PdII-catalyzed mild C-H ortho arylation and intramolecular amination oriented by a phosphinamide group

Article abstract of DOI:10.1002/chem.201303056

A novel protocol for the Pd-catalyzed ortho-arylation of aryl phosphinamide with boronic acid is reported. By using phosphinamide as a new directing group, the reaction proceeds efficiently under mild conditions at 40 °C. Mechanistic studies reveal that the reaction proceeds via a Pd^II to Pd⁰ cycle. The phosphinamide group is also shown to be an effective orienting group for direct C-H amination.

Full text of DOI:10.1002/chem.201303056

DOI: 10.1002/chem.201303056
Communication
&
CÀH Functionalization
PdII-Catalyzed Mild CÀH ortho Arylation and Intramolecular
Amination Oriented by a Phosphinamide Group
Jing Guan,[a, b] Guo-Jie Wu,[c] and Fu-She Han*[a, d]
gated. Very recently, a few papers have appeared in which the
Abstract: A novel protocol for the Pd-catalyzed ortho-aryl-
Pd-[11] or Rh-catalyzed[12] olefination using phosphonic acid as
ation of aryl phosphinamide with boronic acid is reported.
a directing group is reported. In addition, the Pd-catalyzed
By using phosphinamide as a new directing group, the re-
arylation of phosphoramidate [Eq. (1)][13] or phosphate
action proceeds efficiently under mild conditions at 408C.
[Eq. (2)][14] with high-valent diaryliodonium triflates has also
Mechanistic studies reveal that the reaction proceeds via
been presented. However, the P-containing groups in these re-
a PdII to Pd0 cycle. The phosphinamide group is also
actions contained a nitrogen or oxygen atom between the aryl
shown to be an effective orienting group for direct CÀH
carbon and phosphorus atom. Consequently, these methods
amination.
cannot be used for the synthesis of aryl phosphino com-
pounds. As such, protocols for the synthesis of aryl phosphino
derivatives through the direct CÀH functionalization of the
The aryl phosphino compounds, that is, the aryl CÀP bond-
containing derivatives, are valuable structural motifs in a wide
variety of areas such as naturally occurring and designed bio-
active compounds,[1] functional materials,[2] and catalysis.[3]
Conventionally, aryl CÀP bond formation has relied mainly on
the transition-metal-catalyzed cross-coupling of aryl (pseudo)-
halides with H(O)PR2 or HPR2.[4,5] In addition, the nucleophilic
displacement of aryl metallic reagents to X(O)PR2 or XPR2 has
also been frequently used.[6]
substrates containing aryl CÀP bonds are relatively unknown
[Eq. (3)].
With the major advances in transition-metal-catalyzed direct
CÀH functionalization,[7] direct CÀH phosphorylation,[8] particu-
larly the recent success on the intermolecular phosphorylation
of azoles by Li et al.[9] and on 2-arylpyridyl derivatives by Yu
et al.,[10] have appeared to provide a promising approach for
the construction of aryl phosphino derivatives. As another ap-
pealing option for the synthesis of aryl phosphino compounds,
the direct CÀH functionalization by using the readily affordable
phosphino chemicals as substrates should be a far more effi-
cient strategy. Such a strategy takes advantage of using the
phosphino functionality as a directing group, and thereby,
avoiding the trouble of removing directing groups after func-
tionalization. However, this chemistry has been rarely investi-
On the other hand, in cross-coupling reactions, the use of
organoboron reagents takes advantage of the ready availabili-
ty, broad functional group tolerance, low toxicity, and the ease
of separating the boron-containing by-products.[15] Motivated
by our extensive experiences in transition-metal-catalyzed cou-
plings of boron reagents[16] as well as the interest in the devel-
opment of new methods for the construction of aryl CÀP
bonds,[17] we recently initiated a study aimed at achieving the
direct CÀH functionalization of aryl phosphino substrates with
boron reagents. The successful demonstration of this protocol
is presented herein through the CÀH ortho arylation of aryl
phosphinamides with boronic acids. Moreover, the detailed
mechanism is also clarified. In addition, we have also elaborat-
ed that the phosphinamide group can be an effective directing
group for the CÀH activation/CÀN bond forming reaction.
These novel results presented herein provide some new meth-
ods for the direct CÀH functionalization and the versatile syn-
thesis of aryl phosphino compounds.
