Pd-catalyzed selective hydrosilylation of aryl ketones and aldehydes

Article abstract of DOI:10.1016/j.tetlet.2011.10.155

Pd salts in combination with triethylsilane as hydride source and DMF as solvent has been found to be excellent catalytic combination that selectively reduces aryl ketones and aldehydes under mild conditions to afford triethylsilyloxy compounds in excellent yields. Product selectivity to the respective benzyl alcohols can however be achieved when the reaction was performed in DMF/H₂O (4:1) as solvent system.

Full text of DOI:10.1016/j.tetlet.2011.10.155

Tetrahedron Letters 53 (2012) 148–150
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Tetrahedron Letters
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Pd-catalyzed selective hydrosilylation of aryl ketones and aldehydes
⇑
Pandurang V. Chouthaiwale, Varun Rawat, Arumugam Sudalai
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pashan Road, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2011
Revised 27 October 2011
Accepted 30 October 2011
Available online 6 November 2011
Pd salts in combination with triethylsilane as hydride source and DMF as solvent has been found to be
excellent catalytic combination that selectively reduces aryl ketones and aldehydes under mild condi-
tions to afford triethylsilyloxy compounds in excellent yields. Product selectivity to the respective benzyl
alcohols can however be achieved when the reaction was performed in DMF/H2O (4:1) as solvent system.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Aldehydes
Ketones
Hydrosilylation
Palladium
Triethylsilane
The catalytic reduction of carbon-heteroatom multiple bonds
under mild conditions constitutes an important transformation in
organic synthesis and pharmaceutical as well as agrochemical
industry.1 Especially, hydrosilylation of C@X (X = N, O) bonds is a
promising alternative to other reduction methods such as hydroge-
nation, transfer hydrogenation as well as reduction with aluminum
and boron hydrides, owing to its operational simplicity coupled
with high atom-economy.2 Also it combines reduction of carbonyl
functionality with alcohol protection in a single step. Transition
metals such as Zn,3 Fe,4 Rh,5 Cu,6 Re,7 etc.8 and their complexes
are usually utilized as catalysts for hydrosilylation of carbonyl
compounds. Quite recently, the combination of PdCl2/Et3SiH has
been successfully employed for the reduction of alkyl halides to al-
kanes,9a conversion of alcohols to halides and alkanes9b and isom-
erization of 1-alkenes to 2- and 3-alkenes.10 The Pd/hydrosilane
catalytic system is widely used in the following transformation:
hydrosilylation of alkenes11 and alkynes,12 reduction of other func-
tional groups such as azides, imines and nitro groups13 and selec-
combination of Pd(OAc)2/HSiEt3 in DMF at 60 °C results in direct
reduction of 2-pyridinyl naphthyl ester to the corresponding silyl
ether in 48% yield.17 Herein we report an efficient catalytic proto-
col consisting of Pd salts–Et3SiH–DMF combination that can
selectively hydrosilylate various aryl ketones and aldehydes 1,
at ambient condition, to afford the corresponding triethylsilyloxy
compounds 2 and 3 in high yields (Scheme 1).
We observed that when acetophenone was subjected to reduc-
tion with 1.2 equiv of Et3SiH and 0.5 mol % PdCl2 as catalyst in dry
DMF at 25 °C, the corresponding silyl ether (2a) was obtained in
90% yield. In order to study this reaction in a systematic manner,
several Pd salts and solvents have been employed and the results
are presented in Table 1. Notably, DMF was found to be the best
solvent while solvents such as CH2Cl2, 1,2-dichloroethane, toluene
and benzene have failed. An important feature of this protocol is
that product selectivity could be achieved depending upon the
choice of solvents used. For instance, when the reaction was con-
ducted in either DMF–water (4:1) or water as solvent, phenyl eth-
anol was obtained in 85% and 40% yields respectively.18 Thus, both
hydrosilylation and deprotection of the silyl ether were achieved in
tive reduction of
a
,b-unsaturated ketones to saturated ketones.14
More recently, this catalytic system has been reported for the
reduction of aromatic aldehydes, ketones and benzyl alcohols into
the corresponding methylene group15 without much selectivity.
