Rh(I)-catalyzed decarboxylative transformations of arenecarboxylic acids: Ligand- and reagent-controlled selectivity toward hydrodecarboxylation or heck-mizoroki products

Article abstract of DOI:10.1021/ol100001b

(Chemical Equetion Presentation) A Rh(I)-based catalyst system has been developed to promote three types of decarboxylative transformations of arenecarboxylic acids: (1) hydrodecarboxylation, (2) Heck-Mizoroki olefination, and (3) conjugate addition. Scopes of reactions (1) and (2) were studied, and the ligand and reagent dependence of selectivity was explored.

Full text of DOI:10.1021/ol100001b

ORGANIC
LETTERS
2010
Vol. 12, No. 5
992-995
Rh(I)-Catalyzed Decarboxylative
Transformations of Arenecarboxylic
Acids: Ligand- and Reagent-Controlled
Selectivity toward Hydrodecarboxylation
or Heck-Mizoroki Products
Zhong-Ming Sun, Jing Zhang, and Pinjing Zhao*
Department of Chemistry and Molecular Biology, North Dakota State UniVersity,
Fargo, North Dakota 58105-6050
pinjing.zhao@ndsu.edu
Received January 1, 2010
ABSTRACT
A Rh(I)-based catalyst system has been developed to promote three types of decarboxylative transformations of arenecarboxylic acids: (1)
hydrodecarboxylation, (2) Heck-Mizoroki olefination, and (3) conjugate addition. Scopes of reactions (1) and (2) were studied, and the ligand
and reagent dependence of selectivity was explored.
Late transition-metal-catalyzed decarboxylative transforma-
tions of arenecarboxylic acids have generated much interest
in the past few years.1 Advancements in this area would
allow arenecarboxylic acids to be used as readily available
and easy-to-handle building blocks in homogeneous catalysis.
In a typical decarboxylation process, a transition metal aryl
intermediate is generated by the release of CO2.2 Pioneering
work by the Myers group has resulted in the discovery of
Pd-catalyzed decarboxylative Heck-Mizoroki reactions,3
which has inspired the expansion of this decarboxylation
strategy for various catalytic reactions.4-6 For example,
Gooꢀen and co-workers have developed Pd- and Cu-
catalyzed decarboxylative cross-couplings for biaryl synthe-
sis.4 Related decarboxylative cross-couplings have been
reported by several other groups.5 Other important examples
include Pd-, Cu-, and Ag-catalyzed hydrodecarboxylations6
and Rh- and Ir-catalyzed decarboxylative alkyne arylations.7
From the mechanistic viewpoint, these decarboxylative
(3) (a) Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc.
2002, 124, 11250. (b) Tanaka, D.; Romeril, S. P.; Myers, A. G. J. Am.
Chem. Soc. 2005, 127, 10323. (c) Tanaka, D.; Myers, A. G. Org. Lett. 2004,
6, 433. (d) Maehara, A.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008,
10, 1159. (e) Hu, P.; Kan, J.; Su, W.; Hong, M. Org. Lett. 2009, 11, 2341.
(f) Li, Z.; Zhang, S.-L.; Fu, Y.; Shang, R.; Guo, Q.-X.; Liu, L. J. Am. Chem.
Soc. 2009, 131, 8815.
(4) (a) Gooꢀen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662.
(b) Gooꢀen, L. J.; Rodr´ıguez, N.; Melzer, B.; Linder, C.; Deng, G.; Levy,
L. M. J. Am. Chem. Soc. 2007, 129, 4824. (c) Gooꢀen, L. J.; Melzer, B. J.
Org. Chem. 2007, 72, 7473. (d) Gooꢀen, L. J.; Zimmermann, B.; Knauber,
T. Angew. Chem., Int. Ed. 2008, 47, 7103. (e) Gooꢀen, L. J.; Rodr´ıguez,
N.; Lange, P. P.; Linder, C. Angew. Chem., Int. Ed. 2010, DOI: 10.1002/
anie.200905953.
(1) Gooꢀen, L. J.; Rodriguez, N.; Gooꢀen, K. Angew. Chem., Int. Ed.
2008, 47, 3100.