[a] J. Guan, Dr. F.-S. Han
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
5625 Renmin Street, Changchun, Jilin 130022 (China)
E-mail: fshan@ciac.ac.cn
[b] J. Guan
The University of Chinese Academy of Sciences
Beijing 100864 (P. R. China)
[c] G.-J. Wu
Department of Chemistry, Northeast Normal University
Changchun, Jilin 130024 (P. R. China)
[d] Dr. F.-S. Han
State Key Laboratory of Fine Chemicals
Dalian University of Technology, Dalian, 116024, (P. R. China)
In our initial study, the arylation of several diphenyl phosphi-
no derivatives 1a–e was extensively screened by varying the
palladium catalysts, solvents, and temperature (Table 1). We
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201303056.
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Table 1. Optimization of the reaction conditions.[a]
Table 2. Arylation of 1a with various boronic acids.[a]
Entry
Oxidant (equiv)
Base (equiv)
3a/4a
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
Ag2CO3 (1.5)
Ag2O (1.5)
CsF (1.0)
CsF (1.0)
CsF (1.0)
CsF (1.0)
CsF (1.0)
K3PO4 (1.0)
K2CO3 (1.0)
KF (1.0)
1:0.74
–
–
–
–
1:1.1
–
1:1.4
1:0.7
1:0.42
77
trace[c]
19
AgOAc (3.0)
AgBF4 (3.0)
AgNO3 (3.0)
Ag2CO3 (1.5)
Ag2CO3 (1.5)
Ag2CO3 (1.5)
Ag2CO3 (1.5)
Ag2CO3 (1.5)
n.r.[d]
n.r.
77
6
61
Na2CO3 (1.0)
CsF (1.0)
63
76[e]
[a] Reaction conditions: 1a (0.25 mmol), 2a (2.0 equiv), Ag salts (x equiv),
base (1.0 equiv), 10 mol% of Pd(OAc)2, 10 mol% of BQ under nitrogen in
DMF (3 mL) at 408C for 12 h; [b] 3a and 4a were separated by column
chromatography, the yields were calculated based on 1a; [c] monitored
by TLC; [d] no reaction; [e] 50 mol% of BQ was used.
found that among the five derivatives, only phosphinamide 1a
reacted with boronic acid 2a to afford a mixture of mono- and
di-ortho arylated products 3a and 4a in 77% total yield under
the roughly optimized conditions, that is, Pd(OAc)2 (10 mol%),
1,4-benzoquinone (BQ; 10 mol%), Ag2CO3 (1.5 equiv), and CsF
(1.0 equiv) in DMF at 408C for 12 h (entry 1). These preliminary
results indicate that pentafluorophenyl-substituted phosphin-
amide group is a promising directing group for the CÀH aryla-
tion. Notably, the reaction could proceed under mild condi-
tions at 408C. Indeed, the polyfluorophenyl group has been
also well demonstrated by Yu et al.[18] to be a powerful direct-
ing group in the CÀH functionalization of aryl carboxylic
amides, that is, the ArCONHC6F4X (X=F, CN, or CF3) derivatives.
Having optimized the directing group and established the
basic conditions for the arylation, we improved the reaction
conditions (Table 1). An extensive screening of the oxidants
showed that Ag2CO3 was suitable (entries 1–5). In addition, an
evaluation of the base showed that CsF (entry 1) and K3PO4
(entry 6) were the most effective bases although KF and
Na2CO3 also afforded the product in fairly good yields (en-
tries 8 and 9). Finally, it should be mentioned that although
the selectivity for the mono- or diarylation might be improved
by tuning the amount of BQ (entry 10) or the ratio of 1a to 2a
(roughly, 56% of mono- and 64% of diarylated products could
be obtained, respectively, when the ratio of 1a to 2a was 2:1
and 1:4. Only a trace amount of di- and monoarylated prod-
ucts was detected in each case), further optimization was not
executed herein because the mono- and diarylated products
can be separated easily by flash column chromatography.
Thus, for a rapid preparation of both mono- and diarylated
products, we chose the conditions in entry 1 as the appropri-
[a] Reaction conditions: 1a (0.25 mmol), 2 (0.5 mmol), Ag2CO3 (1.5 equiv),
CsF (1.0 equiv), Pd(OAc)2 (10 mol%), BQ (10 mol%) under nitrogen in
DMF (3 mL) at 408C for 12 h; isolated yield. [b] The reaction was run at
808C.
ate conditions to examine the generality of the newly devel-
oped protocol.
