NICKEL BORIDE 1
reduces mono-, di-, tri-, and tetrasubstituted alkenes under mild
Nickel Boride1
conditions (1 atm H2, rt) while leaving many groups unaffected
(e.g. a phenyl ring). There is a significant difference in the rate of
Ni2B
reduction among the various substituted alkenes allowing for se-
lectivity. However, P2 Ni is very sensitive to steric hindrance and
(Ni2B)2
to the alkene substitution pattern. Little or no hydrogenolysis of
[12007-01-1] BNi2 (MW 128.19)
allylic, benzylic, or propargylic substituents is observed with this
InChI = 1/B.2Ni/rBNi2/c1-2-3-1
catalyst; partial reduction of alkynes and dienes are also possible.
InChIKey = WRLJWIVBUPYRTE-QAXWXQGDAA
Some examples of the use of P2 Ni as a hydrogenation catalyst
are shown in Table 1.
(selective hydrogenation catalyst,1a,c,3 desulfurization catalyst;4
reduces nitro5 and other functional groups;1a dehalogenation
catalyst;1b,6 hydrogenolysis7 catalyst)
Table 1 Reduction of alkenes, dienes, and alkynes with P2 Ni
ć%
Physical Data: mp 1230 C.8
Substrate Product Yield (%) Ref.
Solubility: insol aqueous base and most organic solvents; reacts
1-Hexyne Hexane 16 9a
with concentrated aqueous acids.
1-Hexene 68
Form Supplied in: black granules, stoichiometry varies with sup-
Starting material 16
plier.
3-Hexyne Hexane 1 9a
Preparative Methods: to a stirred suspension of 1.24 g (5 mmol)
cis-3-Hexene 96
of powdered Nickel(II) Acetate in 50 mL of 95% ethanol is
trans-3-Hexene 3
added 5 mL of a 1Msolution of Sodium Borohydride in 95%
2-Methyl-1,5-hexadiene 2-Methylhexane 2 9a
ethanol at room temperature (control frothing). Stirring is con- 2-Methyl-1-hexene 96
Other methylhexenes 2
tinued until the gas evolution ceases (usually 30 min). The flask
1,3-Cyclohexadiene Cyclohexane 2 9a
is used directly in the hydrogenation.1c,9a This catalyst is non-
Cyclohexene 89
pyrophoric.
Benzene 9
Handling, Storage, and Precautions: caution must be taken
1-Penten-3-ol 3-Pentanol 100 9a
in handling nickel salts. Ingestion of soluble nickel salts
OH OH
causes nausea, vomiting, and diarrhea. Nickel chloride has an O O
94 14
O O
LD50 (iv) = 40 80 mg kg-1 in dogs. Many nickel salts will
sublime in vacuo. Nickel metal is carcinogenic and certain
F CO2H F CO2H
nickel compounds may reasonably be expected to be carcino-
genic. 75 15
F F
TBSO
H
Catalyst Composition and Structure. The composition of
( )4
the catalyst produced by the reaction of NiII salts and Sodium
100 16
Borohydride is dependent on reaction conditions (solvent, sto-
TBSO
( )3
ichiometry, temperature, etc.).9 X-ray photoelectron spectro-
H
CO2H
( )4 ( )3CO2H
scopy10 showed that the main difference between the P1 form
of nickel boride (P1 Ni) and the P2 form of nickel boride (P2 Ni)
is the amount of NaBO2 adsorbed on to the surface of the catalyst.
O O
P1 Ni (which is prepared in water) has an oxide:boride ratio of 70 17
O O
O O
1:4, while P2 Ni (which is prepared in ethanol) has a ratio of 10:1.
Early studies of the reaction of borohydrides with transition metal
salts11 (FeII, CuII, PdII, NiII, CoII, etc.) showed that the reaction
H H
product is either the metal (as in the case of PdII) or a black granu- H
H
lar solid (as in the case of NiII); in both cases, H2 is evolved.11c,12 O O
50 18
Analysis of the black solid formed from the NiII suggested the
O O
O
H
HO HO
catalyst to be a boride.11c,13 Paul et al.11b examined several NiII O H
salts and found nickel acetate to be most acceptable.
