Rh(I)-Catalyzed olefin hydroarylation with electron-deficient perfluoroarenes

Article abstract of DOI:10.1021/ja102575d

Assisted by a partially aqueous media, a catalyst system of [Rh(cod)(OH)]² and DPPBenzene ligand effectively promotes direct conjugate additions by perfluoroarenes. This formal C-H alkylation process represents a rare example of olefin hydroarylation with electron-deficient arenes. The catalyst system can be modified to selectively form the corresponding olefination products under anhydrous conditions.

Full text of DOI:10.1021/ja102575d

Published on Web 05/03/2010
Rh(I)-Catalyzed Olefin Hydroarylation with Electron-Deficient Perfluoroarenes
Zhong-Ming Sun, Jing Zhang, Rajith S. Manan, and Pinjing Zhao*
Department of Chemistry and Molecular Biology, North Dakota State UniVersity, Fargo, North Dakota 58102
Received March 27, 2010; E-mail: pinjing.zhao@ndsu.edu
Transition-metal-catalyzed olefin hydroarylation has become an
important strategy for alkylarene synthesis.1 These atom-economic
processes have been shown to proceed through aromatic C-H bond
activation and subsequent olefin insertion.2 Such a metal-mediated
pathway is distinct from the conventional Friedel-Crafts mecha-
nism and can promote anti-Markovnikov selectivity.1 Recent
advancements in catalytic C-H activation with or without neigh-
boring directing groups3 have led to significant progress in olefin
hydroarylation with electron-neutral or electron-rich arenes and
heteroarenes.3b,4,5 However, reports on undirected olefin hydroary-
lation with electron-deficient arenes are rare.6 Nakao and Hiyama
have recently reported Ni-catalyzed couplings of pentafluorobenzene
(1a) with 2-vinylnaphthalene or buta-1,3-dienylbenzene to afford
Markovnikov hydroarylation products.7 More recently, Yu and co-
workers reported a Pd(II)-catalyzed direct alkenylation of electron-
poor arenes that proceeds with highly unusual meta-selectivities
and indirectly generates hydroarylation products upon further
hydrogenation.8,9 Herein, we report the first example of undirected
olefin hydroarylation with electron-deficient perfluoroarenes. This
Rh(I) catalysis proceeds with good catalyst efficiency and useful
functional group tolerance. The current catalyst system is operation-
ally simple and can be easily adjusted to selectively generate
alkylation (hydroarylation) or olefination (oxidatiVe arylation)
products.
survey of reaction conditions led to an optimized catalyst system
of 1.5 mol % [(cod)Rh(OH)]2, 3.3 mol % DPPBenzene ligand,19
and a mixed solvent of 10% H2O/dioxane. Under these conditions,
a 1.4:1 mixture of 1a and 2a was heated at 120 °C for 24 h to
generate the anti-Markovnikov hydroarylation product n-butyl
3-pentafluoro-phenylpropionate (3a) in high yield and high selectiv-
ity over the oxidative arylation product 4a20 (93% combined yield,
17:1 selectivity of 3a/4a). The overall reactivity and 3a/4a
selectivity were highly dependent on the conditions of phosphine
ligand, reaction media, and the ratio of 1a/2a (see Table S1 in the
Supporting Information for details). In particular, removing water
cosolvent led to slower reactions and reversed selectivities favoring
oxidative arylation.21 Thus, selective formation of 4a could be
optimized using cis-DPPEthylene ligand,22 anhydrous dioxane
solvent, and a 1:4 ratio of 1a/2a. This direct alkenylation process
consumes excess 2a as a sacrificial hydrogen acceptor,14b,16
providing a useful alternative to a recently reported Pd-based
catalysis using excess Ag2CO3 as the oxidant.9
Table 1. Rh(I)-Catalyzed Hydroarylation with Perfluoroarenesa
We have previously reported a Rh(I)-catalyzed decarboxylative
conjugate addition with polyfluorinated benzoic acids in a partially
aqueous solvent system.10 This method provides a rare example of
catalytic conjugate addition by polyfluoroaryl nucleophiles.11,12
Prompted by this study and by the recent progress in perfluoroarene
C-H functionalization,7,9,13 we aimed to develop a Rh(I)-catalyzed
hydroarylation process with a proposed catalytic cycle as described
below (Scheme 1):14 Aromatic C-H activation of a perfluoroarene
substrate (1) generates a perfluoroarylrhodium(I) intermediate (A).
