A simple and efficient copper-catalyzed procedure for the hydrosilylation of hindered and functionalized ketones

Article abstract of DOI:10.1021/jo050397v

The catalytic hydrosilylation of highly hindered and functionalized ketones is described. The combination of inexpensive catalyst precursors, CuCl and NHC·HX (NHC = N-heterocyclic carbene), leads to a highly efficient reduction mediator for the preparatio

Full text of DOI:10.1021/jo050397v

A Simple and Efficient Copper-Catalyzed Procedure for the
Hydrosilylation of Hindered and Functionalized Ketones
Silvia D´ıez-Gonza´lez, Harneet Kaur, Fabiano Kauer Zinn, Edwin D. Stevens, and
Steven P. Nolan*
Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148
snolan@uno.edu
Received March 2, 2005
The catalytic hydrosilylation of highly hindered and functionalized ketones is described. The
combination of inexpensive catalyst precursors, CuCl and NHC‚HX (NHC ) N-heterocyclic carbene),
leads to a highly efficient reduction mediator for the preparation of silyl ethers from unfunctionalized
and functionalized alkyl, cyclic, bicyclic, aromatic, and heteroaromatic ketones. A series of catalyst
precursors have been structurally characterized and a catalyst-structure activity relationship is
discussed.
Introduction
activity in the hydrosilylation of carbonyl compounds.
Although these protocols are effective for the reduction
of various ketones and aldehydes, the reported catalysts
are quite inactive toward sterically hindered substrates.7
Furthermore, the available stoichiometric procedures for
the reduction of highly hindered carbonyl compounds
require up to 40 equiv of the reducing agent.8
Carbonyl bond reduction in ketones and aldehydes
represents an ubiquitous protocol in organic synthesis.1
Hydrosilylation is especially useful, insofar as it yields
the protected alcohols and uses easy to handle starting
materials.2 A number of transition metal complexes, such
as Ti,3 Rh,4 Ru,5 or Ir,6 have displayed high catalytic
A less costly alternative, with copper as the metal
source, has been developed by Stryker. It made use of
triphenylphosphine as the ligand for the reduction of
simple or R,â-unsaturated aldehydes and ketones.9 But,
to date, the activity of this system has not been tested
with functionalized or sterically demanding carbonyl
compounds. Lipshutz explored various phosphine-ligated
copper hydride systems for the transformation of simple
aldehydes and ketones leading to reduced products.10
Although these systems have been shown to be effective
even for asymmetric hydrosilylation of a variety of
substrates, their reactivity toward highly sterically de-
manding or functionalized ketones has not been exten-
(1) (a) Smith, M. B.; March, J. March’s Advanced Organic Chemistry;
Wiley-Interscience: New York, 2001. (b) Carey, F. A.; Sundberg, R. J.
Advanced Organic Chemistry; Kluwer Academic/Plenum: New York,
2001.
(2) (a) Ojima, I. In The Hydrosilylation Reaction: The Chemistry of
Organosilicon Compounds; Patai, S., Rapaport, Z., Eds.; Wiley: New
York, 1989; p 1479. (b) Ojima, I.; Li, Z.; Zhu, J. In Recent Advances in
the Hydrosilylation Reaction: Chemistry of Organic Silicon Compounds;
Rappaport, Z., Apetorg, Y., Eds: Wiley: New York, 1998; Vol. 2, p 1687.
(3) (a) Carter, M. B.; Schiott, B.; Gutierrez, A.; Buchwald, S. L. J.
Am. Chem. Soc. 1994, 116, 11667-11670. (b) Inma, H.; Mori, M.;
Nakai, T. Synlett 1996, 1229-1230. (c) Rahimian, K.; Harrod, J. F.
Inorg. Chim. Acta 1998, 270, 330-336. (d) Yun, J.; Buchwald, S. L. J.
Am. Chem. Soc. 1999, 121, 5640-5644.
(4) (a) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.;
Kondo, M.; Itoh, K. Organometallics 1989, 8, 846-848. (b) Sawamura,
M.; Kuwano, R.; Ito, Y. Angew. Chem., Int. Ed. Engl. 1994, 33, 111-
113. (c) Sudo, A.; Yoshida, H.; Saigo, K. Tetrahedron: Asymmetry 1997,
8, 3205-3208. (d) Ini, S.; Oliver, A. G.; Tilley, T. D.; Bergman, R. G.
Organometallics 2001, 20, 3839-3841. (e) Tao, B.; Fu, G. C. Angew.
Chem., Int. Ed. 2002, 41, 3892-3894. (f) Reyes, C.; Prock, A.; Giering,
W. P. Organometallics 2002, 21, 546-554.
(5) (a) Zhu, G.; Terry, M.; Zhang, X. J. Organomet. Chem. 1997, 547,
97-101. (b) Nishibayashi, Y.; Takei, I.; Uemura, S.; Hidai, M. Organo-
metallics 1998, 17, 3420-3422. (c) Ohkuma, T.; Koizumi, M.; Yoshida,
M.; Noyori, R. Org. Lett. 2000, 2, 1749-1751. (d) Hashimoto, H.;
Aratani, I.; Kabuto, C.; Kira, M. Organometallics 2003, 22, 2199-2201.
(6) (a) Saito, M.; Nishibayashi, Y.; Uemura, S. Organometallics 2004,
23, 4012-4017. (b) Nishibayashi, Y.; Segawa, K.; Ohe, K.; Uemura, S.
Organometallics 1995, 14, 5486-5487. (c) Kinting, A.; Krenzfeld, H.-
J.; Abicht, H.-P. J. Organomet. Chem. 1989, 370, 343-349.
(7) Shibagaki, M.; Takahshi, K.; Matsushita, H. Bull. Chem. Soc.
Jpn. 1988, 61, 3283-3288.
(8) (a) Caycho, J. R.; Tellado, F. G.; Aramas, P.; Juan, J.; Tellado,
M. Tetrahedron Lett. 1997, 38, 277-280. (b) Yakabe, S.; Hirano, M.;
Morimoto, T. Can. J. Chem. 1998, 76, 1916-1921.
(9) Chen, J.-X.; Daeuble, J. F.; Stryker, J. M. Tetrahedron 2000, 56,
2789-2798. For more details, see also: (a) Daeuble, J. F.; Stryker, J.
M. Catalysis of Organic Reactions; Scaros, M. G., Prunier, M. L., Eds.;
Marcel Dekker: New York, 1995; pp 235-247. (b) Lipshutz, B. H.;
Chrisman, W.; Noson, K. J. Organomet. Chem. 2001, 624, 367-371.
(c) Chen, J.-X.; Daeuble, J. F.; Brestensky, D. M.; Stryker, J. M.
Tetrahedron 2000, 56, 2153-2166. (d) Mahoney, W. S.; Stryker, J. M.
J. Am. Chem. Soc. 1989, 111, 8818-8823.
10.1021/jo050397v CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/07/2005
4784
J. Org. Chem. 2005, 70, 4784-4796

Hydrosilylation of Hindered and Functionalized Ketones
TABLE 1. Hydrosilylation of Hindered Ketones with
SCHEME 1. Hydrosilylation of Simple Ketones
CuCl/IPr‚HBF4
sively studied.11 Therefore, the development of efficient
and general catalytic methods for the reduction of
hindered and functionalized carbonyl compounds is highly
desirable.
In the last 10 years, N-heterocyclic carbenes (NHC)
have emerged as efficient ligands in metal-mediated
reactions.12 Compared to tertiary phosphines, the NHC
ligands have a stronger interaction with the metal center,
thereby minimizing ligand dissociation. In addition, their
significant steric bulk results in metal-NHC complexes
having unique catalytic behavior.13
We and others14 have recently reported the reduction
of carbonyl compounds (simple or R,â-unsaturated) cata-
lyzed by either Cu(I)Cl and a NHC salt or well-defined
complexes such as (IPr)CuCl (IPr ) (N,N′-bis(2,6-diiso-
propylphenyl)imidazol)-2-ylidene) (Scheme 1).
We now wish to report on a related catalytic system
that is highly efficient in the hydrosilylation of hindered
or functionalized alkyl, cyclic, bicyclic, aromatic, and
heteroaromatic ketones.
Results and Discussion
We began our studies using dicyclohexyl ketone as
substrate utilizing the catalytic system we previously
developed at room temperature (see Scheme 1). Unfor-
tunately, the protocol failed even after long reaction
times. Remarkably, on raising the temperature to 80°C,
dicyclohexyl ketone was activated toward hydrosilylation
and afforded 99% of the corresponding silyl ether in 4 h.
These conditions were tested on different hindered
ketones. These results are summarized in Table 1. Even
if total conversions could be obtained in short or reason-
able reaction times in some cases (Table 1, entries 5-7),
the most hindered substrates required higher reaction
temperatures (Table 1, entries 2 and 4). It is noteworthy
a GC conversions (isolated yields) are the average of two runs.
b See text for discussion. c Reaction at 100 °C. d Meso trans/trans:
cis/trans:meso cis/cis. e Cis:trans.
that when two diastereoisomers could be formed, IPr
turned out to be a moderate diastero-directing ligand
(Table 1, entries 3 and 4).
For diastereoselectivity considerations,15 the 2,6-di-
methylcyclohexanone (Table 1, entry 3) is sold as a
mixture of 80:20 cis:trans isomers. From the cis isomer,
both meso cis/cis and meso trans/trans silyl ethers can
be formed and the major product was assigned to be the
meso cis/cis isomer.16 Assignment of the relative config-
uration of (2-tert-butylcyclohexyloxy)silane was made by
comparing experimental spectroscopic data with those
reported in the literature for the corresponding alcohols.17
The cis diastereoisomer, the less stable one, was pre-
dominantly formed with our catalytic system. Similar
results have been observed in the rhodium-catalyzed
hydrosilylation of cyclohexanones.18
(10) (a) Lipshutz, B. H.; Noson, K.; Chrisman, W. J. Am. Chem. Soc.
2001, 123, 12917-12918. (b) Lipshutz, B. H.; Noson, K.; Chrisman,
W.; Lower, A. J. Am. Chem. Soc. 2003, 125, 8779-8789. (c) Lipshutz,
B. H.; Servesko, J. M. Angew. Chem., Int. Ed. 2003, 41, 4789-4792.
(d) Lipshutz, B. H.; Caires, C. C.; Kuipers, P.; Chrisman, W. Org. Lett.
2003, 5, 3085-3088. (e) Lipshutz, B. H.; Servesko, J. M.; Petersen, T.
B.; Papa, P. P.; Lover, A. A. Org. Lett. 2004, 6, 1273-1275.
(11) For selected examples of non-metal-catalyzed reduction of
functionalized ketones see: (a) Yatagai, M.; Ohnuki, T. J. Chem. Soc.,
Perkin Trans. 1 1990, 6, 1826-1828. (b) Ridley, D. D.; Stramow, M. J.
Chem. Soc., Chem. Commun. 1975, 10, 400.
(12) For selected examples see: (a) Navarro, O.; Kelly, R. A., III;
Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194-16195. (b) Viciu, M.
S.; Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4, 4053-4056. (c)
Lee, C. W.; Choi, T.-L.; Grubbs, R. H. J. Am. Chem. Soc. 2002, 124,
3224-3225. (d) Herrmann, W. A.; Bohm, V. P. W.; Gstottmayr, C. W.
K.; Grosche, M.; Reisinger, C. P.; Weskamp, T. J. Organomet. Chem.
2001, 617, 616-628. (e) Frenzel, U.; Weskamp, T.; Kohl, J. F.;
Schattenman, W. C.; Nuyken, O.; Herrmann, W. A. J. Organomet.
Chem. 1999, 586, 563-265.
To improve these results, we examined the influence
of the ligand on the reaction. The structures of the
screened NHC salts are shown in Figure 1.
Their corresponding activity in the hydrosilylation of
dicyclohexyl ketone is illustrated in Table 2. ICy‚HBF4
was found to be the most efficient ligand. The bulkiest
(13) For reviews about NHC see: (a) Herrmann, W. A. Angew.
Chem., Int. Ed. Engl. 2002, 41, 2162-2187. (b) Bourissou, D.; Guerret,
O.; Gabbai, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39-91. (c)
Arduengo, A. J. Acc. Chem. Res. 1999, 32, 913-921.
(14) (a) Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organo-
metallics 2004, 23, 1157-1160. (b) Jurkauskas, V.; Sadighi, J. P.;
Buchwald, S. L. Org. Lett. 2003, 5, 2417-2420.
(15) For more details, see the Experimental Section.
(16) Raban, M.; Lauderback, S. K.; Kost, D. J. Am. Chem. Soc. 1975,
97, 5178-5183.
(17) Fort, Y.; Feghouli, A.; Vanderesse, R.; Caube`re, P. J. Org. Chem.
1990, 55, 5911-5915 and references herein.
(18) Felfo¨ldi, K.; Kapocsi, K.; Barto´k, M. J. Organomet. Chem. 1989,
362, 411-415.
J. Org. Chem, Vol. 70, No. 12, 2005 4785

