; Ryono, L. S. JACS 1975, 97, 3873. and reference 13.
19. (a) Ullmann, F.; Bielecki, J. CB 1901, 34, 2147. (b) Normant, J. F. S 1972, 63. (c) Fanta, P. E. S 1974, 9. (d) Sainsbury, M. T 1980, 36, 3327.
20. (a) Corriu, R. J. P.; Masse, J. P. JCS(C) 1972, 144. (b) Tamao, K.; Sumitani, K.; Kumada, M. JACS 1972, 94, 4374. (c) Reference 2 and references therein.
21. Negishi, E-i.; Takahashi, T.; Baba, S.; Van Horn, D. E.; Okukado, N. JACS 1987, 109, 2393.
22. Ratovelomanana, V.; Linstrumelle, G.; Normant, J-F. TL 1985, 26, 2575.
23. Ratovelomanana, V.; Linstrumelle, G. SC 1984, 14, 179.
24. Johnstone, R. A. W.; McLean, W. N. TL 1988, 29, 5553.
25. Negishi, E-i.; Luo, F-T.; Rand, C. L. TL 1982, 23, 27.
26. Semmelhack, M. F.; Stauffer, R. D.; Rogerson, T. D. TL 1973, 4519.
27. (a) Negishi, E-i.; Baba, S. JCS(C) 1976, 596. (b) Baba, S.; Negishi, E-i. JACS 1976, 98, 6729.
28. Ratovelomanana, V.; Linstrumelle, G. TL 1984, 25, 6001.
29. (a) Okukado, N.; Van Horn, D. E.; Klima, W. L.; Negishi, E-i. TL 1978, 1027. (b) Negishi, E-i.; Okukado, N.; King, A. O.; Van Horn, D. E.; Spiegel, B. I. JACS 1978, 100, 2254.
30. (a) Negishi, E-i.; King, A. O.; Okukado, N. JOC 1977, 42, 1821. (b) Negishi, E-i.; Takahashi, T.; King, A. O. OS 1988, 66, 67.
31. (a) Larson, E. R.; Raphael, R. A. TL 1979, 5041. (b) Ziegler, F. E.; Schwartz, J. A. JOC 1978, 43, 985.
32. (a) Fauvarque, J. F.; Jutand, A. JOM 1977, 132, C17. (b) Fauvarque, J. F.; Jutand, A. JOM 1979, 177, 273.
33. Negishi, E-i.; Matsushita, H.; Okukado, N. TL 1981, 22, 2715.
34. Watanabe, T.; Miyaura, N.; Suzuki, A. JOM 1993, 444, C1.
35. Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. JACS 1985, 107, 972.
36. (a) Hagelee, L.; West, R.; Calabrese, J.; Norman, J. JACS 1979, 101, 4888. (b) Iyoda, M.; Kuwatani, Y.; Oda, M. JACS 1989, 111, 3761.
37. Iyoda, M.; Tanaka, S.; Nose, M.; Oda, M. JCS(C) 1983, 1058.
38. (a) Pasto, D. J.; Mitra, D. K. JOC 1982, 47, 1382. (b) Hashmi, S.; Polborn, K.; Szeimies, G. CB 1989, 2399.
39. (a) Iyoda, M.; Sakaitani, M.; Miyazaki, T.; Oda, M. CL 1984, 2005. (b) Iyoda, M.; Tanaka, S.; Otani, H.; Nose, M.; Oda, M. JACS 1988, 110, 8494.
40. Henningsen, M. C.; Jeropoulos, S.; Smith, E. H. JOC 1989, 54, 3015.
41. (a) Kanai, H.; Hiraki, N. CL 1979, 761. (b) Kanai, H.; Hiraki, N.; Iida, S. BCJ 1983, 56, 1025. (c) Nakamura, A.; Yoshida, T.; Cowie, M.; Otsuka, S.; Ibers, J. A. JACS 1977, 99, 2108.
42. Binger, P.; Brinkmann, A.; McMeeking, J. LA 1977, 1065.
43. Bhatarah, P.; Smith, E. H. JCS(P1) 1992, 2163.

Paul A. Wender & Thomas E. Smith

Stanford University, CA, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.