Room temperature dehalogenation of chloroarenes by polymethylhydrosiloxane (PMHS) under palladium catalysis

Article abstract of DOI:10.1016/S0040-4039(02)02212-8

The first method for the reduction of chloroarenes by polymethylhydrosiloxane (PMHS) is reported. Catalytic amounts of palladium(II) acetate in combination with PMHS and aqueous KF will rapidly hydrodehalogenate aryl chlorides at room temperature. The mildness of the method is demonstrated by its tolerance of ketones, amides, esters, nitriles, ethers, borate esters, and amines.

Full text of DOI:10.1016/S0040-4039(02)02212-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8823–8826
Room temperature dehalogenation of chloroarenes by
polymethylhydrosiloxane (PMHS) under palladium catalysis
Ronald J. Rahaim, Jr. and Robert E. Maleczka, Jr.*
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
Received 4 October 2002; accepted 7 October 2002
Abstract—The first method for the reduction of chloroarenes by polymethylhydrosiloxane (PMHS) is reported. Catalytic amounts
of palladium(II) acetate in combination with PMHS and aqueous KF will rapidly hydrodehalogenate aryl chlorides at room
temperature. The mildness of the method is demonstrated by its tolerance of ketones, amides, esters, nitriles, ethers, borate esters,
and amines. © 2002 Elsevier Science Ltd. All rights reserved.
Polymethylhydrosiloxane (PMHS) is an easily handled,
inexpensive, non-toxic, and mild reducing agent.
Although relatively inert towards organic functionality,
PMHS can transfer its hydride to a variety of metal
catalysts (including Sn, Ti, Zn, Cu, and Pd) that can
then participate in a wide range of reductions.1
Reaction optimization experiments carried out on 4-
chlorotoluene indicated that fluoride was essential for
rapid reaction as only trace quantities of toluene were
produced upon reaction with 5 mol% Pd(OAc)2 and 6
equiv. of PMHS (relative to chloroarene) at room
temperature for 24 h. While the presence of fluoride
was beneficial, too much (>50 mol% based on PMHS)
decreased the efficiency of the reaction. As for the
amount of PMHS required, increasing the equivalency
of PMHS increased the rate of dehalogenation. The
reaction of equal molar amounts of PMHS and 4-
chlorotoluene was complete after 24 h. Using a sixfold
excess of PMHS allowed for near complete reduction
after only 2 h. Upon factoring in the low cost and
mildness of PMHS1 and our desire to maximize reac-
tion efficiency as well as ease of purification and
workup, we settled on 4 equiv. of PMHS and 2 equiv.
of KF as the conditions of choice (Scheme 1).
PMHS hydrodehalogenates aryl bromides and iodides
under palladium catalysis.2 However, to the best of our
knowledge, all attempts to reduce chlorides by such
conditions have failed. This is unfortunate as the for-
mation of arenes from aryl chlorides is an important
chemical transformation.3 The reduction of chloro-
arenes has been studied under a variety of conditions
including free radical,4 catalytic and transfer hydro-
genation,5 oxidative,6 and metal-catalyzed hydride
delivery.2,7–9 Several of these methods employ relatively
expensive silanes7c,e,9b,c or hazardous stannanes,4 for
which PMHS would be an attractive alternative.
A variety of haloarenes were reacted with 4 equiv. of
PMHS, 2 equiv. of an aqueous solution of KF, and 5
Recently, phosphine free palladium catalysts have seen
considerable success in reactions with aryl chlorides.7a,10
Thus, we decided to explore if related systems could
solve the problem of reducing chloroarenes with
PMHS.4 This investigation revealed that catalytic palla-
dium(II) acetate with PMHS in the presence of potas-
sium fluoride reduced chlorobenzene to benzene.11,12
Impressively, this transformation could take place at
room temperature in a matter of minutes (Scheme 1).
mol% Pd(OAc)2 in THF (Table 1).11 Chlorobenzene
12
was efficiently reduced to benzene in 20 min (entry 1).
