Base-free dehydrogenative coupling of enolizable carbonyl compounds with silanes

Article abstract of DOI:10.1021/ol301089r

A dehydrogenative coupling between enolizable carbonyl compounds and equimolar amounts of triorganosilanes catalyzed by a tethered ruthenium complex with a Ru-S bond is reported. The complex is assumed to fulfill a dual role by activating the Si-H bond to release a silicon electrophile and by abstracting an α-proton from the intermediate silylcarboxonium ion, only liberating dihydrogen as the sole byproduct. Reaction rates are exceedingly high at room temperature with very low loadings of the ruthenium catalyst.

Full text of DOI:10.1021/ol301089r

ORGANIC
LETTERS
2012
Vol. 14, No. 11
2842–2845
Base-Free Dehydrogenative Coupling of
Enolizable Carbonyl Compounds with
Silanes
C. David F. Konigs,†,‡ Hendrik F. T. Klare,‡,§ Yasuhiro Ohki,*,§ Kazuyuki Tatsumi,*,§ and
€
Martin Oestreich*,†,‡
€
Institut fu€r Chemie, Technische Universitat Berlin, Strasse des 17. Juni 115, 10623
€
€
Berlin, Germany, Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat
Mu€nster, Corrensstrasse 40, 48149 Mu€nster, Germany, and Department of Chemistry,
Graduate School of Science and Research Center for Materials Science, Nagoya
University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
martin.oestreich@tu-berlin.de; ohki@chem.nagoya-u.ac.jp; i45100a@nucc.cc.nagoya-u.ac.jp
Received April 24, 2012
ABSTRACT
A dehydrogenative coupling between enolizable carbonyl compounds and equimolar amounts of triorganosilanes catalyzed by a tethered
ruthenium complex with a RuꢀS bond is reported. The complex is assumed to fulfill a dual role by activating the SiꢀH bond to release a silicon
electrophile and by abstracting an R-proton from the intermediate silylcarboxonium ion, only liberating dihydrogen as the sole byproduct.
Reaction rates are exceedingly high at room temperature with very low loadings of the ruthenium catalyst.
Coordinatively unsaturated late transition metal com-
plexes with a bulky thiolate ligand are particularly active in
the reversible splitting of dihydrogen.1,2 Quantum-chemi-
cal calculations indicate that, depending on the transition
metal, the activation mechanism is either homolytic (IrꢀS
bond) or heterolytic (RhꢀS bond).3 For the tethered
ruthenium complex 12 (Scheme 1, upper), we believe that
the HꢀH bond is cooperatively activated by the RuꢀS
bond (Scheme 1, lower).2,4 By this, dihydrogen is split into
a hydride and a proton. The same strategy applied to the
chemoselective activation of a SiꢀH bond produces a
metal hydride and a silicon electrophile, likely a sulfur-
stabilized silylium ion or silicon-substituted sulfonium ion
(Scheme 1, lower);4 the tether in 1 is absolutely crucial to
prevent dissociation of the silylated bulky thiol.
The cooperative activation of SiꢀH bonds by 1 at
ambient temperature is a mild method to generate silicon
electrophiles, and our laboratories recently realized its use
in C-3-selective indole CꢀH functionalization.4 Exclusive
bond formation in the C-3 position corroborates an elec-
trophilic aromatic substitution mechanism where the Whe-
land intermediate is deprotonated to yield an indole along
with dihydrogen rather than being reduced to yield an
indoline. With no external added base, the neutral ruthe-
nium hydride complex acts as an internal base and not as a
reducing agent.
†
€
Technische Universitat Berlin.
‡
€
€
Universitat Munster.
(5) Sakamoto, M.; Ohki, Y.; Kehr, G.; Erker, G.; Tatsumi, K.
J. Organomet. Chem. 2009, 694, 2820–2824.
§ Nagoya University.
(1) Ohki, Y.; Sakamoto, M.; Tatsumi, K. J. Am. Chem. Soc. 2008,
130, 11610–11611.
(6) For carbonyl reduction involving SiꢀH bond activation by ruthe-
nium complexes, see selected examples: (a) Nagashima, H.; Suzuki, A.;
Iura, T.; Ryu, K.; Matsubara, K. Organometallics 2000, 19, 3579–3590. (b)
Maifeld, S. V.; Miller, R. L.; Lee, D. Tetrahedron Lett. 2002, 43, 6363–6366.
(c) Hashimoto, H.; Aratani, I.; Kabuto, C.; Kira, M. Organometallics 2003,
22, 2199–2201. (d) Gutsulyak, D. V.; Vyboishchikov, S. F.; Nikonov, G. I.
J. Am. Chem. Soc. 2010, 132, 5950–5951.
(2) Ohki, Y.; Takikawa, Y.; Sadohara, H.; Kesenheimer, C.; Engendahl,
B.; Kapatina, E.; Tatsumi, K. Chem.;Asian J. 2008, 3, 1625–1635.
(3) Tao, J.; Li, S. Dalton Trans. 2010, 39, 857–863.
(4) Klare, H. F. T.; Oestreich, M.; Ito, J.-i.; Nishiyama, H.; Ohki, Y.;
Tatsumi, K. J. Am. Chem. Soc. 2011, 133, 3312–3315.
r
10.1021/ol301089r
Published on Web 05/23/2012
2012 American Chemical Society

