Nickel Complex Reducing Agents1

NaH-t-C5H11ONa-Ni(OAc)2
(NaH)

[7646-69-7]  · HNa  · Nickel Complex Reducing Agents  · (MW 24.00) (t-C5H11ONa)

[14593-46-5]  · C5H11NaO  · Nickel Complex Reducing Agents  · (MW 110.15) (Ni(OAc)2.4H2O)

[6018-89-9]  · C4H14NiO8  · Nickel Complex Reducing Agents  · (MW 248.87)

(reduces many functional groups; couples organic halides; desulfurizes organic substrates; source of hydrogenation catalyst1)

Alternate Name: nickel-containing complex reducing agents (NiCRAs).

Physical Data: black solid of uncertain structure containing Ni0 species.2

Solubility: insol organic solvents.

Preparative Methods: t-C5H11ONa-NiCRA (x.y.z) is conveniently prepared by the reaction of t-C5H11OH (y equiv) with a mixture of Sodium Hydride (x + y equiv) and Nickel(II) Acetate (z equiv) in THF or DME. Commercial NaH (55-60% in oil) is used after three washings with anhydrous THF or DME under N2. t-C5H11OH is distilled from sodium. Ni(OAc)2 is dried in vacuo (15 mmHg) for 16 h at 120-130 °C. Note: t-C5H11ONa-NiCRA (x.y.z) means a reagent obtained from x,y, and z equivalents of NaH, t-C5H11ONa, and Ni(OAc)2, respectively.

Handling, Storage, and Precautions: NiCRAs are nonpyrophoric but are handled and stored under inert atmosphere (N2 or, better, Ar). Hydrolysis must be performed by slow addition of cold water or EtOH to destroy the hydride.

Reductions.

t-C5H11ONa-NiCRAs are significantly less basic than NaH and t-C5H11ONa. t-C5H11ONa-NiCRA (4.2.1) reduces under mild conditions and in good yields aryl halides, including aryl fluorides,3 vinyl, allyl, benzyl, and alkyl halides (I > Br > Cl; primary &egt; secondary &egt; tertiary)4 and monoreduces gem-dihalocyclopropanes.5 It thus allows the removal of a tertiary hydroxy group (eq 1) while all other classical methods were unsuccessful.6

NiCRAs are sensitive to the nature and structure of the halides and allow selective reductions of polyhalogenated substrates, as exemplified in eq 2.5

Except with substrates very sensitive to bases, chemoselective reduction of halides may be easily performed in the presence of alkoxy, acetal, hydroxy, OTHP, carboxy, alkoxycarbonyl, keto, and cyano groups.5 No elimination takes place with 1,2-alkoxy halides (eqs 3 and 4).

NiCRAs are much more powerful than ZnCRAs (see Zinc Complex Reducing Agents) in the reduction of halides. t-C5H11ONa-NiCRA (4.1.1) reduces all classes of ketones or aldehydes and is not very sensitive to steric hindrance.7,8 The efficiency of the reduction may be increased by the addition of electrophilic salts such as Magnesium Bromide or Lithium Chloride (eqs 5 and 6).

Under appropriate conditions, t-C5H11ONa-NiCRAs easily epimerize alcohols.9 This property may be used to reduce ketones with a very high selectivity for the most stable alcohol. In such reactions t-C5H11ONa may be advantageously replaced by the sodium salt of 2,5-dimethyl-2,5-hexanediol.8b

In the presence of Chlorotrimethylsilane (1 equiv), t-C5H11ONa-NiCRA (5.2.1) (or 5.1.1) (t-C5H11ONa-NiCRASi) very efficiently reduces carbon-carbon double bonds. The reagent is sensitive to steric hindrance as well as to electronic effects and allows the selective reduction of dienes, unsaturated ketones, esters, and acids.10 The high selectivity is illustrated in eqs 7-9.

t-C5H11ONa-NiCRA (4.1.1) also selectively reduces a number of a,b-unsaturated ketones, although sometimes less efficiently than t-C5H11ONa-NiCRASi.11 In the reduction of unsaturated carbonyl substrates, NiCRAs are complementary to ZnCRAs, which only reduce the carbonyl groups.

t-C5H11ONa-NiCRA (4.2.1) regioselectively reduces epoxides,12 with the major or only product formed coming from the regioselective attack on the most hindered carbon. This regioselectivity is opposite to that observed with ZnCRAs.