(2) Selected early reports on metal-mediated decarboxylation: (a) (Cu):
Nilsson, M. Acta Chem. Scand. 1966, 20, 423. (b) (Ni): Cookson, P. G.;
Deacon, G. B. J. Organomet. Chem. 1971, 33, C38. (c) (Rh): Deacon, G. B.;
Faulks, S. J.; Miller, J. M. Transition Met. Chem. 1980, 5, 305.
10.1021/ol100001b  2010 American Chemical Society
Published on Web 02/02/2010

transformations of arenecarboxylic acids are also related to
the recent studies on Cu- and Fe-catalyzed decarboxylative
cross-couplings of R-amino acids reported by Li and co-
workers.8
hydride E.3,12 Among possible reactions of E, migratory
insertion with the excess olefin 3 forms another Rh(I) enolate
F. Subsequent hydrolysis of F releases a hydrogenation
byproduct 6 and regenerates A, completing the third catalytic
cycle (decarboxylatiVe Heck-Mizoroki olefination).
Despite the abundance in recent literature on catalytic
decarboxylative reactions, there remains plenty of room for
improvement. Some of the common challenges for existing
methods include limited substrate scopes, relatively harsh
reaction conditions (e.g., reaction temperatures of 150 °C
and above), high catalyst loadings, and the requirement of a
stoichiometric amount of heavy metal additives. In addition,
most decarboxylation reactions were carried out in strongly
polar solvents (e.g., DMF and DMSO), and studies of ligand
effects on overall reactivity and selectivity are rare.1,3f,4e We
herein report a study on decarboxylative formation of
rhodium(I) aryl intermediates and its catalytic applications
in the selectiVe formation of hydrodecarboxylation and
Heck-Mizoroki products.
Scheme 1. Working Hypothesis for Rh(I)-Catalyzed
Decarboxylative Transformations of Arenecarboxylic Acids That
Lead to Various Products
Our previous results on Rh(I)-mediated stoichiometric
decarboxylations9 have led us to propose an overall mecha-
nistic picture involving three potential catalytic cycles sharing
common intermediates (Scheme 1): (1) Starting with a Rh(I)
hydroxo complex A, reaction with acid 1 forms a Rh(I)
carboxylato intermediate B. Subsequent release of CO2 from
B generates the key reactive intermediate of Rh(I) aryl
complex C. In an aqueous reaction media, hydrolysis of C
releases the arene product 2 and regenerates A, completing
the first catalytic cycle (hydrodecarboxylation).6 (2) Alter-
natively, intermediate C could undergo migratory insertion
with added olefin substrates, such as a R,ꢀ-unsaturated
carbonyl derivative 3, forming a new C-C bond in a Rh(I)
enolato intermediate D. Hydrolysis of D releases the
conjugate addition product 5 and regenerates A, completing
the second catalytic cycle (decarboxylatiVe conjugate addi-
tion).9-11 (3) ꢀ-Hydrogen elimination with intermediate D
would release a Heck-Mizoroki product 4 and form a Rh(I)
With our previous studies on Rh(I)-catalyzed decarboxy-
lative conjugate additions in a mixed toluene-H2O media,9
we seek to modify our catalyst system for the selective
formation of other desired products. Our efforts in catalyst
development have been guided by the following mechanistic
insights (Scheme 1): (1) the hydrodecarboxylation catalytic
cycle would become the dominant pathway in an aqueous
media and without added olefins, and the overall reactivity
likely depends on a rate-limiting decarboxylation step
(BfC). (2) Selectivity of Heck-Mizoroki vs conjugate
addition products (4:5) is determined by competitive ꢀ-H
elimination vs hydrolysis of the enolato intermediate D.11
Both steps are expected to be significantly influenced by
ligand effects,12 and lower water content should slow down
hydrolysis and favor Heck-Mizoroki product formation. (3)
The use of excess olefin substrate 3 as a sacrificial hydrogen
acceptor (EfF) provides an operationally simple alternative
(5) (a) Forgione, P.; Brochu, M.-C.; St-Onge, M.; Thesen, K. H.; Bailey,
M. D.; Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350. (b) Becht, J.-M.;
Catala, C.; Le Drian, C.; Wagner, A. Org. Lett. 2007, 9, 1781. (c)
Voutchkova, A.; Coplin, A.; Leadbeater, N. E.; Crabtree, R. H. Chem.
