Hydrosilylation of carbonyl-containing substrates catalyzed by an electrophilic η1-silane iridium(III) complex

Article abstract of DOI:10.1021/om100818y

Hydrosilylation of a variety of ketones and aldehydes using the cationic iridium catalyst (POCOP)Ir(H)(acetone)⁺, 1 (POCOP = 2,6-bis(di-tert-butylphosphinito)phenyl), is reported. With triethyl silane, all but exceptionally bulky ketones undergo quantitative reactions employing 0.5 mol % catalyst in 20-30 min at 25 °C. Hydrosilylation of esters and amides results in over-reduction and cleavage of C-O and C-N bonds, respectively. The diastereoselectivity of hydrosilylation of 4-tert-butyl cyclohexanone has been examined using numerous silanes and is highly temperature dependent. Using EtMe₂SiH, analysis of the ratio of cis:trans hydrosilylation products as a function of temperature yields values for ΔΔH ^? (ΔH^?(trans) - ΔH ^?(cis)) and ΔΔS^? (ΔS ^?(trans) - ΔS^?(cis)) of -2.5 kcal/mol and -6.9 eu, respectively. Mechanistic studies show that the ketone complex (POCOP)Ir(H)(ketone)⁺ is the catalyst resting state and is in equilibrium with low concentration of the silane complex (POCOP)Ir(H)(HSiR ₃)⁺. The silane complex transfers R₃Si ⁺ to ketone, forming the oxocarbenium ion R₃SiOCR' ₂⁺, which is reduced by the resulting neutral dihydride 3, (POCOP)Ir(H)₂, to yield product R₃SiOCHR'₂ and (POCOP)IrH⁺, which closes the catalytic cycle.

Full text of DOI:10.1021/om100818y

Organometallics 2010, 29, 6057–6064 6057
DOI: 10.1021/om100818y
Hydrosilylation of Carbonyl-Containing Substrates Catalyzed by an
Electrophilic η1-Silane Iridium(III) Complex
Sehoon Park and Maurice Brookhart*
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill,
North Carolina 27599-3290, United States
Received August 20, 2010
Hydrosilylation of a variety of ketones and aldehydes using the cationic iridium catalyst (POCOP)-
Ir(H)(acetone)þ, 1 (POCOP = 2,6-bis(di-tert-butylphosphinito)phenyl), is reported. With triethyl silane,
all but exceptionally bulky ketones undergo quantitative reactions employing 0.5 mol % catalyst in
20-30 min at 25 °C. Hydrosilylation of esters and amides results in over-reduction and cleavage of C-O
and C-N bonds, respectively. The diastereoselectivity of hydrosilylation of 4-tert-butyl cyclohexanone
has been examined using numerous silanes and is highly temperature dependent. Using EtMe2SiH, anal-
ysis of the ratio of cis:trans hydrosilylation products as a function of temperature yields values for ΔΔH‡
(ΔH‡(trans) - ΔH‡(cis)) and ΔΔS‡ (ΔS‡(trans) - ΔS‡(cis)) of -2.5 kcal/mol and -6.9 eu, respectively.
Mechanistic studies show that the ketone complex (POCOP)Ir(H)(ketone)þ is the catalyst resting state
and is in equilibrium with low concentration of the silane complex (POCOP)Ir(H)(HSiR3)þ. The silane
complex transfers R3Siþ to ketone, forming the oxocarbenium ion R3SiOCR02þ, which is reduced by the
resulting neutral dihydride 3, (POCOP)Ir(H)2, to yield product R3SiOCHR02 and (POCOP)IrHþ, which
closes the catalytic cycle.
Introduction
Scheme 1
Hydrosilylation of carbonyl functionalities is an exten-
sively explored and widely used synthetic methodology.1
This process provides an alternative to hydride reductions
of ketones and aldehydes as well as a convenient one-step
process for converting these substrates directly to protected
alcohols, which circumvents the normal two-step procedure:
reduction to alcohol followed by silyl protection. Several
different hydrosilylation mechanisms have been shown to
operate, dependent on the nature of the catalyst. Late metal
catalysts typically proceed through a “Chalk-Harrod”
pathway, in which the key step involves oxidative addition
of the silane to a low-valent metal center.2 Early metal
catalysts where oxidative addition is disfavored proceed via
σ bond metathesis mechanisms.3
*To whom correspondence should be addressed. E-mail: mbrookhart@
unc.edu.
(1) Reviews on hydrosilation: (a) 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. (b) Nishiyama, H.; Itoh, K. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: New York,
ꢀ
2000. (c) Marciniec, B.; Gulinski, J. J. Organomet. Chem. 1993, 446, 15.
(2) (a) Chalk, A. J.; Harrod, J. F. J. Am. Chem. Soc. 1965, 87, 16.
(b) Ojima, I.; Nihonyanagi, M.; Nagai, Y. J. Chem. Soc., Chem. Commun.
1972, 938. (c) Ojima, I.; Nihonyanagi, M.; Kogure, T.; Kumagai, M.; Horiuchi,
S.; Nakatsugawa, K.; Nagai, Y. J. Organomet. Chem. 1975, 94, 449.
(d) Kobayashi, M.; Koyama, T.; Ogura, K.; Seto, S.; Ritter, F. J.; Brueggemann-
Rotgans, I. E. M. J. Am. Chem. Soc. 1980, 102, 6602. (e) Semmelhack, M. F.;
Misra, R. N. J. Org. Chem. 1982, 47, 2469. (f ) Ojima, I.; Kogure, T.
Organometallics 1982, 1, 1390. (g) Brunner, H.; Becker, R.; Riepl, G.