Chloroarenes bearing electron neutral, donating or
releasing groups were all reduced smoothly. Most
reductions were complete in less than 4 h. Even steri-
cally hindered 2-chloro-m-xylene (entry 12) was quanti-
Keywords: hydrodehalogenation; chlorides; reduction; palladium;
PMHS.
* Corresponding author.
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02212-8

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R. J. Rahaim, Jr., R. E. Maleczka, Jr. / Tetrahedron Letters 43 (2002) 8823–8826
Table 1. Room temperature Pd-catalyzed hydrodehalogenations with 2 equiv. KF and 4 equiv. PMHS11
Entry
Starting material
Pd-catalyst
Time (h)
Product
% Yielda
1
2
3
4
5
6
7
8
Chlorobenzene
4-Chlorotoluene
4-Chlorotoluene
4-Chlorotoluene
4-Chlorotoluene
4-Chlorotoluene
4-Chlorotoluene
4-Chlorotoluene
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
1 mol% Pd(OAc)2
0.1 mol% Pd(OAc)2
5 mol% Pd(CN)2
5 mol% Pd(NH2)Cl2
5 mol% Pd(acac)2
5 mol% Pd black
5 mol% PdCl2
0.3
3
10
54
3
3
3
3
3
Benzene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
95
95
96
24
0
0
73
94
78
9
4-Chlorotoluene
Toluene
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
4-Chlorotoluene
2-Chlorotoluene
5 mol% Pd2(dba)3
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% PdCl2
3
3
8
Toluene
Toluene
m-Xylene
m-Xylene
m-Xylene
Naphthalene
Phenol
Anisole
Aniline
Aniline
Aniline
Aniline
Aniline
Benzoic acid
Methyl benzoate
Methyl benzoate
Methyl benzoate
Methyl benzoate
Benzamide
Benzamide
Benzonitrile
Benzonitrile
Trifluorotoluene
Trifluorotoluene
Pyridine
Pyridine
Pyridine
Pyridine
4-Phenyl-2-butanone
Fluorobenzene
Benzene
Benzene
Benzene
96
100
100
0
2-Chloro-m-xylene
2-Chloro-m-xylene
2-Chloro-m-xylene
1-Chloronaphthalene
4-Chlorophenol
4-Chloroanisole
4-Chloroaniline
4-Chloroaniline
4-Chloroaniline
14
17
4
17
1.5
0.5
1
29
0.75
0.75
24
3
5 mol% Pd2(dba)3
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
1 mol% Pd(OAc)2
0.1 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
1 mol% Pd(OAc)2
0.1 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd black
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
5 mol% Pd(OAc)2
50
96, 82b
0
100
99, 87b
98
97
94
99
0
84
3-Chloroaniline
2-Chloroaniline
4-Chlorobenzoic acid
Methyl 4-chlorobenzoate
Methyl 2-chlorobenzoate
Methyl 2-chlorobenzoate
Methyl 2-chlorobenzoate
4-Chlorobenzamide
2-Chlorobenzamide
4-Chlorobenzonitrile
2-Chlorobenzonitrile
4-Chlorobenzotrifluoride
2-Chlorobenzotrifluoride
4-Chloropyridine·HCl
3-Chloropyridine
1
9
98, 76b
100
100
99, 83b
89
81
90
96
99
54
1.5
0.75
0.5
1
4
4
1.5
1
1.5
1.5
18
20
18
6
3
3
6
96
97
94
0
2-Chloropyridine
2-Chloropyridine
4-(4-Chlorophenyl)-2-butanone
1-Chloro-4-fluorobenzene
1,2-Dichlorobenzenec
1,3-Dichlorobenzenec
1,4-Dichlorobenzenec
1-Chloro-4-iodobenzenec
3-Chloro-5-methylphenylpinacolborane
95, 85b
92
98
98
98
Chlorobenzene
3-Methylphenylpinacolborane
93
85b
a Yields are an average of two runs and unless otherwise noted were determined by NMR (internal standard).
b Isolated yield.
c Run with 4 equiv. of PMHS and 2 equiv. of KF per halogen.
tatively reduced at room temperature, albeit after a
somewhat extended (8 h) reaction time. Substituted
pyridines (entries 34–36) also perform well under the
reaction conditions, including 2-chloropyridine which
has afforded poor yields in other systems.8a Dihalo-
genated arenes can also be reduced with 4 equiv. of
PMHS per halogen13 (entries 40–43).
