NICKEL COMPLEX REDUCING AGENTS 1
and allow selective reductions of polyhalogenated substrates, as
Nickel Complex Reducing Agents1
exemplified in eq 2.5
Cl
Cl
NaH t C5H11ONa Ni(OAc)2
t-C5H11ONa NiCRA (4.2.1)
+ (2)
DME, 65 �C
Br
(NaH)
traces
96%
[7646-69-7] HNa (MW 24.00)
InChI = 1/Na.H/rHNa/h1H
Except with substrates very sensitive to bases, chemoselective
InChIKey = MPMYQQHEHYDOCL-RVEWWXDUAC
reduction of halides may be easily performed in the presence of
(t-C5H11ONa)
alkoxy, acetal, hydroxy, OTHP, carboxy, alkoxycarbonyl, keto,
[14593-46-5] C5H11NaO (MW 110.15)
and cyano groups.5 No elimination takes place with 1,2-alkoxy
InChI = 1/C5H11O.Na/c1-4-5(2,3)6;/h4H2,1-3H3;/q-1;+1
halides (eqs 3 and 4).
InChIKey = CGRKYEALWSRNJS-UHFFFAOYAC
t-C5H11ONa NiCRA (4.2.1)
(Ni(OAc)2�4H2O) OMe
OMe
DME, 65 �C
[6018-89-9] C4H14NiO8 (MW 248.87)
(3)
90%
Br
InChI = 1/2C2H4O2.Ni.4H2O/c2*1-2(3)4;;;;;/h2*1H3,(H,3,4);;
4*1H2/q;;+2;;;;/p-2/f2C2H3O2.Ni.4H2O/q2*-1;m;;;;
O
O
t-C5H11ONa NiCRA (4.2.1)
InChIKey = OINIXPNQKAZCRL-YNARRYDOCG
DME, 65 �C
O
O
(4)
(reduces many functional groups; couples organic halides; de- 100%
Br
sulfurizes organic substrates; source of hydrogenation catalyst1)
NiCRAs are much more powerful than ZnCRAs (see Zinc
Alternate Name: nickel-containing complex reducing agents
Complex Reducing Agents) in the reduction of halides. t-C5H11
(NiCRAs).
Physical Data: black solid of uncertain structure containing Ni0 ONa NiCRA (4.1.1) reduces all classes of ketones or aldehydes
and is not very sensitive to steric hindrance.7,8 The efficiency of
species.2
the reduction may be increased by the addition of electrophilic
Solubility: insol organic solvents.
salts such as Magnesium Bromide or Lithium Chloride (eqs 5
Preparative Methods: t-C5H11ONa NiCRA (x.y.z) is conven-
and 6).
iently prepared by the reaction of t-C5H11OH (y equiv) with
a mixture of Sodium Hydride (x + y equiv) and Nickel(II) Ac-
t-C5H11ONa NiCRA (4.1.1)
t-Bu
etate (z equiv) in THF or DME. Commercial NaH (55 60% in t-Bu
MgBr2, THF, 63 �C
O (5)
OH
oil) is used after three washings with anhydrous THF or DME
~100%
t-Bu
t-Bu
under N2. t-C5H11OH is distilled from sodium. Ni(OAc)2 is
ć%
dried in vacuo (15 mmHg) for 16 h at 120 130 C. Note: t-
t-C5H11ONa NiCRA (4.1.1)
OOH
C5H11ONa NiCRA (x.y.z) means a reagent obtained from x,y, MgBr2, THF, 63 �C
(6)
and z equivalents of NaH, t-C5H11ONa, and Ni(OAc)2, respec-
85%
tively.
Handling, Storage, and Precautions: NiCRAs are nonpyrophoric
Under appropriate conditions, t-C5H11ONa NiCRAs easily
but are handled and stored under inert atmosphere (N2 or, better,
epimerize alcohols.9 This property may be used to reduce ke-
Ar). Hydrolysis must be performed by slow addition of cold
tones with a very high selectivity for the most stable alcohol. In
water or EtOH to destroy the hydride.