Scheme 1. Tethered Ruthenium Complex 1 with a Polar RuꢀS
Bond in HꢀH and SiꢀH Bond Activation [ArF = 3,5-Bis-
(trifluoromethyl)phenyl and Si = Triorganosilyl]
Scheme 2. Reduction (left) or Dehydrogenation (right) in the
Reaction of Enolizable Carbonyl Compounds and Silanes
Catalyzed by 1
We, therefore, asked ourselves whether 1 would cata-
lyze, as with dihydrogen,2,5 the reduction of enolizable
carbonyl compounds6,7 (IfIIfIII, Scheme 2, left) or
would result in the dehydrogenative formation of silyl enol
ethers (IfIIfIV, Scheme 2, right). The latter, catalyzed by
various transition metal complexes, is not unprecedented,8ꢀ17
but there are only a few general protocols.11,14ꢀ17 More-
over, these known systems usually require an external base
or thiol whereas our protocol would be base-free with the
release of dihydrogen. We report here the dehydrogenative
silylation of enolizablecarbonyl compounds catalyzed by1
under neutral conditions to access the synthetically useful
class of silyl enol ethers.18
Table 1. Survey of Silanes and Reaction Temperatures in the
Dehydrogenative Couplinga
chemo-
temp time
selectivity yield
entry
1
SiH
[°C] [min] compd
ratioc
[%]d
Me2PhSiH
rt
5
4a,
10a
85:15
93
Our investigation commenced with a screening of dif-
ferent triorganosilanes 3aꢀ3f in the dehydrogenative cou-
pling of acetophenone (2a) catalyzed by 1 (Table 1). The
nonhindered silanes 3a and 3b showed full conversion at
(3a)
2
3
4
ꢀ20
65
60
30
5
53:47
84:16
83:17
85
70
89
MePh2SiH
(3b)
rt
5a,
11a
6a,
12a
7a,
13a
8a,
14a
9a,
15a
5
6
7
8
EtMe2SiH
(3c)
rt
5
97:3
70:30
80:20
ꢀ
91
87
(7) (a) Larson, G. L.; Fry, J. L. In Organic Reactions; Denmark, S. E.,
Ed.; Wiley: Hoboken, NJ, 2008; Vol. 71, pp 1ꢀ737. (b) Rendler, S.;
Oestreich, M. In Modern Reduction Methods; Andersson, P. G., Munslow,
I. J., Eds.; Wiley-VCH: Weinheim, 2008; pp 183ꢀ207.
(8) Ojima, I.; Nagai, Y. J. Organomet. Chem. 1973, 57, C42–C44.
(9) (a) Frainnet, E.; Martel-Siegfried, V.; Brousse, E.; Dedier, J.
J. Organomet. Chem. 1975, 85, 297–310. (b) Frainnet, E.; Bourhis, R.
J. Organomet. Chem. 1975, 93, 309–324.
(10) Ojima, I.; Nihonyanagi, M.; Kogure, T.; Kumagai, M.;
Horiuchi, S.; Nakatsugawa, K.; Nagai, Y. J. Organomet. Chem. 1975,
94, 449–461.
(11) Sakurai, H.; Miyoshi, K.; Nakadaira, Y. Tetrahedron Lett. 1977,
2671–2674.
Et3SiH
(3d)
65
65
30
30
30
e
Ph3SiH
(3e)
ꢀ
f
t-BuMe2SiH 65
(3f)
ꢀ
a All reactions were conducted according to the general procedure at
a concentration of 0.5 M of 3 (cf. the Supporting Information). b Con-
version was monitored by GLC analysis. c Ratio of silyl enol ether
(4aꢀ9a) and silyl ether (10aꢀ15a) was determined by GLC-MS analysis.
d Combined yield after catalyst removal. e Incomplete conversion. f No
reaction.
(12) Fuchikami, T.; Ubukata, Y.; Tanaka, Y. Tetrahedron Lett. 1991,
32, 1199–1202.
(13) Nagashima, H.; Ueda, T.; Nishiyama, H.; Itoh, K. Chem. Lett.
1993, 347–350.
(14) Igarashi, M.; Sugihara, Y.; Fuchikami, T. Tetrahedron Lett.
1999, 40, 711–714.
ambient temperature and yielded the desired silyl enol
ethers 4a and 5a (dehydrogenation path) along with
the undesired silyl ether 10a and 11a (reduction path)
in promising ratios of 85:15 and 83:17, respectively
(Table 1, entries 1 and 4). Good chemical yields were
obtained in both cases. Those ratios were substantially
deteriorated at lower temperatures and remained the same
(15) Ozawa, F.; Yamamoto, S.; Kawagishi, S.; Hiraoka, M.; Ikeda,
S.; Minami, T.; Ito, S.; Yoshifuji, M. Chem. Lett. 2001, 972–973.
(16) Thiot, C.; Wagner, A.; Mioskowski, C. Org. Lett. 2006, 8, 5939–
5942.
(17) Gao, R.; Yi, C. S. ACS Catal. 2011, 1, 544–547.
(18) (a) Brownbridge, P. Synthesis 1983, 1–28. (b) Brownbridge, P.
Synthesis 1983, 85–104. (c) Kobayashi, S.; Manabe, K.; Ishitani, H.;
Matsuo, J.-I. In Science of Synthesis; Fleming, I., Ed.; Thieme: Stuttgart,
2002; Vol. 4, pp 317ꢀ369.
Org. Lett., Vol. 14, No. 11, 2012
2843