(entry 16) and 4-chlorobenzoic acid (entry 23) did not
reduce.16
The presence of additional substituents can retard the
reaction. For example, certain para-substituted aryl
chlorides proved surprisingly sluggish. The reduction of
1-chloro-4-fluorobenzene (entry 39) was only 78% com-
plete by GC after 12 h and required 20 h before the
reaction was complete. Likewise, entry 38 required 18 h
for full consumption of 4-(4-chlorophenyl)-2-butanone.
Most unusual was the hydrodehalogenation of 1-chloro-
4-iodobenzene (entry 43), which after 3 h afforded only
chlorobenzene.17 In contrast, chlorobenzene and
iodobenzene were reduced to benzene in 20 min.
These conditions are compatible with a variety of
functional groups including ethers (entry 17), amines
(entries 18–22), esters (entries 24–27), amides (entries
28–29), nitriles (entries 30–31), ketones (entry 3814),
aryl fluorides (entry 39), and borate esters (entry
4415). Of the substrates studied only 4-chlorophenol

R. J. Rahaim, Jr., R. E. Maleczka, Jr. / Tetrahedron Letters 43 (2002) 8823–8826
8825
References
Having proved the reduction of chloroarenes by
hypercoordinate PMHS under Pd-catalysis to be mild,
rapid, and general, we looked to see if the palladium
loading could be lowered below 5 mol%. Though
longer reaction times were required, the hydrodehalo-
genations of 4-chlorotoluene, 4-chloroaniline, and
methyl 2-chlorobenzoate in the presence of only 1
mol% Pd(OAc)2 were all high yielding (entries 3, 19,
and 26, respectively). Decreasing the catalyst loading
by another order of magnitude (0.1 mol%) still
allowed for the efficient, though slow, dechlorination
of 4-chloroaniline and methyl 2-chlorobenzoate
(entries 20 and 27, respectively). However, for 4-
chlorotoluene (entry 4) diminishing returns set in at
this loading.
1. (a) Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J.
Chem. Soc., Perkin Trans. 1 1999, 3381–3391; (b) Lipow-
itz, J.; Bowman, S. A. Aldrichim. Acta 1973, 6, 1–6; (c)
Fieser, M.; Fieser, L. F. Reagents for Organic Synthesis;
Wiley: New York, 1974; Vol. 4, pp. 393–394.
2. (a) Maleczka, R. E., Jr.; Rahaim, R. J., Jr.; Teixeira, R.
Tetrahedron Lett. 2002, 43, 7087–7090; (b) Pri-Bar, I.;
Buchman, O. J. Org. Chem. 1986, 51, 734–735.
3. For reviews, see: (a) Hudlicky, M. In Comprehensive
Organic Synthesis; Trost, B. M.; Fleming, I., Ed.; Perga-
mon: Oxford, 1991; Vol. 8, pp. 895–922; (b) Entwistle, I.
D.; Wood, W. W. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Ed.; Pergamon: Oxford, 1991;
Vol. 8, pp. 955–981; (c) Pinder, A. R. Synthesis 1980,
425–452.
We also screened the efficacy of other phosphine
free18 palladium sources. In these experiments
Pd(CN)2 and Pd(NH2)Cl2 failed to reduce 4-chloro-
toluene (entries 5–6). While Pd(acac)2, palladium
black, PdCl2, and Pd2(dba)3 dechlorinated 4-chloro-
toluene (entries 7–10), these catalysts proved consider-
ably less efficient than Pd(OAc)2 with other substrates
(e.g. entries 13, 14, and 37). Thus, on balance,
4. (a) Studer, A.; Amrein, S. Synthesis 2002, 835–849; (b)
Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. J. Am.
Chem. Soc. 2002, 124, 906–907; (c) Neumann, W. P.
Synthesis 1987, 665–683 and references cited therein.