We first examined the scope and limitation of this protocol
by varying the aryl boronic acids (Table 2). A range of aryl bor-
onic acids 2 reacted effectively with diphenyl phosphinamide
1a to afford a mixture of mono- and di-ortho arylated product
3 and 4 in high overall yields in which the phenyl ring of the
substituent was either unsubstituted (3b and 4b) or decorated
by electron-rich (3a, 4a, 3c–3e and 4c–4e) and electron-defi-
cient groups (3 f–3o and 4 f–4o). Interestingly, the diarylation
occurred exclusively in the same aryl ring as confirmed by
NMR analysis and a X-ray single crystal structure of 10b de-
rived from 4c (Figure 1b and Table 4). The exact origin of such
selectivity is unclear, but increased acidity of the aryl proton
due to the enlarged aromatic system after the first arylation
seems to be the most reasonable explanation. Notably, the
mild reaction conditions allowed a flexible incorporation of
various labile functionalities such as OMe, Cl, F, CF3, CO2Me,
CN, and NO2 groups into the biaryls. The Cl, F, CN, and NO2
groups, which are potential leaving groups in transition-metal-
catalyzed cross-couplings, were particularly well tolerated. The
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Table 3. Arylation of various phosphinamides with boronic acids.[a]
Table 4. Direct intramolecular CÀH amination.[a]
[a] Reaction conditions: 4 or 7 (0.25 mmol), Ag2CO3 (1.5 equiv), K2HPO4
(1.0 equiv), Pd(OAc)2 (10 mol%), BQ (10 mol%) under nitrogen in DMF
(3 mL) at 808C for 12 h; isolated yield.
fluorophenyl moieties, are anticipated to have interesting bio-
logical activities, which we are currently investigating. Com-
pounds 3, 4, 6, and 7 are thus considered to be important sub-
strates for further transformation, for example, CÀH activaton/
CÀN formation (vide infra). In addition, the phosphinamides
can be used as Brønsted acid catalysts or precursors for the
preparation of novel biaryl or triaryl phosphine ligands.
[a] Reaction conditions: 5 (0.25 mmol), 2 (0.5 mmol), Ag2CO3 (1.5 equiv),
CsF (1.0 equiv), Pd(OAc)2 (10 mol%), BQ (10 mol%) under nitrogen in
DMF (3 mL) at 408C for 12 h; isolated yield. [b] The reaction was run for
22 h. [c] The reaction was run at 808C.
Having extensively investigated the substrate scope and lim-
itation of the protocol, we shifted our attention to the mecha-
nistic studies. Treatment of 1a with 1.0 equivalent of Pd(OAc)2
produced a stable arylpalladated PdII complex 8 with the incor-
poration of one DMF molecule [Eq. (4)]. The structure of 8 was
confirmed by 1H, 13C, and 31P NMR spectroscopy, and X-ray
crystallography (Figure 1a).[20] In the single-crystal structure,
the DMF molecule was replaced by two H2O molecules, since 8
was crystallized from a mixture of acetone and H2O.
survival of these functionalities enables one to further modify
the biaryl or triaryl systems.
The reaction efficacy of a range of aryl phosphinamides (5a–
d) was also inspected (Table 3). For the diaryl phosphinamides
whose aryl ring was modified by an electron-donating Me (5a
and 5b) or an electron-withdrawing F group (5c), the arylation
proceeded smoothly with various types of boronic acids such
as the electron-rich Me- and tBu-, or the electron-deficient CF3-
substituted aryl boronic acids (6a–i, 7a–c, and 7g–i, respec-
tively). Of note, only monoarylated products 6d–f were afford-
ed for the di-ortho-methylphenyl phosphinamide 5b. The reac-
tivity of alkyl aryl phosphinamdes such as 5d was somewhat
lowered. Moderately high yields of 6j and 6k, as well as 7j
and 7k were afforded when 5d was allowed to react with the
electron-rich boronic acids. In contrast only trace amounts of
6l and 7l were observed in reactions with the electron-defi-
cient boronic acids.
Since phosphino and fluoro groups have been widely dem-
onstrated to be important functionalities in many bioactive
aryl compounds,[1,19] the synthesized polyaryl phosphinamides
3, 4, 6, and 7, whose structures feature phosphino and penta-
Figure 1. Single crystal structures of a) 8 (DMF was replaced by two H2O
molecules), and b) 10b.