Organometallics 1984, 3, 1354. (h) Brunner, H.; Kurzinger, A. J. Organomet.
Chem. 1988, 346, 413. A catalytic reductive silation of 4-tert-butyl cyclo-
hexanone using 0.012% Zn(OSO2CH3)2 in combination with lithium
hydride and chlorotrimethylsilane gives predominantly the less stable
reduction product with 72% cis-selectivity: (i) Ohkuma, T.; Hashiguchi,
S.; Noyori, R. J. Org. Chem. 1994, 59, 217. ( j) Zheng, G. Z.; Chan, T. H.
Organometallics 1995, 14, 70. (k) Wright, M. E.; Cochran, B. B. Organome-
tallics 1996, 15, 317. (l) Nagashima, H.; Suzuki, A.; Iura, T.; Ryu, K.; Matsubara,
K. Organometallics 2000, 19, 3579. (m) Tao, B.; Fu, G. C. Angew. Chem., Int.
Ed. 2002, 41, 3892. (n) Gade, L. H.; Cesar, V.; Bellemin-Laponnaz, S. Angew.
Chem., Int. Ed. 2004, 43, 1014.
(3) (a) Glaser, P. B.; Tilley, T. D. J. Am. Chem. Soc. 2003, 125, 13640.
(b) Parks, D. J.; Blackwell, J. M.; Piers, W. E. J. Org. Chem. 2000, 65, 3090.
(c) Caseri, W.; Pregosin, P. S. Organometallics 1988, 7, 1373. (d) Hanna,
P. K.; Gregg, B. T.; Cutler, A. R. Organometallics 1991, 10, 31.
(e) Cavanaugh, M. D.; Gregg, B. T.; Cutler, A. R. Organometallics 1996, 152764.
(f ) Gregg, B. T.; Cutler, A. R. J. Am. Chem. Soc. 1996, 118, 10069.
(g) Kennedy-Smith, J. J.; Nolin, K. A.; Gunterman, H. P.; Toste, F. D. J. Am.
Chem. Soc. 2003, 125, 4056. (h) Nolin, K. A.; Ahn, R. W.; Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 17168. (i) Blanc, A.; Toste, F. D. Angew. Chem., Int.
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R. G.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 14684. (k) Fernandes, A. C.;
Fernandes, R.; Romao, C. C.; Royo, B. Chem. Commun. 2005, 213. (l) Royo,
B.; Romao, C. C. J. Mol. Catal. A: Chem. 2005, 236, 107. (m) Ison, E. A.;
Trivedi, E. R.; Corbin, E. A.; Abu-Omar, M. M. J. Am. Chem. Soc. 2005,
127, 15374. (n) Ison, E. A.; Cessarich, J. E.; Du, G. D.; Franwick, P. E.; Abu-
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r
2010 American Chemical Society
Published on Web 10/18/2010
pubs.acs.org/Organometallics

6058 Organometallics, Vol. 29, No. 22, 2010
Park and Brookhart
Scheme 2
Recently, high-valent metal oxo complexes have been shown
to serve as hydroþsilylation catalysts. Abu-Omar reported that
the Re(O)(hoz)2 (hoz = 2-(20-hydroxyphenyl)-2-oxazoline)
catalyst operates via a σ bond metathesis mechanism.3m-o
Through extensive mechanistic studies Toste and Bergman
established that hydrosilylations catalyzed by (PPh3)2Re(O)2I
occur by a unique mechanism that involves addition of the
silane across the RedO bond, insertion of the carbonyl
functionality into the resulting Re-H bond, and elimination
of the hydrosilylation product, which closes the cycle and
regenerates the RedO bond.3g-j Piers has reported that
Ph3SiH in combination with catalytic amounts of (C6F5)3B
achieves hydrosilylation of carbonyl compounds.3b,4a,4b Sur-
prisingly, although the carbonyl compounds exhibit much
higher binding affinities to (C6F5)3B than Ph3SiH, the mecha-
nism involves activation of the silane through coordination to
(C6F5)3B, transfer of Ph3Siþ to the carbonyl functionality, and
reduction of the resulting Ph3SiOC(R)(R0)þ by (C6F5)3BH-
(Scheme 1).
We have recently reported reduction of R-X bonds (X =
Cl, Br, I, OR) using the silane complex 2, a potent R3Siþ
donor.5 The mechanism was shown to involve transfer of
R3Siþ to X to generate R3Si-X-Rþ followed by hydride
reduction of this species by the iridium dihydride complex 3,
formed upon silyl transfer (see Scheme 2).
The most convenient precatalyst was found to be the
stable, crystalline, easily isolated acetone complex, 1. Treat-
ment with excess triethylsilane rapidly generates silane com-
plex 2 in situ and one equivalent of Et3SiOCH(CH3)2, the
acetone hydrosilylation product (eq 1). These observations
suggested
Results and Discussion
Hydrosilylation of Carbonyl-Containing Substrates Cata-
lyzed by 1. Complex 15a together with Et3SiH initiates hydro-
silylations of ketones, aldehydes, esters, and amides at room
temperature. Results of hydrosilylation of several carbonyl-
containing substrates are summarized in Table 1. Ketones
undergo hydrosilylation rapidly to attain quantitative con-
versions in 0.3-0.5 h at room temperature (200 TOs)
(Table 1, entries 1-6). Hydrosilylations of ketones bearing
exceptionally bulky alkyl substituents, diisopropyl ketone
(entry 2) and methyl tert-butyl ketone (entry 3), are rapidly
and quantitatively achieved. The exceptional efficiency of
the hydrosilylation is illustrated by the quantitative hydro-
silylation of methyl tert-butyl ketone in 30 min using a 0.075 mol %
catalyst loading (1330 TOs, entry 4). Hydrosilylation
of acetophenone yields 94% of the corresponding silyl alkyl
ether and 6% of ethylbenzene, which results from further
cleavage of the silyl alkyl ether (entry 5). The competitive
hydrosilylation reaction between acetophenone and 40-(tri-
fluoromethyl)acetophenone (entry 6) shows that the activity
of the more basic acetophenone is ca. 4 times greater than that
of 40-(trifluoromethyl)acetophenone. Hydrosilylation of alde-
hydes with excess silane often results in secondary cleavage of
the resultant silyl alkyl ether.5b However, using just over 1
equiv of Et3SiH, benzaldehyde undergoes quantitative hydro-
silylation in 0.3 h to yield the silyl benzyl ether (entry 7).