D´ıez-Gonza´lez et al.
SCHEME 2. Synthesis of (ICy)CuCl
FIGURE 1. Structures of saturated and unsaturated NHC
salts.
TABLE 2. Effect of NHC‚HX on the Hydrosilylation of
Dicyclohexyl Ketone
min but surprisingly the use of dimethylphenylsilane led
to incomplete conversion even after 18 h. Phenyl and
diphenylsilane led to complete consumption of the di-
cyclohexyl ketone in 30 min, but, as expected, multiple
hydrosilylated products were obtained for those cases. As
all products would lead to the same alcohol after acidic
workup, these hydrosilanes remain interesting when an
alcohol is the target product. Nevertheless, as we were
interested in isolating the corresponding silyl ethers,
Et3SiH was chosen as the hydride source as it is the most
efficient in terms of cost and reactivity.
Base and silane loadings were optimized to 20 mol %
of NaOtBu and 5 equiv of Et3SiH, respectively. In some
cases, the hydrosilylation reactions could be carried out
with 12 mol % of base with no deleterious effect on
reaction time, but this was not general. Control reactions,
using the optimized conditions, where CuCl and ICy‚
HBF4 were used independently and exclusively resulted
in the starting material recovery.
conversion
after 1 ha
max conversion
(time)a
entry
NHC‚HX
1
2
IPr‚HBF4
IPr‚HCl
20
2
100 (4 h)
79 (24 h)
13 (24 h)
8 (20 h)
100 (7 h)
100 (1.5 h)
100 (4 h)
100 (1 h)
100 (3 h)
100 (5 h)
100 (3.5 h)
3
SIPr‚HBF4
SIPr‚HCl
IMes‚HBF4
IMes‚HCl
SIMes‚HBF4
ICy‚HBF4
IAd‚HBF4
IAd‚HCl
0
4
0
5
11
82
30
100
35
18
33
6
7
8
9
10
11
ItBu‚HBF4
a GC conversions (%) are the average of at least two runs.
We had previously shown that well-defined (NHC)CuCl
complexes, such as (IPr)CuCl, could be easily prepared
from the corresponding imidazolium salt and copper(I)
chloride. Moreover, they present a higher activity than
the in situ catalyst.14a Under the same conditions, the
synthesis of (ICy)CuCl (1) was achieved in good yield
(Scheme 2).20
The structure of this complex was elucidated by single-
crystal diffraction from suitable crystals grown from a
CH2Cl2/hexane solution. The resulting ball-and-stick
drawing for 1 is shown in Figure 2. Only the formation
of a monocarbene complex was observed under these
conditions. The Cu-C1 bond length (1.925 Å) is compa-
rable to known Cu-C bonds in carbene complexes.21
Optimization studies carried out with the well-defined
catalyst resulted in a reduced loading of base (NaOtBu,
12 mol %) and silane (Et3SiH, 3 equiv) as compared with
the in situ generated catalytic system.
carbene salts (IAd‚HX and ItBu‚HBF4) yielded the hy-
drosilylated product in good reaction times (3-5 h, Table
2, entries 9-11), which let us presume that electronic
effects rather that steric effects may be the determinant
feature in this reaction. As electronic factors governing
NHC ligands are not yet fully understood,19 it is hard to
rationalize the screening results. The hexameric complex
[(PPh3)CuH]6, known as an excellent reagent for conduct-
ing reductions of carbonyl compounds,9 was employed in
the hydrosilylation of dicyclohexyl ketone at 80 °C, but
no conversion was observed. Instead, a copper mirror
readily formed at this temperature. A similar reaction
at room temperature failed to yield the hydrosilylated
product and did not result in catalyst decomposition.
The influence of the copper source on the reaction
under conditions described in Table 2 was investigated.
Similar results were obtained with CuCl and CuBr, but
CuI required longer reaction times (4 h). Cu(II) salts such
as CuCl2 and Cu(OAc)2 were also screened. Interestingly,
the latter afforded the silylated product in 80% yield after
24 h at 80 °C. The activation pathway of this Cu(II) salt
is not fully understood and investigations are ongoing
in our laboratories to elucidate these aspects of the
chemistry.
A number of dialkyl ketones with varying steric
congestion around the carbonyl bond could be hydro-
silylated efficiently with the in situ system or the well-
defined catalyst as illustrated in Table 3. Even highly
(20) For details of other copper complexes, see: (a) Mankad, N. P.;
Gray, T. G.; Laitar, D. S.; Sadighi, J. P. Organometallics 2004, 23,
1191-1193. (b) Mankad, N. P.; Laitar, D. S.; Sadighi, J. P. Organo-
metallics 2004, 23, 3369-3371.
(21) For example, Arnold has reported a bond length of 1.960 Å in
copper complexes with chelating alkoxy-N-heterocyclic carbenes: Ar-
nold, P. L.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C. Chem. Commun.
2001, 2340-2341.
Further sources of hydride were also examined. tert-
Butyldimethylsilane yielded the expected product in 45
(19) Dorta, R.; Stevens, E. D.; Scott, N. M.; Costabile, C.; Cavallo,
L.; Hoff, C. D.; Nolan, S. P. J. Am. Chem. Soc. 2005, 127, 2485-2495.
4786 J. Org. Chem., Vol. 70, No. 12, 2005

Hydrosilylation of Hindered and Functionalized Ketones
TABLE 3. Hydrosilylation of Hindered Ketones Mediated by CuCl/ICy‚HBF4 or (ICy)CuCl
a 20 mol % of NaOtBu, 5 equiv of Et3SiH. b 12 mol % of NaOtBu, 3 equiv of Et3SiH. c GC conversions (isolated yields) are the average
of two runs.
which shows that the present catalyst is quite robust. In
all examples, the well-defined catalyst allowed shorter
reaction times, achieving a higher or comparable conver-
sion. When the expected product could be obtained as two
different diastereoismers, no diastereoselectivity was
observed. In the case of the dimethylcyclohexanone
(Table 3, entry 3), the resulting product was obtained as
a mixture 48/48/2 (meso trans/trans:meso cis/cis:cis/
trans). The different ratios of the cis/trans product
obtained under these conditions or with IPr‚HBF4 as
ligand precursor (Table 1, Entry 3) might be obtained as
a result of the base-catalyzed equilibrium between both
FIGURE 2. Ball-and-stick drawing for (ICy)CuCl (1). Selected
bond lengths (Å): C1-Cu ) 2.114(11), Cu-Cl ) 2.136(4).
isomers of the starting material. From the 2-tert-butyl-
cyclohexanone (Table 3, entry 6), a 50/50 mixture of
isomers was formed. In fact, it has been shown that there
is only a slight difference between the two faces of the
carbonyl group due to the twisted conformation of this
ketone and therefore a more hindered catalyst is needed
to observe a diastereoselectivity.22 Silylated products
formed from trimethylcyclohexanone, fenchone, and cam-
phor (Table 3, entries 4, 9, and 10) presented a major
diastereoisomer but this diastereoselectivity can be ex-
Selected bond angle (deg): C1-Cu-Cl ) 170.6(3). Hydrogens
are omitted for clarity.
unreactive ketones such as 2,2,4,4-tetramethyl-3-pen-
tanone (Table 3, entry 2) and 2,2,6,6-tetramethylcyclo-
hexanone (Table 3, entry 5) were successfully reduced
within reasonable reaction times. These catalytic systems
were also employed in the hydrosilylation of bulky
bicyclic and aromatic ketones (Table 3, entries 9-15).
Interestingly, the purity of the ketone was not crucial in
this series of experiments and technical grade benzophe-
none was successfully reduced under these conditions,
(22) Boone, J. R.; Ashby, E. C. Top. Stereochem. 1979, 2, 53-95.
J. Org. Chem, Vol. 70, No. 12, 2005 4787