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The reaction of 1.0 equivalent of PdII complex 8 with
2.0 equivalent of boronic acid 2a in the absence of Ag2CO3 af-
forded exclusively the monoarylated product 3a in excellent
isolated yield (Scheme 1A, 93%). The palladium black was ap-
Scheme 2. Proposed reaction mechanism.
starts with the aryl palladation of 1a with PdII to give a PdII
complex 8. Transmetalation of 8 with the boronic acids affords
the diaryl palladated intermediate 9. Reductive elimination of
9 under the assistance of BQ generates the product 3 and Pd0.
Oxidation of Pd0 by Ag2CO3 regenerates PdII, which brings the
reaction to the next cycle. The formation of diarylated 4
should follow the same mechanism as the formation of 3 with
the monoarylated 3 as reactants.
Scheme 1. Reaction of palladium complex 8 with boronic acid 2a.
Finally, the facile and mild direct CÀH arylation oriented by
phosphinamide groups as well as the clarification of the reac-
tion mechanism led us to investigate the phosphinamide
group directed CÀH activation/CÀN bond forming reaction be-
cause aryl CÀN formation is one of the most popular reactions
in synthetic chemistry due to the ubiquity of aryl amino com-
pounds. However, the methods for aryl amination by CÀH acti-
vation have been far less investigated compared with those for
the direct CÀH activation/CÀC bond formation.[22] Therefore,
this reaction could provide a new pathway for the straightfor-
ward functionalization of aryl phosphino derivatives through
a direct aryl CÀH amination reaction. To demonstrate the feasi-
bility of this unprecedented strategy, we first investigated the
intramolecular reaction by using several representative com-
pounds in Table 2 and Table 3 as substrates. On the basis of
the extensive experience obtained from the above CÀH aryla-
tion, we immediately found that the intramolecular amination
could proceed smoothly under conditions similar to those for
the arylation, the only differences being the CsF base was
changed to K2HPO4 and the reaction temperature was elevated
from 408C to 808C. As shown in Table 4, a range of substrates
was aminated effectively to afford the cyclic polyaryl phosphin-
amides 10a–f in high yields even though the conditions were
not carefully optimized. The structure of the products was
characterized by NMR spectroscopy and mass spectrometry.
Compound 10b was also determined by X-ray crystallography
(Figure 1b).[20] Thus, we have shown that the phosphinamide
group is also a powerful directing group for CÀH amination.
Most significantly, in some recent reports, derivatives with
a core skeleton of a six-membered cyclic phosphinamide like
compound 10 have been demonstrated to exhibit potential
utility in a wide range of areas, such as the antiinflammatory
and antiarthritic fields,[23] and optoelectronic and flam-retard-
parently precipitated out from the reaction system. In compari-
son, when a catalytic amount of 8 (10 mol%) was used to cata-
lyze the reaction of 1a and 2a in the presence of Ag2CO3
(Scheme 1B), both the monoarylated 3a and the diarylated 4a
were produced in an approximate 1:2 ratio in 77% overall
yield. These results clearly imply that the reaction proceeds via
a PdII to Pd0 cycle, wherein 8 is the catalytically active metal
species and Ag2CO3 serves as the oxidant to oxidize Pd0 to PdII,
which brings the reaction to the next cycle.
We also examined the role of BQ in the transformation. Sur-
prisingly, we found that when 1.0 equivalent of
8 and
2.0 equivalent of 2a were allowed to react in the absence of
BQ, almost no reaction was observed. Alternatively, when a cat-
alytic amount of complex 8 (10 mol%) was used to catalyze
the reaction of 1a and 2a in the presence of 1.0 equivalent of
BQ and a catalytic amount of Ag2CO3 (10 mol%), only 14% of
monoarylated 3a was obtained. These results combined with
those in Scheme 1 reveal that BQ functions neither as an oxi-
dant to oxidize Pd0 to PdII nor as a co-oxidant to oxidize Ag0 in
the reaction system. On the other hand, we have also demon-
strated that the formation of palladium complex 8 was not af-
fected by the presence or the absence of BQ [Eq. (4)]. Thus, it
appears that BQ plays its critical role in the transmetalation or
reductive elimination step. Indeed, previous reports have sug-
gested that BQ could improve the reaction through promoting
the reductive elimination in CÀH activation/CÀC bond forma-
tion reactions.[21]
On the basis of the NMR spectroscopic and X-ray single crys-
tal studies, along with a series of control experiments, we pro-
pose a reaction mechanism for this transformation. As illustrat-
ed in Scheme 2 with 1a as a model substrate, the reaction
ant applications.[24]
.
