Rhodium-catalyzed selective C-H activation/olefination of phenol carbamates

Article abstract of DOI:10.1021/ol201140q

Rh(III)-catalyzed ortho C-H activation/olefination of phenol carbamates has been developed. High regioselectivity is observed with a range of phenol carbamates enabling efficient coupling with acrylates and styrenes. This reaction exhibits different react

Full text of DOI:10.1021/ol201140q

ORGANIC
LETTERS
2011
Vol. 13, No. 12
3235–3237
Rhodium-Catalyzed Selective CꢀH
Activation/Olefination of Phenol
Carbamates
Tian-Jun Gong,† Bin Xiao,†,‡ Zhao-Jing Liu,† Jian Wan,† Jun Xu,† Dong-Fen Luo,†
Yao Fu,† and Lei Liu*,†,‡
Department of Chemistry, Joint Laboratory of Green Synthetic Chemistry, University of
Science and Technology of China, Hefei 230026, China, and Department of Chemistry,
Tsinghua University, Beijing 100084, China
lliu@mail.tsinghua.edu.cn
Received April 29, 2011
ABSTRACT
Rh(III)-catalyzed ortho CꢀH activation/olefination of phenol carbamates has been developed. High regioselectivity is observed with a range of
phenol carbamates enabling efficient coupling with acrylates and styrenes. This reaction exhibits different reactivity as compared to the Pd-
catalyzed ortho-arylation reaction of phenol esters and provides a new approach for the synthesis of ortho-substituted phenols.
The oxidative Heck reaction, as pioneered by Fujiwara
and Moritani, represents an atom-economic strategy to
directly functionalize arenes without prior activation of the
reactants.1 Pd is the most frequently used catalyst in this
transformation, and a directing group such as an amide or
carboxylic acid is usually needed to control the regioselec-
tivity in the CꢀH activation process.2 Extending this idea
to other transition metals, several groups showed recently
that Rh can also catalyze the oxidative Heck reaction with
the assistance of several directing groups including amide,
oxime, pyridyl, ketone, and carboxyl.3ꢀ8 In comparison to
the Pd-catalyzed processes, the use of Rh hasbeen found to
† University of Science and Technology of China.
‡ Tsinghua University.
(1) Fujiwara, Y.; Moritani, I.; Matsuda, M. Tetrahedron 1968, 24,
4819.
(2) Some recent examples: (a) Wang, D.-H.; Engle, K. M.; Shi, B.-F.;
Yu, J.-Q. Science 2010, 327, 315. (b) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q.
J. Am. Chem. Soc. 2009, 131, 5072. (c) Rubia-Garcia, A.; Arrayas, R. G.;
Carretero, J. C. Angew. Chem., Int. Ed. 2009, 48, 6511. (d) Cho, S. H.;
Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130, 9254. (e) Grimster,
N. P.; Cauntlett, C.; Godfrey, C. R. A.; Gaunt, M. J. Angew. Chem., Int.
Ed. 2005, 44, 3125. (f) Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries,
A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M.
J. Am. Chem. Soc. 2002, 124, 1586. (g) Miura, M.; Tsuda, T.; Satoh, T.;
Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211.
(3) (a) Stuart, D. R.; Bertrand-Laperle, M.; Burgess, K. M. N.;
Fagnou, K. J. Am. Chem. Soc. 2008, 130, 16474. (b) Guimond, N.;
Gouliaras, C.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 6908. (c)
Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132,
9585. (d) Hyster, T. K.; Rovis, T. J. Am. Chem. Soc. 2010, 132, 10565. (e)
Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc.
2010, 132, 18326. (f) Patureau, F. W.; Glorius, F. J. Am. Chem. Soc.
2010, 132, 9982. (g) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F.
J. Am. Chem. Soc. 2011, 133, 2350. (h) Wang, F.; Song, G.; Li, X. Org.
Lett. 2010, 12, 5430. (i) Huestis, M. P.; Chan, L.; Stuart, D. R.; Fagnou,
K. Angew. Chem., Int. Ed. 2011, 50, 1338. (j) Su, Y.; Zhao, M.; Han, K.;
Song, G.; Li, X. Org. Lett. 2010, 12, 5462.
(4) (a) Guimond, N.; Fagnou, K. J. Am. Chem. Soc. 2009, 131, 12050.
(b) Fukutani, T.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. Chem.
Commun. 2009, 5141. (c) Tsai, A. S.; Brasse, M.; Bergman, R. G.;
Ellman, J. A. Org. Lett. 2011, 13, 540.
(5) (a) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem.,
Int. Ed. 2008, 47, 4019. (b) Li, L.; Brennessel, W. W.; Jones, W. D. J. Am.
Chem. Soc. 2008, 130, 12414. (c) Guan, Z.-H.; Ren, Z.-H.; Spinella,
S. M.; Yu., S.; Liang, Y.-M.; Zhang, X. J. Am. Chem. Soc. 2009, 131,
729. (d) Morimoto, K.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2010, 12, 2068. (e) Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Org.
Chem. 2009, 74, 7094.
(6) (a) Patureau, F. W.; Besset, T.; Glorius, F. Angew. Chem., Int. Ed.
2011, 50, 1064. (b) Patureau, F. W.; Besset, T.; Kuhl, N.; Glorius, F.
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r
10.1021/ol201140q
2011 American Chemical Society
Published on Web 05/23/2011

