Intermolecular dehydrative coupling reaction of aryl ketones with cyclic alkenes catalyzed by a well-defined cationic ruthenium-hydride complex: A novel ketone olefination method via vinyl C-H bond activation

Article abstract of DOI:10.1021/om100051h

The cationic ruthenium-hydride complex [(η⁶-C ₆H₆)(PCy₃)(CO)RuH]⁺BF ₄^- was found to be a highly effective catalyst for the intermolecular olefination reaction of aryl ketones with cycloalkenes. The preliminary mechanistic analysis revealed that an electrophilic ruthenium-vinyl complex is the key species for mediating both vinyl C-H bond activation and the dehydrative olefination steps of the coupling reaction.

Full text of DOI:10.1021/om100051h

Organometallics 2010, 29, 1883–1885 1883
DOI: 10.1021/om100051h
Intermolecular Dehydrative Coupling Reaction of Aryl Ketones with
Cyclic Alkenes Catalyzed by a Well-Defined Cationic
Ruthenium-Hydride Complex: A Novel Ketone Olefination Method via
Vinyl C-H Bond Activation
Chae S. Yi* and Do W. Lee
Department of Chemistry, Marquette University, Milwaukee, Wisconsin 53201-1881
Received January 21, 2010
Summary: The cationic ruthenium-hydride complex [(η6-C6H6)-
compounds with unactivated olefins would be highly desirable,
but this still largely remains an elusive goal. Inspired by the
recent progress on electrophilic C-H activation methods,7 we
have been exploring the coupling reactions of ketones and
amines by using cationic ruthenium catalysts.8 This report deli-
neates a catalytic ketone olefination method that occurs from
the intermolecular dehydrative coupling reaction of aryl ke-
tones and cyclic alkenes involving vinyl C-H bond activation.
We have devised a convenient method to synthesize a
cationic ruthenium-hydride complex from the protonation
reaction of {[(PCy3)(CO)RuH]4(μ4-O)(μ3-OH)(μ2-OH)} (1)
(eq 1).9 Thus, the treatment of 1 (200 mg, 0.12 mmol) with
-
(PCy3)(CO)RuH]þBF4 was found to be a highly effective
catalyst for the intermolecular olefination reaction of aryl
ketones with cycloalkenes. The preliminary mechanistic ana-
lysis revealed that an electrophilic ruthenium-vinyl complex is
the key species for mediating both vinyl C-H bond activation
and the dehydrative olefination steps of the coupling reaction.
The Wittig reaction constitutes one of the most versatile
olefination methods, and its synthetic prowess has been im-
mensely demonstrated over the years in both laboratory-scale
and industrial processes.1 Despite its synthetic versatility,
however, Wittig and related Peterson and Horner-Emmons
olefination methods require stoichiometric amounts of ylides
(or carbanion equivalents), which pose debilitating problems of
the formation and removal of byproducts, especially for large-
scale industrial applications. The Perkin and related aldol-type
condensation/dehydration reactions have also been commonly
used as carbonyl olefination methods, but these also suffer
from similar restricted functional group compatibility and the
formation of copious amounts of byproducts.2 Considerable
research progress has been achieved in the development of
transition-metal-based carbonyl olefination methods that are
more functional group tolerant and environmentally compa-
tible, including Tebbe’s and Petasis Ti reagents,3 carbonyl-
to-diazo coupling,4 decarbonylative coupling reactions of
aldehydes and alkynes,5 and Pd-catalyzed coupling reactions.6
From both synthetic and environmental points of view, the
development of a catalytic version of the carbonyl olefina-
tion methods from the intermolecular coupling of carbonyl
HBF4 OEt2 (64 μL) in C6H6 at room temperature cleanly led
3
to the formation of the cationic ruthenium-hydride complex
2, which was isolated as an ivory-colored solid in 95% yield.