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[7] For selected recent reviews, see: a) A. J. Hickman, M. S. Sanford, Nature
2012, 484, 177; b) B.-J. Li, Z.-J. Shi, Chem. Soc. Rev. 2012, 41, 5588;
c) G. Y. Song, X. W. Li, Chem. Soc. Rev. 2012, 41, 3651; d) K. M. Engle, T.-S.
Mei, M. Wasa, J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788; e) C. S. Yeung,
V. M. Dong, Chem. Rev. 2011, 111, 1215; f) L. McMurray, F. O. Hara, M. J.
Gaunt, Chem. Soc. Rev. 2011, 40, 1885; g) T. Newhouse, P. S. Baran,
Angew. Chem. 2011, 123, 3422; Angew. Chem. Int. Ed. 2011, 50, 3362;
h) M. C. Willis, Chem. Rev. 2010, 110, 725; i) L.-M. Xu, B.-J. Li, Z. Yang, Z.-J.
Shi, Chem. Soc. Rev. 2010, 39, 712; j) C. C. C. Johansson, T. J. Colacot,
Angew. Chem. 2010, 122, 686; Angew. Chem. Int. Ed. 2010, 49, 676; k) X.
Chen, K. M. Bengle, D.-H. Wang, J.-Q. Yu, Angew. Chem. 2009, 121, 5196;
Angew. Chem. Int. Ed. 2009, 48, 5094; l) L. Ackermann, R. Vicente, A. R.
Kapdi, Angew. Chem. 2009, 121, 9976; Angew. Chem. Int. Ed. 2009, 48,
9792.
[8] For Pd-catalyzed intramolecular C–P forming reactions, see: a) Y. Kuni-
nobu, T. Yoshida, K. Takai, J. Org. Chem. 2011, 76, 7370; for reactions via
free-radical pathway, see: b) C.-B. Xiang, Y.-J. Bian, X.-R. Mao, Z.-Z.
Huang, J. Org. Chem. 2012, 77, 7706; c) H. Wang, X. Li, F. Wu, B. Wang,
Synthesis 2012, 44, 941; d) T. Kagayama, A. Nakano, S. Sakaguchi, Y. Ishii,
Org. Lett. 2006, 8, 407; e) X.-J. Mu, J.-P. Zou, Q.-F. Qian, W. Zhang, Org.
Lett. 2006, 8, 5291.
In summary, we have achieved Pd-catalyzed direct CÀH aryl-
ation and intramolecular amination using phosphinamide as
a new directing group. These novel protocols are mild,
straightforward, generally applicable, and efficient, and there-
by, open new avenues not only for the direct CÀH functionali-
zation, but also for the straightforward synthesis of valuable
biaryl phosphino compounds. Moreover, we have proposed
a clear mechanism for the transformation. The results provide
important information toward a deeper understanding of the
direct CÀH functionalization since, although CÀH functionaliza-
tion has been extensively studied, direct evidence for the reac-
tion mechanism has not really been forthcoming. As such, the
mechanism provided herein should prove useful for the design
of more efficient catalysts or for the development of new reac-
tions. Efforts towards improving the selectivity of mono- or di-
arylation reaction as well as achieving other types of direct CÀ
H functionalization using phosphinamide as directing group
are currently underway in our laboratory.
[9] C. Hou, Y. Ren, R. Lang, X. Hu, C. Xia, F. Li, Chem. Commun. 2012, 45,
5181.
[10] C.-G. Feng, M. Ye, K.-J. Xiao, S. Li, J.-Q. Yu, J. Am. Chem. Soc. 2013, 135,
9322.
[11] a) X. Meng, S. Kim, Org. Lett. 2013, 15, 1910; b) L. Y. Chan, S. Kim, T. Ryu,
P. H. Lee, Chem. Commun. 2013, 49, 4682.
[12] a) Y. Unoh, Y. Hashimoto, D. Takeda, K. Hirano, T. Satoh, M. Miura, Org.
Lett. 2013, 15, 3258; b) J. Seo, Y. Park, I. Jeon, T. Ryu, S. Park, P. H. Lee,
Org. Lett. 2013, 15, 3358.
[13] B. C. Chary, S. Kim, Y. Park, J. Kim, P. H. Lee, Org. Lett. 2013, 15, 2692.
[14] a) L. Y. Chan, L. Cheong, S. Kim, Org. Lett. 2013, 15, 2186; b) W. H. Jeon,
T. S. Lee, E. J. Kim, B. Moon, K. Kang, Tetrahedron 2013, 69, 5152.
[15] N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.