Commun. 2008, 6312. (d) Shang, R.; Fu, Y.; Li, J. B.; Zhang, S. L.; Guo,
Q. X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 5738. (e) Shang, R.; Fu, Y.;
Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu, L. Angew. Chem., Int. Ed. 2009, 48,
9350. (f) Cornella, J.; Lu, P.; Larrosa, I. Org. Lett. 2009, 11, 5506.
(6) (a) Dickstein, J. S.; Mulrooney, C. A.; O’Brien, E. M.; Morgan,
B. J.; Kozlowski, M. Org. Lett. 2007, 9, 2441. (b) Gooꢀen, L. J.; Thiel,
W. R.; Rodriguez, N.; Linder, C.; Melzer, B. AdV. Synth. Catal. 2007, 349,
2241. (c) Gooꢀen, L. J.; Manjolinho, F.; Khan, B. A.; Rodriguez, N. J.
Org. Chem. 2009, 74, 2620. (d) Nu´n˜ez Magro, A. A.; Eastham, G. R.; Cole-
Hamilton, D. J. Dalton Trans. 2009, 4683. (e) Gooꢀen, L. J.; Linder, C.;
Rodriguez, N.; Lange, P. P.; Fromm, A. Chem. Commun. 2009, 7173. (f)
Cornella, J.; Sanchez, C.; Banawa, D.; Larrosa, I. Chem. Commun. 2009,
7176. (g) Lu, P.; Sanchez, C.; Cornella, J.; Larrosa, I. Org. Lett. 2009, 11,
5710.
for the reported Pd-catalyzed decarboxylative Heck-Mizoroki
3a-c
reactions using Ag2CO3
dants.
or 1,4-benzoquinone3e as oxi-
We began our investigation by studying Rh(I)-catalyzed
hydrodecarboxylation of arenecarboxylic acids, and selected
results are summarized in Table 1. 2,6-Difluoro-4-methoxy-
benzoic acid (1a) was picked as a model substrate due to
the high reactivity of ortho-fluorinated benzoic acids in our
previous study on Rh(I)-catalyzed decarboxylative conjugate
additions.9 In addition, the relatively less volatile 1,3-
difluoro-5-methoxybenzene (2a) allows convenient product
characterization by GC analysis. Under the optimized condi-
tions of [(cod)Rh(OH)]2 (0.5 mol %), DPPP ligand (1.1 mol
(7) (a) Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362.
(b) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74,
3478.
(8) (a) Bi, H.-P.; Zhao, L.; Liang, Y.-M.; Li, C.-J. Angew. Chem., Int.
Ed. 2009, 48, 792. (b) Bi, H.-P.; Chen, W.-W.; Liang, Y.-M.; Li, C.-J.
Org. Lett. 2009, 11, 3246.
(9) Sun, Z.-M.; Zhao, P. Angew. Chem., Int. Ed. 2009, 48, 6726.
(10) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am.
Chem. Soc. 2002, 124, 5052
.
(11) (a) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Mart´ın-Matute,
B. J. Am. Chem. Soc. 2001, 123, 5358. (b) Zou, G.; Guo, J.; Wang, Z.;
(12) Mechanism study on ꢀ-H elimination of Pt(II) enolates: Alexanian,
Huang, W.; Tang, J. Dalton Trans. 2007, 3055
Org. Lett., Vol. 12, No. 5, 2010
.
E. J.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 15627.
993

%), NaOH additive (1.0 equiv),13 mixed solvent of
toluene-H2O (∼7:1), and 110 °C, 1a underwent smooth
hydrodecarboxylation to give a near-quantitative yield within
12 h (entry 7). It is noteworthy that in contrast to the typical
reaction media in Ag- or Pd-catalyzed protodecarboxylations6
more polar solvents such as THF, dioxane, and DMF were
detrimental to the current catalyst system (entries 15-17).