Complex 1 catalyzes the hydrosilylation of ethyl acetate to
afford silyl ethyl ether and diethyl ether in 2:1 ratio (entry 8).
This results from formation of the acetal and subsequent
cleavage of either of the C-O bonds as shown in eq 2.
that 2 should function as a hydrosilylation catalyst. We
report here synthetic and mechanistic details of the catalytic
hydrosilylation of a variety of carbonyl-containing com-
pounds employing this system, which proves to be excep-
tionally active and highly efficient.
In contrast, the hydrosilylation of methyl isobutyrate exhi-
bits only cleavage of the C-OMe bond of the acetal to give
only isobutyl silyl ether and methyl silyl ether (entry 9). This
selectivity can be attributed to a sterically demanding envi-
ronment around oxygen in the C--OSiEt3 bond. Introduction
of an electron-withdrawing group into the R-position of the
ester enables a single hydrosilylation even with excess Et3SiH
to selectively form the corresponding acetal (entry 10). The
preference for single hydrosilylation is likely due to the
decreased basicity of the acetal formed via initial hydro-
silylation and the decreased tendency for ionization of the
silated acetal.
(4) (a) Parks, D. J.; Piers, W. E. J. Am. Chem. Soc. 1996, 118, 9440.
(b) Parks, D. J.; Piers, W. E.; Parvez, M.; Atencio, R.; Zaworotko, M. J.
Organometallics 1998, 17, 1369.
(5) (a) Yang, J.; Brookhart, M. J. Am. Chem. Soc. 2007, 129, 12656.
(b) Yang, J.; White, P. S.; Brookhart, M. J. Am. Chem. Soc. 2008, 130,
17509. (c) Yang, J.; White, P. S.; Schauer, C; Brookhart, M. Angew. Chem.,
Int. Ed. 2008, 47, 4141. (d) Yang, J.; Brookhart, M. Adv. Synth. Catal. 2009,
351, 175.

Article
Organometallics, Vol. 29, No. 22, 2010 6059
Table 1. Hydrosilylation of Carbonyl Functions by 1a
a Reaction conditions: 0.5 mol % 1, solvent = C6D5Cl, 3 equiv of Et3SiH, and room temperature. b Determined by 1H NMR. c 0.075 mol % 1. d 6% of
ethylbenzene formed. e [A]:[B]:[Et3SiH]:[1] = 100:100:100:1. f Minor unidentified signals observed in NMR. g 1.2 equiv of Et3SiH employed. h Use of
Me2EtSiH instead of Et3SiH affords quantitatively the corresponding acetal in only 0.3 h.
N,N-Diethyl acetamide is slowly hydrosilated (42% con-
version in 16 h) to give Et3N together with the disiloxane
(entry 11). After 16 h, no further consumption of the amide is
observed. The retarded hydrosilylation may result from the
deactivation of the electrophilic catalytic Ir species by excess
Et3N formed during reaction. The sequence responsible for
product formation is shown in eq 3 and is similar to that
proposed for ester reduction.
been extensively studied6 and found to preferentially give
the trans-alcohol via an axial attack of the hydride (eq 4,
path a). Several explanations have been advanced for this
diastereoselectivity including the straightforward propo-
sition that there are unfavorable eclipsing interactions
between the axial C-H bonds at C2 and C6 and the
(6) (a) Noyce, D. S.; Denney, D. B. J. Am. Chem. Soc. 1950, 72, 5743.
(b) Cram, D. J.; Abd Elhafez, F. A. J. Am. Chem. Soc. 1952, 74, 5828.
(c) Barton, D. H. R. J. Chem. Soc. 1953, 1027. (d) Schlesinger, H. I.; Brown,
H. C.; Hoekstra, H. R.; Rapp, L. R. J. Am. Chem. Soc. 1953, 75, 199.
(e) Dauben, W. G.; Fonken, G. J.; Noyce, D. S. J. Am. Chem. Soc. 1956, 78,
2579. (f ) Dauben, W. G.; Bozak, R. E. J. Org. Chem. 1959, 24, 1596.
(g) Wheeler, D. M. S.; Huffman, J. W. Experientia 1960, 16, 516.
(h) Haubenstock, H.; Eliel, E. L. J. Am. Chem. Soc. 1962, 84, 2363.
(i) Haubenstock, H.; Eliel, E. L. J. Am. Chem. Soc. 1962, 84, 2368.
(j) House, H. O.; Babad, H.; Toothill, R. B.; Noltes, A. W. J. Org. Chem.
1962, 27, 4141. (k) Richer, J. C. J. Org. Chem. 1965, 30, 324. (l) Brown,
H. C.; Deck, H. R. J. Am. Chem. Soc. 1965, 87, 5620. (m) Ashby, E. C.;
Sevenair, J. P.; Dobbs, F. R. J. Org. Chem. 1971, 36, 197. (n) Eliel, E. L.;
Senda, Y. Tetrahedron 1970, 26, 2411. (o) Wigfield, D. C.; Phelps, D. J. J.