D´ıez-Gonza´lez et al.
TABLE 4. Biphenylphosphine Screening for the
Hydrosilylation of Dicyclohexyl Ketone
FIGURE 3. Ball-and-sick drawing for [(t-Bu3P)CuCl]4 (2).
Selected bond lengths (Å): P1-Cu1 ) 2.2005(8), P2-Cu2 )
2.2027(8), Cu1-Cl1 ) 2.4265(8), Cu1-Cl2 ) 2.4224(8), Cu2-
Cl1 ) 2.4668(8), Cu2-Cl2 ) 2.4346(8). Selected bond angles
(deg): P1-Cu1-Cl1 ) 123.78(3), P1-Cu1-Cl2 ) 123.07(3),
Cl2-Cu1-Cl1 ) 93.84(3), P2-Cu2-Cl2 ) 124.68(3), P2-
Cu2-Cl1 ) 121.22(3), Cl2-Cu2-Cl1 ) 93.87(3). Hydrogens
are omitted for clarity.
sions in silylated ether were obtained and the dicyclo-
hexyl ketone was recovered after the reaction. These facts
suggest that the in situ formed complexes may have low
catalytic activity under these conditions. Increasing the
σ-donor effect (Table 4, entries 2 and 3) or the π-donor
effect of the phosphine (Table 4, entries 4 and 5) did not
lead to more efficient reactions. No reaction took place
when di-tert-butylphosphines (biphenyl, 2-methylbi-
phenyl, 1,1′-binaphthyl, or 2′-(N,N-dimethylamino)bi-
phenyl) were used, even if the quantitative formation of
the corresponding complexes was observed by 31P NMR.24
This fact, along with the low reaction rates obtained in
the other examples suggest that steric bulk might dictate
the reactivity of the complex toward the ketone. As no
complex was formed in the case of a diphenylphosphine
(Table 4, entry 6), the electronic aspects may have an
important influence in the formation of the complexes.
It is of note that in all examples, when dicyclopropyl
ketone was used as starting material, no conversion was
observed even after long reaction times (24-48 h) with
biphenylphosphine ligands.
Triaryl- and trialkylphosphines were also tested under
these conditions. PPh3 did not yield any product after 12
h. Low conversions were observed with PEt3 and PtBu3‚
HBF4 (10% and 40% after 12 h). The best results were
obtained with PiPr3 and PCy3, 98% of conversion after
12 h.
All attempts to synthesize Cu(I) well-defined complexes
with PiPr3 or PCy3 failed. Nevertheless, we were able to
prepare a (tBu3P)CuCl complex under the reaction condi-
tions described for the synthesis of (ICy)CuCl although
in a considerably lower yield (Scheme 3).
a GC conversions (isolated yields) are the average of two runs.
b P ) free phosphine; [Cu] ) corresponding complex.
SCHEME 3. Synthesis of (tBu3P)CuCl
plained by the structure of the starting material. In the
case of the silyl ether corresponding to camphor (Table
3, entry 9), the endo isomer was only observed as traces
in the 1H NMR spectrum, and as expected, the endo
product was preferentially formed from the fenchone
(Table 3, entry 10).23
As the NHC-Cu(I) complex is air stable and its
handling does not require inert conditions, open air
reactions were also tested. Formation of the silylated
product from dicyclohexyl ketone was observed under
these conditions. However, resulting yields were not
reproducible as in solution the active species rapidly
underwent decomposition to afford copper(II) products.
As NHCs have been traditionally considered “phos-
phine-mimics” and complementary to elegant work by
Lipshutz using bidentate phosphines,10 some tertiary
phosphines were screened to allow a comparison. The
results for the hydrosilylation of dicyclohexyl ketone
catalyzed by CuCl/biphenylphosphine systems are pre-
sented in Table 4. 31P NMR experiments were performed
for each screened phosphine to ensure the formation of
the corresponding phosphine-copper complex. Total
transformation of the starting phosphines was observed
in all cases but for the triisopropylbiphenylphosphine
(Table 4, entry 2), which was only partially converted into
the corresponding copper complex. However, low conver-
(23) Stothers, J. B.; Tan C. T.; Teo, K. C. Can. J. Chem. 1976, 54,
1211-1221.
(24) 31P NMR (P ) free phosphine, [Cu] ) copper-phosphine
complex): (a) 2-di-tert-butylphosphino-biphenyl, P: 39.58, [Cu]: 21.38.
(b) 2-di-tert-butylphosphino-2′-methyldiphenyl, P: 23.89, [Cu]: 130.79.
(c) racemic-2-di-tert-butylphosphino-1,1′-dinaphthyl, P: 24.48, [Cu]:
36.45. (d) 2-di-tert-butylphosphino-2′-(N,N-dimethylamino)biphenyl,
P: 28.29, [Cu]: 39.64.
4788 J. Org. Chem., Vol. 70, No. 12, 2005

Hydrosilylation of Hindered and Functionalized Ketones
TABLE 5. Hydrosilylation of Functionalized Ketones with CuCl/ICy‚HBF4 or (ICy)CuCl
a 20 mol % of NaOtBu, 5 equiv of Et3SiH. b 12 mol % of NaOtBu, 3 equiv of Et3SiH. c GC conversions (isolated yields) are the average
of two runs.
Suitable single crystals of this phosphine-copper
complex were grown from a saturated THF solution, to
elucidate its structure by single-crystal diffraction. The
corresponding ball-and-stick drawing for [(t-Bu3P)CuCl]4
(2) is shown in Figure 3. For the phosphine-copper
complex, formation of a “cubane-like” structure was
observed. It adopts a slightly distorted cubic arrangement
with four copper atoms, each having a tetrahedral
environment with three bridging chlorides and a phos-
phine ligand. This type of structure has already been
observed for other phosphine-Cu(I) complexes.25 The
average distances in the core are Cu-Cl ) 2.438 Å and
Cu-P ) 2.202 Å. The high steric congestion and degree
of coordination around the metal centers in this phos-
phine-copper complex, when compared with the mono-
meric NHC-copper complex, may explain its lack of
reactivity toward hydrosilylation.
We have shown that, in the present system, NHCs are
more efficient ligands in the hydrosilylation of ketones
than the tested tertiary phosphines. We suspect that
their specific shape may protect and stabilize the metal
center facilitating the coordination of the substrate.
To enlarge the scope of our catalytic system, a number
of functionalized ketones were tested with the in situ
catalyst as well as with the well-defined complex. Amines
and ethers (Table 5, entries 1, 2, and 9) reacted success-
fully under these conditions. In the presence of halogen
and trifluoromethyl substituents on the aromatic ring,
good yields were obtained in short reaction times (Table
5, entries 3-5). However, electron-donating groups in the
aromatic ring or a pyranyl ring led to slower reaction
rates (Table 5, entries 7 and 10) and no reaction was
observed in the case of an acetylbenzonitrile and tetra-
hydrothiopyranone (Table 5, entries 8 and 11). A long
reaction time was required to reduce the 2-acetylpyridine,
and 2-acetylthiophene did not yield any hydrosilylated
product under these conditions (Table 5, entries 12 and
13). In the case of 2-methoxycyclohexanone (Table 5,
entry 9), no steric or chelation effect was observed and
the corresponding silyl ether was obtained as a 50/50
mixture of diastereoisomers.
Since reduced products from heteroaromatic ketones
can be useful intermediates for the synthesis of biologi-
cally active compounds,26 we closely examined the reac-
tivity of pyridine and thiophene acetophenones (Table 5,
entries 12 and 13). It is well-known that copper forms
strong bonds with nitrogen or sulfur and so the presence
of these heteroatoms in the starting material might
sequester the metal center inhibiting the catalytic cycle.
To avoid this process, the reactivity of different imid-
(25) Churchill, M. R.; DeBoer, B. G.; Mendak, S. J. Inorg. Chem.
1975, 14, 2041-2047.
J. Org. Chem, Vol. 70, No. 12, 2005 4789

D´ıez-Gonza´lez et al.
TABLE 6. Effect of NHC‚HX on the Hydrosilylation of
2-acetylpyridine
conversion
after 3 ha
max conversiona
(time)
entry
NHC‚HX
1
2
IPr‚HBF4
IPr‚HCl
20
3
90 (24 h)
100 (72 h)
60 (20 h)
15 (29 h)
98 (4.5 h)
100 (6.5 h)
100 (3 h)
98 (8 h)
3
SIPr‚HBF4
SIPr‚HCl
IMes‚HBF4
IMes‚HCl
SIMes‚HBF4
ICy‚HBF4
IAd‚HBF4
IAd‚HCl
0
FIGURE 4. Ball-and-stick drawing for (SIMes)CuCl (3).
Selected bond lengths (Å): C1-Cu ) 1.882(4), Cu-Cl )
2.099(11). Selected bond angle (deg): C1-Cu-Cl ) 178.48(13).
Hydrogens are omitted for clarity but for the imidazolium ring.
4
0
5
56
42
100
40
27
35
6
7
8
TABLE 8. Optimization of Hydrosilylation with
(SIMes)CuCl Catalyst
9
100 (9 h)
100 (8 h)
10
TABLE 7. Optimization of Hydrosilylation with CuCl/
SIMes‚HBF4 Catalyst
X mol %
Y equiv
of Et3SiH
time
(h)
GC conversion
(%)a
entry
of NaOtBu
1
2
3
4
5
6
7
12
8
5
5
5
5
3
2
1
1.5
1
0.5
24
0.5
0.5
18
100
100
100
0
100
100
0
3
mol % of
NaOtBu
equiv of
Et3SiH
time
(h)
GC conversion
(%)a
0
entry
3
1
2
3
4
5
6
20
12
8
3
12
20
5
5
5
5
3
3
3
2
1
24
6
3.5
100
100
100
0
100
100
3
3
a GC conversions are the average of at least two runs.
a GC conversions are the average of at least two runs.
Base and hydrosilane loading optimization showed
surprising results. Not only did lower base loadings not
require longer reaction times but complete conversion
was reached in only 1 h when 8 mol % of NaOtBu was
used (Table 7). When less that 5 equiv of hydrosilane was
used, the reaction still reached completion but in longer
reaction times.
SCHEME 4. Synthesis of (SIMes)CuCl
Such results led us to synthesize a well-defined cop-
per(I) chloride complex bearing a SIMes ligand to com-
pare its activity to the in situ system. The protocol
employed for the preparation of (ICy)CuCl (1) was
successful and afforded the expected (SIMes)CuCl (3) in
good yield (Scheme 4).
The structure of 3 was elucidated by single-crystal
diffraction from suitable crystals grown from a CH2Cl2/
hexane solution. The resulting ball-and-stick drawing for
3 is shown in Figure 4. In the case of (SIMes)CuCl, the
structure is analogous to that observed for (ICy)CuCl (1),
but the bond length between the copper center and the
carbenic carbon is shorter than that for the latter (1.882
and 1.925 Å, respectively). This suggests that the satu-
rated NHC ligand binds more strongly to the metal
center.
Base and silane loadings were optimized for the
hydrosilylation reaction mediated by (SIMes)CuCl (3). As
for the in situ system with SIMes‚HBF4, decreasing base
loading led to faster completion of the reaction and we
were able to reach total conversion in 30 min with only
3 mol % of NaOtBu (Table 8). As expected, no reaction
was observed in the absence of base. The same reaction
times leading to identical conversions were observed with
5, 3, or 2 equiv of silane.
azolium salts in the hydrosilylation of the 2-acetylpyri-
dine was studied. The results are presented in Table 6.
In this case, SIMes‚HBF4 turned out to be the best ligand
precursor for the hydrosilylation of 2-acetylpyridine by
Et3SiH. It is of note that IMes‚HBF4 and IMes‚HCl also
lead to interesting conversions but longer reaction times
are required.
(26) (a) Wishka, D. G.; Graber, D. R.; Seest, E. P.; Dolak, F. H.; Watt,
W.; Morris, J. J. Org. Chem. 1998, 63, 7851-7859. (b) Deeter, J.;
Frazier, J.; Staten, G.; Staszak, M.; Weigel, L. Tetrahedron Lett. 1990,
31, 7101-7104. (c) Labelle, M.; Belley, M.; Gareau, Y.; Gauthier, J.
Y.; Guay, D.; Gordon, R.; Grossman, S. G.; Jones, T. R.; Leblanc, Y.;
McAuliffe, M.; McFarlane, C.; Masson, P.; Metters, K. M.; Ouimet, N.;
Patrick, D. H.; Piechuta, H.; Rochette, C.; Sawyer, N.; Xiang, Y. B.;
Pickett, C. B.; Ford-Hutchinson, A. W.; Zamboni, R. J.; Young, R. N.
Bioorg. Med. Chem. Lett. 1995, 5, 283-288.
4790 J. Org. Chem., Vol. 70, No. 12, 2005

