Et3SiH and Wilkinson’s catalyst effect the efficient reduction
of nitrobenzenes (Scheme 1).
quantitatively afforded aniline within 30 min. To build from
this result, the reduction of 2-nitrotoluene was screened
against a variety of palladium and fluoride sources, solvents,
and siloxanes/silanes. In the absence of a palladium catalyst
no amine formation was seen after 1 day. With the necessity
of palladium established, a number of catalysts were tested
in the reaction. Of these, Pd(OAc)2 and Pd/C gave the highest
yields (70 and 62%, respectively). In contrast, added Ph3P
or the use of phosphine-bearing catalysts shut down the
reductions. Pd(OAc)2 was selected for further optimization
studies owing to its relatively low cost and previously noted14
functional group tolerance.
Scheme 1. Previous Examples of Nitroarene Reductions
Using Silyl Hydrides10,13
To learn the importance of fluoride in the reductions,
reactions were run fluoride free. Under such conditions, no
amine products were observed after 1 h, but at 24 h
2-aminotoluene was obtained in 50% yield. Presumably,
fluoride aids formation of polycoordinate siloxane intermedi-
ates, allowing for facile transfer of the hydride.8b In this role,
most simple anhydrous alkaline fluoride salts (LiF, NaF, KF,
CsF) proved equally effective. TBAF could also be em-
ployed, but only when used in substoichiometric amounts
(10 mol %) and under cryogenic (-78 °C) conditions. Use
of 1 equiv of TBAF at -78 °C or in any amount at room
temperature caused the reaction mixtures to turn into a solid
mass via sol-gel formation.
Changing the reaction solvent dramatically affected reac-
tion efficiency. Reductions in THF and EtOAc gave the
highest yields, whereas only starting material was recovered
with reactions run in DMF or NMP. Perhaps most surpris-
ingly, catalyst insolubility and gel formation upon prolonged
stirring in Et2O were observed.
Recent studies of PMHS as a reagent for organic synthesis
suggest that additional opportunities may exist for its use in
nitro reductions. Prior work on the reactivity of PMHS in
the presence of transition-metal catalysts revealed that the
combination of catalytic Pd(OAc)2, PMHS, and aqueous KF
will efficiently and mildly hydrodehalogenate aryl chlo-
rides,14 allow for 1,4-reduction of enones,15 and facilitate the
reductive cleavage of benzylic C-O bonds, all at room
temperature.16 The reactivity of this reduction system is likely
due in part to the formation of palladium nanoparticles, as
recognized by Chauhan.17
While screening substrates in Pd(OAc)2/PMHS/KF deha-
logenations,14 we found that 1-chloro-4-nitrobenzene was
converted to aniline (Scheme 2). Given this result, the limited
Scheme 2. Preliminary Pd(OAc)2/PMHS/KF Nitro Reduction
Nearly all silanes and siloxanes screened (Table 1) were
able to efficiently reduce 2-nitrotoluene to 2-aminotoluene
Table 1. Silane/Siloxane Screening
nature of prior works, and the low toxicity and cost of
PMHS12 and related silyl hydrides, a full study on nitro
reductions using Pd(OAc)2/PMHS/KF was warranted.
To begin, we simply subjected nitrobenzene to our
dehalogenation conditions. Gratifyingly, these conditions
%
%
(12) For reviews of PMHS as a reagent for organic synthesis, see: (a)
Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin Trans.
1 1999, 3381-3391. (b) Lavis, J. M.; Maleczka, R. E., Jr. Polymethyl-
hydrosiloxane (PMHS). In eEROS-Electronic Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Crich, D., Fuchs, P. L., Wipf, P., Eds.;
Wiley: New York 2003; [Online].
(13) Brinkman, H. R.; Miles, W. H.; Hilborn, M. D.; Smith, M. C. Synth.
Commun. 1996, 26, 973-980.
(14) Rahaim, R. J., Jr.; Maleczka, R. E., Jr. Tetrahedron Lett. 2002, 43,
8823-8826.
entry
Si-H species
PHMS
Et3SiH
TMS3SiH
EtO(Me)2SiH
yielda entry
Si-H species
yielda
1
2
3
4
5
100
100
23
6
7
8
9
10
Me(MeO)2SiH
Me(TMSO)2SiH
(TMSO)3SiH
bis-siloxaneb
methyhydro-
cyclosiloxanes
97
90
0
100
30
100
TMSO(Me)2SiH 100
(15) Muchnij, J. A.; Maleczka, R. E., Jr. Chemoselective Conjugate
Reduction of R,â-Unsaturated Carbonyl Compounds with Polymethyl-
hydrosiloxane. Presented at the 37th Organosilicon Symposium, Philadelphia,
PA, May 20-22, 2004; Poster P-34.
a Determined by 1H NMR with CH2Cl2 as an internal standard (two run
average). b 1,3-Bis(trimethylsiloxy)-1,3-dimethyldisiloxane.
(16) Rahaim, R. J, Jr.; Maleczka, R. E., Jr. A Versatile and Mild Reducing
Method of Activated Alkenes, Alkynes, Halides, Nitro Groups, and Benzylic
Oxygens via a Combination of Pd(OAc)2, Poly(methyl-hydrosiloxane), and
Aqueous KF. Presented at the 37th Organosilicon Symposium, Philadelphia,
PA, May 20-22, 2004; Poster P-35.
(17) (a) Chauhan, B. P. S.; Rathore, J. S.; Bandoo, T. J. Am. Chem. Soc.
2004, 126, 8493-8500. For related observations see: (b) Fowely, L. A.;
Michos, D.; Luo, X.-L.; Crabtree, R. H. Tetrahedron Lett. 1993, 34, 3075-
3078. (c) Tour, J. M.; Pendalwar, S. L.; Cooper, J. P. Chem. Mater. 1990,
2, 647-649.
with the Pd(OAc)2/KF aq/THF combination. Nonetheless,
PMHS remained the silyl hydride of choice. A byproduct of
the silicone industry, PMHS is inexpensive and tends to be
much more air and moisture stable than other silanes.12,18
Indeed, PMHS can be stored on the bench for long periods
of time (years), and no extraordinary measures are needed
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Org. Lett., Vol. 7, No. 22, 2005