Org. Chem. 1976, 41, 2396. (p) McMahon, R. J.; Wiegers, K. E.; Smith,
S. G. J. Org. Chem. 1981, 46, 99.
Stereochemistry of Hydrosilylation of 4-tert-Butyl Cyclo-
hexanone. Reductions of 4-tert-butyl cyclohexanone by var-
ious metal hydrides, especially LiAlH4 and NaBH4, have

6060 Organometallics, Vol. 29, No. 22, 2010
Park and Brookhart
Table 2. Hydrosilylation of 4-tert-Butylcyclohexanone with Various Alkylsilanes Catalyzed by 1a
entry
catalyst mol %
silane
solvent
T, °C
t, h
conversionb %
trans/cisb %
1
2
3
4
5
6
7
8
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.39
1.39
EtMe2SiH
EtMe2SiH
EtMe2SiH
Et2MeSiH
Et3SiH
i-PrMe2SiH
t-BuMe2SiH
(i-Pr)3SiH
(t-Bu)2SiH2
EtMe2SiH
Et3SiH
CD2Cl2
C6D5Cl
toluene-d6
C6D5Cl
C6D5Cl
C6D5Cl
C6D5Cl
C6D5Cl
C6D5Cl
CD2Cl2
CD2Cl2
22
22
22
22
22
22
80
80
0.3
0.3
0.3
0.3
0.3
0.3
2
quant.
quant.
quant.
quant.
quant.
quant.
quant.
quant.
quant.
quant.
quant.
55:45
69:31
75:25c
74:26
68:32
76:24
87:13
51:49
57:43e
82:18f
88:12f
12
9
10
11
22
-20
-20
1.5
0.5
0.5
a Reaction conditions: 3 equiv of silane in C6D5Cl (0.3 mL). b Determined by NMR spectroscopy. c 1 is not completely soluble in toluene-d8. e 39% of
di-tert-butyl silyl enol ether is observed. f 4 equiv of silane used.
Table 3. Hydrosilylation of 4-tert-Butyl Cyclohexanone with
EtMe2SiH at Various Reaction Temperaturesa
incoming hydride reagent during equatorial attack (eq 4,
path b).7
entry
T, °C
t, h
conversionb %
trans/cis ratiob %
1
2
3
4
-60
-30
0
17
3
1
quant.
quant.
quant.
quant.
92:8
86:14
77:23
70:30
17
3
a Reaction conditions; 4 equiv of EtMe2SiH, 1.39 mol % of 1 in
CD2Cl2 (1 mL). b Determined by 1H NMR spectroscopy.
The diastereoselectivity of hydrosilylations of cyclohexa-
nones has also received attention. Semmelhack has examined
the hydrosilylation of 4-tert-butyl cyclohexanone by various
di- and trialkylsilanes using classical catalysts (PPh3)3RhCl(I)
and (PPh3)3RuCl2(II), which operate by the Chalk-Harrod
mechanism.2e Bulky triethyl- and triphenylsilanes provide
predominantly the more stable trans silyl ether with up to
95% diastereoselectivity, whereas the less bulky diethyl- and
diphenylsilanes give the corresponding silyl ethers with a
trans/cis ratio of ca. 50:50. On the other hand, hydrosilylation
by diphenylsilane using (PPh3)4RhH(I) has been reported to
give a 84:16 (trans/cis) ratio of diasteromers.2j A triruthenium
carbonyl cluster-catalyzed hydrosilylation of 4-tert-butyl cy-
clohexanone affords predominantly the cis-diastereomer with
triethylsilane,2l which contrasts with the results of the hydro-
silylation by the mononuclear Rh or Ru complexes. Most
recently, Toste et al. have obtained silyl ethers with a high
trans selectivity (>96%) using the dioxorhenium(V) catalyst
(PPh3)2Re(O)2I, which operates by the non-Chalk-Harrod
mechanism described above.3j These studies prompted us to
examine the diastereoselectivities of hydrosilylation of 4-tert-
butyl cyclohexanone using catalyst 1, where product ratios
depend on axial versus equatorial attack of iridium dihydride
3 on the silated ketone (see below).
Resultsof the hydrosilylation of 4-tert-butyl cyclohexanone
using various silanes and different solvents are shown in Table 2.
In chlorobenzene, there is little difference in diastereoselec-
tivity as the bulk of the silane ranges from dimethylethylsilane
(trans/cis = 69:31) to methyldiethylsilane (74:26) to triethyl-
silane (68:32) to dimethylisopropylsilane (76:24). Dimethyl-
tert-butylsilane and triisopropylsilane are sufficiently unreac-
tive that the reactions must be carried out at 80 °C; however,
quantitative conversions can be obtained and result in 87:13 and
51:49 trans/cis product ratios, respectively. In the case of di-
tert-butylsilane, selectivity drops to 57:43, but the hydrosilylation
Figure 1. Plot of ln[cis]/[trans] vs 1/T using the data from Table 3.
products are accompanied by a side reaction to form 39% of
the silyl enol ether. (Semmelhack et al. observed the same side
product in the hydrosilylation using (EtO)3SiH.2e)
Solvent effects on diastereoselectivity are also minimal.
Hydrosilylation with dimethylethylsilane in methylene chlo-
ride, chlorobenzene, and toluenevaries from trans/cis=55:45
to 69:31 to 75:25, respectively. The most dramatic effect on
selectivity is seen with variation in reaction temperature.