Generally, hydrosilylation of carbonyl compounds with silicon
hydride leads to the formation of the corresponding alcohols, but
to retain the silyl group as a protecting group is certainly more
useful, as they are valuable synthetic intermediates and mono-
mers for the production of organosilane polymers and materi-
als.16 Chatani and co-workers have observed that the catalytic
OSiEt3
R
O
Pd(OAc)2 (0.5 mol%),
Ar
Ar
R
Et3SiH (1.2 equiv),
DMF, 2 h, 25 °C
2, R = alkyl, aryl
3, R = H
1
R = H, alkyl, aryl
Ar = phenyl, naphthyl,
heteroaryl, etc
50-98%
⇑
Corresponding author. Tel.: +91 20 25902565; fax: +91 20 25902676.
E-mail address: a.sudalai@ncl.res.in (A. Sudalai).
Scheme 1. Pd-catalyzed hydrosilylation of aryl ketones and aldehydes.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.155

P. V. Chouthaiwale et al. / Tetrahedron Letters 53 (2012) 148–150
149
Table 1
We also attempted to induce chirality in the molecule using differ-
ent chiral Pd catalysts (entries 9 and 10) but with no asymmetric
induction. With Pd(OAc)2 as catalyst, other hydrosilanes such as
Ph2SiH2 and polymethylhydrosiloxane (PMHS) were examined
and found to be unreactive. In order to understand the scope and
generality of the reaction, a wide range of aryl ketones were sub-
jected to hydrosilylation under this reaction condition.21 As can
be seen from Table 2, the method worked exceedingly well in all
the aryl ketones. Substrates containing bulky groups, such as tetra-
lone, 9-fluorenone and 2-methyl-1-phenylpropan-1-one were
readily converted to the corresponding silyl ethers in excellent
yields. However, in case of chloro substituted aryl ketone (entry
g), dehaloganated silyl ether was obtained in moderate yield (50%).
In order to extend the scope of the Pd-catalyzed hydrosilylation,
a wide range of functionalized aromatic aldehydes including in-
dole-3-carboxaldehyde were subjected to the optimized conditions
(Table 3).21 Indeed, the protocol gave excellent yields of the respec-
tive hydrosilylated products (entries a–n). The method has shown
high tolerance for other sensitive functional groups such as ester,
fluoro, hydroxyl, amine, imine, olefin and alkyne present either
on aromatic nucleus or aliphatic system. In case of chloro substi-
tuted aryl aldehydes, the corresponding dehaloganated silyl ether
was obtained in 51–54% yield along with 10% of dechlorinated
benzaldehyde (entry f). For bromobenzaldehydes, the exclusive
product obtained was the debrominated benzaldehyde (entry g).
Pd-catalyzed hydrosilylation of acetophenone: effect of solvent and catalysta
Entry
1
Catalyst
Solvent
Yield (%)
Pd(OAc)2
CH3CN
DMF
Water
DMF–water (4:1)
DMF
60
98
40b
85b
90
2
3
4
5
6
7
8
9
10
PdCl2
Pd(PhCN)2Cl2
DMF
94
Pd(dba)2
DMF
60
Pd(Ph3P)4
DMF
DMF
DMF
DMF
DMF
DMF
95
96
95
Sulflimine palladacycle19
Saccharin palladium complex20
10%Pd/C
89
Pd [(R,R)-BINAP]Cl2
Pd[(À)-sparteine](OAc)2
80c
82c
Reagents and conditions:
a
Acetophenone (1 mmol), Pd(OAc)2 (0.5 mol %), Et3SiH (1.2 mmol), solvent
(2 ml), 25 °C, 1 h.
b
Phenyl ethanol was obtained.
No optical induction observed.
c
a single step with Pd salts in catalytic amount. Moreover, all the Pd
catalysts gave excellent yields of hydrosilylated products; the
highest yield of silylether was obtained with Pd(OAc)2 (98%) while
Pd(dba)2 gave the lowest yield (60%). Sulfilimine palladacycle19
and Pd–saccharin complex20 also gave high yields of silyl ether.
Table 2
Pd-catalyzed hydrosilylation of aryl ketonesa
Entry
Substrate
Product (2)
Yieldb,c (%)
a
b
c
d
e
f
g
h
i
Acetophenone
1-Phenylethoxy-triethylsilane
1-p-Tolylethoxy-triethylsilane
1-(4-Methoxyphenyl)-ethoxytriethylsilane
1-Phenylpropoxy-triethylsilane
2-Methyl-1-phenylprop-oxytriethylsilane
Diphenylmethoxy-triethylsilane
98 (85)
96 (80)
80
4-Methylacetophenone
4-Methoxyaceto-phenone
Propiophenone
2-Methyl-1-phenyl-propan-1-one
Benzophenone
4-Chlorobenzo-phenone
1-Tetralone
2-Acetylnaphthalene
1-Indanone
96
96 (79)
95 (86)
50d
91
96 (84)
95
Diphenylmethoxy-triethylsilane
1,2,3,4-Tetrahydro-naphthalen-1-yloxy-triethylsilane
1-Naphthalen-2-ylethoxy-triethylsilane
2,3-Dihydro-1H-inden-1-yloxytriethylsilane
9H-Fluoren-9-yloxy-triethylsilane
j
k
9-Fluorenone
95
Reagents and conditions:
a
Ketones (1 mmol), Pd(OAc)2 (0.5 mol %), Et3SiH (1.2 mmol), dry DMF (2 ml), 25 °C, 1 h.
