Chemoselectivity in catalytic C-C and C-H bond activation: Controlling intermolecular carboacylation and hydroarylation of alkenes

Full text of DOI:10.1002/anie.200902215

Angewandte
Chemie
DOI: 10.1002/anie.200902215
Homogeneous Catalysis
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Chemoselectivity in Catalytic C C and C H Bond Activation:
Controlling Intermolecular Carboacylation and Hydroarylation of
Alkenes**
Michael T. Wentzel, Venkata Jaganmohan Reddy, Todd K. Hyster, and Christopher J. Douglas*
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A major challenge in the development of carbon–carbon s-
C C or ortho-C H activation of ketones is controlled by the
appropriate choice of catalyst and solvent.
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bond (C C) activation is competitive activation and func-
[1]
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tionalization at C H bonds, which are typically more
Our success with intramolecular carboacylation[6] led us to
contemplate an intermolecular variant (1 + 2!3 + 4,
accessible to metal catalysts (Figure 1). As a result, catalytic
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Scheme 1) for convergent syntheses. Previously, C C activa-
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Figure 1. C C and C H activation reactions.
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C C activation and functionalization is an under-developed
strategy in synthetic organic chemistry.[2] We are aware of only
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a few prior studies in which competitive C C and C H
activation pathways can be controlled. A series of reports
from Nakao, Hiyama et al. elegantly demonstrated that
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Scheme 1. Catalytic C C activation reactions with 8-acylquinolines.
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nickel-catalyzed aryl C CN or ortho-C H activation can be
controlled by ligand or substrate choice.[3] In both cases an
alkyne was inserted into the activated bond. Jones and co-
tion of 5 with [{RhCl(C2H4)2}2] and excess C2H4 yielded
fragmentation products 7 and styrene (8) via a Rh-H
intermediate (6).[7] This unusual hydroacylation provides the
products in good yield, but C2H4 was the only alkene capable
of this reaction.[8]
We chose [2.2.1]bicycloheptenes for initial study to avoid
intermediates with accessible syn-b-hydrides. We heated
equimolar amounts of 5 and norbornene for 24 h in the
presence of rhodium catalysts (Table 1). Although Wilkin-
sonꢀs catalyst was ineffective (entry 1), [{RhCl(C2H4)2}2]
resulted in the formation of a new product (10).[9,10] This
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ꢀ
workers studied competitive C CN and C H activation
reactions in allyl cyanides.[4] Milstein and co-workers have
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extensively studied C C and C H activation in toluene-based
pincer systems.[5]
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As organic substrates for C C and C H bond activation
become more complex, controlling competing pathways
becomes critically important. To this end, we are investigating
direct inter- and intramolecular[6] alkene carboacylation with
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unstrained ketones by C C activation. Herein, we report that
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C H activation is likely directed by the oxygen atom of the
ketone. In CH3CN, the conversion decreased, but a small
amount of carboacylation product 9 formed (entry 3).[11,12]
A
[*] M. T. Wentzel, V. J. Reddy, T. K. Hyster,[+] Prof. C. J. Douglas
Department of Chemistry, University of Minnesota
Twin Cities, 207 Pleasant St. SE, Minneapolis, MN 55455 (USA)
Fax: (+1)612-626-7541
E-mail: cdouglas@umn.edu
[+] UMN Undergraduate Research, 2007–2008.
switch to [Rh(cod)2]OTf provided higher conversion, but
poor chemoselectivity (entry 5). A solvent screen (entries 6–
9) showed that the product distribution depended on the
solvent, with THF providing complete selectivity for 9
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(entry 9). It is remarkable that one can select exclusive C C
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or C H activation and functionalization by the appropriate
[**] We acknowledge the donors of the ACS Petroleum Research Fund
for partial support (47565-G1). We thank Dr. Letitia Yao (NMR
spectroscopy), Matthew Meyer and Jacob Schmidt (mass spec-
trometry), and UMN (start-up funds).
choice of catalyst and solvent. The addition of phosphine
ligands to the [Rh(cod)2]OTf/THF reactions decreased the
yield without affecting the 9/10 ratio (entries 10 and 11). In all
cases, 9 and 10 were obtained with good diastereocontrol
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902215.
1
(>95:5 by H NMR spectroscopy). Excess alkene (10 equiv)
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Communications
Table 1: Carboacylation and hydroarylation with 5.
Table 2: Variation of the quinoline and alkene substrates.