Table 2. Dehydrogantive Coupling of Para-Substituted Aceto-
phenones Using Silanes 3a and 3ca
Table 3. Dehydrogenative Coupling of Ortho-Substituted
Acetophenones and Related Compounds Using Silane 3aa
Me2PhSiH (3a)
EtMe2SiH (3c)
ratio
ratio
X
of
yield
of
yield
[%]d
entry compd compd 4/10c
[%]d compd 6/12c
1
2
3
4
5
OCH3
2b
4b,
10b
4c,
10:90
43:57
65:35
88:12
95:5
97
96
93
91
88
6b,
12b
6c,
41:59
91:9
98
CH3
2c
90
97
92
82
10c
4d,
10d
4e,
12c
6d,
12d
6e,
Cl
98:2
2d
OTf
2e
90:10
97:3
10e
4f,
12e
6f,
CF3
2f
10f
12f
a All reactions were conducted according to the general procedure at
a concentration of 0.5 M of 3 (cf. the Supporting Information). b Con-
version was monitored by GLC analysis. c Ratio of silyl enol ether
(4bꢀ4f or 6bꢀ6f) and silyl ether (10bꢀ10f or 12bꢀ12f) was determined
by GLC-MS analysis. d Combined yield after catalyst removal.
at elevated reaction temperatures (e.g., with 3a, Table 1,
entries 2 and 3); no conversion was seen at ꢀ78 °C. We
were then delighted to find that, with rarely used silane 3c,
an excellent selectivity of 97:3 in favor of dehydrogenation
was obtained (Table 1, entry 5). With a catalyst loading as
low as 0.5 mol %, complete conversion and 91% isolated
yield were reached within 5 min, requiring neither a base
nor a hydrogen acceptor. More bulky silanes 3dꢀ3f either
afforded more of the reduced carbonyl compound at
slower reaction rate (Table 1, entries 6 and 7) or did not
react at all (Table 1, entry 8).
a All reactions were conducted according to the general procedure at
a concentration of 0.5 M of 3 (cf. the Supporting Information). b Con-
version was monitored by GLC analysis. c Ratio of silyl enol ether
(4gꢀ4m) and silyl ether (10gꢀ10m) was determined by GLC-MS
analysis. d Analytically pure product after catalyst removal. e The reac-
tion of 2g with 3c afforded 6g and 12g in a ratio of 83:17 in 96% yield.
Having established the new catalytic system, we next
focused on the substrate scope by using different para-
substituted acetophenones (2bꢀ2f, Table 2). We observed
a clear trend in the electronic effect of the X group;
electron-donating groups steer the catalysis toward reduc-
tion while electron-withdrawing X groups favor the dehy-
drogenation path. The effect is strong with Me2PhSiH (3a,
Table 2, columns 3ꢀ5) and weaker with EtMe2SiH (3c,
Table 2, columns 6ꢀ8). A far less pronounced electronic
effect is exerted by an X group in the ortho-position of the
corresponding acetophenones 2gꢀ2k using Me2PhSiH
(3a, Table 3, entries 1ꢀ5). Only the strongly electron-
donating methoxy group is detrimental while the other X
groupsaretolerated. Itisimportanttonote thoughthatthe
poor 35:65 ratio (2gf4g/10g) with 3a is dramatically
improved to 83:17 (2gf6g/12g) with less hindered silane
Scheme 3. Probing Diastereoselective Silyl Enol Ether Forma-
tion
3c (cf. footnote e in Table 3). That example nicely demon-
strates that, for critical carbonyl compounds, EtMe2SiH
(3c) might even reverse the selectivity found with Me2Ph-
SiH (3a). Our survey also included cyclic substrate 2l
2844
Org. Lett., Vol. 14, No. 11, 2012