allow lower catalytic loadings, highly functional group
tolerance, and a wider range of synthetic utility.
para to the methyl substituent presumably due to steric
reasons. Change of the solvent to DMF, DMSO, and
toluene inhibited the process (entries 4ꢀ6), whereas the
reactions in THF and THP (tetrahydropyran) gave yields
of 54% and 74% (entries 7ꢀ8). Note that the use of the
AgSbF6 (4 mol %) additive is crucial (entry 9). Moreover,
without addition of [RhCp*Cl2]2 the reaction did not take
place (entry 10).
In this context, we now report that carbamate-protected
phenols can be selectively olefinated in the presence of a
Rh(III) catalyst. This study was a continuation of our
recent work on Pd-catalyzed CꢀH activation/arylꢀaryl
coupling of phenol esters.9 In related studies Bedford10a
and Dong10b also described Pd-catalyzed ortho-arylation
of phenol carbamates. However, after many tests we failed
to use the ester or carbamate as a directing group in a Pd-
catalyzed oxidative Heck reaction. Accordingly we turned
our attention to the Rh catalyst systems and fortunately
obtained some success. It is important to note that pro-
tected phenols (either in the ester or carbamate form) have
not been examined in Rh-catalyzed CꢀH activation and
functionalization reactions.11
Scheme 1. Phenol Carbamate Scopea
Table 1. Rh-Catalyzed Oxidative Heck Reactiona
additive
temp
isolated
entry
R
(4 mol %)
solvent
(°C)
yield (%)
1
Piv
None
t-AmOH
t-AmOH
t-AmOH
DMF
120
120
120
120
120
120
80
<5
10
70
<5
<5
<5
54
74
<5
0
2
Piv
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
None
3
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
4
5
DMSO
toluene
THF
6
7
8
THP
110
110
110
9
10b
THP
AgSbF6
THP
a Reaction conditions: phenol ester or carbamate (0.25 mmol), butyl
acrylate (0.50 mmol), [RhCp*Cl2]2 (1 mol %), Cu(OAc)2 (2 equiv),
solvent (1 mL), 24 h, under Ar. b Without [RhCp*Cl2]2.
Our work started with the oxidative Heck reaction of
m-cresol pivalate (Table 1). We found that the desired
transformation did not proceed efficiently under the reac-
tionconditionsdescribedintheprevious studies3ꢀ7 (entries
1ꢀ2). On the basis of the previous work10 by Bedford and
Dong we then tested m-cresol N,N-dimethyl carbamate.
We were pleased to observe that [RhCp*Cl2]2 (1 mol %)
exhibited notable catalytic activity in t-AmOH (tert-amyl
alcohol) to afford the desired product in good isolated
yield (70%) in the presence of AgSbF6 (4 mol %) and 2
equiv of Cu(OAc)2 (entry 3). This reaction is highly
regioselective leading to olefination only at the CꢀH bond
a Reaction conditions: phenol carbamate (0.25 mmol), n-butyl acry-
late (0.50 mmol), [RhCp*Cl2]2 (1 mol %), AgSbF6 (4 mol %), Cu(OAc)2
(2 equiv), THP (1 mL), 110 °C, 24 h, under Ar. bA minor product (ca.
30% yield) was also observed for which the olefination occurred at the
position ortho to OMe. cn-Butyl acrylate (1.25 mmol).
To explore the substrate scope, we examined different
types of phenol carbamates in the reaction (Scheme 1).
Electron-neutral and electron-rich phenol carbamates
were found to be favored in the reaction (1aꢀ1l), whereas
some electron-poor substrates (e.g., NO2-substituted ones)
could not be efficiently converted (data not shown). A
special electron-poor substrate was 1m. This acetyl sub-
stituted phenol carbamate could participate in the reac-
tion, but the product was bis-olefinated. This observation
is consistent with the previous finding that ketone
was also a good directing group in Rh-catalyzed CꢀH
functionalization.6a Moreover, halide functional groups
(9) Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.; Yi, J.; Liu, L.
J. Am. Chem. Soc. 2010, 132, 468.
(10) (a) Bedford, R. B.; Webster, R. L.; Mitchell, C. Org. Biomol.
Chem. 2009, 7, 4853. (b) Zhao, X.; Yeung, C. S.; Dong, V. M. J. Am.
Chem. Soc. 2010, 132, 5837.
(11) During the preparation of our manuscript, we noted a related
study on Rh(III)-catalyzed ortho CꢀH olefination of benzoic esters:
Park, S. H.; Kim, J. Y.; Chang, S. Org. Lett. 2011, 13, 2372.
3236
Org. Lett., Vol. 13, No. 12, 2011