Isolated yield.
The number in the parenthesis refers to isolated yield of the corresponding benzyl alcohol when DMF–water (4:1) was employed.
ꢀ12% Of the corresponding unsubstituted acetophenone was obtained.
b
c
d
Table 3
Pd-catalyzed hydrosilylation of aryl aldehydesa
Entry
Substrates
Product (3)
Yieldb,c (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
Benzaldehyde
4-Methylbenzaldehyde
4-Methoxy-benzaldehyde
Benzyloxytriethylsilane
4-Methylbenzyloxy-triethylsilane
4-Methoxybenzyloxy-triethylsilane
4-(Methylthio)benzyloxy-triethylsilane
3,4-(Methylenedioxy)benzyloxy-triethylsilane
Benzyloxytriethylsilane
Benzaldehyde
4-Fluorobenzyloxytriethylsilane
4-(Trifluoromethyl)benzyloxy-triethylsilane
Methyl 3,5-dimethoxy-2-((triethylsilyloxy)methyl)benzoate
4-Hydroxy-3-methoxybenzyl-oxytriethylsilane
3-(((Triethylsilyl)oxy)-methyl)-indole
Methyl 3-(4-(((triethylsilyl)-oxy)methyl)phenyl)acrylate
Methyl 3-(4-(((triethylsilyl)oxy)methyl)phenyl)propanoate
93 (87)
93
96 (90)
75
96 (90)
51–54d
87–88
81
90
92
81
87
4-(Methylthio)-benzaldehyde
3,4-(Methylenedioxy)-benzaldehyde
2-, 3- or 4-Chloro-benzaldehyde
2-, 3- or 4-Bromo-benzaldehyde
4-Fluorobenzaldehyde
4-(Trifluoromethyl)-benzaldehyde
Methyl 2-formyl 3,5-dimethoxybenzoate
4-Hydroxy-3-methoxy-benzaldehyde
Indole-3-carboxaldehyde
Methyl 3-(4-formyl-phenyl)acrylate
Methyl 3-(4-formyl-phenyl)propanoate
86
85
Reagents and conditions:
a
Aldehyde (1 mmol), Pd(OAc)2 (0.5 mol %), Et3SiH (1.2 mmol), dry DMF (2 ml), 25 °C, 1 h.
Isolated yield.
The number in the parenthesis refers to isolated yield of the corresponding benzyl alcohol when DMF–water (4:1) was employed.
ꢀ10% Of the corresponding unsubstituted benzaldehyde was obtained.
b
c
d

150
P. V. Chouthaiwale et al. / Tetrahedron Letters 53 (2012) 148–150
Table 4
however be obtained in excellent yields when the reaction was
performed in DMF/H2O (4:1) as solvent system.
Pd-catalyzed hydrosilylation of carbonyl compounds: competitive experimentsa
Entry Substrates
Product
Yieldb,c
(%)
Acknowledgments
a
b
c
d
e
f
PhCH2CH2COCH3 + PhCOCH3
PhCH(OSiEt3)CH3
PhCH2OSiEt3
PhCH(OSiEt3)CH3
PhCH2OSiEt3
PhCH2OSiEt3
4-CF3
96
91
94
88
84
90
PhCH2CH2COCH3 + PhCHO
PhCH2CH2COCH3 + PhCOCH3
PhCH2CH2CHO + PhCHO
PhCHO + PhCOCH3
The authors P.V.C. and V.R. thank CSIR and DST, New Delhi
(No. SR/S1/OC-67/2010) for the financial support.
References and notes
4-CF3 PhCHO + 4-CH3 PhCHO
PhCH2OSiEt3 + 4-
CH3 PhCH2OSiEt3
(2.5:1)
1. Handbook of Homogeneous Hydrogenation; De Vries, J. G., Elsevier, C. J., Eds.;
Wiley-VCH: Weinheim, Germany, 2007.