5. For a review, see: (a) Urbano, F. J.; Marinas, J. M. J.
Mol. Catal. A: Chem. 2001, 173, 329–345. See also (b)
Cucullu, M. E.; Nolan, S. P.; Belderrain, T. R.; Grubbs,
R. H. Organometallics 1999, 18, 1299–1304; (c) Blum, J.;
Rosenfeld, A.; Gelman, F.; Schumann, H.; Avnir, D. J.
Mol. Catal. A: Chem. 1999, 146, 117–122.
12
Pd(OAc)2 appears to be the most universal catalyst
for room temperature hydrodehalogenations with KF/
PMHS.
6. Bressan, M.; d’Alessandro, N.; Liberatore, L.; Morvillo,
A. Coord. Chem. Rev. 1999, 185–186, 385–402 and refer-
ences cited therein.
Finally, a limited investigation suggests that the ratio
of water to THF can influence the course of these
reductions. Increasing the water/THF ratio from 2/5
to 3/5 decreased the required reaction time for the
reduction of 4-chlorotoluene from 3 h to 1. However,
this proved a delicate balance as any further increase
in the amount of water prohibited the reaction from
going to completion. Additional studies on this water
effect and other aspects of these reductions, including
mechanism, continue and will be reported elsewhere.
7. For some recent examples Pd-mediated reductions, see:
(a) Viciu, M. S.; Grasa, G. A.; Nolan, S. P. Organometal-
lics 2001, 20, 3607–3612; (b) Kang, R.; Ouyang, X.; Han,
J.; Zhen, X. J. Mol. Catal. A: Chem. 2001, 175, 153–159;
(c) Villemin, D.; Nechab, B. J. Chem. Res., Synop. 2000,
432–434; (d) Lassova´, L.; Lee, H. K.; Hor, T. S. A. J.
Org. Chem. 1998, 63, 3538–3543; (e) Boukherroub, R.;
Chatgilialoglu, C.; Manuel, G. Organometallics 1996, 15,
1508–1510.
8. For some recent examples Ni-mediated reductions, see:
(a) Desmarets, C.; Kuhl, S.; Schneider, R.; Fort, Y.
Organometallics 2002, 21, 1554–1559; (b) Lipshutz, B. H.;
Tomioka, T.; Sato, K. Synlett 2001, 970–973; (c) Lip-
shutz, B. H.; Tomioka, T.; Pfeiffer, S. S. Tetrahedron
Lett. 2001, 42, 7737–7740.
9. For some recent examples Rh-mediated reductions, see:
(a) Atienza, M. A.; Esteruelas, M. A.; Fernandez, M.;
Herrero, J.; Oliva´n, M. New J. Chem. 2001, 25, 775–776;
(b) D´ıaz, J.; Esteruelas, M. A.; Herrero, J.; Moralejo, L.;
Oliva´n, M. J. Catal. 2000, 195, 187–192; (c) Esteruelas,
M. A.; Herrero, J.; Lo´pez, F. M.; Mart´ın, M.; Oro, L. A.
Organometallics 1999, 18, 1110–1112.
In summary KF(aq), PMHS, and catalytic Pd(OAc)2
in THF is a mild and efficient system for the room
temperature19 dechlorination of aryl chlorides. Under
these conditions, electron neutral, rich, or poor
chloroarenes can be rapidly hydrodechlorinated at
room temperature. Ketones, amides, esters, nitriles,
ethers, borate esters and amines are tolerated by the
reaction, whereas phenols and carboxylic acids are
not. Dehalogenations can be accomplished with as
low as 0.1 mol%, however 1–5 mol% Pd(OAc)2 repre-
sent a more general catalyst loading.