Hydrogenation of Alkenes and Alkynes. Brown has de-
scribed two forms of nickel boride (P1 Ni and P2 Ni)9 which are Under more forcing conditions (30 psi in a Parr apparatus),
hydrogenation catalysts. In a comparison of P1 Ni to W2 Raney Russell19 was able to reduce unsaturated ethers, alcohols, alde-
Nickel (Ra Ni) as a hydrogenation catalyst, P1 Ni was found to be hydes, esters, amines, and amides to their saturated counterparts
somewhat more active (as measured by the t1/2 for hydrogenation without hydrogenolysis. Unsaturated nitriles19b were reduced to
of several alkenes).9a What is more important in the comparison primary amines while epoxides were unaffected by the reagent.
of Ra Ni and P1 Ni is the lower incidence of double-bond iso- Both dimethoxyborane (eq 1)20 and Lithium Aluminum Hydride
merization observed with P1 Ni vs. Ra Ni (3% vs. 20%). P1 Ni (eq 2)21 can replace NaBH4 in these reactions.
Avoid Skin Contact with All Reagents
2 NICKEL BORIDE
O O
(MeO)2BH (8 equiv)
1963, Truce and Roberts24 reported the use of NiCl2/NaBH4 in
NiB2 (0.5 equiv)
the partial cleavage of a dithioacetal (eq 4).
(1)
MeOH
93%
O
O
NiCl2, NaBH4
(4)
H H
1. LiBH4 (0.5 equiv)
reflux
NiCl2 (0.5 equiv)
PhS SPh 71% PhS
(2)
2. CH2N2
95%
H H
Since then, there have been numerous examples of the use of
CO2HCO2Me
NiII salt/NaBH4 in desulfurization reactions;.4 in many cases the
yields are greater than those seen with Raney nickel25 (eq 5) (note:
caution must be exercised when using NaBH4 in DMF).
Heteroarenes. Nose and Kudo22 examined the reduction of
quinaldine (1) with a variety of transition metal salts (CoCl2,
H
S H
NiCl2, CuCl2, CrCl3) in the presence of NaBH4; only Nickel(II) NiCl2, NaBH4
DMF
Chloride was effective (eq 3).
S
(5)
90%
OAc
OAc
Raney Ni gave 85%
NiCl2 (1.4 mmol)
H
H
NaBH4 (32 mmol)
(3)
N N
MeOH, rt
H
93%
(1)
Boar et al.26 used nickel boride in a protection deprotection
scheme for triterpenoid ketones (eq 6).
Partial reduction of a series of heteroaromatics was examined
using NiCl2/NaBH4 in methanol at room temperature (Table 2).
The authors suggest that the reduction proceeds through a NiCl2
NiCl2, NaBH4
complex of the arene; however, other workers1a dispute this mech-
EtOH, H2O
anism.
H3BO3
S
Table 2 Reduction of heteroaromatics with NiCl2/NaBH4
O
Substrate Product Yield (%)
CrO3
+ (6)
83
HO O O
N
H
N
mixture is not separated 87% from acetal
H
N
N
99
NiII/NaBH4 is an effective reagent for desulfurization of thioa-
N
H mides,27 thioethers,28 and sulfides.4,29 Back and co-workers4,30
N
has reported extensive studies of the scope, stereochemistry, and
mechanism of nickel (and cobalt) boride desulfurizations. In gen-
96
NH
N
eral, nickel boride is a more effective desulfurization catalyst
than Cobalt Boride (other metals such as Mo, Ti, Cu, and Fe
were completely ineffective). Lithium Borohydride can be used
83
in place of NaBH4 while Sodium Cyanoborohydride cannot.
N
Sulfides, thioesters, thiols, disulfides, and sulfoxides are reduced
H
N
to hydrocarbons by Ni2B, while sulfoxides are stable. Esters,
H
chloro groups, and phenyl groups are stable to Ni2B. Iodides, ni-
N
N
tro groups, nitriles, and alkenes are reduced completely by Ni2B,
54
while bromides, aldehydes, ketones, and cyclopropanes show vari-
N
H
N
able reactivity (eqs 7 10).