PhCHO
Ph
g
PhCH2OSiEt3
PhCH2OSiEt3
91
83
2. (a) Ojima, I. In The Chemistry of Organic Silicon Compounds; Patai, S., Rappoport,
Z., Eds.; Wiley: New York, 1989; Vol. 1, (b) Ojima, I.; Li, Z.; Zhu, J. In The
Chemistry of Organic Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; John
Wiley & Sons: New York, 1998; Vol. 2, (c) Carpentier, J.-F.; Bette, V. Curr. Org.
Chem. 2002, 6, 913; (d) Riant, O.; Mostefa, N.; Courmarcel, J. Synthesis 2004,
2943.
3. Inagaki, T.; Yamada, Y.; Phong, L. T.; Furuta, A.; Ito, J.-I.; Nishiyama, H. Synlett
2009, 253.
4. (a) Inagaki, T.; Phong, L. T.; Furuta, A.; Ito, J.-I.; Nishiyama, H. Chem. Eur. J. 2010,
16, 3090; (b) Yang, J.; Tilley, T. D. Angew. Chem., Int. Ed. 2010, 49.
5. Anada, M.; Tanaka, M.; Suzuki, K.; Nambu, H.; Hashimoto, S. Chem. Pharm. Bull.
2006, 54, 1622.
PMP
Ph-CHO
h
Ph
N
Reagents and conditions:
a
1:1 Molar equivalents of substrates (5 mmol each), Pd(OAc)2 (0.5 mol %), Et3SiH
(6 mmol), dry DMF (10 ml), 25 °C, 1 h.
b
Isolated yield.
1H NMR spectrum of the crude sample indicates no reaction for other substrate.
c
6. (a) Diez-Gonzalez, S.; Stevens, E. D.; Scott, N. M.; Petersen, J. L.; Nolan, S. P.
Chem. Eur. J. 2008, 14, 158; (b) Fujihara, T.; Semba, K.; Terao, J.; Tsuji, Y. Angew.
Chem., Int. Ed. 2010, 49, 1472.
7. Dong, H.; Berke, H. Adv. Synth. Catal. 2009, 351, 1783.
8. (a) Diez-Gondlez, S.; Nolan, S. P. Org. Prep Proc. Int. 2007, 39, 523;
(b)Hydrosilylation A Comprehensive Review on Recent Advances; Marciniec, B.,
Ed.; Springer: Netherlands, 2009. chap. 9.
+
2 Et3SiH Pd(OAc)2
2 Et3Si(OAc) + H2
Et3SiH
Pd(0)
OSiEt3
9. (a) Boukherroub, R.; Chatgilialoglu, C.; Manuel, G. Organometallics 1996, 15,
1508; (b) Ferreri, C.; Costantino, C.; Chatgilialoglu, C.; Boukherroub, R.; Manuel,
G. J. Organomet. Chem 1998, 554, 135.
Ar
10. Mirza-Aghayan, M.; Boukherroub, R.; Bolourtchian, M.; Tabar-Hydar, K.;
Hoseini, M. J. Organomet. Chem. 2003, 678, 1.
11. Mirza-Aghayan, M.; Boukherroub, R.; Bolourtchian, M. Appl. Organomet. Chem.
2006, 20, 214.
O
12. Motoda, D.; Shinokubo, H.; Oshima, K. Synlett 2002, 9, 1529.
13. Mandal, P. K.; McMurray, J. S. J. Org. Chem. 2007, 72, 6599.
14. (a) Keinan, E.; Greenspoon, N. J. Am. Chem. Soc. 1986, 108, 7314; (b) Mirza-
Aghayan, M.; Boukherroub, R.; Bolourtchian, M.; Rahimifard, M. J. Organomet.
Chem. 2007, 692, 5113.
15. (a) Mirza-Aghayan, M.; Boukherroub, R.; Rahimifard, M. J. Organomet. Chem.
2008, 693, 3567; (b) Mirza-Aghayan, M.; Boukherroub, R.; Rahimifard, M.
Tetrahedron Lett. 2009, 50, 5930–5932.
16. Sprengers, J. W.; de Greef, M.; Duin, M. A.; Elsevier, C. J. Eur. J. Inorg. Chem. 2003,
3811.
17. Nakanishi, J.; Tatamidani, H.; Fukumoto, Y.; Chatani, N. Synlett 2006, 6, 869.
18. Mirza-Aghayan, M.; Boukherroub, R.; Bolourtchian, M. J. Organomet. Chem.
2005, 690, 2372.