Table 2. Substrate Scope of Rh-Catalyzed
Protodecarboxylationa
Table 1. Optimization of Rh-Catalyzed Protodecarboxylationa
entry
ligandb
none
PEt3
PtBu3
temp (°C) cosolvent 2a yield (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14d
15e
16e
17e
110
110
110
110
110
110
110
110
110
110
110
110
100
80
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
toulene
THF
0
0
0
PPh3
0
DPPMethane
DIPHOS
DPPP
<3
78
99
95
0
54
57
31
41
13
68
21
<5
DPPB
DPPPentane
(rac)BINAP
BIPHEP
DPPF
DPPP
DPPP
DPPP
DPPP
DPPP
a Reaction conditions: acid 1 (0.225 mmol, 1.0 equiv); NaOH (1.0 equiv);
[(cod)Rh(µ-OH)]2/DPPP (0.005/0.011 equiv); toluene-H2O (0.8/0.15 mL).
b Isolated yields; 19F-NMR (entries 1-9) or GC yields (entries 10-15) listed
in parentheses. c Using 1.5 mol % Rh dimer and 3.3 mol % DPPP; Na2CO3
in place of NaOH; toluene-H2O (2.0 mL/200 µL). d Using 1.5 mol % Rh
dimer and 3.3 mol % DPPP; toluene-H2O (2.0 mL/200 µL). e Using 0.5
mol % Rh dimer and 1.1 mol % DPPP; THF-H2O (2.0 mL/350 µL).
110
110
110
dioxane
DMF
a Reaction conditions: 1a (0.225 mmol, 1.0 equiv), NaOH (1.0 equiv),
[(cod)Rh(µ-OH)]2 (0.005 equiv), ligand (0.031 equiv of monophosphine,
0.011 equiv of bisphosphine), toluene-H2O (1.0 mL/150 µL), 12 h.
b Ligands: DPPMethane ) bis(diphenylphosphino)-methane, DIPHOS )
1,2-bis(diphenylphosphino)ethane, DPPP ) 1,3-bis(diphenylphosphino)-
propane, DPPB ) 1,4-bis(diphenylphosphino)butane, DPPPentane ) 1,5-
bis(diphenylphosphino)pentane, BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-
binaphthyl, BIPHEP ) 2,2′-bis(diphenylphosphino)-1,1′-biphenyl, DPPF
) 1,1′-bis(diphenylphosphino)ferrocene. c GC yields. d 0.015/0.033 equiv
of [(cod)Rh(µ-OH)]2/ DPPP. e Cosolvent/H2O (1.5 mL/0.2 mL), 24 h.
corresponding perfluorobenzenes in high yields within 12 h
(entries 1-6). Replacing one of the ortho-fluorines with a
methoxy or CF3 group also led to high reactiviy (entries
7-9). In particular, satisfactory yield was achieved with
2,3,4,5-tetrafluoro-6-methoxybenzoic acid at a lower reaction
temperature of 90 °C (entry 9). Further replacing both ortho-
fluorines with methoxy or ethoxy groups reduced the
reactivity to some extent, although high yields were still
achievable with higher catalyst loadings (3% Rh) and
elongated reaction time at 120 °C (entries 10-12).14 Both
ortho-substituents appeared to be important to promote
decarboxylation reactivity.9 For example, 2-fluorobenzoic
acid reacted reluctantly at 150 °C, giving fluorobenzene in
less than 10% yield (entry 13). Benzoic acid and 2-meth-
oxybenzoic acid remained entirely unreactive under current
catalytic conditions. The high catalyst efficiency prompted
us to test other types of carboxylic acids that have been
studied in catalytic decarboxylative transformations, and the
preliminary results were quite encouraging: 2- and 4-nitro-
phenylacetic acids15 and indole-3-carboxylic acid3d under-
The hydrodecarboxylation reactivity was significantly
influenced by phosphine ligands: no reaction occurred
without any ligand or with monophosphine ligands (Table
1, entries 1-4). In comparison, reactivity increased using
bisphosphine ligands with the ligand backbone increasing
from 1- to 3-carbon, peaking with the DPPP ligand (entries
5-7). Lower reactivity was observed with bisphosphines of
4-carbon backbones (entries 8 and 10-11), while no reaction
occurred with DPPPentane, which has a 5-carbon backbone
(entry 9).
With the standard reaction conditions established, the
substrate scope was explored for Rh(I)-catalyzed hydrode-
carboxylation (Table 2). Consistent with our previous results
on decarboxylative conjugate additions,9 2,6-difluorinated
benzoic acids displayed excellent reactivities, forming the
(14) A monodeuterated product 2l-d1 was generated under analogous
conditions using D2O in place of H2O, with near-quantitative deuterium
incorporation at the expected 2-position (see Supporting Information).