H
N
N
52
Ni2B
Ph
C7H15Ph + (7)
Ph
N
(3.5 equiv)
H
N
SPh
24% 52%
O
Ni2B
Desulfurization. While Raney nickel23 is the traditional re-
(8)
PhCH2OH
agent for desulfurization reactions, it has several drawbacks (i.e.
(3.5 equiv)
Ph SPh
91%
strongly basic, pyrophoric, sensitivity to air and moisture). In
A list of General Abbreviations appears on the front Endpapers
NICKEL BORIDE 3
H H
Ni2B
N N
Table 3 Reduction of nitroarenes with NiII/borohydride reagents
(9)
(3.5 equiv)
Substrate Reagent Product Yield (%)
68%
S
PhNO2 2 equiv Ni2B, MeOH PhNH2 35a
PhNO2 1 equiv Ni2B, 15N NH4OH PhNH2 965a
Br
PhNO2 0.1 equiv Ni2B, 5 equiv Azoxybenzene 895b
Ni2B
NaBH4
+ biphenyl (10)
(3.5 equiv) 4-ClC6H4NO2 1 equiv Ni2B, 3N HCl 4-ClC6H4NH2 965a
S
S 4-CNC6H4NO2 2 equiv Ni2B, 3N HCl 4-CNC6H4NH2 605a
11% 77%
6-Nitroquinoline 1 equiv Ni2B, 15N NH4OH 6-Aminoquinoline 865a
1-Nitronaphthalene NiCl2 NaBH4 (2:1) 1-Aminonaphtha- 855d
lene
Using deuterium labelling, Back showed that desulfurization
4-IC6H4NO2 4 equiv Ni2B, IN HCl 4-IC6H4NH2 7634
occurs with retention of configuration, unlike Raney nickel, which
NO2 NH2
involved a radical mechanism. The suggested mechanism of desul-
CO2Me CO2Me
furization involves an oxidative addition reductive elimination se- 8534
4 equiv Ni2B, IN HCl
quence via a nickel hydride intermediate.
I I
Reduction of Other Nitrogenous Functional Groups. Pri-
mary, secondary, and tertiary aliphatic nitro groups are reduced
Table 4 Reduction of oximes to amines with NiCl2/NaBH4
to amines with NiCl2/NaBH4.5c Hydrazine hydrate has also been
Substrate Product Yield (%)
used with Ni2B to reduce both aryl and aliphatic nitro groups in a
synthesis of tryptamine (eqs 11 and 12).31
NH2
BnO
BnO
Ni2B 92
NOH NH2
N2H2" H2O
N
(11)
91%
1:2
N
NO2 H
NHOH NH2
NO2 NH2
95
Ni2B
BnO BnO
N2H2" H2O
(12)
71%
NOH
N N
H H
NH2
90
Reductive cleavage of thioethers and reduction of nitro groups NH2
has been combined in a synthesis of pyrrolidones (eq 13).32
1:1
NOH NH2
PhS NO2 SPh
NiCl2
70
MeOC(O) CO2Me
MeOH
57%
Isoxazoles are reduced to ²-amino enones in high yield us-
CO2Me CO2Me
+ (13)
ing the NiCl2/NaBH4 system.38 Dihydroisoxazolones are reduced
O O
N N
with a high degree of diastereoselectivity with the NiCl2/NaBH4
H H
1:1
system.39
Like Co2B, Ni2B5b reduces nitroarenes to anilines and azoxy-
Dehalogenation. Many Ä…-bromo ketones6a are cleanly re-
benzenes to azobenzenes (Table 3); unlike Co2B, Ni2B reduces
duced to the parent ketone with nickel boride in DMF (caution).
oximes33 to amines (Table 4).
Vicinal dibromides are reduced to alkenes (eq 15).