Subsequent insertion with an activated olefin substrate (2) forms a
Rh(I) enolate (B),15 which releases the desired hydroarylation
product (3) upon protonation. By including H2O in the solvent
system, hydrolysis of B can be promoted over ꢀ-H elimination to
inhibit the formation of oxidative arylation product 4.10,16 Mean-
while, a Rh(I) hydroxide (C) will be formed, which undergoes C-H
activation with 1 and completes the proposed catalytic cycle.17,18
a Conditions: 1 (0.70 mmol, 1.4 equiv), 2 (0.50 mmol, 1.0 equiv),
[(cod)Rh(OH)]2 (0.015 equiv), DPPBenzene (0.033 equiv), dioxane/H2O
(1.5/0.15 mL), 120 °C, 24 h; average isolated yields from two runs;
ratio of 3:4 in parentheses. b GC yield of dialkylation product in
parentheses; other byproducts detected in <5% yields. c 10 equiv of 1
was used in reaction. d GC yield. e Containing 2-4% byproduct 4.
Scheme 1
Under the optimized conditions for hydroarylation, 1a was
effectively coupled with various acryl esters in high yields and high
selectivities over oxidative arylation (Table 1, products 3a-f). The
relatively mild conditions and the absence of base additives allowed
selective hydroarylation for a hydroxy-functionalized acryl ester
without dehydrogenation or hydroalkoxylation (3e),23 providing a
useful handle for further transformations. Acrylamide and N,N-
dimethylacrylamide gave hydroarylation products in high selectivi-
We began our study with Rh(I)-catalyzed reactions between
pentafluorobenzene (1a) and n-butyl acrylate (2a). An extensive
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C O M M U N I C A T I O N S
ties but moderate yields (3g, 3h). In contrast, R,ꢀ-unsaturated
ketones reacted smoothly with 1a in good yields and >50:1
selectivities (3i, 3j). No reaction occurred with less reactive olefins
such as 2-cyclohexenone, styrene, or 1-hexene, and further catalyst
development is needed to address this limitation.
tandem sequence of C-H activation and competitive conjugate
addition vs Heck-Mizoroki olefination. Current efforts are focused
on mechanism studies and further catalyst development for broader
synthetic applications.
Acknowledgment. This work is dedicated to the memory of
Keith Fagnou. Financial support for this work was provided by
ND EPSCoR seed grant and NDSU startup fund.
Various perfluoroarenes in addition to 1a also reacted with 2a
to form hydroarylation products in good selectivities (Table 1,
3k-t). Lower reactivity was displayed by substrates with less fluoro
substituents (3p, 3r-t) or with electron-donating para-substituents
(3l-n). A para-aniline derivative (3n) could be generated in 40%
yield without N-protection, but the analogous para-phenol substrate
was unreactive. When multiple aromatic C-H bonds were available,
a mixture of mono- and dialkylation products was formed, with
monoalkylated arene being the major product (3p-r). The low
reactivity of 1,3,5-trifluorobenzene required a 10:1 ratio of arene/
olefin to generate the monoalkylation product in 78% yield (3s).
Notably, 1,3-difluorobenzene reacted exclusively at the 2-position,
albeit with very low reactivity (3t). These substituent effects
supported a rate-limiting arene C-H activation step, which appeared
to be assisted by ortho-F substituents and by the overall electron
deficiency of the aromatic system.24,25 A concerted C-H activation
pathway, such as internal electrophilic substitution (IES),18 is likely
involved, although other possibilities17a cannot be excluded without
further mechanistic investigation.
Supporting Information Available: Experimental procedures and
spectral data. This material is available free of charge via the Internet
at http://pubs.acs.org.
References
(1) (a) Hartwig, J. F. Organotransition Metal Chemistry; University Science
Books: 2009; pp 846-852. (b) Gunnoe, T. B.; Periana, R. A. In Handbook
of C-H Transformations; Dyker, G., Ed.; Wiley-VCH: 2005; Vol. 1, pp
180-187.
(2) (a) Oxgaard, J.; Muller, R. P.; Goddard, W. A.; Periana, R. A. J. Am. Chem.
Soc. 2004, 126, 352. (b) Lail, M.; Bell, C. M.; Conner, D.; Cundari, T. R.;
Gunnoe, T. B.; Petersen, J. L. Organometallics 2004, 23, 5007. (c) Oxgaard,
J.; Periana, R. A.; Goddard, W. A., III. J. Am. Chem. Soc. 2004, 126, 11658.