Quinoline Alkene
Cond.[a] Products
Yield[b]
39%
(60%)
A
Entry
Catalyst[b]
Solvent
T
Yield, 9/10[a]
1
2
3
4
5
6
7
8
[Rh(PPh3)3]Cl
[{RhCl(C2H4)2}2][c]
[{RhCl(C2H4)2}2][c]
[Rh(cod)2]BF4
[Rh(cod)2]OTf
[Rh(cod)2]OTf
[Rh(cod)2]OTf
[Rh(cod)2]OTf
[Rh(cod)2]OTf
[Rh(cod)2]OTf
[Rh(cod)2]OTf
PhCH3
PhCH3
CH3CN
PhCH3
PhCH3
PhCF3
(CH2Cl)2
CH3CN
THF
1308C
1308C
1008C
1308C
1308C
1308C
1308C
1008C
1008C
1008C
1008C
>10%, –
79%, 0:1
35%, ꢁ1:20
38%, 1:6
56%, 4:5
44%, 1:5
62%, 1:7
41%, 5:3
50%, 1:0
20%, 1:0
12%, 1:0
44%
(65%)
A
41%
(60%)
9
10
11
A
A
THF[d]
THF[e]
[a] Yields and ratios by 1H NMR spectroscopy with an internal standard.
[b] Catalyst loading 10 mol% unless otherwise noted. [c] 5 mol%
catalyst used. [d] With 20 mol% PPh3. [e] With 20 mol% P(tBu)3. The
values in bold show the most selective reactions. cod=1,5-cycloocta-
diene, THF=tetrahydrofuran, OTf=trifluoromethane sulfonate.
44%
(64%)
30%,
(66%),
18/19;
1:1
B
B
did not improve the yields of 9 and 10 under the conditions
shown for entries 9 and 2, respectively.
We examined other 8-acylquinolines with bridged cyclo-
alkenes (Table 2). We used the optimized conditions from
Table 1 to examine substituent effects rather than reoptimize
each substrate pair. Exchanging the 8-benzoyl group for
24%
24%
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acetyl resulted in C H activation products being avoided
altogether, even when [{RhCl(C2H4)2}2] was used in PhCH3
(conditions A). The use of functionalized alkenes (13 and 15)
increased the propensity of 5 to undergo hydroarylation
rather than carboacylation. Alkenes 13 and 15 did not
undergo carboacylation even with [Rh(cod)]OTf in THF
(conditions B). Diol 15 underwent spontaneous cyclization to
a THF ring along with concurrent hydroarylation. By adding a
para-CH3 group (17, Table 2), selectivity was complete for
B
[a] Conditions A: [{RhCl(C2H4)2}2] (5 mol%), PhCH3, 1308C, 24 h. Con-
ditions B: [Rh(cod)2]OTf (10 mol%), THF, 1008C, 24 h. [b] Yields after
chromatography, (%) yields based on recovered starting material.
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C H activation under conditions A, but conditions B gave an
approximately 1:1 mixture of 18 and 19. Changing the CH3
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group of 17 to CF3 (20) suppressed the C H activation
pathway, thus suggesting that more-electron-rich aryl ketones
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undergo C H activation more readily under conditions B.
When alkene 22 was used, the yield was similar, but the
diastereomer ratio decreased (ca. 4:1, anti/syn).
Scheme 2). Using the same catalyst/solvent combination as
[6,7]
ꢀ
used in previous C C activation studies,
we exclusively
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One hypothesis to explain these data is equilibration of
the carboacylation product 9 to the hydroarylation product 10
with [{RhCl(C2H4)2}2] in PhCH3. Since C C activation is
form the product resulting from C H activation (10). Since
both I and II are accessed under these conditions and since 9
and 10 do not equilibrate, we conclude that II is simply more
apt toward migratory insertion than I when chloride is present
in a nonpolar solvent. By changing the catalyst counterion
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sometimes thought to be reversible,[13] and b-carbon elimi-
nation in norbornyl systems is also known,[14,15] we tested this
hypothesis by subjecting pure 9 to conditions A. No trace of
10 was detected by 1H NMR spectroscopy, thereby ruling out
this rationale.
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(OTf), a mixture of both C H (9) and C C (10) activated
products was formed [Table 1, entry 4]. Furthermore, by
switching to a more polar solvent (THF) with OTf as the
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Based on our findings and previous results, we presume
that 5 can form two possible intermediates (I and II,
counterion, the C C activation pathway is selected exclu-
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sively. When R = Me (11), only C C activation (III) occurs—
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Angewandte
Chemie
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[2] Reviews on C C bond
activation: a) C. Nꢁjera,
J. M. Sansano, Angew.
Chem. 2009, 121, 2488;
Angew. Chem. Int. Ed.
2009, 48, 2452; b) Y. J.
Park, J.-W Park, C.-H.
Jun, Acc. Chem. Res. 2008,
41, 222; c) D. Neꢂas, M.
Kotora, Curr. Org. Chem.
2007, 11, 1566; d) M. Mur-
akami, Y. Eto in Activation
of Unreactive Bonds and
Organic Synthesis (Ed: S.
Murai), Springer, New
York, 1999, p. 97.
[3] a) Y. Nakao, K. S. Kanyiva,
S. Oda, T. Hiyama, J. Am.
Chem. Soc. 2006, 128,
8146; b) Y. Nakao, S. Oda,
Scheme 2. Mechanistic considerations.