(I, Br, Cl) were well tolerated (1e, 1f, 1j, 1l), with no Heck-
type coupling or proto-dehalogenation products being
detected. This particular feature shows one important
advantage of the Rh-catalyzed transformation in compar-
ison to many Pd-catalyzed ones, because the halogenated
products may allow further functionalization via cross-
coupling reactions.
Scheme 3. Alkene Scopea
High regioselectivity was observed for most of the
substrates favoring the CꢀH functionalization at a steri-
cally less hindered position. However, it is interesting to
note that, in the substrate 1o, the olefination occurred at
the 8-position of the coumarin ring. This observation
might be explained by the participation of the coumarin
1-oxygen in the CꢀH activation process, but at the same
time we must note that 1d was still mainly olefinated at the
position para to the methoxyl group.
Furthermore, the present reaction provides a means to
achieve 3,30-bisolefination of BINOL (1q). HPLC ana-
lysis indicated that the chirality of BINOL was main-
tained during the transformation. The reaction was also
applicable to the olefination of biologically relevant
compounds (1r). Interestingly, for a pyrrole-containing
substrate (Scheme 2), the Rh catalyst caused CꢀH
olefination on the phenyl ring (1s), whereas the Pd
catalyst caused CꢀH olefination on the pyrrole ring.
Thus, the use of Rh can lead to new selectivity in the
CꢀH functionalization.
a Reaction conditions: phenol carbamate (0.25 mmol), olefin (0.50
mmol), [RhCp*Cl2]2 (2 mol %), AgSbF6 (8 mol %), Cu(OAc)2 (2 equiv),
THP (1 mL), 24 h, 110 °C, under Ar. b80 °C.
CꢀH functionalization reaction.3e According to their
study, the mechanism of thetransformationshould involve
a cyclometalation step through the concerted metala-
tionꢀdeprotonation mechanism. This step is presumably
followed by olefin insertion and β-hydride elimination to
provide the target product. Rh(III) is reduced to Rh(I) in
the process, which is reoxidized by Cu(II) to generate the
catalytically active Rh(III) species.
Scheme 2. Selective CꢀH Activation
Scheme 4. Kinetic Isotope Effect
The scope of the reaction with respect to the alkene
reactant is shown in Scheme 3. Both substituted styrenes
and acrylates of various alcohols were smoothly incorpo-
rated to afford the corresponding products in good yields.
The halide functional groups were again tolerated (2b-2d)
showing no proto-dehalogenation or Heck-type coupling.
In addition, (methylsulfonyl)ethene (2g) and diethyl vinyl-
phosphonate (2h) could be used as the substrates. None-
theless, our current method does not allow for the coupling
of unactivated, aliphatic alkenes.4c
A significant kinetic isotope effect (kH/D = 3.1) was
observed (Scheme 4). This observation indicated that the
CꢀH bond cleavage is most likely involved in the rate-
limiting step of the transformation. Fagnou et al. reported
a similar kinetic isotope effect in a related Rh-catalyzed
In summary, we report a practical protocol for the
Rh(III)-catalyzed ortho CꢀH activation/olefination of
phenol carbamates. This reaction complements the re-
cently developed Pd-catalyzed processes for the ortho-
arylation of phenol esters and carbamates. Because sub-
stituted phenols are important organic intermediates, the
present reaction is likely to find synthetic utility.
Acknowledgment. We thank the NSFC (Nos. 20932006
and 91013007).
Supporting Information Available. Experimental de-
tails. This material is available free of charge via the
Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 12, 2011
3237