Reduction of Other Nitrogenous Functional Groups. HO HO
Borane Tetrahydrofuran/NiCl2 has been used to reduce chiral
NiCl2, NaBH4
(15)
cyanohydrins to ethanol amines in high yield.35 Azides are cleanly
DMF
reduced to amines in good yield with nickel boride.36 Azides are
O O
80%
O O
Br
reduced in preference to hindered aliphatic nitro groups (eq 14).37 Br
O O
O OMe
O OMe
NiCl2 (1 equiv)
NaBH4 (4 equiv)
Aryl and certain alkyl chlorides can be dehalogenated1a,1b,6b
(14)
N3
H2N
EtOH
with a variety of NiII/hydride agents (e.g. NaBH2(OCH2CH2
NO2
NO2
OMe)2, Triethylsilane, NaBH4). Lin and Roth have effected the
Avoid Skin Contact with All Reagents
4 NICKEL BORIDE
NiCl2 (1 equiv)
clean debromination of aryl bromides40 using Dichlorobis(tri- NHTs NHTs
NaBH4 (20 equiv)
phenylphosphine)nickel(II)/NaBH4 in DMF (caution); Tris(tri- (24)
MeOH
phenylphosphine)nickel(0) is assumed to be the active catalyst. OTs
95%
Russel and Liu41 demonstrated that reductive cleavage of an OTs
iodide goes with retention when NiCl2/NaBH4 is used (cf. in-
version seen with LiAlH4; eq 16).
O OTs
OH
NiCl2 (1 equiv)
NaBH4 (20 equiv)
O OMe
O OMe
NaBD4, NiCl2
(25)
O
O
(16)
MeOH
EtOH
77%
Ph
O OBz Ph
O OBz
94%
I
D
A variety of allylic functional groups44 (alcohols, esters, silyl
ethers, ketones, and hydroperoxides) have been reduced with
Hydrogenolysis. Ni2B has been used to hydrogenolyze ben- Ni2B. The combination of Chlorotrimethylsilane/Ni2B will se-
zylic (eqs 17 19),7a allylic (eqs 20 22),7b,42 and propargylic lectively reduce an aldehyde in the presence of a ketone.45
(eq 23)7b esters in good yields. Selenides46 and tellurides47 are reductively cleaved by Ni2B
with retention of stereochemistry. The phenyl selenyl group is
NiCl2, NaBH4
cleaved in preference to the thio phenyl group.
OAc (17)
(2:1)
95%
Me2N
Me2N
1. (a) Ganem, B.; Osby, J. O., Chem. Rev. 1986, 86, 763. (b) Wade, R.,
CO2Me CO2Me
J. Mol. Catal. 1983, 48, 273. (c) Hudlicky, M.; Reductions in Organic
NiCl2, NaBH4
Chemistry; Wiley: New York, 1984.
(18)
OAc
(2:1)
2. It should be noted that Ni2B represents a nominal stoichiometry for the
76%
reagent prepared by the action of NaBH4 on a NiII salt. Several NixBy
species have been described in the literature. Chemical Abstracts uses the
OAc OAc OAc
NiCl2, NaBH4
registry number [12619-90-8] to designate nickel boride of unspecified
(19)
stoichiometry. [12007-02-2] and [12007-00-0] are the registry numbers
(2:1)
for Ni3B and NiB, respectively. These are the most widely cited
83%
synthetically useful reagents.
NiCl2, NaBH4 3. (a) Brown, C. A., J. Org. Chem. 1970, 35, 1900. (b) Brown, C. A.; Ahuja,
OAc (20)
V. K., J. Org. Chem. 1973, 38, 2226.
(2:1)
93% 4. (a) Back, T. G.; Baron, D. L.; Yang, K., J. Org. Chem. 1993, 58, 2407.
(b) Back, T. G.; Yang, K.; Krouse, R. H., J. Org. Chem. 1992, 57, 1986.
5. (a) Nose, A.; Kudo, T., Chem. Pharm. Bull. 1989, 37, 816. (b) Nose, A.;
Kudo, T., Chem. Pharm. Bull. 1988, 36, 1529. (c) Osby, J. O.; Ganem, B.,
OAc
Tetrahedron Lett. 1985, 26, 6413. (d) Nose, A.; Kudo, T., Chem. Pharm.
NiCl2, NaBH4
Bull. 1981, 29, 1159.
+ (21)
2:1
6. (a) Sarma, J. C.; Borbaruah, M.; Sharma, R. P., Tetrahedron Lett. 1985,
95%
26, 4657. (b) Tabaei, S-M. H.; Pittman, C. V., Tetrahedron Lett. 1993,
34, 3264.
1:1
7. (a) He, Y.; Pan, X.; Wang, S.; Zhao, H., Synth. Commun. 1989, 19, 3051.