Hydrosilylation of Hindered and Functionalized Ketones
TABLE 9. Hydrosilylation of Heteroaromatic Ketones
SCHEME 5. Proposed Mechanism for the
Copper-Catalyzed Hydrosilylation of Ketones
explain why an excess of base is generally required to
complete the reaction. The (SIMes)CuCl-catalyzed hy-
drosilylation of heteroaromatic ketones is the first ex-
ample of this reaction where no excess of base is used.
As it is well-known that hydrosilanes are prone to
nucleophilic attack, we propose that the excess of base
that is generally required would interact with the hy-
drosilane and facilitate the second σ-bond metathesis.
Further efforts to fully understand the mechanism of this
catalytic system are underway.
a 8 mol % of NaOtBu, 5 equiv of Et3SiH. b 3 mol % of NaOtBu,
2 equiv of Et3SiH. c GC conversions (isolated yields) are the
average of two runs. d 12 mol % of NaOtBu. e 8 mol % of NaOtBu.
The optimized conditions for the hydrosilylation of
2-acetylpyridine were tested with other heteroaromatic
ketones. The results are shown in Table 9. Good results
were obtained for all the examined substrates, except in
the case of 2-acetylthiazole and 2-acetyl-1-methylpirrole
(Table 9, entries 4 and 5) where larger amounts of base
were required to carry out the reaction in reasonable
reaction times. The asymmetric hydrosilylation of hetero-
aromatic ketones has already been reported by Lipshutz
et al.27 Interestingly, their chiral phosphine-Cu(I) system
failed to yield any product from 2-acetylthiophene or
2-acetyl-1-methylpyperidine even though it allowed the
formation of several alcohols in excellent yields and
moderate to good ee.
Conclusions
In summary, a reagent prepared in situ from sub-
stoichiometric quantities of CuCl and a NHC salt as
ligand precursor has been found to possess excellent
reactivity in the hydrosilylation of hindered and func-
tionalized ketones. This method combines the versatility
of ICy‚HBF4 toward a wide variety of substrates with the
possibility of varying the ligand precursor to improve
conversions/activity as a function of specific carbonyl
compounds. This has been demonstrated in the hydro-
silylation of heteroaromatic ketones with SIMes as the
NHC of choice. The corresponding well-defined com-
plexes, (NHC)CuCl, can be readily prepared by a general
scheme that is applicable to numerous imidazolium salts.
Both the in situ generated and the well-defined systems
give cleanly, high yields of products in short to interme-
diate reaction times. The combination of a copper(I) salt
and an inexpensive ligand precursor would appear to be
a practical and economical methodology in the area of
reduction of carbonyl compounds. Applications to other
carbonyl and carbonyl-type substrates and further stud-
ies on the diastereoselectivity of this catalyst system are
currently being pursued in our laboratories.
These results for the hydrosilylation of heteroaromatic
ketones are also interesting in terms of mechanistic
insights. The proposed mechanism for the copper-
catalyzed hydrosilylation of ketones is shown in Scheme
5. First, formation of (NHC)CuOtBu from (NHC)CuCl and
NaOtBu occurs. This step has been confirmed as forma-
tion of (NHC)copper alkoxide complexes under these
1
conditions has been observed by H NMR.20b It is then
postulated that the active catalyst, a NHC copper hydride
species, is formed by a σ-bond metathesis between the
(NHC)CuOtBu and the hydrosilane. Addition of hydride
to the carbonyl carbon would result in a copper alkoxide
that would undergo another σ-bond metathesis28 with the
hydrosilane to form the expected silyl ether and re-
generate the active catalyst. This proposed mechanism
is in agreement with the experimental evidence for the
phosphine-copper catalyst systems,29 but it does not
Experimental Section
General Considerations. All ketones were used as re-
ceived. Copper(I) chloride and sodium tert-butoxide were stored
under argon in a glovebox containing less than 1 ppm O2. The
imidazolium salts were synthesized according to literature
procedures.30 Solvents were distilled from appropriate drying
agents. Flash column chromatography was performed on silica
(27) Lipshutz, B. H.; Lower, A.; Noson, K. Org. Lett. 2002, 4, 4045-
4548.
(28) Lorenz, C.; Schubert, U. Chem. Ber. 1995, 128, 1267-1269.
(29) (a) Pagenkopf, B. L.; Kru¨ger, J.; Stojanovic, A.; Carreira, E. M.
Angew. Chem., Int. Ed. 1998, 37, 3124-3126. (b) Moritami, Y.; Appella,
D. H.; Jurkauskas, V.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122,
6797-6798. (c) Yun, J.; Buchwald, S. L. Org. Lett. 2001, 3, 1129-1131.
1
gel 60 (320-400 mesh). H NMR and 13C NMR spectra were
J. Org. Chem, Vol. 70, No. 12, 2005 4791