A. Yada, T. Hiyama, Tetra-
hedron 2006, 62, 7567; c) Y.
despite the use of chloride in a nonpolar solvent—since an
Nakao, S. Oda, T. Hiyama, J. Am. Chem. Soc. 2004, 126, 13904.
[4] N. M. Brunkan, D. M. Brestensky, W. D. Jones, J. Am. Chem.
Soc. 2004, 126, 3627.
intermediate analogous to II cannot form.[16]
ꢀ
We have reported the activation of an unstrained C C
[5] S.-Y. Liou, M. E. van der Boom, D. Milstein, Chem. Commun.
1998, 687, and references therein.
[6] A. M. Dreis, C. J. Douglas, J. Am. Chem. Soc. 2009, 131, 412.
[7] J. W. Suggs, C.-H. Jun, J. Chem. Soc. Chem. Commun. 1985, 92.
[8] The authors did not specify the alkenes examined, reporting,
“The exchange reaction with alkenes other than ethylene was
not efficient.” See Ref. [7].
s bond and subsequent intermolecular carboacylation of an
ꢀ
olefin that forms two new C C s bonds. According to our
knowledge, this is the first reported example of its kind. These
ꢀ
ꢀ
results provide a basis for controlling C C and C H
activation reaction pathways, which will help in the develop-
ꢀ
ment of future catalytic C C activation reactions.
[9] Compounds were characterized by H NMR, 13C NMR, and IR
1
spectroscopy, and mass spectrometry. NOE, COSY, HMQC, or
DEPT were performed when appropriate.
[10] Selected examples of ketone-directed C(sp ) H activation and
Experimental Section
2
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ꢀ
Representative procedure for carboacylation (C C activation):
alkylation: a) K. Tsuchikama, Y. Kuwata, K.-Y. Tahara, Y.
Yoshinami, T. Shibata, Org. Lett. 2007, 9, 3097; b) vinylic C H
Quinoline
5
(25.2 mg, 0.11 mmol), norbornene (10.3 mg,
ꢀ
0.11 mmol), and [Rh(cod)2]OTf (5.2 mg, 0.011 mmol) were sus-
pended in THF (0.325 mL). The reaction vessel was sealed under
N2 with a Teflon-lined screw-cap, heated to 1008C, and maintained for
24 h. The reaction was allowed to cool to room temperature and
filtered through Celite with the aid of ethyl acetate (5 mL). The
filtrate was concentrated and the resulting residue was analyzed by
1H NMR spectroscopy with 4-methoxyacetophenone as an internal
standard (50% yield from 5). Concentration and purification by
column chromatography (ethyl acetate/hexanes) provided 9 as an oil
(18.0 mg, 0.55 mmol, 50%): see the Supporting Information for
details.
example: B. M. Trost, K. Imi, I. W. Davies, J. Am. Chem. Soc.
1995, 117, 5371; c) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A.
Kamatani, M. Sonoda, N. Chatani, Nature 1993, 366, 529.
[11] a) The anti stereochemistry in 9 likely results from epimerization
after carboacylation. Related epimerization: P. Mayo, W. Tam,
Tetrahedron 2002, 58, 9527; b) 9 was prepared independently.[12]
[12] See the Supporting Information.
[13] a) K. Ruhland, A. Obenhuber, S. D. Hoffman, Organometallics
2008, 27, 3482; b) see Ref. [4]; c) J. W. Suggs, C.-H. Jun, J. Am.
Chem. Soc. 1984, 106, 3054.
[14] Recent examples of b-carbon elimination in unstrained systems:
a) R. Shintani, K. Takatsu, T. Hayashi, Org. Lett. 2008, 10, 1191;
b) M. Iwasaki, S. Hayashi, K. Hirano, H. Yorimitsu, K. Oshima,
Received: April 25, 2009
Published online: July 9, 2009
´
J. Am. Chem. Soc. 2007, 129, 4463; c) M. Tursky, D. Neꢂas, P.
Drabina, M. Sedlꢁk, M. Kotora, Organometallics 2006, 25, 901.
[15] b-Carbon elimination in norbornyl systems: a) A. Rudolph, N.
Rackelmann, M. Lautens, Angew. Chem. 2007, 119, 1507;
Angew. Chem. Int. Ed. 2007, 46, 1485; b) F. Faccini, E. Motti,
M. Catellani, J. Am. Chem. Soc. 2004, 126, 78.
[16] When 7-benzoylquinoline and norbonene were heated under
conditions A, alkylation at the quinoline 2-position was obtained
in analogy to: J. C. Lewis, R. G. Bergman, J. A. Ellman, J. Am.
Chem. Soc. 2007, 129, 5332.
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Keywords: C C activation · C H activation · chemoselectivity ·
homogeneous catalysis · rhodium
.
ꢀ
[1] Reviews on C H activation: a) H. M. L. Davies, J. R. Manning,
Nature 2008, 451, 417 – 424; b) K. Godula, D. Sames, Science
2006, 312, 67; c) F. Kakiuchi, N. Chatani, Adv. Synth. Catal. 2003,
345, 1077.
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