10. For recent examples, see: (a) Viciu, M. S.; Kissling, R.
M.; Stevens, E. D.; Nolan, S. P. Org. Lett. 2002, 4,
2229–2231; (b) Grasa, G. A.; Viciu, M. S.; Huang, J.;
Zhang, C.; Trudell, M. L.; Nolan, S. P. Organometallics
2002, 21, 2866–2873; (c) Huang, T. H.; Chang, H. M.;
Wu, M. Y.; Cheng, C. H. J. Org. Chem. 2002, 67, 99–105;
(d) Botella, L.; Najera, C. Angew. Chem., Int. Ed. 2002,
41, 179–181; (e) Heidenreich, R. G.; Kohler, K.; Krauter,
J. G. E.; Pietsch, J. Synlett 2002, 1118–1122; (f) Kabalka,
G. W.; Namboodiri, V.; Wang, L. J. Chem. Soc., Chem.
Commun. 2001, 775; (g) LeBlond, C. R.; Andrews, A. T.;
Sun, Y.; Sowa, J. R., Jr. Org. Lett. 2001, 3, 1555–1557.
Acknowledgements
We thank the Center for Fundamental Materials
Research (MSU) and the NSF (CHE-9984644) for
generous support, as well as the American Chemical
Society’s Project SEED for supporting Mr. Jeremy L.
L. D. Brown, who we thank for performing impor-
tant screening reactions.

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R. J. Rahaim, Jr., R. E. Maleczka, Jr. / Tetrahedron Letters 43 (2002) 8823–8826
14. 4-(4-Chlorophenyl)butan-2-one was prepared according
to: Buntin, S. A.; Heck, R. F. Org. Synth. 1983, 61,
82–84.
15. 3-Chloro-5-methylphenylpinacolborane was prepared
according to the general method of: Cho, J.-Y.; Tse, M.
K.; Holmes, D.; Maleczka, R. E., Jr.; Smith, M. R., III
Science 2002, 295, 305–308.
16. This failure was not entirely surprising as 4-bromophenol
and 4-bromobenzoic acid were not reduced with PMHS,
KF, and catalytic (Ph3P)2PdCl2 (Ref. 2a).
17. Even after 48 h only chlorobenzene was present. Similar
observations were made by Tashiro and co-workers dur-
ing dehalogenations with metallic calcium in ethanol. See:
Mitoma, Y.; Nagashima, S.; Simion, C.; Simion, A. M.;
Yamada, T.; Mimura, K.; Ishimoto, K.; Tashiro, M.
Environ. Sci. Technol. 2001, 35, 4145–4148.
11. An oven dried round bottom flask was charged with 1.0
mmol of aryl chloride in 5 mL THF (0.2 M solution) and
0.05 equiv. of Pd(OAc)2.12 The flask was sealed with a
septum and flushed with nitrogen. While flushing the
reaction, 2 equiv. of KF in 2 mL of degassed water were
introduced by syringe. PMHS (4 equiv.) was then injected
dropwise into the reaction mixture. The reaction was
stirred until complete as judged by disappearance of the
starting material (GC analysis). Upon complete reduc-
tion, the reaction mixture was added to a 3 M solution of
NaOH. After stirring 5 h to hydrolyze unreacted PMHS,
the mixture was extracted several times with Et2O. The
combined organics were dried over MgSO4 and concen-
trated. The crude material was then either distilled or
purified by silica gel chromatography. (When column
chromatography was needed, initial elution with CCl4/
hexanes (1:1) was useful in removing silane byproducts.)
12. Palladium(II) acetate purchased from Strem or Aldrich’s
99.9+% Pd(OAc)2 performed well in this study, however,
the reactions were much less efficient when run with
Aldrich’s 98% Pd(OAc)2.
18. Phosphine bearing catalysts fail to reduce chloroarenes
(Ref. 2).
19. For other recent examples of room temperature dechlori-
nations, see: (a) Massicot, F.; Schneider, R.; Fort, Y.;
Illy-Cherrey, S.; Tillement, O. Tetrahedron 2000, 56,
4765–4768 (Ni–l clusters); (b) Rajagopal, S.; Spatola, A.
F. J. Org. Chem. 1995, 60, 1347–1355 (Pd/C, formate); (c)
Ref. 4b (InCl3/NaBH4), Ref. 7e (PdCl2/Et3SiH), and Ref.
17 (Ca/EtOH).
13. These substrates could be reduced with 4 equiv. of PMHS
per equivalent of arene, however, these reactions took
2–4 times longer.