D´ıez-Gonza´lez et al.
recorded on a 400 MHz spectrometer at room temperature.
Chemical shifts (δ) are reported with respect to tetramethyl-
silane as internal standard in ppm. All reported yields are
isolated yields and are the average of at least two runs.
Synthesis of (L)CuCl Complexes (L ) NHC or PR3).
The procedure provided in ref 14a was used for the synthesis
of the complexes.
product was purified by flash chromatography on silica gel
(pentane) to afford 0.237 g (92% yield) of the title compound
as a colorless oil. (B) Using the general procedure with
(ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2,2,4,4-
tetramethylpentanone (0.175 mL, 1 mmol) was hydrosilylated
by triethylsilane. The residue was purified by flash chroma-
tography on silica gel (pentane) to afford 0.238 g (92% yield)
1
1
(ICy)CuCl (1). H NMR (400 MHz, CDCl3) δ 6.93 (s, 2H),
of the title compound as a colorless oil. H NMR (400 MHz,
4.37-4.23 (m, 2H), 2.14-2.02 (m, 4H), 1.94-1.83 (m, 4H),
CDCl3) δ 3.13 (s, 1H), 0.99 (t, J ) 8.0 Hz) and 0.97 (s) (27H),
0.66 (q, 6H, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 87.8,
37.8, 29.2, 7.3, 5.9; MS (EI), m/z 258 (M+). Elemental analysis
calcd for C15H34OSi (268.51): C, 69.69; H, 13.26. Found: C,
69.92; H, 13.61.
1.80-1.57 (m, 6H), 1.55-1.37 (m, 4H), 1.31-1.14 (m, 2H). 13
C
NMR (100 MHz, acetone-d6) δ 174.2, 119.5, 62.1, 35.4, 26.3,
25.8. Elemental analysis calcd for C15H24CuClN2 (331.17): C,
54.37; H, 7.30; N, 8.45. Found: C, 54.26; H, 7.00; N, 8.15.
[(tBu3P)CuCl]4 (2). 31P (160 MHz, d8-THF) δ 63.5. Elemen-
tal analysis calcd for C12H27ClCuP (301.32): C, 47.83; H, 9.03.
Found: C, 47.96; H, 9.24.
(2,6-Dimethylcyclohexyloxy)triethylsilane (Table 3,
Entry 3). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 2,6-dimethylcyclohexanone (0.14 mL, 1
mmol) was hydrosilylated by triethylsilane. The crude product
was purified by flash chromatography on silica gel (pentane)
to afford two diastereoisomers of the title compound (0.111 and
0.107 g respectively, 90% yield).32 (B) Using the general
procedure with (ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv
of Et3SiH, 2,6-dimethylcyclohexanone (0.14 mL, 1 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane) to afford
two diastereoisomers of the title compound (0.118 and 0.114
g respectively, 97% yield).32 Meso trans/trans: 1H NMR (400
MHz, CDCl3) δ 3.61 (br s, 1H), 1.69-1.56 (m, 2H), 1.48-1.16
(m, 6H), 0.99 (t, 9H, J ) 8.0 Hz), 0.88 (d, 6H, J ) 6 Hz), 0.62
(q, 6H, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 76.7, 38.4,
27.8, 26.2, 19.5, 7.2, 5.7; MS (EI), m/z 242 (M+). Elemental
analysis calcd for C14H30OSi (242.47): C, 69.35; H, 12.47.
Found: C, 69.29; H, 12.69. Meso cis/cis: 1H NMR (400 MHz,
CDCl3) δ 2.78 (t, 1H, J ) 9.2 Hz), 2.78-1.61 (m, 1H), 1.61-
1.51 (m, 1H), 1.49-1.28 (m, 4H), 0.98 (t, J ) 8.0 Hz) and 0.96
(d, 6H, J ) 8.0 Hz) (15H), 0.64 (q, 6H, J ) 8.0 Hz); 13C NMR
(100 MHz, CDCl3) δ 83.8, 40.3, 34.6, 25.6, 19.7, 7.2, 5.7; MS
(EI), m/z 242 (M+). Elemental analysis calcd for C14H30OSi
(242.47): C, 69.35; H, 12.47. Found: C, 69.70; H, 12.76.
Triethyl(2,2,6-trimethylcyclohexyloxy)silane (Table 3,
Entry 4). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 2,2,6-trimethylcyclohexanone (0.14 mL,
1 mmol) was hydrosilylated by triethylsilane. The crude
product was purified by flash chromatography on silica gel
(pentane) to afford two diastereoisomers of the title compound
(0.094 and 0.142 g respectively, 92% yield) as a colorless oil.
(B) Using the general procedure with (ICy)CuCl, 12 mol % of
NaOtBu, and 3 equiv of Et3SiH, 2,2,6-trimethylcyclohexanone
(0.14 mL, 1 mmol) was hydrosilylated by triethylsilane. The
crude product was purified by flash chromatography on silica
gel (pentane) to afford two diastereoisomers of the title
compound (0.095 and 0.143 g respectively, 93% yield) as a
colorless oil. DIA-1: 1H NMR (400 MHz, CDCl3) δ 3.24 (br s,
1H), 1.81-1.67 (m, 1H), 1.55-1.36 (m, 3H), 1.36-1.23 (m, 2H),
1.23-1.16 (m, 1H), 0.98 (t, 9H, J ) 8.0 Hz), 0.87 (s) and 0.85
(d, J ) 7.2 Hz) (9H), 0.62 (q, 6H, J ) 8.0 Hz); 13C NMR (400
MHz, CDCl3) δ 80.8, 35.8, 33.1, 32.6, 29.0, 28.0, 25.0, 21.6,
19.4, 7.2, 5.7; MS (EI) m/z 256 (M+). Elemental analysis calcd
for C15H32OSi (256.22): C, 70.24; H, 12.57. Found: C, 0.70.18;
H, 12.68. DIA-2: 1H NMR (400 MHz, CDCl3) δ 2.90 (d, 1H, J
) 9.6 Hz), 1.68-1.58 (m, 1H), 1.56-1.42 (m, 2H), 1.42-1.31
(m, 3H), 1.31-1.08 (m, 1H), 0.98 (t, 9H, J ) 8.0 Hz), 0.91 (s)
and 0.89 (d, J ) 6.0 Hz) and 0.85 (s) (9H), 0.65 (q, 6H, J ) 8.0
Hz); 13C NMR (100 MHz, CDCl3) δ 85.1, 40.0, 36.5, 35.2, 34.7,
30.5, 21.6, 20.1, 18.8, 7.2, 5.7; MS (EI) m/z 256 (M+). Elemental
analysis calcd for C15H32OSi (256.22): C, 70.24; H, 12.57.
Found: C, 70.00, H, 12.24.
(SIMes)CuCl (3). 1H NMR (400 MHz, CDCl3) δ 6.96 (s, 4H),
3.96 (s, 4H), 2.32 (s, 12H), 2.30 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 202.8, 138.7, 135.3, 135.0, 129.7, 50.9, 21.0, 18.0.
Elemental analysis calcd for C21H26CuClN2 (405.44): C, 62.21;
H, 6.46; N, 6.91. Found: C, 62.60; H, 6.52; N, 6.80.
General Procedure A for the Hydrosilylation of Ke-
tones (in situ system). In an oven-dried vial fitted with a
septum screw cap, copper(I) chloride (3 mg, 0.03 mmol, 3 mol
%), the imidazolium salt (9.6 mg if ICy‚HBF4 or 11.8 mg if
SIMes‚HBF4, 0.03 mmol, 3 mol %), and sodium tert-butoxide
(8-20 mol %) were charged inside a glovebox and stirred in
dry toluene (2 mL) at 80°C outside of the glovebox for 10 min
before triethylsilane (0.8 mL, 5 mmol, 5 equiv) was added
through the septum with a syringe. After 20 min more of
stirring, the ketone (1 mmol) was added. When the ketone was
a solid, it was added as a solution in toluene. The reaction
was allowed to proceed at 80°C and monitored by GC. After
consumption of the starting ketone or no further conversion,
the reaction mixture was allowed to cool to room temperature,
opened to air, and filtered through a plug of active charcoal
and Celite with ethyl acetate as solvent. The organic phase
was concentrated in vacuo and the purity of the residue
checked on GC and 1H NMR. Flash chromatography was then
performed unless crude product was estimated to be greater
than 95% pure.
General Procedure B for the Hydrosilylation of Ke-
tones (well-defined catalyst). The procedure described
above was used with (NHC)CuCl (10 mg if (ICy)CuCl or 12
mg if (SIMes)CuCl, 0.03 mmol, 3 mol %), sodium tert-butoxide
(3-12 mol %), and triethylsilane (2-3 equiv) for 1 mmol of
starting ketone.
(1-Isopropyl-2-methylpropoxy)triethylsilane (Table 3,
Enty 1). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 2,4-dimethylpentanone (0.14 mL, 1 mmol)
was hydrosilylated by triethylsilane. A colorless oil was
obtained as the pure product after concentration of the filtrate
(0.218 g, 96% yield). (B) Using the general procedure with
(ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2,4-
dimethylpentanone (0.14 mL, 1 mmol) was hydrosilylated by
triethylsilane. The residue was purified by flash chromatog-
raphy on silica gel (pentane) to afford 0.217 g (94% yield) of
the title compound as a colorless oil. Spectroscopic data were
consistent with previously reported data for this compound.31
(1-tert-Butyl-2,2-dimethylpropoxy)triethylsilane (Table
3, Entry 2). (A) Using the general procedure with ICy‚HBF4
and 20 mol % of NaOtBu, 2,2,4,4-tetramethylpentanone (0.175
mL, 1 mmol) was hydrosilylated by triethylsilane. The crude
(30) (a) Arduengo, A. J.; Krafczyk, R.; Schmutzler, R.; Craig, H. A.;
Goerlich, J. R.; Marshall, W. J.; Unverzagt, M. Tetrahedron 1999, 55,
14523-14534. (b) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am.
Chem. Soc. 1991, 113, 361-363. (c) Arnold, P. L.; Cloke, F. G. N.;
Geldbach, T.; Hitchcock, P. B. Organometallics 1999, 18, 3228-3233
(d) Arduengo, A. J.; Gamper, S. F.; Calabrese, J. C.; Davidson, F. J. J.
Am. Chem. Soc. 1994, 116, 4391-4393. (e) Arduengo, A. J.; Davidson,
F.; Kraftczyk, R.; Marshall, W. J.; Tamm, M. Organometallics 1998,
17, 3375-3382.
(32) In the second fraction of the flash chromatography, two dia-
stereoisomers were present but only the major one, the meso cis/cis,
could be fully characterized. The presence of the cis/trans isomer as
minor product was evidenced by the presence of a doublet of doublets
at 3.29 ppm (J ) 7.6, 4.0 Hz) in the 1H NMR spectrum.
(31) Barden, J.; Fleming, J. Chem. Commun. 2001, 22, 2366-2367.
4792 J. Org. Chem., Vol. 70, No. 12, 2005