at room temperature but could be improved to a reason-
able level at ꢀ78 °C. Using MePh2SiH (3b) or EtMe2SiH
(3c) instead of Me2PhSiH (3a) showed no enhancement of
the Z/E ratio. Other dialkyl ketones 18ꢀ22 also reacted
cleanly according to the dehydrogenation path (Table 4),
and those catalyses where regioisomers could form af-
forded the less substituted double bond isomer with high
preference (abstraction of methyl . methylene > methine
protons). While cyclohexanone derivative 21 yielded a
decent regioisomeric mixture (Table 4, entry 4), methyl-
substituted 19 and 22 were converted into single isomers
(Table 4, entries 2 and 5).
Table 4. Dehydrogenative Coupling of Dialkyl Ketones: Con-
trol of the Regioselectivitya
To summarize, we disclose here a particularly mild
method for the dehydrogenative transformation of ke-
tones into silyl enol ethers. The catalysis proceeds within
minutes at room temperature with 0.5 mol % of the
cationic ruthenium complex 1, affording high isolated
yields. We emphasize that no base must be added and
dihydrogen is the sole byproduct. The chemoselectivity,
which is either proton abstraction from (dehydrogenation
path) or hydride addition to (reduction path) the inter-
mediate silylcarboxonium ion, is dependent on the size of
the triorganosilane employed. EtMe2SiH (3c) was found to
be superior to routinely used Me2PhSiH (3a) in several
cases. By using either of these triorganosilanes, excellent
chemoselectivity ratios in favor of dehydrogenation are
obtained.
Acknowledgment. This research was supported by
the Deutsche Forschungsgemeinschaft (International
a All reactions were conducted according to the general procedure at
a concentration of 0.5 M of 3 (cf. the Supporting Information). b Con-
version was monitored by GLC analysis. c Ratio of silyl enol ethers
(23ꢀ27/230ꢀ270) and silyl ether (28ꢀ32) was determined by GLC-MS
analysis. d Analytically pure product after catalyst removal.
€
Research Training Group Munster-Nagoya, GRK 1143
with predoctoral fellowships to C.D.F.K., 2011ꢀ2012 and
H.F.T.K., 2007ꢀ2010), the G-COE program in chemistry
(Nagoya), and a Grant-in-Aid for Scientific Research
(No. 18GS0207) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. M.O. is indebted
to the Einstein Foundation (Berlin) for an endowed
professorship.
(Table 3, entry 6) and hindered acetophenone 2m (Table 3,
entry 7). Comparison of the ratios in Tables 2 and 3
suggests that steric factors might override electronic ef-
fects. Moreover, the size of the silicon group is a decisive
parameter, and ifsmall enough, itappearstobring forward
proton abstraction (IIfIV) rather than hydride transfer
(IIfIII) by the ruthenium hydride complex (cf. Scheme 2).
The possibility of double bond isomer formation was
probed in the dehydrogenative coupling of symmetric
ketone16(Scheme 3). Diastereocontrol was only moderate
Supporting Information Available. Experimental de-
tails, characterization data, and 1H, 13C, and 29Si NMR
spectra for all compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 11, 2012
2845