(b) Ipaktschi, J., Chem. Ber. 1983, 117, 3320 (Chem. Abstr. 1985, 102,
94 904x).
H
8. This is the melting point of Ni2B formed by fusion of the elements Adv.
OH
O
NiCl2, NaBH4
HO
Chem. Ser. 1961, 32, 53). Material prepared by the reduction of NiCl2
ć%
O
(2:1) with NaBH4 begins to decompose at 100 C when heated in vacuo with
H
100%
liberation of H2 (Maybury, P. C.; Mitchell, R. W.; Hawthorne, M. F., J.
MeO
O
Chem. Soc. (C) 1974, 534).
H
9. (a) This procedure provides the P2 form of nickel boride, which is a
OH
selective hydrogenation catalyst. Brown, H. C.; Brown, C. A., J. Am.
HO
(22) Chem. Soc. 1963, 85, 1005. (b) Brown, H. C.; Brown, C. A., J. Am. Chem.
H
H
Soc. 1963, 85, 1003. This paper reports the preparation and properties of
O
MeO P1 nickel boride. P1 nickel boride is more active, in some applications,
O
than Raney nickel. (c) Destefanis, H.; Acosta, D.; Gonzo, E., Catal.
Today 1992, 15, 555. This group describes the use of BH3jHF complex
to prepare Ni3B and Ni4B3 using Ni(OAc)2 and NiCl2, respectively,
and their use as hydrogenation catalysts.
NiCl2, NaBH4
(23)
OAc 10. Schreifels, J. A.; Maybury, C. P.; Swartz, W. E., J. Org. Chem. 1981, 46,
(2:1)
AcO
OAc 1263.
35%
11. (a) Paul, R.; Buisson, P.; Joseph, N., Ind. Eng. Chem. 1952, 44, 1006
(Chem. Abstr. 1952, 46, 9960e). (b) Paul, R.; Buisson, P.; Joseph, N.,
Enol tosylates and aryl tosylates are deoxygenated in good to C. R. Hebd. Seances Acad. Sci., Ser. C 1951, 232, 627 (Chem. Abstr.
1951, 45, 10 436h). (c) Schlesinger, H. R.; Brown, H. C.; Finholt, A. E.;
excellent yields43 (eqs 24 and 25)
Gilbreath, J. R.; Hoekstra Hyde, E. K., J. Am. Chem. Soc. 1953, 75, 215.
A list of General Abbreviations appears on the front Endpapers
NICKEL BORIDE 5
12. Brown, H. C.; Brown, C. A., J. Am. Chem. Soc. 1962, 84, 1493. 33. Ipaktschi, J., Chem. Ber. 1984, 117, 856 (Chem. Abstr. 1984, 101, 22
611f).
13. A boride of the same composition had been previously described (Stock,
A.; Kuss, E., Chem. Ber. 1914, 47, 810 (Chem. Abstr. 1914, 8, 2129). 34. Seltzman, H. H.; Berrang, B. B., Tetrahedron Lett. 1993, 34, 3083.
14. Jefford, C. W.; Jaggi, D.; Bernardinelli, G.; Boukouvalas, J., Tetrahedron 35. Lu, Y.; Meit, C.; Kunesch, N.; Poisson, J., Tetrahedron: Asymmetry 1990,
Lett. 1987, 28, 4041. 1, 707.
15. Novak, J.; Salemink, C. A., J. Chem. Soc., Perkin Trans. 1 1982, 2403. 36. Sarma, J. C.; Sharma, R. P., Chem. Ind. (London) 1987, 764.
16. Miller, J. G.; Ochlschlager, A. C., J. Org. Chem. 1984, 49, 2332. This 37. Guilano, R. M.; Deisenroth, T. W., J. Carbohydr. Res 1987, 6, 295.
reaction uses TMEDA as an additive.
38. (a) Koroleva, E. V.; Lakhvich, F. A.; Yankova, T. V., Khim. Geterotsikl.
17. Kido, F.; Abe, T.; Yoshikoshi, A., J. Chem. Soc. (C) 1986, 590. Soedin. 1987, 11, 1576 (Chem. Abstr. 1988, 109, 928 546). (b) Oliver, J.
E.; Lusby, W. R., Tetrahedron 1988, 44, 1591.