The 1H NMR of 2 in CD2Cl2 showed the Ru-H signal at δ
-10.39 (d, JPH = 25.9 Hz), and a single phosphine peak was
observed at δ 72.9 ppm by 31P{1H} NMR. The molecular
structure of 2 as established from X-ray crystallography
showed a three-legged piano-stool geometry, which is
capped by a η6-benzene moiety.10
Having a well-defined cationic ruthenium-hydride com-
plex 2 in hand, we next explored its catalytic activity for the
coupling reaction of aryl ketones and alkenes. We initially
anticipated the formation of the ortho C-H insertion pro-
duct 3, in light of the reported results on the chelate-directed
coupling reaction of aryl ketones and alkenes.11 Instead, the
*To whom correspondence should be addressed. E-mail: chae.yi@
marquette.edu.
(1) Recent reviews: (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev.
1989, 89, 863–927. (b) Cristau, H.-J. Chem. Rev. 1994, 94, 1299–1313.
(c) Shen, Y. Acc. Chem. Res. 1998, 31, 584–592.
(2) (a) Smith, M. B.; March, J. March’s Advanced Organic Chemistry,
5th ed.; Wiley: New York, 2001. (b) Carey, F. A.; Sundberg, R. J. Advanced
Organic Chemistry, Part B: Reactions and Synthesis, 4th ed.; Springer:
New York, 2000.
(3) (a) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc.
1978, 100, 3611–3613. (b) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc.
1990, 112, 6392–6394.
(7) (a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.;
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550–557.
(8) (a) Yi, C. S.; Yun, S. Y.; Guzei, I. A. J. Am. Chem. Soc. 2005, 127,
5782–5783. (b) Yi, C. S.; Lee, D. W. Organometallics 2009, 28, 4266–4268.
(9) Yi, C. S.; Zeczycki, T. N.; Guzei, I. A. Organometallics 2006, 25,
1047–1051.
(4) (a) Mirafzal, G. A.; Cheng, G.; Woo, L. K. J. Am. Chem. Soc.
2002, 124, 176–177. (b) Cheng, G.; Mirafzal, G. A.; Woo, L. K. Organo-
metallics 2003, 22, 1468–1474. (c) Chen, Y.; Huang, L.; Zhang, X. P. Org.
Lett. 2003, 5, 2493–2496.
(10) Similar cationic ruthenium-hydride complexes have recently
been synthesized: (a) Saker, O.; Mahon, M. F.; Warren, J. E.;
Whittlesey, M. K. Organometallics 2009, 28, 1976–1979. (b) Lee, J. P.;
Ke, Z.; Ramírez, M. A.; Gunnoe, T. B.; Cundari, T. R.; Boyle, P. D.; Petersen,
J. L. Organometallics 2009, 28, 1758–1775.
(11) (a) Kakiuchi, F.; Murai, S. In Topics in Organometallic Chemis-
try: Activation of Unreactive Bonds and Organic Synthesis; Murai, S., Ed.;
Springer: New York, 1999; Vol. 3. (b) Kakiuchi, F.; Murai, S. Acc. Chem. Res.
2002, 35, 826–834. (c) Kakiuchi, F. In Topics in Organometallic Chemistry:
Directed Metallation; Chatani, N., Ed.; Springer: Berlin, 2007; Vol. 24.
ꢀ
(5) (a) Varela, J. A.; Gonzalez-Rodrıguez, C.; Rubın, S. G.; Castedo,
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therein.