19. Thakur, V. V.; Ramesh Kumar, N. S. C.; Sudalai, A. Tetrahedron Lett. 2004, 45,
2915.
20. Ramesh Kumar, N. S. C.; Victor Paul Raj, I.; Sudalai, A. J. Mol. Cat. A.: Chemical
2007, 269, 218.
21. General experimental procedure for the hydrosilylation of aryl ketones and
aldehydes:
Ar
Et3SiPdH
Scheme 2. Catalytic cycle for Pd-catalyzed hydrosilylation of aromatic ketones and
aldehydes.
On the other hand, p-fluorobenzaldehyde underwent the reaction
smoothly to give the corresponding hydrosilylated product with-
out the fluoro group being affected.23 However, the reaction failed
in the case of aliphatic ketones and aldehydes, which is a limitation
of this protocol. This catalytic system can be unique in selectively
hydrosilylating aromatic ketones or aldehydes in the presence of
aliphatic ketones or aldehydes. This was substantiated by carrying
out the competitive experiments involving 1:1 molar equivalents
of aliphatic ketones/aldehydes and aromatic ketones/aldehydes,
results of which are presented in Table 4. As can be seen from Table
4, acetylene and imine groups were not affected in the presence of
aromatic aldehyde. For 4-phenylbut-3-en-2-one and cinnamalde-
hyde, the corresponding saturated 4-phenyl-2-butanone and
hydrocinnamaldehyde were obtained in 78% and 69% yields
respectively. The catalytic cycle for the Pd-catalytic hydrosilylation
process is shown in Scheme 2. The first step involves the reaction
of Pd(OAc)2 with Et3SiH to give the active metallic Pd(0) species.
The oxidative addition of Et3SiH with Pd(0) then leads to the for-
mation of highly reactive intermediate Et3SiPdH complex,22 which
transfers hydride to aromatic carbonyl compounds followed by
reductive elimination affording aryloxy silylated compounds along
with the liberation of Pd(0).
To a stirred solution of palladium catalyst (0.5 mol %) in dry DMF (2.0 mL) was
added aryl ketones or aryl aldehydes (1.0 mmol) followed by the addition of
triethylsilane (1.2 mmol). The resulting solution was then stirred for 1 h. After
completion of the reaction, it was subsequently loaded directly onto the
column (silica gel 60–120 mesh) for purification using petroleum ether as
eluents to afford pure 2 or 3, respectively.
Spectral data for compound 2f: Yield: 91%; colorless liquid; 1H NMR (200 MHz,
CDCl3): d 0.60 (q, J = 8.1 Hz, 6H), 0.93 (t, J = 8.0 Hz, 9H), 1.58–2.01 (m, 4H),
2.57–2.82 (m, 2H), 4.72 (t, J = 4.3 Hz, 1H) 6.92–7.07 (m, 3H), 7.26–7.29 (m, 1H);
13C NMR (50 MHz, CDCl3): d 5.4, 7.0, 19.5, 29.1, 33.1, 69.2, 125.1, 126.9, 127.9,
128.5, 136.6, 139.8; Anal. Calcd for C16H26Osi: C, 73.22; H, 9.98. Found: C,
73.28; H, 9.82.
Spectral data for compound 3e: 96%; colorless liquid; 1H NMR (200 MHz, CDCl3):
d 0.61 (q, J = 8.0 Hz, 6H), 0.93 (t, J = 8.3 Hz, 9H), 4.61 (s, 2H), 5.93 (s, 2H), 6.74 (d,
J = 1.0 Hz, 2H), 6.82 (s, 1H); 13C NMR (50 MHz, CDCl3): d 4.4, 6.7, 64.5, 100.6,
107.1, 107.8, 119.3, 135.2 146.4, 147.5; Anal. Calcd for C14H22O3Si: C, 63.12; H,
8.32. Found: C, 63.28; H, 8.20.
In conclusion, we have shown that Pd salts are highly effective
catalysts for selective hydrosilylation of aryl ketones and alde-
hydes, when carried out in DMF as solvent at 25 °C and triethylsi-
lane as hydride source. The corresponding benzylic alcohols could
22. (a) Kunai, A.; Sakurai, T.; Toyoda, E.; Ishikawa, M.; Yamamoto, Y.
Organometallics 1994, 13, 3233; (b) Ferreri, C.; Costantino, C.; Chatgilialoglu,
C.; Boukherroub, R.; Manuel, G. J. Organomet. Chem. 1998, 554, 135.
23. Dong, H.; Berke, H. Adv. Synth. Catal. 2009, 351, 1783–1788.