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-C5H11
Reductions. t-C5H11ONa NiCRAs are significantly less ba-
ONa NiCRA (5.2.1) (or 5.1.1) (t-C5H11ONa NiCRASi) very ef-
sic than NaH and t-C5H11ONa. t-C5H11ONa NiCRA (4.2.1) re-
ficiently reduces carbon carbon double bonds. The reagent is sen-
duces under mild conditions and in good yields aryl halides, in-
sitive to steric hindrance as well as to electronic effects and allows
cluding aryl fluorides,3 vinyl, allyl, benzyl, and alkyl halides (I
the selective reduction of dienes, unsaturated ketones, esters, and
> Br > Cl; primary e" secondary e" tertiary)4 and monoreduces
acids.10 The high selectivity is illustrated in eqs 7 9.
gem-dihalocyclopropanes.5 It thus allows the removal of a ter-
tiary hydroxy group (eq 1) while all other classical methods were
t-C5H11ONa NiCRA (5.2.1)
1 equiv TMSCl, THF, 45 �C
unsuccessful.6
(7)
98%
O O
1. SOCl2
2. t-C5H11ONa NiCRA (4.2.1)
O
O t-C5H11ONa NiCRA (5.1.1)
THF, 63 �C
N N
OH 1 equiv TMSCl, THF, 45 �C
(1)
45% (8)
99%
n n
t-C5H11ONa NiCRA (5.1.1)
n = 2, 3
1 equiv TMSCl, THF, 45 �C
(9)
97%
O O
NiCRAs are sensitive to the nature and structure of the halides
Avoid Skin Contact with All Reagents
2 NICKEL COMPLEX REDUCING AGENTS
t-C5H11ONa NiCRA (4.1.1) also selectively reduces a number Unsymmetrical cross-couplings may be performed in fair to
of ą,�-unsaturated ketones, although sometimes less efficiently good yields simply by addition of two aryl halides to the reagent
than t-C5H11ONa NiCRASi.11 In the reduction of unsaturated (eq 16).
carbonyl substrates, NiCRAs are complementary to ZnCRAs,
which only reduce the carbonyl groups.
t-C5H11ONa NiCRA (4.2.1)
t-C5H11ONa NiCRA (4.2.1) regioselectively reduces epoxi-
2 equiv bipy, 1 equiv KI
des,12 with the major or only product formed coming from the
THF, C6H6, 63 �C
regioselective attack on the most hindered carbon. This regiose-
lectivity is opposite to that observed with ZnCRAs.
Finally, anilines are easily prepared from the corresponding ni-
MeO Br Cl CF3 Br Cl (16)
tro derivatives using t-C5H11ONa NiCRA (7.1.1) as the reducing
73%
OMe F
62%
agent.13
F
Reductive Desulfurization. t-C5H11ONa NiCRAs as such
or in the presence of a ligand (t-C5H11ONa NiCRALs) very MeO CF3
efficiently and chemoselectively desulfurize thiols, thioethers,
OMe
dithioacetals, sulfoxides, and sulfones.14 Ketones, esters, and
carbon carbon double bonds are tolerated (eqs 10 12). Under ap-
propriate conditions, monodesulfurization of dithioacetals may be
Hydrogenation Catalyst. A nonpyrophoric hydrogenation
easily performed (eq 13).
catalyst, referred to as Nic, may be easily obtained from t-C5H11
ONa NiCRA by simple addition of a catalytic amount of the
reagent to the reaction medium when the solvent is protic. In apro-
t-C5H11ONa NiCRA (5.2.1)
O O
THF, 63 �C
tic solvent, NaH is neutralized with t-C5H11OH before use. If
SMe
Ni/S = 20
necessary, soluble alkoxide is removed by washing with EtOH
(10)
90%
(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
t-C5H11ONa NiCRA (2.2.1)
Ph
Sodium t-Pentoxide.
DME, 65 �C
SO2 Ph
Ni/S = 10
(11)
96%
Ph
1. CaubŁre, P., Top. Curr. Chem. 1978, 73, 50; Angew. Chem., Int. Ed. Engl.
1983, 22, 599; Pure Appl. Chem. 1985, 57, 1875 Rev. Heteroatom Chem.
t-C5H11ONa NiCRA (5.2.1)
1991, 4, 78.
THF, 63 �C
S
Ni/S = 30
Ph
2. Brunet, J. J.; Besozzi, D.; Courtois, A.; CaubŁre, P., J. Am. Chem. Soc.
Ph
(12)
100% 1982, 104, 7130.