Hydrosilylation of Hindered and Functionalized Ketones
Triethyl(2,2,6,6-tetramethylcyclohexyloxy)silane (Table
3, Entry 5). (A) Using the general procedure with ICy‚HBF4
and 20 mol % of NaOtBu, 2,2,6,6-tetramethylcyclohexanone
(0.175 mL, 1 mmol) was hydrosilylated by triethylsilane. The
crude product was purified by flash chromatography on silica
gel (pentane) to afford 0.244 g (90% yield) of the title compound
as a colorless oil. (B) Using the general procedure with
(ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2,2,6,6-
tetramethylcyclohexanone (0.175 mL, 1 mmol) was hydro-
silylated by triethylsilane. The crude product was purified by
flash chromatography on silica gel (pentane) to afford 0.244 g
7.2, 5.6; MS (IE) m/z 310 (M+). Elemental analysis calcd for
C19H38OSi (310.59): C, 73.47; H, 12.33. Found: C, 73.75; H,
12.50.
Triethyl(1,7,7-trimethylbicyclo[2.2.1]hept-2-yloxy)-
silane (Table 3, Entry 9). (A) Using the general procedure
with ICy‚HBF4 and 20 mol % of NaOtBu, D(+)-camphor (0.152
g, 1 mmol) was hydrosilylated by triethylsilane. The crude
product was purified by flash chromatography (pentane) to
afford 0.257 g (96% yield) of the title compound as a colorless
oil. (B) Using the general procedure with (ICy)CuCl, 12 mol
% of NaOtBu, and 3 equiv of Et3SiH, D(+)-camphor (0.152 g, 1
mmol) was hydrosilylated by triethylsilane. The crude product
was purified by flash chromatography on silica gel (pentane)
to afford 0.244 g (91% yield) of the title compound as a colorless
1
(90% yield) of the title compound as a colorless oil. H NMR
(400 MHz, CDCl3) δ 3.05 (s, 1H), 1.58-1.38 (m, 3H), 1.34-
1.22 (m, 1H), 1.20-1.09 (m, 2H), 0.99 (t, 9H, J ) 8.0 Hz), 0.885
(s) and 0.878 (s) (12H), 0.66 (q, 6H, J ) 8.0 Hz); 13C NMR (100
MHz, CDCl3) δ 85.7, 40.2, 36.6, 33.0, 20.2, 18.6, 7.3, 5.8; MS
(EI) m/z 270 (M+). Elemental analysis calcd for C16H34OSi
(270.53): C, 71.04; H, 12.67. Found: C, 71.15; H, 12.88.
oil.
1H NMR (400 MHz, CDCl3) δ 3.53 (dd, 1H, J ) 7.6, 3.2
Hz), 1.78-1.58 (m, 4H), 1.52-1.41 (m, 1H), 1.00 (s, 3H), 0.98-
0.88 (m) containing 0.94 (t, J ) 7.9 Hz) (11H), 0.83 (s, 3H),
0.79 (s, 3H), 0.54 (q, 6H, J ) 7.9 Hz); 13C NMR (100 MHz,
CDCl3) δ 79.6, 49.1, 46.5, 45.3, 42.4, 34.0, 27.4, 20.6, 20.1, 11.9,
6.9, 4.9; MS (EI) m/z 268 (M+). Elemental analysis calcd for
C16H32OSi (268.51): C, 71.57; H, 12.01. Found: C, 71.34; H,
12.04.
(2-tert-Butylcyclohexyloxy)triethylsilane (Table 3, En-
try 6). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 2-tert-butylcyclohexanone (0.175 mL, 1
mmol) was hydrosilylated by triethylsilane. The crude product
was purified by flash chromatography on silica gel (pentane)
to afford two diastereoisomers of the title compound (0.146 and
0.122 g respectively, 99.5% yield). (B) Using the general
procedure with (ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv
of Et3SiH, 2-tert-butylcyclohexanone (0.175 mL, 1 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane) to afford
two diastereoisomers of the title compound (0.136 and 0.113
g respectively, 92% yield). Cis diastereoisomer: 1H NMR (400
MHz, CDCl3) δ 4.26 (br s, 1H), 1.79-1.66 (m, 2H), 1.65-1.50
(m, 3H), 1.50-1.23 (m, 3H), 1.20-0.98 (m, 1H), 0.96 (t, 9H, J
) 8.0 Hz), 0.94 (s, 9H), 0.64 (q, 6H, J ) 8.0 Hz); 13C NMR
(100 MHz, CDCl3) 68.8, 52.5, 35.6, 32.6, 28.5, 27.3, 21.6, 20.4,
7.1, 5.5; MS (IE) m/z 270 (M+). Elemental analysis calcd for
C16H34OSi (270.53): C, 71.04; H, 12.67. Found: C, 70.71; H,
13.00. Trans diastereoisomer: 1H NMR (400 MHz, CDCl3) δ
3.56 (dt, 1H, J ) 9.8, 4.3 Hz), 1.93-1.84 (m, 1H), 1.82-1.70
(m, 1H), 1.70-1.56 (m, 2H), 1.41-1.22 (m, 2H), 1.22-1.07 (m,
3H), 0.96 (t, J ) 8.0 Hz) and 0.95 (s) (18H), 0.62 (q, 6H, J )
8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 74.7, 53.3, 37.6, 32.9,
29.3, 26.7, 26.2, 25.1, 7.1, 5.7; MS (IE) m/z 270 (M+). Elemental
analysis calcd for C16H34OSi (270.53): C, 71.04; H, 12.67.
Found: C, 71.20; H, 12.36.
(Dicyclopropylmethoxy)triethylsilane (Table 3, Entry
7). (A) Using the general procedure with ICy‚HBF4 and 20 mol
% of NaOtBu, dicyclopropyl ketone (0.11 mL, 1 mmol) was
hydrosilylated by triethylsilane. A colorless oil was obtained
as the pure product after concentration of the filtrate (0.212
g, 94% yield). (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, dicyclopropyl
ketone (0.11 mL, 1 mmol) was hydrosilylated by triethylsilane.
A colorless oil was obtained as the pure product after concen-
tration of the filtrate (0.224 g, 99% yield). Spectroscopic data
were consistent with previously reported data for this
compound.14a Elemental analysis calcd for C13H26OSi (226.43):
C, 68.96; H, 11.57. Found: C, 68.89; H, 11.95.
Triethyl(1,3,3-trimethylbicyclo[2.2.1]hept-2-yloxy)-
silane (Table 3, Entry 10). (A) Using the general procedure
with ICy‚HBF4 and 20 mol % of NaOtBu, (+)-1,3,3-trimethyl-
2-norbornanone (0.16 mL, 1 mmol) was hydrosilylated by
triethylsilane. The crude product was purified by flash chro-
matography on silica gel (pentane) to afford 0.194 g (96% yield)
of the title compound as a 90/10 mixture of isomers as a
colorless oil. (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, (+)-1,3,3-
trimethyl-2-norbornanone (0.16 mL, 1 mmol) was hydrosilyl-
ated by triethylsilane. The crude product was purified by flash
chromatography (pentane) and obtained as a 90/10 mixture
of isomers as a colorless oil in 93% yield (0.188 g).33 1H NMR
(400 MHz, CDCl3) δ 3.25 (s, 1H, E), 2.96 (s, 1H, e), 1.84-1.69
(m, 1H, E+e), 1.68-1.59 (m, 2H, e), 1.59-1.49 (m, 2H, E),
1.46-1.36 (m, 2H, E+e), 1.08-0.92 (m) containing 1.01 (s,
E+e), 0.97 (t, J ) 8.0 Hz, E+e), 0.94 (s, E+e) (17H), 0.87 (s,
3H, E), 0.78 (s, 3H, e), 0.59 (q, J ) 8.0 Hz, E) and 0.58 (q, J )
8.0 Hz, e) (6H); 13C NMR (100 MHz, CDCl3) δ 86.8 (e), 85.4
(E), 49.7 (E), 49.6 (e), 48.4 (E), 41.22 (e), 40.97 (E), 39.7 (E),
33.6 (e), 30.5 (E), 26.29 (E), 26.16 (e), 25.76 (e), 25.39 (E), 24.3
(e), 21.1 (E), 20.0 (E), 17.9 (e), 7.04 (E), 5.27 (E), 5.17 (e); MS
(EI) m/z 268 (M+). Elemental analysis calcd for C16H32OSi
(268.51): C, 71.57; H, 12.01. Found: C, 71.71; H, 12.51.
(Diphenylmethoxy)triethylsilane (Table 3, Entry 11).
(A) Using the general procedure with ICy‚HBF4 and 20 mol
% of NaOtBu, benzophenone (0.189 g, 1 mmol) was hydro-
silylated by triethylsilane. A colorless oil was obtained as the
pure product after concentration of the filtrate (0.295 g, 99%
yield). (B) Using the general procedure with (ICy)CuCl, 12 mol
% of NaOtBu, and 3 equiv of Et3SiH, benzophenone (0.189 g,
1 mmol) was hydrosilylated by triethylsilane. A colorless oil
was obtained as the pure product after concentration of the
filtrate (0.296 g, 99% yield). 1H NMR (400 MHz, CDCl3) δ 7.36
(d, 4H, J ) 7.2 Hz), 7.28 (t, 4H, J ) 7.2 Hz), 7.20 (t, 2H, J )
7.2 Hz), 5.75 (s, 1H), 0.88 (t, 9H, J ) 7.9 Hz), 0.56 (q, 6H, J )
7.9 Hz); 13C NMR (100 MHz, CDCl3) δ 145.2, 128.1, 126.9,
126.3, 76.3, 6.7, 4.8; MS (EI), m/z 298 (M+). Elemental analysis
calcd for C19H26OSi (298.18): C, 76.45; H, 8.78. Found: C,
76.81; H, 8.80.
(Dicyclohexylmethoxy)triethylsilane (Table 3, Entry
8). (A) Using the general procedure with ICy‚HBF4 and 20
mol % of NaOtBu, dicyclohexyl ketone (0.20 mL, 1 mmol) was
hydrosilylated by triethylsilane. A colorless oil was obtained
as a pure product after concentration of the filtrate (0.307 g,
99% yield). (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, dicyclohexyl
ketone (0.20 mL, 1 mmol) was hydrosilylated by triethylsilane.
A colorless oil was obtained as the pure product after concen-
tration of the filtrate (0.306 g, 99% yield). 1H NMR (400 MHz,
CDCl3) δ 3.14 (t, 1H, J ) 6.0 Hz), 1.85-1.70 (m, 6H), 1.70-
1.59 (m, 2H), 1.59-1.48 (m, 2H), 1.47-1.33 (m, 2H), 1.28-
0.93 (m) and 0.97 (t, J ) 8.1 Hz) (19H), 0.61 (q, 6H, J ) 8.1
Hz); 13C NMR (100 MHz, CDCl3) δ 81.9, 41.1, 30.7, 28.1, 26.7,
(Phenyl-o-tolylmethoxy)triethylsilane (Table 3, Entry
12). (A) Using the general procedure with ICy‚HBF4 and 20
mol % of NaOtBu, 2-methylbenzophenone (0.18 mL, 1.0 mmol)
was hydrosilylated by triethylsilane. The crude product was
(33) After several flash chromatographies, a fraction which con-
tained only the major isomer was isolated. This allowed us to assign
partially the NMR signals of each diastereoisomer (E: endo, major; e:
exo, minor). For the minor diastereoisomer not all the 13C resonances
could be unequivocally assigned because of overlap with those from
the endo diastereoisomer.
J. Org. Chem, Vol. 70, No. 12, 2005 4793

