LETTER
Nb-Catalyzed Reduction of Monofluoroarenes with LiAlH4
1283
Table 3 Scope and Limitations
dition of LiAlH4 onto the arene ligand of 3 takes place10,11
and the resulting anionic charge is delocalized effectively
when an extra phenyl group is placed para or ortho to the
fluorine atom. Subsequent elimination of fluoride from
the resulting intermediate 4 gives h6-arene complex 5.
Liberation of the arene product from 5 regenerates niobi-
um(III) species 2, which allows the reaction to proceed
catalytically.12
NbCl5 5 mol%
LiAlH4
ArF
+
ArH
DME, 85 °C
2 mol. amt.
Entry ArF
Time
(h)
ArH
Yield
(%)a
Ph2
1
4.0
91 (–)
90 (–)
Ph
F
F
F
LiAlH4, DME
2
10.0
NbCl5
[NbX3H2(DME)]
– H2
1
Ph
Ph
Ar
H
Ar
F
EtO
EtO
[NbX3(DME)]
3
10.2
4.0b
Quant. (–)
Ph
Ph
2
4
5
–
98 (–)
Ph2
H
F
Ph
Ph
Ph
F
Cl
F
19
0.6
– (76)
(DME)NbX3
(DME)NbX3
H
F
F
Ph2
6
7
5
3
6.0
4.0
91 (–)
64 (34)
F
Ph
Ph
Ph
Ph
Ph
F
LiAlH4
(DME)NbX3
8
9
8.0c
90 (–)
93 (–)
90 (–)
Ph
OEt
4
OEt
Scheme 1 Supposed reaction mechanism
Ph2
F
F
4.0
In summary, we found that NbCl5 catalyzes reduction of
monofluoroarenes with LiAlH4.
Ph2
10
8.0d
Br
References
F
11
2.2
81 (–)
(1) For review, see: (a) Kiplinger, J. L.; Richmond, T. G.;
Osterberg, C. E. Chem. Rev. 1994, 94, 373. (b) Alonso, F.;
Beletskaya, I. P.; Yus, M. Chem. Rev. 2002, 102, 4009.
(2) For examples, see: (a) Aizenberg, M.; Milstein, D. Science
1994, 265, 359. (b) Aizenberg, M.; Milstein, D. J. Am.
Chem. Soc. 1995, 117, 8674. (c) Edelbach, B. L.; Jones, W.
D. J. Am. Chem. Soc. 1997, 119, 7734. (d) Braun, T.;
Cronin, L.; Higgitt, C. L.; McGrady, J. E.; Perutz, R. N.;
Reinhold, M. New J. Chem. 2001, 25, 19. (e) Kraft, B. M.;
Jones, W. D. J. Organomet. Chem. 2002, 658, 132.
(f) Laev, S. S.; Evtefeev, V. U.; Shteingarts, V. D. J.
Fluorine Chem. 2001, 110, 43.
(3) For examples of stoichiometric reductions, see:
(a) Imamoto, T.; Takeyama, T.; Kusumoto, T. Chem. Lett.
1985, 1491. (b) Kraft, B. M.; Lachicotte, R. J.; Jones, W. D.
J. Am. Chem. Soc. 2001, 123, 10973. (c) For catalytic
reductions, see: Li, H.; Liao, S.; Xu, Y. Chem. Lett. 1996,
1059. (d) See further: Yang, H.; Gao, H.; Angelici, R. J.
Organometallics 1999, 18, 2285. (e) Young, R. J. Jr.;
Grushin, V. V. Organometallics 1999, 18, 294. (f) Kuhl, S.;
Schneider, R.; Fort, Y. Adv. Synth. Catal. 2003, 345, 341.
(g) Cellier, P. P.; Spindler, J.-F.; Taillefer, M.; Cristau, H.-J.
Tetrahedron Lett. 2003, 44, 7191. (h) See also: Yus, M.
Synlett 2001, 1197.
6.0d
–
F
F
91 (–)
Ph2
12
13
F
F
Ph
F
0.25e
Ph
– (6)
80
PhCH2Ph
14
6.2
13 (76)
PhCH2
F
a Recoveries of starting material are indicated in parentheses (%).
b 3.5 molar amounts of LiAlH4 was used.
c 10 Mol% of NbCl5 and 10 mol% of Et3N were used.
d 10 Mol% of NbCl5 and 6 molar amounts of LiAlH4 were used.
e 6 Molar amounts of LiAlH4 was used. A few percents yield of
m-hydrodefluorinated product was detected by GC-MS analysis.
and trifluorobiphenyl mainly gave 80% yield of a p-hy-
drodefluorinated product after 15 minutes reflux (entry
13). 2) An assistance of an extra phenyl group on fluo-
robenzene ring was necessary for the reaction to proceed
because p-benzyl(fluoro)benzene afforded only 13%
yield of diphenylmethane (entry 14).
Based on the substituent effect mentioned as above, we
now surmise that aromatic nucleophilic substitution might
take place (Scheme 1): NbCl5 and LiAlH4 undergo hy-
dride-halogen exchange to give niobium(V) di- or polyhy-
dride species 1 and subsequent reductive elimination of
dihydrogen7 forms niobium(III) species 2.8 Compound 2
undergoes complexation with the fluoroarene to form the
18-electron h6-arene complex 39 which contains a DME
molecule as a bidentate ligand. Aromatic nucleophilic ad-
(4) Oshima and Sato reported reduction of organic compounds
employing stoichiometric amounts of low valent niobium
species generated from NbCl5 and NaAlH4. See: Sato, M.;
Oshima, K. Chem. Lett. 1982, 157.
(5) p-Fluorobiphenyl reacted with LiAlH4 alone to give 13%
yield of biphenyl and 81% recovery of the starting material
after 4 h reflux in DME.
(6) Typical Procedure: To a DME solution (3 mL) of p-
fluorobiphenyl (217 mg, 1.26 mmol) and NbCl5 (17 mg, 0.06
mmol) was added LiAlH4 (96 mg, 2.52 mmol) in one
Synlett 2004, No. 7, 1282–1284 © Thieme Stuttgart · New York