Using dimethylethylsilane in methylene chloride, the selec-
tivity increases from 55:45 at 22 °C to 82:18 at -20 °C, while
for triethylsilane the selectivity is 68:22 at 22 °C in chloro-
benzene and increases to 88:12 at -20 °C in methylene
chloride. Temperature effects are examined in more detail
in the next section.
Hydrosilylation of 4-tert-Butyl Cyclohexanone: Effect of
Reaction Temperature on Diastereoselectivity. Although ap-
preciable efforts have been dedicated to the elucidation of
factors affecting the diastereoselectivity of metal hydride
reductions of 4-tert-butyl cyclohexanone, there have been
limited studies of temperature effects on selectivity.8 Thus,
we have examined the diastereoselectivity of hydrosilylation
of 4-tert-butyl cyclohexanone with dimethylethylsilane over
(7) (a) Coxon, J. M.; Houk, K. N.; Luibrand, R. T. J. Org. Chem.
1995, 60, 418. (b) Li, H.; le Noble, W. J. Recl. Trav. Chim. Pays-Bas 1992,
111, 199. (c) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
2199. (d) Cherest, M.; Felkin, H. Tetrahedron Lett. 1968, 2205. (e) Cherest,
M.; Felkin, H. Tetrahedron Lett. 1973, 4307.

Article
Organometallics, Vol. 29, No. 22, 2010 6061
Table 4. Hydrosilylations of Alkyl-Substituted Cyclohexanone Derivatives Catalyzed by 1a
entry
ketone
silane
T, °C
t, h
conversionb %
trans/cis ratiob %
1
2
3
4
3,3,5-trimethylcyclohexanone
2-methylcyclohexanone
2-tert-butylcyclohexanone
camphor
EtMe2SiH
EtMe2SiH
EtMe2SiH
EtMe2SiH
22
22
22
0
0.3
0.5
0.5
2
quant.
quant.
quant.
quant.
86:14
29:71
24:76
21:79c
a Reaction conditions; 0.5 mol % of 1 and 3 equiv of silane in C6D5Cl. b Determined by NMR spectroscopy. c exo/endo ratio.
Scheme 3. Proposed Catalytic Cycle for the Iridium-Catalyzed
Hydrosilylation of Acetone with Triethylsilane
a wide range of temperatures. These data provide informa-
tion concerning differences of enthalpies and entropies of
activation for the two pathways. The trans/cis product ratio
for the hydrosilylation of 4-tert-butyl cyclohexanone in
CD2Cl2 at various reaction temperatures is shown in Table
3. A plot of ln[cis]/[trans] versus 1/T made using the data in
Table 3 provides a good linear regression with R2 = 0.993 as
shown in Figure 1. By using the relationship shown in eq 5
(derived from the Erying equation), ΔΔH‡ (ΔH‡(trans) -
ΔH‡(cis)) and ΔΔS‡ (ΔS‡(trans) - ΔS‡(cis)) were calculated
to be -2.5 kcal/mol and -6.9 eu, respectively.
½cisꢀ
ΔH‡ðtransÞ - ΔH‡ðcisÞ ΔS‡ðcisÞ - ΔS‡ðtransÞ
ln
¼
þ
½transꢀ
RT
R
ð5Þ
The stereodetermining step is attack of 3 on the silated
ketone (eq 6; see below for mechanistic considerations), and
thus axial attack is strongly favored enthalpically over
equatorial attack but strongly disfavored entropically. Since
this is a bimolecular reaction, both activation entropies are
no doubt negative, so axial attack must exhibit a more
negative entropy of activation relative to equatorial attack.
The reasons for these significant differences are not clear.
cyclohexanone, 2-tert-butyl cyclohexanone, and camphor
with dimethylethylsilane are summarized in Table 4.
3,3,5-Trimethyl cyclohexanone undergoes quantitative
hydrosilylation with dimethylethylsilane in 0.3 h to give the
silyl alkyl ether with 86% trans diastereoselectivity (entry 1).
The preference for trans stereochemistry can be attributed to
blocking of the axial approach of the bulky iridium dihydride
by the axial methyl group at C3. (Trans selectivity ranging
from 52% to 83% is seen in hydride reductions of 3,3,5-
trimethyl cyclohexanone.)6h,i,n,p 2-Alkylcyclohexanone deriv-
atives possessing large equatorial alkyl substituents are
reported to inhibit axial attack of metal hydrides.6a,e,l,m
For example, reduction of 2-methyl cyclohexanone by LiAlH4
affords alcohols with a trans/cis selectivity of ca. 73:27. How-
ever, when the steric bulk of the C2 substituent is increased
to tert-butyl, axial approach is somewhat inhibited to yield
product alcohols with slight cis selectivity (50-64%). The
hydrosilylation of 2-methyl cyclohexanone by 1 at 22 °C
proceeds rapidly to give the silyl alkyl ether with 71% cis
selectivity (entry 2). The use of 2-tert-butyl cyclohexanone in
the hydrosilylation leads to a slight increase in the cis selectivity
to 76% (entry 3). The steric impact of 2-substituents is signif-
icantly greater in these cases compared to the metal reductions.
The hydrosilylation of camphor at 0 °C yields the exo and endo
isomers in 21:79 ratio, respectively (entry 4). In the
(Ph3P)4RhH-catalyzed hydrosilylation of camphor with di-
phenylsilane the opposite selectivity is observed, with an exo:
endo product ratio of 64:36 reported.2j
It is noteworthy that the iridium-catalyzed hydrosilylation of
4-tert-butyl cyclohexanone has considerably larger differ-
ences in the activation parameters relative to reductions by
LiAlH4 and NaBH4 (for LiAlH4, ΔΔH‡ = -0.8 kcal/mol
and ΔΔS‡ = 2.0 eu).8d In these cases the temperature depen-
dence of the product ratio is small and ΔΔS‡ is small and
positive, in contrast to a large negative value for the hydro-
silylation.