Finally, anilines are easily prepared from the corresponding nitro derivatives using t-C5H11ONa-NiCRA (7.1.1) as the reducing agent.13

Reductive Desulfurization.

t-C5H11ONa-NiCRAs as such or in the presence of a ligand (t-C5H11ONa-NiCRALs) very efficiently and chemoselectively desulfurize thiols, thioethers, dithioacetals, sulfoxides, and sulfones.14 Ketones, esters, and carbon-carbon double bonds are tolerated (eqs 10-12). Under appropriate conditions, monodesulfurization of dithioacetals may be easily performed (eq 13).

Coupling Reactions.

t-C5H11ONa-NiCRALs very efficiently couple aryl as well as heteroaryl halides (eqs 14 and 15).15

Unsymmetrical cross-couplings may be performed in fair to good yields simply by addition of two aryl halides to the reagent (eq 16).

Hydrogenation Catalyst.

A nonpyrophoric hydrogenation catalyst, referred to as Nic, may be easily obtained from t-C5H11ONa-NiCRA by simple addition of a catalytic amount of the reagent to the reaction medium when the solvent is protic. In aprotic solvent, NaH is neutralized with t-C5H11OH before use. If necessary, soluble alkoxide is removed by washing with EtOH (Nicw). Nic is very efficient in atmospheric hydrogenation of carbon-carbon double bonds, ketones, and aldehydes and in the selective partial hydrogenation of carbon-carbon triple bonds.16

Related Reagents.

Sodium Hydride-Nickel(II) Acetate-Sodium t-Pentoxide.


1. Caubère, P. Top. Curr. Chem. 1978, 73, 50; AG(E) 1983, 22, 599; PAC 1985, 57, 1875; Rev. Heteroatom Chem. 1991, 4, 78.
2. Brunet, J. J.; Besozzi, D.; Courtois, A.; Caubère, P. JACS 1982, 104, 7130.
3. Guillaumet, G.; Mordenti, L.; Caubère, P. JOM 1975, 92, 43 (CA 1975, 83, 131 349g).
4. Vanderesse, R.; Brunet, J. J.; Caubère, P. JOC 1981, 46, 1270.
5. Guillaumet, G.; Mordenti, L.; Caubère, P. JOM 1975, 102, 353 (CA 1976, 84, 73 704b).
6. Jamart-Grégoire, B.; Fort, Y.; Zouaoui, M. A.; Caubère, P. SC 1993, 23, 885.
7. Brunet, J. J.; Mordenti, L.; Caubère, P. JOC 1978, 43, 4804.
8. (a) Feghouli, A.; Fort, Y.; Vanderesse, R.; Caubère, P. TL 1988, 29, 1379. (b) Fort, Y.; Feghouli, A.; Vanderesse, R.; Caubère, P. JOC 1990, 55, 5911.
9. Feghouli, G.; Vanderesse, R.; Fort, Y.; Caubère, P. TL 1988, 29, 1383. Vanderesse, R.; Feghouli, G.; Fort, Y.; Caubère, P. JOC 1990, 55, 5916.
10. Fort, Y.; Vanderesse, R.; Caubère, P. TL 1986, 27, 5487.
11. Mordenti, L.; Brunet, J. J.; Caubère, P. JOC 1979, 44, 2203.
12. Fort, Y.; Vanderesse, R.; Caubère, P. TL 1985, 26, 3111.
13. Feghouli, G.; Vanderesse, R.; Fort, Y.; Caubère, P. JCS(P1) 1989, 2069.
14. Becker, S.; Fort, Y.; Vanderesse, R.; Caubère, P. TL 1988, 29, 2963. Becker, S.; Fort, Y.; Vanderesse, R.; Caubère, P. JOC 1989, 54, 4848. Becker, S.; Fort, Y.; Caubère, P. JOC 1990, 55, 6194.
15. Vanderesse, R.; Brunet, J. J.; Caubère, P. JOM 1984, 264, 263. Vanderesse, R.; Fort, Y.; Becker, S.; Caubère, P. TL 1986, 27, 3517. Vanderesse, R.; Lourak, M.; Fort, Y.; Caubère, P. TL 1986, 27, 5483. Lourak, M. Thesis, University of Nancy I, 1990. Lourak, M.; Vanderesse, R.; Fort, Y.; Caubère, P. TL 1988, 29, 545. Lourak, M.; Vanderesse, R.; Fort, Y.; Caubère, P. JOC 1989, 54, 4840. Lourak, M.; Vanderesse, R.; Fort, Y.; Caubère, P. JOC 1989, 54, 4844.
16. Brunet, J. J.; Gallois, P.; Caubère, P. JOC 1980, 45, 1937. Gallois, P.; Brunet, J. J.; Caubère, P. JOC 1980, 45, 1946.

Paul Caubère

University of Nancy I, France



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