(3) (a) Lyons, T. W.; Sanford, M. S. Chem. ReV. 2010, 110, 1147. (b) Colby,
D. A.; Bergman, R. G.; Ellman, J. A. Chem. ReV. 2010, 110, 624. (c) Chen,
X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009,
48, 5094. (d) ActiVation and Functionalization of C-H Bonds; Goldman,
A. S., Goldberg, K. I., Eds; ACS Symposium Series 885; American
Chemical Society: Washington, DC, 2004.
(4) Reviews on olefin hydroarylation with the assistance of neighboring
directing groups: (a) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35,
826. (b) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731.
(5) Undirected olefin hydroarylation: (Ir) (a) Matsumoto, T.; Taube, D. J.;
Periana, R. A.; Taube, H.; Yoshida, H. J. Am. Chem. Soc. 2000, 122, 7414.
(b) Matsumoto, T.; Periana, R. A.; Taube, D. J.; Yoshida, H. J. Mol. Catal.
A 2002, 180, 1. (c) Periana, R. A.; Liu, X. Y.; Bhalla, G. Chem. Commun.
2002, 3000 (Ru). (d) Lail, M.; Arrowood, B. N.; Gunnoe, T. B. J. Am.
Chem. Soc. 2003, 125, 7506. (e) Foley, N. A.; Lail, M.; Lee, J. P.; Gunnoe,
T. B.; Cundari, T. R.; Petersen, J. L. J. Am. Chem. Soc. 2007, 129, 6765 (Pt).
(f) Karshtedt, D.; Bell, A. T.; Tilley, T. D. Organometallics 2004, 23, 4169.
(g) Luedtke, A. T.; Goldberg, K. I. Angew. Chem., Int. Ed. 2008, 47,
7694. (h) McKeown, B. A.; Foley, N. A.; Lee, J. P.; Gunnoe, T. B.
Organometallics 2008, 27, 4031 (Rh). (i) For Rh-catalyzed olefin hy-
droarylation with N-heterocycles, see ref 3b.
Table 2. Examples of Oxidative Arylation with Perfluoroarenesa
(6) For a Pt-catalyzed hydroarylation with CF3C6H5 (TON ) 2), see ref 5g.
(7) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc.
2008, 130, 16170. It should be noted that, in contrast to olefin insertion
into a metal-aryl linkage (ref 2), olefin insertion into a Ni hydride linkage
was most likely involved to promote Markovnikov selectivity. See ref 4
for more details.
(8) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 5072.
(9) Pd-catalyzed direct olefination of perfluoroarenes using Ag2CO3 as oxidant
was recently reported: Zhang, X.; Fan, S.; He, C.-Y.; Wan, X.; Min, Q.-
Q.; Yang, J.; Jiang, Z.-X. J. Am. Chem. Soc. 2010, 132, 4506.
(10) Sun, Z.-M.; Zhao, P. Angew. Chem., Int. Ed. 2009, 48, 6726.
(11) To the best of our knowledge, transition-metal-catalyzed conjugate addition
with perfluoroarylboronic acids has not been reported.
(12) Pd-catalyzed Heck-Mizoroki olefination using perfluoroarylbromides was
pioneered by Espinet and Milstein: Albeniz, A. C.; Espinet, P.; Martin-
Ruiz, B.; Milstein, D. J. Am. Chem. Soc. 2001, 123, 11504.
(13) Representative examples: (a) Lafrance, M.; Rowley, C.; Woo, T. K.; Fagnou,
K. J. Am. Chem. Soc. 2006, 128, 8754. (b) Do, H.-Q.; Daugulis, O. J. Am.
Chem. Soc. 2008, 130, 1128. (c) Wei, Y.; Zhao, H.; Kan, J.; Su, W.; Hong,
M. J. Am. Chem. Soc. 2010, 132, 2522.
a Conditions: 1 (0.50 mmol, 1.0 equiv), 2 (2.0 mmol, 4.0 equiv),
[(cod)Rh(OH)]2 (0.015 equiv), cis-DPPethylene (0.033 equiv), dioxane
(1.5 mL), 120 °C, 24 h; E-isomers only; average isolated yields from
two runs; ratio of 4:3 in parentheses.b DPPBenzene ligand (0.033 equiv)
and 6.0 equiv of 2a were used.c 14% of dialkenylation product was also
detected; total yield of other byproducts <5%.d Containing 4-8%
byproduct 3; further purification attempts were not successful.