Hydrosilylation of Alkyl-Substituted Cyclohexanone Deriv-
atives Catalyzed by 1. We have examined the hydrosilyla-
tions of other alkyl-substituted cyclohexanone derivatives
to probe the diastereoselectivities in these cases. Results of
hydrosilylation of 3,3,5-trimethyl cyclohexanone, 2-methyl
Mechanistic Investigation of the Hydrosilylation of Ke-
tones. Based on earlier mechanistic investigations of silane
reductions of alkyl halides and alkyl ethers using iridium
complex 1, our working hypothesis concerning the catalytic
mechanism of hydrosilylation of ketones is shown in Scheme 3
and illustrated with acetone. Binding triethylsilane to the
(8) (a) Lansbury, P. T.; Macleay, R. E. J. Org. Chem. 1963, 28, 1940.
(b) Wigfield, D. C.; Phelps, D. J. J. Org. Chem. 1976, 41, 2396. (c) Ashby,
E. C.; Boone, J. R. J. Org. Chem. 1976, 41, 2890. (d) Rosenberg, R. E.;
Vilardo, J. S. Tetrahedron Lett. 1996, 37, 2185.

6062 Organometallics, Vol. 29, No. 22, 2010
Park and Brookhart
Scheme 4
Scheme 5. Free Energy Diagram for the Iridium-Catalyzed Hy-
drosilylation of Acetone with Triethyl Silane
electrophilic iridium center in 2 renders this complex a potent
Et3Siþ donor, which can transfer Et3Siþ to acetone, forming
the oxocarbenium ion, 4, and iridium dihydride, 3. The
dihydride, earlier established as a good hydride donor,5b
reacts with 4 to produce hydrosilated product, 5, and the
cationic hydride, 6, which then reenters the catalytic cycle.
Low-temperature reactions were carried out to probe the
details of this cycle. 13C-labeled acetone, (CH3)213CO), was
employed to allow monitoring by 13C as well as 1H and 31P
NMR spectroscopy. Initially, the equilibrium between 1 and 2
was probed, as shown in Scheme 4. Reaction of 1 (containing
unlabeled bound acetone) with triethylsilane (4 equiv) in
CD2Cl2 at 25 °C rapidly produced 1 equiv of Et3SiOCHMe2
(1H NMR) and silane complex 2 (21%), CD2Cl2 complex 6
(48%), and cationic trihydride 7 (31%) (Scheme 4A). The
complexes were identified by 31P NMR shifts. The trihydride
results from reaction of 2 with traces of water.9 This solution
was cooled to -70 °C, and (CH3)2*CO (2 equiv) was added.
Acetone immediately displaces silane from 2 and CD2Cl2
from 6 to give a solution containing acetone complex 1* (ca.
64%) andtrihydride7 (ca. 34%) andtraces of solventcomplex
6 (Scheme 4B). 1H NMR spectroscopy was used to determine
the ratio of free acetone (δ 2.13, doublet, J13C-H = 5 Hz) to
bound acetone (δ2.57, doublet, J13C-H = 5 Hz) as 64:36. No
silane complex can be easily detected (<0.5%), and no
hydrosilylation product is formed. The hydrosilylation prod-
uct of (CH3)2*CO, Et3SiO*CHMe2, can be distinguished
from Et3SiOCHMe2 since the CH resonance at δ3.99 is split
into a doublet with J13C-H = 138.5 Hz. These results imply
that the equilibrium between 1 and 2, not surprisingly, lies
strongly to the left and that equilibrium is established rapidly
relative to product formation.
(31P NMR), which yields an equilibrium constant of 1.4 ꢁ
10-3 at -50 °C (eq 7):10
½ðCH3Þ2CdOꢀ ½2ꢀ
Keq
¼
¼ 0:053 ꢁ 0:027
½Et3SiHꢀ ½1ꢀ
¼ 1:4 ꢁ 10- 3, - 50°C
ð7Þ
While these experiments establish a rapid equilibrium be-
tween 1 and 2 during catalysis with the ketone complex as the
nearly exclusive resting state, they do not provide a decision
as to whether step I, silation of acetone, or step II, reduction
of 4 by iridium dihydride 3, is turnover-limiting (Scheme 5).
Either scenario predicts that the turnover frequency is zero-
order in ketone and first-order in Et3SiH. Indeed that has
been confirmed for reduction of 4-tert-butyl cyclohexanone
at -60 °C under typical catalytic conditions. Figure 2 (left)
shows a typical plot of the initial rate of disappearance of
4-tert-butyl cyclohexanone (1.06 M) using Et3SiH (0.639 M)
and complex 1 (6.4 mM) in CD2Cl2. Figure 2 (right) shows a
To quantitatively assess Keq, 16 equiv of Et3SiH was added
to this solution (Scheme 4C). Even under these conditions no
silane complex 2 could be detected by 31P NMR spectros-
copy. Upon warming this solution in the NMR probe to
-50 °C, catalytic hydrosilylation begins as shown by the
appearance in the 1H NMR spectrum of Et3SiO*CHMe2. As
acetone is consumed and the ratio of Et3SiH to free acetone
further increases, a point is reached where finally a sufficient
quantity of silane complex is formed that the equilibrium
constant can be measured. After 10 min at -50 °C, the ratio
of free acetone to Et3SiH is 1:18.9 (1H NMR), and the
ratio of acetone complex 1 to silane complex 2 is 37.5:1
(10) The reaction of acetone-2-13C (3 equiv) with a solution contain-
ing 2, 6, and 7 in a ratio of 0.68:0.12:0.19 in the presence of excess
triethylsilane (90 equiv) at -70 °C leads to hydrosilation (36% con-
version) in 5 min to afford Et3SiO-13CHMe2, 5. 1H and 31P NMR spectra
at -70 °C exhibit the proton resonances for triethylsilane and free
acetone-2-13C, and the phosphorus resonances of iridium species 1
(61%) and 2 (9%) as well as 6 (2%) and 7 (28%). On the basis of these
NMR data, the equilibrium constant, K (-70 °C), between 1 and 2 can
be calculated to be 1.8 ꢁ 10-3, in agreement with the value of 1.4 ꢁ 10-3
obtained at -50 °C.