r
2010 American Chemical Society
Published on Web 03/19/2010
pubs.acs.org/Organometallics

1884 Organometallics, Vol. 29, No. 8, 2010
Yi and Lee
Table 2. Coupling Reaction of Aryl Ketones and Cyclic Alkenesa
Scheme 1
Table 1. Catalyst Survey for the Coupling Reaction of Aceto-
phenone and Cyclopentenea
conversn
(%)b
entry
catalyst
additive
4a:5a
1
2
3
4
5
6
7
8
9
10
1
1
0
50
0
HBF4 OEt2
3
1:1
RuHCl(CO)(PCy3)2
RuHCl(CO)(PCy3)2
2
HBF4 OEt2
3
6
12c
60
8
2
HBF4 OEt2
3
1:1
RuH2(CO)(PPh3)3
RuCl2(PPh3)3
RuCl3 3H2O
HBF4 OEt2
3
HBF4 OEt2
3
<5
0
0
HBF4 OEt2
3
3
Ru3(CO)12
NH4PF6
HBF4 OEt2
11d [RuH(CO)(PCy3)2(S)2]þBF4
0
-
3
12
13
14
15
Re(CO)3(THF)2Br
Au(PPh3)3Cl
HBF4 OEt2
HBF4 OEt2
HBF4 OEt2
<5
<5
0
3
3
3 þ
-
Cy3PH BF4
0
a Reaction conditions: ketone (0.7 mmol), alkene (14 mmol), 2 (20 mg,
a Reaction conditions: acetophenone (0.1 mmol), cyclopentene
(2.0 mmol), catalyst (10 mg, 5 mol %), additive (2 equiv to catalyst),
C6H5Cl (2 mL), 110 °C, 15 h. b Conversion was determined by GC on the
basis of acetophenone. c Three different double bond isomers formed
from dehydrogenation of 3. d S = CH3CN.
5 mol %), HBF4 OEt2 (10 μL, 2 equiv), C6H5Cl (2 mL), 110 °C, 15 h.
3
b Determined by GC on the basis of ketone. c Combined isolated yield of
4 and 5 determined from the hydrogenation product 6. d Contained 28%
of PhCH2CH2Ph. eA 4:1 ratio of 4l and 5l was formed in the crude
product mixture. f10 mol % of 2 was used. g ∼10% of the ortho C-H
insertion product 3 was also formed.
treatment of acetophenone with excess cyclopentene in the
presence of 2/HBF4 OEt2 (5 mol %) in C6H5Cl cleanly
3
produced a ∼1:1 ratio of double bond isomers of the
olefination products 4a and 5a, without forming any ortho
C-H insertion product 3 (Scheme 1).
mixture of 4 and 5 with H2 (2 atm) at 110 °C in the presence
of 2/HBF4 OEt2 (5 mol %) in C6H5Cl cleanly led to the
3
olefin-hydrogenated product 6, which was isolated by column
chromatography on silica gel. The isolated yield of 6 is given
in Table 2.
The preliminary survey of ruthenium catalysts showed
that both in situ formed 1/HBF4 OEt2 and the isolated
3
catalyst 2/HBF4 OEt2 exhibited uniquely high activity for
3
The following experiments were performed to gain mecha-
nistic insights into the olefination reaction. First, the deuterium-
labeling pattern was examined from the treatment of aceto-
phenone-d8 (90 mg, 0.7 mmol) with excess cyclopentene
the coupling reaction (Table 1). The addition of HBF4 OEt2
3
was found to be critical for giving the olefination products,
since the catalyst 2 alone exhibited a modest activity for the
ortho C-H insertion products (entries 5 and 6).12 One of the
most remarkable features of the coupling reaction is that a
direct ketone olefination has been achieved from the inter-
molecular dehydrative coupling reaction of aryl ketones and
unactivated alkenes without employing any reactive reagents.
The scope of the olefination reaction was explored by using
(0.95 g, 14 mmol) and 2/HBF4 OEt2 (5 mol %). Extensive
3
H/D exchange was found to occur on the methyl group of
both 4a and 5a as well as on cyclopentene, without signi-
ficant exchange on the ortho positions of the phenyl group
as examined by 1H and 2H NMR.12 The coupling reaction of
acetophenone with a 1:1 mixture of 1-hexene and cyclo-
pentene under the competitive conditions yielded the olefination
products 4a and 5a predominantly over the C-H insertion
product type 3(4a þ 5a:3= 11:1). These results indicate that the
vinyl C-H activation is rapid and reversible and that this step
is favored over the arene ortho C-H activation for the cyclo-
pentene case.