Examples of oxidative arylation were provided in Table 2 to
evaluate its utility as a simple protocol for perfluoroarene alkeny-
lation.9 1a reacted with various acryl esters to give the desired olefin
products in good yields and good selectivities (4a-e). Several other
perfluoroarenes also reacted with 2a to selectively form the
oxidative arylation products in moderate to good yields (4f-j).
However, the reactivity and functional group tolerance were
generally lower than those for the corresponding hydroarylation,26
and DPPBenzene ligand was used in place of cis-DPPEthylene to
improve the yields with less reactive perfluorarenes (4h-j). Due
to the higher olefin/arene ratios needed for selective oxidative
arylation, dialkenylation became more competitive and could take
over as the major process (e.g., 4j, 4j′).
(14) (a) This catalytic cycle draws parallels with Rh(I)-catalyzed 1,4-addition
with phenylboronic acid in a partially aqueous media: Hayashi, T.;
Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124,
5052. (b) The oxidative arylation pathway likely consumes excess olefin
as a sacrificial hydrogen acceptor. See Scheme S1 in the Supporting
Information for more details.
(15) Although shown as C-bound here, Rh enolates can adapt other coordination
modes, such as oxa-π-allylrhodium species as described in ref 14.
(16) Sun, Z.-M.; Zhang, J.; Zhao, P. Org. Lett. 2010, 12, 992.
(17) Stoichiometric and catalytic C-H activation by Rh(I) hydroxide: (a) Kloek,
S. M.; Heinekey, D. M.; Goldberg, K. I. Angew. Chem., Int. Ed. 2007, 46,
4736. (b) Bercaw, J. E.; Hazari, N.; Labinger, J. A. Organometallics 2009,
28, 5489.
(18) Selected mechanism studies on arene C-H activation by various transition
metal hydroxides: (a) Tenn, W. J., III.; Young, K. J. H.; Bhalla, G.; Oxgaard,
J.; Goddard, W. A., III; Periana, R. A. J. Am. Chem. Soc. 2005, 127, 14172.
(b) Feng, Y.; Lail, M.; Barakat, K. A.; Cundari, T. R.; Gunnoe, T. B.;
Petersen, J. L. J. Am. Chem. Soc. 2005, 127, 14174. (c) Cundari, T. R.;
Grimes, T. V.; Gunnoe, T. B. J. Am. Chem. Soc. 2007, 129, 13172. (d)
Bercaw, J. E.; Hazari, N.; Labinger, J. A.; Oblad, P. F. Angew. Chem., Int.
Ed. 2008, 47, 9941. (e) Meier, S. K.; Young, K. J. H.; Ess, D. H.; Tenn,
W. J., III.; Oxgaard, J.; Goddard, W. A., III; Periana, R. A. Organometallics
2009, 28, 5293.
In summary, we have developed a Rh(I)-based catalyst system
for the effective couplings between perfluoroarenes and R,ꢀ-
unsaturated carbonyl derivatives. Selective formation of hydroary-
lation and oxidative arylation products was achieved via a proposed
(19) DPPBenzene: 1,2-bis(diphenylphosphino)benzene.
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(20) 4a: (E)-n-butyl-3-pentafluorophenylacrylate. The Z isomers did not form
in detectable amounts for oxidative arylations throughout the current
study.
(21) (a) Too much water content also slowed down the reaction, presumably
due to solubility problems and inhibition of arene C-H activation which
generates H2O (Scheme 1, CfA). (b) In a D2O reaction media, mono
D-incorporation was detected at the R-position of product 3d (see
Supporting Information).
(22) cis-DPPEthylene: cis-1,2-bis(diphenylphosphino)ethylene.
(23) Farnworth, M. V.; Cross, M. J.; Louie, J. Tetrahedron Lett. 2004, 45, 7441.
(24) (a) Evans, M. E.; Burke, C. L.; Yaibuathes, S.; Clot, E.; Eisenstein, O.;
Jones, W. D. J. Am. Chem. Soc. 2009, 131, 13464. (b) Clot, E.; Megret,
C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem. Soc. 2009, 131, 7817.
(25) 1,3-Dimethoxybenzene, a common reactive substrate for Friedel-Crafts
alkylation, did not show any hydroarylation reactivity in this study.
(26) For example, the acrylate analogue of 3e could not be generated in
acceptable yields, presumably due to competitive aldehyde formation by
dehydrogenation.
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