(9) The trihydride is inert and is carried through the next sequence of
reactions.

Article
Organometallics, Vol. 29, No. 22, 2010 6063
Figure 2. (Left) Plot of concentration of 4-tert-butyl cyclohexanones [ketone] vs time for the hydrosilylation of 4-tert-butyl cyclo-
hexanone catalyzed by 1 at -60 °C. (Right) Plot of the initial rate, Vi, of 4-tert-butyl cyclohexanone vs 4-tert-butyl cyclohexanone
concentration at -60 °C.
temperature dependence. Analysis of product ratios as a
function of temperature yields values for ΔΔH‡ (ΔH‡(trans) -
ΔH‡(cis)) and ΔΔS‡ (ΔS‡(trans) - ΔS‡(cis)) of -2.5 kcal/
mol and -6.9 eu, respectively.
A mechanistic study of the reaction showed that the ketone
and silane complexes are in rapid equilibrium relative to the
rate of catalytic hydrosilylation and that the ketone complex
is strongly favored and can be viewed as the resting state.
Catalysis ensues by silation of ketone by the cationic silane
complex followed by reduction of this species by the resul-
tant iridium dihydride. Low-temperature mechanistic stud-
ies revealed that the ketone complex is the dominant resting
state in rapid equilibrium with silane complex 2. The turn-
over-limiting step in this catalytic cycle is either silation of
ketone by 2 or the reduction of resultant oxocarbenium ion
Figure 3. Plot of the initial rate, Vi, of disappearance of 4-tert-
via a hydride transfer from iridium dihydride 3. The turnover
butyl cyclohexanone vs Et3SiH concentration at -60 °C.
frequency is first-order in silane and zero-order in ketone, in
accord with this proposal. This mechanism is similar to that
plot of the initial rates of disappearance of 4-tert-butyl cyclo-
hexanone at various concentrations of 4-tert-butyl cyclohex-
anone using 1.87 M Et3SiH and 6.4 mM 1 in CD2Cl2 at
-60 °C. This plot establishes that the turnover frequency is
zero-order in ketone. Figure 3 shows a plot of the initial rates
of disappearance of 4-tert-butyl cyclohexanone (0.32-1.06
M) at various concentrations of Et3SiH using complex 1
(6.4 mM) in CD2Cl2 (-60 °C). This plot shows clearly that
the turnover frequency is first-order in silane.
proposed by Piers for hydrosilylation of ketones using
(C6F5)3B/Ph3SiH, where the silane is activated by (C6F5)3B
and transfers Ph3Siþ to ketone.4a
Experimental Section
General Procedures. All manipulations were carried out using
standard Schlenk, high-vacuum, and glovebox techniques. Ar-
gon and nitrogen were purified by passing through columns of
˚
BASF R3-11 catalyst (Chemalog) and 4 A molecular sieves.
Jian et al. has reported the Ir-catalyzed reduction of alkyl
halides by Et3SiH and proposed a quite similar catalytic cycle
to Scheme 3 based on the kinetic data, although, as here, they
were not able to distinguish whether the silation of alkyl
halides, RX, or the transfer of hydride to Et3SiXRþ was the
turnover-limiting step.5a
THF was distilled under a nitrogen atmosphere from sodium
benzophenone ketyl prior to use. Pentane, methylene chloride,
and toluene were passed through columns of activated alu-
mina11 and degassed by either freeze-pump-thaw methods or
˚
purging with argon. Benzene and acetone were dried with 4 A molec-
ular sieves and degassed by freeze-pump-thaw methods. Silanes
were dried with LiAlH4 or 4 A molecular sieves and vacuum
transferred into a sealed flask. All of the other substrates purchased
˚
Conclusions
˚
from Sigma-Aldrich were dried with either K2CO3 or 4 A molecular
sieves and vacuum transferred into a sealed flask for the substrate
with boiling point less than ca. 110 °C, except that 4-tert-butyl
cyclohexanone was purified by sublimation at ca. 40 °C. Deuterated
solvents (CD2Cl2, C6D5CD3, C6D5Cl) for NMR were dried with
Iridium complex 1 is a highly active, long-lived catalyst for
hydrosilylation of a variety of ketones and aldehydes with
trialkylsilanes to afford the corresponding silyl alkyl ethers
in excellent yields. Highly hindered ketones such as diiso-
propyl ketone are effective substrates. The majority of the
cases studied here have used Et3SiH as the silane, but several
other silanes including the bulky (i-Pr)3SiH have been shown
to be effective with cyclohexanone. Hydrosilylation of esters
leads to “over-reduction” and cleavage of C-O bonds.
Similarly, diethyl acetamide reacts to yield triethylamine.