D´ıez-Gonza´lez et al.
purified by flash chromatography on silica gel (pentane:Et2O,
99:1) to afford 0.287 g (92% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2-methylbenzo-
phenone (0.18 mL, 1.0 mmol) was hydrosilylated by triethyl-
silane. A colorless oil was obtained as a pure product after
concentration of the filtrate (0.300 g, 96% yield). 1H NMR (400
MHz, CDCl3) δ 7.60 (d, 1H, J ) 7.2 Hz), 7.10-7.45 (m, 7H),
7.06 (d, 1H, J ) 7.2 Hz), 5.89 (s, 1H), 2.20 (s, 3H), 0.87 (t, 9H,
J ) 8.0 Hz), 0.56 (q, 6H, J ) 8.0 Hz); 13C NMR (100 MHz,
CDCl3) δ 144.1, 142.7, 134.7, 130.4, 128.0, 127.1, 127.0, 126.8,
126.7, 125.8, 74.1, 19.5, 6.7, 4.9; MS (EI) m/z 312 (M+).
Elemental analysis calcd for C20H28OSi (312.52): C, 76.86; H,
9.03. Found: C, 76.87; H, 9.03.
on alumina (pentane) to afford 0.211 g (92% yield) of the title
compound as a colorless oil. (B) Using the general procedure
with (ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH,
N-methylpiperidin-4-one (0.125 mL, 1 mmol) was hydro-
silylated by triethylsilane. The crude product was purified by
filtration on alumina (pentane) to afford 0.213 g (93% yield)
1
of the title compound as a colorless oil. H NMR (400 MHz,
CDCl3) δ 3.75-3.59 (m, 1H), 3.59-2.74 (m, 2H), 2.25 (s, 3H),
2.20-2.05 (m, 2H), 1.85-1.71 (m, 2H), 1.70-1.51 (m, 2H), 0.96
(t, 9H, J ) 8.0 Hz), 0.58 (q, 6H, J ) 8.0 Hz); 13C NMR (100
MHz, CDCl3) δ 67.7, 53.3, 46.2, 35.0, 6.7, 4.8; MS (EI), m/z
229 (M+). Elemental analysis calcd for C12H27NOSi (229.43):
C, 62.82; H, 11.86; N, 6.10. Found: C, 62.96; H, 11.65; N, 5.92.
2-(3-Diethylamino)propyloxytriethylsilane (Table 5,
Entry 2). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 1-diethylaminopropan-2-one (0.155 mL,
1 mmol) was hydrosilylated by triethylsilane. The crude
product was purified by flash chromatography on silica gel
(pentane) to afford 0.228 g (93% yield) of the title compound
as a colorless oil. (B) Using the general procedure with
(ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH,
1-diethylaminopropan-2-one (0.155 mL, 1 mmol) was hydro-
silylated by triethylsilane. The crude product was purified by
flash chromatography on silica gel (pentane) to afford 0.230 g
(2,2-Dimethyl-1-phenylpropoxy)triethylsilane (Table
3, Entry 13). (A) Using the general procedure with ICy‚HBF4
and 20 mol % of NaOtBu, 2,2-dimethylpropiophenone (0.17 mL,
1.0 mmol) was hydrosilylated by triethylsilane. A colorless oil
was obtained as the pure product after concentration of the
filtrate (0.264 g, 99% yield). (B) Using the general procedure
with (ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH,
2,2-dimethylpropiophenone (0.17 mL, 1.0 mmol) was hydro-
silylated by triethylsilane. A colorless oil was obtained as the
pure product after concentration of the filtrate (0.262 g, 97%
1
1
yield). H NMR (400 MHz, CDCl3) δ 7.17-7.28 (m, 5H), 4.29
(94% yield) of the title compound as a colorless oil. H NMR
(s, 1H), 0.86 (s, 9H), 0.84 (t, 9H, J ) 8.2 Hz), 0.45 (q, 6H, J )
8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 142.9, 128.0, 127.0,
126.7, 82.8, 36.3, 26.1, 6.8, 4.8; MS (EI) m/z 278 (M+).
Elemental analysis calcd for C17H30OSi (278.50): C, 73.31; H,
10.86. Found: C, 73.18; H, 11.12.
(400 MHz, CDCl3) δ 3.82 (sextuplet, 1H, J ) 6.3 Hz), 2.68-
2.36 (m, 5H), 2.35-2.20 (m, 1H), 1.17 (d, 3H, J ) 6.3 Hz),
1.02-0.92 (m, 15H), 0.60 (q, 6H, J ) 7.9 Hz); 13C NMR (100
MHz, CDCl3) δ 67.5, 61.7, 48.1, 22.5, 12.0, 6.8, 4.9; MS (EI),
m/z 245 (M+). Elemental analysis calcd for C13H31NOSi
(245.48): C, 63.61; H, 12.73; N, 5.71. Found: C, 63.83; H,
12.83; N, 5.82.
Triethyl(1-o-tolylethoxy)silane (Table 3, Entry 14). (A)
Using the general procedure with ICy‚HBF4 and 20 mol % of
NaOtBu, 2′-methylacetophenone (0.175 mL, 1.0 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane:Et2O, 95:
5) to afford 0.235 g (94% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2′-methylaceto-
phenone (0.175 mL, 1.0 mmol) was hydrosilylated by triethyl-
silane. The crude product was purified by flash chromatogra-
phy on silica gel (pentane:Et2O, 95:5) to afford 0.240 g (96%
[1-(2-Chlorophenyl)ethoxy]triethylsilane (Table 5, En-
try 3). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 2′-chloroacetophenone (0.13 mL, 1 mmol)
was hydrosilylated by triethylsilane. The crude product was
purified by flash chromatography on silica gel (pentane:Et2O,
98:2) to afford 0.256 g (95% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2′-chloroacetophe-
none (0.13 mL, 1 mmol) was hydrosilylated by triethylsilane.
The crude product was purified by flash chromatography on
silica gel (pentane:Et2O, 98:2) to afford 0.262 g (97% yield) of
the title compound as a colorless oil. 1H NMR (400 MHz,
CDCl3) δ 7.64 (d, 1H, J ) 8.0 Hz), 7.26 (d, 1H, J ) 8.0 Hz),
7.14 (t, 2H, J ) 8.0 Hz), 5.24 (q, 1H, J ) 6.4 Hz), 1.40 (d, 3H,
J ) 6.4 Hz), 0.91 (t, 9H, J ) 8.0 Hz), 0.58 (q, 6H, J ) 8.0 Hz);
13C NMR (100 MHz, CDCl3) δ 144.4, 130.6, 128.9, 127.8, 127.0,
126.9, 67.1, 25.5, 6.7, 4.7. MS (EI), m/z 272 (M+), 270 (M+).
Elemental analysis calcd for C14H23ClOSi (315.32): C, 62.08;
H, 8.56. Found: C, 62.43; H, 8.58.
1
yield) of the title compound as a colorless oil. H NMR (400
MHz, CDCl3) δ 7.54 (d, 1H, J ) 7.2 Hz), 7.22-7.07 (m, 3H),
5.05 (q, 1H, J ) 6.4 Hz), 2.31 (s, 3H), 1.38 (d, 3H, J ) 6.4 Hz),
0.91 (t, 9H, J ) 7.9 Hz), 0.56 (q, 6H, J ) 7.9 Hz); 13C NMR
(100 MHz, CDCl3) δ 145.0, 132.8, 129.8, 126.4, 126.0, 125.3,
67.3, 25.7, 18.7, 6.6, 4.6; MS (EI) m/z 250 (M+). Elemental
analysis calcd for C15H26OSi (250.45): C, 71.23; H, 10.46.
Found: C, 71.00; H, 10.72.
Triethyl[1-(2,4,6-trimethylphenyl)ethoxyl]silane (Table
3, Entry 15). (A) Using the general procedure with ICy‚HBF4
and 20 mol % of NaOtBu, 2′,4′,6′-trimethylacetophenone (0.17
mL, 1.0 mmol) was hydrosilylated by triethylsilane. The crude
product was purified by flash chromatography on silica gel
(pentane) to afford 0.209 g (75% yield) of the title compound
as a colorless oil. (B) Using the general procedure with
(ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH, 2′,4′,6′-
trimethylacetophenone (0.17 mL, 1.0 mmol) was hydrosilylated
by triethylsilane. The crude product was purified by flash
chromatography on silica gel (pentane) to afford 0.222 g (80%
[1-(4-Bromophenyl)ethoxy]triethylsilane (Table 5, En-
try 4). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 4′-bromoacetophenone (0.20 g, 1 mmol)
was hydrosilylated by triethylsilane. The crude product was
purified by flash chromatography on silica gel (pentane:Et2O,
98:2) to afford 0.299 g (95% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, 4′-bromoacetophe-
none (0.20 g, 1 mmol) was hydrosilylated by triethylsilane. The
crude product was purified by flash chromatography on silica
gel (pentane:Et2O, 98:2) to afford 0.314 g (99% yield) of the
1
yield) of the title compound as a colorless oil. H NMR (400
MHz, CDCl3) δ 6.78 (s, 2H), 5.25 (q, 1H, J ) 6.6 Hz), 2.40 (s,
6H), 2.24 (s, 3H), 1.45 (d, 3H, J ) 6.6 Hz), 0.89 (t, 9H, J ) 7.9
Hz), 0.54 (q, 6H, J ) 7.9 Hz); 13C NMR (100 MHz, CDCl3) δ
138.8, 135.8, 135.2, 130.1, 67.8, 23.2, 20.7, 20.5, 6.9, 5.0; MS
(EI) m/z 278 (M+). Elemental analysis calcd for C17H30OSi
(278.50): C, 73.31; H, 10.86. Found: C, 73.06; H, 10.83.
1
title compound as a colorless oil. H NMR (400 MHz, CDCl3)
δ 7.42 (d, 2H, J ) 8.4 Hz), 7.21 (d, 2H, J ) 8.4 Hz), 4.82 (q,
1H, J ) 6.4 Hz), 1.39 (d, 3H, J ) 6.4 Hz), 0.91 (t, 9H, J ) 8.0
Hz), 0.57 (q, 6H, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ
146.0, 137.8, 131.2, 127.0, 69.9, 27.2, 6.7, 4.8; MS (EI), m/z
316 (M+), 314 (M+). Elemental analysis calcd for C14H23BrOSi
(315.32): C, 53.33; H, 7.35. Found: C, 53.49; H, 7.45.
4-(N-Methylpiperidinoxy)triethylsilane (Table 5, En-
try 1). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, N-methylpiperidin-4-one (0.125 mL, 1
mmol) was hydrosilylated by triethylsilane. As the crude
product decomposed on silica gel, it was purified by filtration
[1-(2-(Trifluoromethyl)phenyl)ethoxy]triethylsilane
(Table 5, Entry 5). (A) Using the general procedure with ICy‚
HBF4 and 20 mol % of NaOtBu, 2′-(trifluoromethyl)acetophe-
4794 J. Org. Chem., Vol. 70, No. 12, 2005