(15) Pd-catalyzed decarboxylative allylation of nitrobenzene acetic esters:
Waetzig, S. R.; Tunge, J. A. J. Am. Chem. Soc. 2007, 129, 14860.
(13) See ref 9 for a discussion on the potential roles of added NaOH.
994
Org. Lett., Vol. 12, No. 5, 2010

went hydrodecarboxylation with a slightly modified protocol
in THF-H2O (entries 14-15), giving high product yields
under mild reaction conditions (90-100 °C).
reactive substrates, such as 2-cyclohexen-1-one, ethyl (E)-
2-crotonate, and styrene, were entirely unreactive.
We then turned our attention to catalytic decarboxylative
Heck-Mizoroki reactions. A model reaction between 2,6-
difluorobenzoic acid (1f) and n-butyl acrylate (3a) has been
previously investigated and reported.9 While the general
catalyst system was similar to that of hydrodecarboxylation,
both the overall yield and the selectivity were highly
dependent on the choice of phosphine ligand.16 In Scheme
2, we summarized the optimized conditions that favored the
Heck-Mizoroki product 4a over the conjugate addition
product 5a. A combined yield of 75% and 19:1 selectivity
of 4a:5a was achieved using 1.5 mol % of [(cod)Rh(OH)]2
and 3.3 mol % of the bisphosphine ligand (R,R)-DIOP.17
A
lower yield of 64% was observed when 2.0 equiv of 3a was
used instead of 3.0 equiv, although the 19:1 selectivity
remained unchanged. The role of excess olefin as a sacrificial
hydrogen acceptor was supported by the detection of butyl
propionate as a byproduct (Scheme 1, formation of 6).11
Scheme 2
.
Optimized Reaction Conditions for a Rh(I)-Catalyzed
Decarboxylative Heck-Mizoroki Reaction
Figure 1. Isolated yields and selectivity of decarboxylative
Heck-Mizoroki vs conjugate addition products under standard
conditions.
In summary, a Rh(I)-based catalyst system has been
developed for various decarboxylative transformations of
ortho-substituted arenecarboxylic acids. By exploiting sig-
nificant ligand and reagent effects on reaction pathways,
highly selective formation of hydrodecarboxylation and
Heck-Mizoroki products has been achieved with low
catalyst loadings and under mild conditions. Current efforts
are focused on further mechanistic probing to improve the
catalyst efficiency and to overcome the limitation on substrate
scopes.
Under the established standard reaction conditions, 3a was
tested with other arenecarboxylic acids for Rh(I)-catalyzed
decarboxylative Heck-Mizoroki olefination (Figure 1, prod-
ucts 4a-g). With the exception of pentafluorobenzoic acid
(product 4g), 2,6-difluorinated benzoic acids all gave the
desired olefin products in good yields and with high
selectivities over conjugate addition. 2,4,6-Trimethoxyben-
zoic acid was less reactive toward 3a, giving Heck-Mizoroki
product 4l in 54% yield together with 41% yield of the
protodecarboxylation byproduct 2k. For the scope of electron-
poor olefin substrates, ethyl- and tert-butyl acrylate reacted
with 1a to give Heck-Mizoroki products 4h and 4i in good
yields. N,N-Dimethylacrylamide and methyl vinyl ketone
showed poor reactivity (Figure 1, product 4j, 4k), while less
Acknowledgment. Financial support for this work was
provided by ND EPSCoR seed grant (EPS-0447679) and
NDSU start-up fund. We thank Zhuo (Troy) Chen and
Anthony F. X. Pillai of North Dakota State University for
experimental assistance and Dr. Yong-Hua Yang of North
Dakota State University for insightful discussions.
(16) For example, the DIPHOS, DPPP, and DPPB ligands, while being
the best ligands to promote hydrodecarboxylation (Table 1), gave good to
excellent overall yields yet very poor selectivities. In contrast, BIPHEP
and racemic BINAP ligands efficiently promoted the formation of conjugate
addition byproduct. Please see ref 9 for details.
(17) (R,R)-DIOP ) (4R,5R)-(-)-4,5-bis(diphenylphosphanylmethyl)-2,2-
dimethyl-1,3-dioxolane.
Supporting Information Available: Full experimental
details and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL100001B
Org. Lett., Vol. 12, No. 5, 2010
995