The diastereoselectivity of the hydrosilylation of 4-tert-butyl
cyclohexanone with 1 and EtMe2SiH shows unprecedented
˚
CaH2 or 4 A molecular sieves and vacuum transferred into a sealed
flask. NMR spectra were recorded on Bruker spectrometers (DRX-
400, AVANCE-400, AMX-300, and DRX-500). 1H and 13C NMR
spectra were referenced to solvent peaks. Ph3C[B(C6F5)4],12
(11) (a) Alaimo, P. J.; Peters, D. W.; Arnold, J.; Bergman, R. G.
J. Chem. Educ. 2001, 78, 64. (b) Pangborn, A. B.; Giardello, M. A.; Grubbs,
R. H.; Rosen, R. K.; Timmers, F. J. Organometallics 1996, 15, 1518.
(12) Scott, V. J.; C-elenligil-C-etin, R.; Ozerov, O. V. J. Am. Chem. Soc.
2005, 127, 2852.

6064 Organometallics, Vol. 29, No. 22, 2010
Park and Brookhart
Scheme 6. Equilibrium between 1 and 2 at -50 °C
(POCOP)Ir(H)2,13 and [(POCOP)Ir(H)(acetone)]þ[B(C6F5)4]-,
1,5 were prepared according to published procedures.
General Procedure for the Hydrosilylation of Substrates with
Et3SiH in C6D5Cl. Et3SiH (0.48 mL, 3.00 mmol, 3 equiv) was
added to a solution of 1 (6.7 mg, 0.005 mmol, 0.5 mol %) in
C6D5Cl (0.3 mL) in a medium-walled J. Young NMR tube, and
the contents were well shaken. The substrate (1.00 mmol, 1
equiv) was then added, and the reaction was allowed to stand at
room temperature. The progress was followed by NMR spec-
troscopy. With the exception of diethyl acetamide (entry 11,
Table 1) conversions are quantitative and no starting material
remains at the end of the reaction. NMR data for the hydro-
silated products in Table 1 are available in the Supporting
Information.
General Procedure for the Hydrosilylation of 4-tert-Butyl
Cyclohexanone with Various Silanes in C6D5Cl. Silane (3.00
mmol, 3 equiv) was added to a solution of 1 (6.7 mg, 0.005
mmol, 0.5 mol %) in C6D5Cl (0.3 mL) in a medium-walled J.
Young NMR tube, and the contents were well shaken. 4-tert-
Butyl cyclohexanone (154 mg, 1.00 mmol, 1 equiv) was then
added and the reaction was allowed to stand at room temperature
for the specified time. The reaction mixture was then analyzed by
NMR spectroscopy. NMR data for the hydrosilated products in
Table 2 are available in the Supporting Information.
General Procedure for the Hydrosilylation of Alkyl-Substitut-
ed Cyclohexanone Derivatives with EtMe2SiH in C6D5Cl. Silane
(0.40 mL, 3.00 mmol, 3 equiv) was added to a solution of 1
(6.7 mg, 0.005 mmol, 0.5 mol %) in C6D5Cl (0.3 mL) in a
medium-walled J. Young NMR tube, and the contents were well
shaken. Alkyl-substituted cyclohexanone derivatives (1.00 mmol,
1 equiv) were then added, and the reaction mixtures were allowed
to stand at room temperature or 0 °C for a specific time. The
reaction mixtures were then analyzed by NMR spectroscopy.
NMR data for the hydrosilated products in Table 4 are available
in the Supporting Information.
General Procedure for Kineic Studies (CD2Cl2). Et3SiH was
added to a solution of 1 (6.7 mg, 0.005 mmol) in CD2Cl2 in a
medium-walled J. Young NMR tube, and the solution was well
shaken. The NMR tube was placed in a bath at -100 °C to freeze
the solution, and then 4-tert-butyl cyclohexanone in CD2Cl2
(0.32-1.06 M) was added on the top of the frozen solution
at -100 °C. After briefly shaking, the NMR tube was quickly
placed in the NMR probe precooled to -70 °C. The reaction
was allowed to warm to -60 °C, and the ratio of 4-tert-butyl
cyclohexanone to the silyl ether product was monitored with
respect to time by 1H NMR. The data were analyzed using the
method of initial rates, and the initial reduction rates were
obtained from the linear portion of the concentration versus
time curve in the early stage of the reaction (Figures 2 and 3).
Low-Temperature Reaction of 1, Et3SiH, and Acetone-2-13C,
-70 to -50 °C. To the solution of 1 (10.05 mg, 0.0075 mmol)
in CD2Cl2 in a medium-walled J. Young NMR tube was added
4 equiv of Et3SiH (4.8 μL, 0.03 mmol), and the solution was
stirred at 22 °C for 30 min. The solution was cooled to -70 °C,
and 1 equiv of acetone-2-13C was added from a stock solution of
acetone-2-13C in CD2Cl2. After briefly shaking, the NMR tube
was quickly placed in the NMR probe precooled to -80 °C. The
reaction was allowed to warm to -70 °C and monitored by
NMR spectroscopy. After NMR experiments at -70 °C, 16
equiv of Et3SiH was additionally added to the solution while
keeping the temperature at -70 °C, followed by warming the
solution to -50 °C. The hydrosilylation of acetone-2-13C with
Et3SiH began at -50 °C, and the concentration of all species was
monitored by NMR spectroscopy to determine the equilibrium
constant between 1 and 2 (Scheme 6).5a,b
Acknowledgment. We gratefully acknowledge funding
by the National Institutes of Health (Grant No. GM
28939).
Supporting Information Available: Text and figures giving
NMR data for hydrosilated products obtained in this work.
This material is available free of charge via the Internet at http://
pubs.acs.org.
(13) Goettker-Schnetmann, I.; White, P.; Brookhart, M. Organome-
tallics 2004, 23, 1766.