Hydrosilylation of Hindered and Functionalized Ketones
none (0.15 mL, 1 mmol) was hydrosilylated by triethylsilane.
The crude product was purified by flash chromatography on
silica gel (pentane:Et2O, 95:5) to afford 0.221 g (72% yield) of
the title compound as a colorless oil. (B) Using the general
procedure with (ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv
of Et3SiH, 2′-(trifluoromethyl)acetophenone (0.15 mL, 1 mmol)
was hydrosilylated by triethylsilane. The crude product was
purified by flash chromatography on silica gel (pentane:Et2O,
95:5) to afford 0.268 g (88% yield) of the title compound as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.86 (d, 1H, J ) 7.8
Hz), 7.60-7.46 (m, 2H), 7.30 (t, 1H, J ) 7.8 Hz), 5.25 (q, 1H,
J ) 6.1 Hz), 1.41 (d, 3H, J ) 6.1 Hz), 0.87 (t, 9H, J ) 8.0 Hz),
0.54 (q, 6H, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 146.6,
123.1, 127.6, 126.7, 125.9, 124.9 (q, JC-F ) 6 Hz), 123.2, 66.1,
27.8, 6.6, 4.6. Elemental analysis calcd for C15H23F3OSi
(304.42): C, 59.18; H, 7.62. Found: C, 58.96; H, 7.34.
(100 MHz, CDCl3) δ 67.0, 65.5, 36.0, 6.8, 4.8. Elemental
analysis calcd for C11H24O2Si (216.39): C, 61.05; H, 11.18.
Found: C, 60.96; H, 11.31.
[1-(Pyridin-2-yl)ethoxy]triethylsilane (Table 9, Entry
1). (A) Using the general procedure with SIMes‚HBF4 and 8
mol % of NaOtBu, 2-acetylpyridine (0.11 mL, 1 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane:Et2O, 95:
5) to afford 0.222 g (94% yield) of the title compound as a light
yellow oil. (B) Using the general procedure with (SIMes)CuCl,
3 mol % of NaOtBu, and 2 equiv of Et3SiH, 2-acetylpyridine
(0.11 mL, 1 mmol) was hydrosilylated by triethylsilane. The
crude product was purified by flash chromatography on silica
gel (pentane-Et2O, 95:5) to afford 0.222 g (94% yield) of the
title compound as a light yellow oil. 1H NMR (400 MHz, CDCl3)
δ 8.44 (d, 1H, J ) 4.0 Hz), 7.72-7.63 (m, 1H), 7.51 (d, 1H, J
) 8.0 Hz), 7.17-7.06 (m, 1H), 4.92 (q, 1H, J ) 6.4 Hz), 1.44
(d, 3H, J ) 6.4 Hz), 0.89 (t, 9H, J ) 8.0 Hz), 0.51 (q, 6H, J )
8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 165.8, 148.3, 136.5,
121.6, 119.2, 71.8, 25.5, 6.7, 4.7. Elemental analysis calcd for
C13H23NOSi (237.15): C, 65.77; H, 9.76; N, 5.90. Found: C,
65.56; H, 10.01; 5.79.
[1-(Furanyl-2-yl)ethoxy]triethylsilane (Table 9, Entry
2). (A) Using the general procedure with SIMes‚HBF4 and 8
mol % of NaOtBu, 2-acetylfurane (0.110 g, 1 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane:Et2O, 95:
5) to afford 0.209 g (92% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (SIMes)-
CuCl, 3 mol % of NaOtBu, and 2 equiv of Et3SiH, 2-acetyl-
furane (0.110 g, 1 mmol) was hydrosilylated by triethylsilane.
The crude product was purified by flash chromatography on
silica gel (pentane:Et2O, 95:5) to afford 0.212 g (94% yield) of
the title compound as a colorless oil. 1H NMR (400 MHz,
CDCl3) δ 7.34 (d, 1H, J ) 2.6 Hz), 6.34-6.24 (m, 1H), 6.18 (d,
1H, J ) 2.6 Hz), 4.88 (q, 1H, J ) 6.4 Hz), 1.50 (d, 3H, J ) 6.4
Hz), 0.94 (t, 9H, J ) 8.0 Hz), 0.61 (q, 6H, J ) 8.0 Hz); 13C
NMR (100 MHz, CDCl3) δ 158.2, 141.2, 109.9, 104.7, 64.1, 22.9,
6.6, 4.6. Elemental analysis calcd for C12H22O2Si (226.14): C,
63.66; H, 9.80. Found: C, 63.62; H, 10.08.
[1-(Thien-2-yl)ethoxy]triethylsilane (Table 9, Entry 3).
(A) Using the general procedure with SIMes‚HBF4 and 8 mol
% of NaOtBu, 2-acetylthiophene (0.11 mL, 1 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane-Et2O, 95:
5) to afford 0.237 g (98% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (SIMes)-
CuCl, 3 mol % of NaOtBu, and 2 equiv of Et3SiH, 2-acetyl-
thiphene (0.11 mL, 1 mmol) was hydrosilylated by triethyl-
silane. A colorless oil was obtained as the pure product after
concentration of the filtrate (0.235 g, 97% yield). 1H NMR (400
MHz, CDCl3) δ 7.18 (d, 1H, J ) 3.6 Hz), 6.95-6.87 (m, 1H),
6.88 (d, 1H, J ) 3.6 Hz), 5.14 (q, 1H, J ) 6.4 Hz), 1.55 (d, 3H,
J ) 6.4 Hz), 0.96 (t, 9H, J ) 7.9 Hz), 0.63 (q, 6H, J ) 7.9 Hz);
13C NMR (100 MHz, CDCl3) δ 151.5, 126.3, 123.6, 122.0, 66.9,
27.1, 6.8, 4.7. Elemental analysis calcd for C12H22OSSi
(242.45): C, 59.75; H, 9.15. Found: C, 59.62; H, 9.45.
[1-(4-(Dimethylamino)phenyl)-2,2,2-trifluoroethoxy]-
triethylsilane (Table 5, Entry 6). (A) Using the general
procedure with ICy‚HBF4 and 20 mol % of NaOtBu, 4′-
(dimethylamino)-2,2,2-trifluoroacetophenone (0.217 g, 1 mmol)
was hydrosilylated by triethylsilane. The crude product was
purified by flash chromatography on silica gel (pentane:Et2O,
95:5) to afford 0.310 g (93% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (ICy)CuCl,
12 mol % of NaOtBu, and 3 equiv of Et3SiH, 4′-(dimethyl-
amino)-2,2,2-trifluoroacetophenone (0.217 g, 1 mmol) was
hydrosilylated by triethylsilane. A colorless oil was obtained
as the pure product after concentration of the filtrate (0.320
1
g, 96% yield). H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H, J )
8.4 Hz), 7.68 (d, 2H, J ) 8.8 Hz), 4.82 (q, 1H, J ) 6.4 Hz),
2.95 (s, 6H), 0.90 (t, 9H, J ) 8.0 Hz), 0.62-0.50 (m, 6H); 13C
NMR (100 MHz, CDCl3) δ 150.9, 128.4, 125.9, 123.0 (q, JC-F
) 14 Hz), 111.7, 73.3 (q, JC-F ) 32 Hz), 40.3, 6.4, 4.5.
Elemental analysis calcd for C16H26F3NOSi (333.46): C, 57.63;
H, 7.86; N, 4.20. Found: C, 58.00; H, 8.01; N, 3.99.
(2-Methoxycyclohexyloxy)triethylsilane (Table 5, En-
try 9). (A) Using the general procedure with ICy‚HBF4 and
20 mol % of NaOtBu, 2-methoxycyclohexanone (0.125 mL, 1
mmol) was hydrosilylated by triethylsilane. The crude product
was purified by flash chromatography on silica gel (pentane:
Et2O, 95:5) to afford 0.232 g (95% yield) of the title compound
as a 50/50 mixture of two diastereoisomers as a colorless oil.
(B) Using the general procedure with (ICy)CuCl, 12 mol % of
NaOtBu, and 3 equiv of Et3SiH, 2-methoxycyclohexanone
(0.125 mL, 1 mmol) was hydrosilylated by triethylsilane. The
crude product was purified by flash chromatography on silica
gel (pentane:Et2O, 95:5) to afford 0.229 g (94% yield) of the
title compound as a 50/50 mixture of two diastereoisomers as
a colorless oil. 1H NMR (400 MHz, CDCl3) δ 3.86-3.80 (m, 1H),
3.53-3.45 (m, 1H), 3.39 (s, 3H), 3.37 (s, 3H), 3.21-3.15 (m,
1H), 2.98-2.81 (m, 1H), 2.02-1.91 (m, 1H), 1.87-1.70 (m, 3H),
1.69-1.49 (m, 4H), 1.43-1.36 (m, 3H), 1.34-1.16 (m, 5H), 0.97
(t, 18H, J ) 7.8 Hz), 0.61 (q, J ) 7.8 Hz) and 0.60 (q, J ) 7.8
Hz) (12H); 13C NMR (100 MHz, CDCl3) δ 83.7, 80.9, 73.7, 70.4,
57.4, 56.6, 33.6, 31.4, 28.8, 27.0, 23.3, 22.0, 21.8, 6.83, 6.79,
4.9. Elemental analysis calcd for C13H28O2Si (244.45): C, 63.87;
H, 11.55. Found: C, 63.53; H, 11.51.
Triethyl(tetrahydro-2H-pyran-4-yloxy)silane (Table 5,
Entry 10). (A) Using the general procedure with ICy‚HBF4
and 20 mol % of NaOtBu, tetrahydropyran-4-one (0.093 mL, 1
mmol) was hydrosilylated by triethylsilane. The crude product
was purified by flash chromatography on silica gel (pentane-
Et2O, 90:10) to afford 0.123 g (57% yield) of the title compound
as a colorless oil. (B) Using the general procedure with
(ICy)CuCl, 12 mol % of NaOtBu, and 3 equiv of Et3SiH,
tetrahydropyran-4-one (0.093 mL, 1 mmol) was hydrosilylated
by triethylsilane. The crude product was purified by flash
chromatography on silica gel (pentane:Et2O, 90:10) to afford
0.141 g (65% yield) of the title compound as a colorless oil. 1H
NMR (400 MHz, CDCl3) δ 4.01-3.88 (m, 2H), 3.88-3.75 (m,
1H), 3.51-3.33 (m, 2H), 1.83-1.70 (m, 2H), 1.67-1.48 (m, 2H),
0.96 (t, 9H, J ) 7.9 Hz), 0.60 (q, 6H, J ) 7.9 Hz); 13C NMR
[1-(Thiazol-2-yl)ethoxy]triethylsilane (Table 9, Entry
4). (A) Using the general procedure with SIMes‚HBF4 and 12
mol % of NaOtBu, 2-acetylthiazole (0.10 mL, 1 mmol) was
hydrosilylated by triethylsilane. The crude product was puri-
fied by flash chromatography on silica gel (pentane:Et2O, 95:
5) to afford 0.222 g (91% yield) of the title compound as a
colorless oil. (B) Using the general procedure with (SIMes)-
CuCl, 8 mol % of NaOtBu, and 2 equiv of Et3SiH, 2-acetyl-
thiazole (0.10 mL, 1 mmol) was hydrosilylated by triethyl-
silane. The crude product was purified by flash chromatogra-
phy on silica gel (pentane:Et2O, 95:5) to afford 0.230 g (95%
1
yield) of the title compound as a colorless oil. H NMR (400
MHz, CDCl3) δ 7.69 (d, 1H, J ) 2.8 Hz), 7.22 (d, 1H, J ) 2.8
Hz), 5.17 (q, 1H, J ) 6.4 Hz), 1.58 (d, 3H, J ) 6.4 Hz), 0.97 (t,
9H, J ) 7.8 Hz), 0.66 (q, 6H, J ) 7.8 Hz); 13C NMR (100 MHz,
J. Org. Chem, Vol. 70, No. 12, 2005 4795

D´ıez-Gonza´lez et al.
CDCl3) δ 178.1, 142.3, 118.3, 69.2, 25.4, 6.7, 4.7. Elemental
analysis calcd for C12H21NOSSi (243.44): C, 54.27; H, 8.69;
N, 5.75. Found: C, 54.48; H, 8.80; N, 5.60.
106.0, 64.4, 34.4, 23.9, 6.8, 5.0. Elemental analysis calcd for
C13H25NOSi (239.43): C, 65.21; H, 10.52; N, 5.85. Found: C,
65.42; H, 10.69; N, 5.92.
[1-(N-Methylpiperin-2-yl)ethoxy]triethylsilane (Table
9, Entry 5). (A) Using the general procedure with SIMes‚HBF4
and 12 mol % of NaOtBu, 2-acetyl-N-methylpiperidine (0.12
mL, 1 mmol) was hydrosilylated by triethylsilane. The crude
product was purified by flash chromatography on silica gel
(pentane:Et2O, 95:5) to afford 0.232 g (97% yield) of the title
compound as a colorless oil. (B) Using the general procedure
with (SIMes)CuCl, 8 mol % of NaOtBu, and 2 equiv of Et3SiH,
2-acetyl-N-methylpiperidine (0.12 mL, 1 mmol) was hydro-
silylated by triethylsilane. The crude product was purified by
flash chromatography on silica gel (pentane:Et2O, 95:5) to
afford 0.222 g (93% yield) of the title compound as a colorless
oil. 1H NMR (400 MHz, CDCl3) δ 6.52 (d, 1H, J ) 4.4 Hz),
6.06-5.91 (m, 2H), 4.95 (q, 1H, J ) 6.4 Hz), 3.68 (s, 3H), 1.54
(d, 3H, J ) 6.4 Hz), 0.91 (t, 9H, J ) 8.0 Hz), 0.55 (q, 6H, J )
8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 135.8, 122.6, 106.2,
Acknowledgment. The National Science Founda-
tion is gratefully acknowledged for the support of this
work. S.D.G. thanks the Education, Research and
Universities Department of the Basque Government
(Spain) for a postdoctoral fellowship.
Supporting Information Available: Crystallographic
information files (CIF) of complexes 1-3. This material is
available free of charge via the Internet at http://pubs.acs.org.
These files also have been deposited with the CCDC, 12 Union
Road, Cambridge, CB2 1EZ, U.K., and can be obtained on
request free of charge, by quoting the publication citation and
deposition numbers 264856-264858.
JO050397V
4796 J. Org. Chem., Vol. 70, No. 12, 2005