18. Lee, K-H.; Ibuka, T.; Sims, D.; Muraoka, O.; Kiyokawa, H.; Hall, I.
H.; Kim, H. L., J. Med. Chem. 1981, 24, 924. When Pt2O was used, 39. (a) Lakhvich, F. A.; Koroleva, E. V.; Antonevich, I. Q.; Yankova, T.
only 20% of the desired product was isolated; the major product was the V., Zh. Org. Khim. 1990, 26, 1683 (Chem. Abstr. 1991, 114, 81 311).
tetrahydro compound. (b) Annunziata, R.; Cinquini, M.; Cozzi, F.; Gilardo, A.; Restelli, A., J.
Chem. Soc., Perkin Trans. 1 1985, 2289.
19. (a) Russell, T. W.; Hoy, R. C., J. Org. Chem. 1971, 36, 2018. (b) Russell,
T. W.; Hoy, R. C.; Cornelius, J. E., J. Org. Chem. 1972, 37, 3552. 40. Lin, S. T.; Roth, J. A., J. Org. Chem. 1979, 44, 309.
20. Nose, A.; Kudo, T., Chem. Pharm. Bull. 1990, 38, 1720. 41. Russel, R. N.; Liu, H. W., Tetrahedron Lett. 1989, 30, 5729.
21. Jung, M.; Elsohly, H. N.; Croon, E. M.; McPhail, D. R.; McPhail, A. T., 42. Jiang, B.; Zhao, H.; Pan, X.-F., Synth. Commun. 1987, 17, 997.
J. Org. Chem. 1986, 51, 5417.
43. Wang, F.; Chiba, K.; Tada, M., J. Chem. Soc., Perkin Trans. 1 1992, 1897.
22. Nose, A.; Kudo, T., Chem. Pharm. Bull. 1984, 32, 2421.
44. (a) Sarma, D. N.; Sharma, R. P., Tetrahedron Lett. 1985, 26, 2581.
23. Pettit, G. R.; van Tamelen, E. E., Org. React. 1962, 62, 347. (b) Zaman, S. S.; Sarma, J. C.; Sharma, R. P., Chem. Ind. (London)
1991, 509. (c) Sarma, D. N.; Sharma, R. P., Tetrahedron Lett. 1985, 26,
24. Truce, W. E.; Roberts, F. E., J. Org. Chem. 1963, 28, 961.
371.
25. Zaman, S. S.; Sarmah, P.; Barus, N. C.; Sharma, R. P., Chem. Ind.
45. Borbaruah, M.; Barua, N. C.; Sharma, R. P., Tetrahedron Lett. 1987, 28,
(London) 1989, 806.
5741.
26. Boar, R. B.; Hawkins, D. W.; McGhie, J. F.; Barton, D. H. R., J. Chem.
46. (a) Back, T. G.; Birss, V. I.; Edwards, M.; Krishna, M. V., J. Org. Chem.
Soc., Perkin Trans. 1 1973, 654.
1988, 53, 3815. (b) Back, T. G., J. Chem. Soc. (C) 1984, 1417.
27. Guziec, F. S.; Wasmund, L. M., Tetrahedron Lett. 1990, 31, 23.
47. (a) Barton, D. H. R.; Fekih, A.; Lusinchi, X., Tetrahedron Lett. 1985,
28. (a) Euerby, M. R.; Waigh, R. D., Synth. Commun. 1986, 16, 779.
26, 6197. (b) Barton, D. H. R.; Bohe, L.; Lusinchi, X., Tetrahedron Lett.
(b) Euerby, M. R.; Waigh, R. D., J. Chem. Soc. (C) 1981, 127.
1990, 31, 93.
29. Truce, W. E.; Perry, F. M., J. Org. Chem. 1965, 30, 1316.
30. Back, T. G.; Yang, K., J. Chem. Soc. (C) 1990, 819.
31. Lloyd, D. H.; Nichols, D. E., J. Org. Chem. 1986, 51, 4294. Thomas J. Caggiano
32. Posner, G. H.; Crouch, R. D., Tetrahedron 1990, 46, 7509. Wyeth-Ayerst Research, Princeton, NJ, USA
Avoid Skin Contact with All Reagents