S
3. Guillaumet, G.; Mordenti, L.; CaubŁre, P., J. Organomet. Chem. 1975,
92, 43(Chem. Abstr. 1975, 83, 131 349g).
t-C5H11ONa NiCRA (4.2.1) 4. Vanderesse, R.; Brunet, J. J.; CaubŁre, P., J. Org. Chem. 1981, 46, 1270.
2 equiv bipy, DME, 65 �C
Ph
5. Guillaumet, G.; Mordenti, L.; CaubŁre, P., J. Organomet. Chem. 1975,
S
Ni/S = 20
Ph
(13) 102, 353 (Chem. Abstr. 1976, 84, 73 704b).
90% SEt
S
6. Jamart-Gr�goire, B.; Fort, Y.; Zouaoui, M. A.; CaubŁre, P., Synth.
Commun. 1993, 23, 885.
7. Brunet, J. J.; Mordenti, L.; CaubŁre, P., J. Org. Chem. 1978, 43, 4804.
8. (a) Feghouli, A.; Fort, Y.; Vanderesse, R.; CaubŁre, P., Tetrahedron Lett.
Coupling Reactions. t-C5H11ONa NiCRALs very effi-
1988, 29, 1379. (b) Fort, Y.; Feghouli, A.; Vanderesse, R.; CaubŁre, P.,
ciently couple aryl as well as heteroaryl halides (eqs 14 and 15).15 J. Org. Chem. 1990, 55, 5911.
9. Feghouli, G.; Vanderesse, R.; Fort, Y.; CaubŁre, P., Tetrahedron Lett.
1988, 29, 1383. Vanderesse, R.; Feghouli, G.; Fort, Y.; CaubŁre, P., J.
t-C5H11ONa NiCRA (4.2.1)
Org. Chem. 1990, 55, 5916.
2 equiv bipy, THF, 1 equiv KI
10. Fort, Y.; Vanderesse, R.; CaubŁre, P., Tetrahedron Lett. 1986, 27, 5487.
63 �C
2 Cl (14)
11. Mordenti, L.; Brunet, J. J.; CaubŁre, P., J. Org. Chem. 1979, 44, 2203.
90%
12. Fort, Y.; Vanderesse, R.; CaubŁre, P., Tetrahedron Lett. 1985, 26, 3111.
13. Feghouli, G.; Vanderesse, R.; Fort, Y.; CaubŁre, P., J. Chem. Soc., Perkin
Trans. 1 1989, 2069.
t-C5H11ONa NiCRA (4.2.1)
14. Becker, S.; Fort, Y.; Vanderesse, R.; CaubŁre, P., Tetrahedron Lett. 1988,
Cl
4 equiv Ph3P, DME, 63 �C
29, 2963. Becker, S.; Fort, Y.; Vanderesse, R.; CaubŁre, P., J. Org. Chem.
(15)
2
88%
1989, 54, 4848. Becker, S.; Fort, Y.; CaubŁre, P., J. Org. Chem. 1990,
N N
N
55, 6194.
A list of General Abbreviations appears on the front Endpapers
NICKEL COMPLEX REDUCING AGENTS 3
15. Vanderesse, R.; Brunet, J. J.; CaubŁre, P., J. Organomet. Chem. 1984, 16. Brunet, J. J.; Gallois, P.; CaubŁre, P., J. Org. Chem. 1980, 45,
264, 263. Vanderesse, R.; Fort, Y.; Becker, S.; CaubŁre, P., Tetrahedron 1937. Gallois, P.; Brunet, J. J.; CaubŁre, P., J. Org. Chem. 1980, 45,
Lett. 1986, 27, 3517. Vanderesse, R.; Lourak, M.; Fort, Y.; CaubŁre, 1946.
P., Tetrahedron Lett. 1986, 27, 5483. Lourak, M. Thesis, University
of Nancy I, 1990. Lourak, M.; Vanderesse, R.; Fort, Y.; CaubŁre, P.,
Paul CaubŁre
Tetrahedron Lett. 1988, 29, 545. Lourak, M.; Vanderesse, R.; Fort, Y.;
University of Nancy I, Nancy, France
CaubŁre, P., J. Org. Chem. 1989, 54, 4840. Lourak, M.; Vanderesse, R.;
Fort, Y.; CaubŁre, P., J. Org. Chem. 1989, 54, 4844.
Avoid Skin Contact with All Reagents