2/HBF4 OEt2 catalyst (Table 2). Aryl ketones with a para
3
electron-donating group were found to modestly promote the
coupling reaction (entries 2 and 3), while both terminal and
internal olefins such as 1-hexene and 2-hexenes yielded the
C-H insertion products 3 under similar conditions.8b Both
cyclopentene and cyclohexene were found to be suitable sub-
strates, but sterically demanding cyclic alkenes such as cyclo-
octene and methylcyclopentene as well as trisubstituted olefins
yielded <5% of the coupling products. A considerably higher
conversion was achieved for naphthyl-substituted ketones
(entries 8-11). In most cases, high selectivity for the olefina-
tion products of the types 4 and 5 was observed over the ortho
C-H insertion product of type 3, where the formation of a
nearly 1:1 ratio of the double-bond isomers of 4 and 5 was
observed in the crude product mixture. To obtain combined
isolated yields, the hydrogenation reaction was performed on
the crude product mixture. Thus, the treatment of a product
To discern the nature of catalytically relevant species, the
reaction of 2 with cyclopentene was monitored by NMR. The
treatment of 2 (20 mg, 35 μmol) with excess cyclopentene
(24 mg, 10 equiv) in CD2Cl2 slowly formed the new cationic
-
complex [CpRu(CO)(PCy3)(c-C5H8)]þBF4 (7) within 3 h at
100 °C, along with Cy3PHþBF4-, free benzene, and cyclopen-
tane. The structure of 7 was tentatively assigned on the basis of
NMR spectroscopic data. Trapping of 7 with PhCN resulted in
-
the stable nitrile complex [CpRu(CO)(PCy3)(NCPh)]þBF4
(8) (Scheme 2).12 The formation of cyclopentadienyl complex 8
can be readily rationalized from the dehydrogenation of cyclo-
pentene and the elimination of cyclopentane.
(12) See the Supporting Information for the experimental details.

Communication
Organometallics, Vol. 29, No. 8, 2010 1885
Scheme 2
Scheme 3. Mechanistic Rationale for the Ketone Olefination
Though details of the coupling reaction still remain to be
established, we propose a mechanistic rationale that invokes
both olefinic C-H bond activation and dehydrative carbo-
nyl olefination steps (Scheme 3). We propose that the
electrophilic Ru-vinyl complex 9, initially generated from
the vinyl C-H activation of cycloalkene, is the key species
for the coupling reaction. The dative coordination of ketone
substrate followed by the alkenyl group migration to the
electrophilic carbonyl carbon would yield the alcohol pro-
duct after transfer of a hydrogen obtained from vinyl C-H
activation of a coordinated alkene to the alkoxide ligand.
While the formation of metal-vinyl species has been well
documented in the C-H bond activation literature,13 its
synthetic utility has not been fully exploited in catalytic
coupling reactions. The detailed mechanistic steps for the
formation of the olefin products 4 and 5 from the alcohol are
not clear at the present time, but it can be envisaged from an
acid-catalyzed reductive dehydration of the alcohol, in light
of the well-known alcohol dehydration reactions.
In summary, a novel catalytic ketone olefination method
has been developed from the intermolecular coupling reac-
tion of aryl ketones with cyclic alkenes. The electrophilic
nature of the ruthenium catalyst 2 seems to be an essential
feature for mediating both vinyl C-H bond activation and
the subsequent dehydrative coupling steps of the reaction.
The scope and synthetic efficacy of the catalytic method are
currently being investigated.
Acknowledgment. Financial support from the Natio-
nal Institutes of Health, General Medical Sciences
(Grant No. R15 GM55987) is gratefully acknowledged.
Supporting Information Available: Text, tables, figures,
and a CIF file giving experimental procedures, spectroscopic
data for organic products, and X-ray crystallographic data
for 2. This material is available free of charge via the Internet
at http://pubs.acs.org.
(13) (a) Stoutland, P. O.; Bergman, R. G. J. Am. Chem. Soc. 1985,
107, 4581–4582. (b) Renkema, K. B.; Kissin, Y. V.; Goldman, A. S. J. Am.
Chem. Soc. 2003, 125, 7770–7771.