[16] For Ni-catalyzed Suzuki–Miyaura coupling, see our recent extensive
review: a) F.-S. Han, Chem. Soc. Rev. 2013, 42, 5270; for Cu-catalyzed CÀ
N or CÀC bond forming reactions, see: b) Y. Li, L.-X. Gao, F.-S. Han,
Chem. Commun. 2012, 48, 2719; c) Y. Li, L.-X. Gao, F.-S. Han, Chem. Eur.
J. 2010, 16, 7969; d) Y. Ye, Y.-H. Wang, P.-T. Liu, F.-S. Han, Chin. J. Org.
Chem. 2013, 31, 27.
Experimental Section
Details are provided in the Supporting Information.
Acknowledgements
Financial support from the “Hundred Talent Program” of CAS,
and State Key Laboratory of Fine Chemicals (KF1201) is ac-
knowledged.
Keywords: amination · arylation · CÀH functionalization ·
palladium · phosphinamide
[17] a) Y.-L. Zhao, G.-J. Wu, Y. Li, L.-X. Gao, F.-S. Han, Chem. Eur. J. 2012, 18,
9622; b) Y.-L. Zhao, G.-J. Wu, F.-S. Han, Chem. Commun. 2012, 48, 5868.
[18] For selected examples, see: a) X. Wang, D. Leow, J.-Q. Yu, J. Am. Chem.
Soc. 2011, 133, 13864; b) K. S. L. Chan, M. Wasa, X. Wang, J.-Q. Yu,
Angew. Chem. 2011, 123, 9247; Angew. Chem. Int. Ed. 2011, 50, 9081.
[19] For selected reviews on fluoro compounds in biology, see: a) M. E.
Phelps, Proc. Natl. Acad. Sci. USA 2000, 97, 9226; b) K. Mꢁller, C. Faeh, F.
Diederich, Science 2007, 317, 1881.
[20] CCDC- 941503 and CCDC-941504 contain the supplementary crystallo-
graphic data of the Pd complex and compound 10b, respectively.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[21] For selected examples, see: a) B.-F. Shi, N. Maugel, Y.-H. Zhang, J.-Q. Yu,
Angew. Chem. 2008, 120, 4960; Angew. Chem. Int. Ed. 2008, 47, 4882;
b) M. S. Chen, N. Prabagaran, N. A. Labenz, M. C. White, J. Am. Chem.
Soc. 2005, 127, 6970.
[1] For selected examples, see: a) Q. Dang, Y. Liu, D. K. Cashion, S. R. Kasib-
hatla, T. Jiang, F. Taplin, J. D. Jacintho, H. Li, Z. Sun, Y. Fan, J. DaRe, F.
Tian, W. Li, T. Gibson, R. Lemus, P. D. van Poelje, S. C. Potter, M. D. Erion,
J. Med. Chem. 2011, 54, 153; b) P. Lassaux, M. Hamel, M. Gulea, H. Del-
brꢁck, P. S. Mercuri, L. Horsfall, D. Dehareng, M. Kupper, J.-M. Frꢂre, K.
Hoffmann, M. Galleni, C. Bebrone, J. Med. Chem. 2010, 53, 4862.
[2] For selected examples, see: a) T. Bock, H. Mçhwald, R. Mꢁlhaupt, Macro-
mol. Chem. Phys. 2007, 208, 1324; b) L. A. Rusch-Salazar, V. V. Sheares, J.
Polym. Sci. Part A 2003, 41, 2277; c) O. R. Evans, D. R. Manke, W. Lin,
Chem. Mater. 2002, 14, 3866; d) S. Jin, K. E. Gonsalves, Macromolecules
1998, 31, 1010.
[3] For a recent review, see: M.-N. Birkholz, Z. Freixa, P. W. N. M. van Leeu-
wen, Chem. Soc. Rev. 2009, 38, 1099.
[4] For selected reviews of Pd-catalyzed C–P formations, see: a) A. L.
Schwan, Chem. Soc. Rev. 2004, 33, 218; b) D. S. Glueck, Chem. Eur. J.
2008, 14, 7108; c) S. Greenberg, D. W. Stephan, Chem. Soc. Rev. 2008,
37, 1482.
[22] G.-W. Wang, T.-T. Yuan, D.-D. Li, Angew. Chem. 2011, 123, 1416; Angew.
Chem. Int. Ed. 2011, 50, 1380.
[5] For selected examples of Cu-catalyzed cross-couplings, see: a) D.
Gelman, L. Jiang, S. L. Buchwald, Org. Lett. 2003, 5, 2315; b) D. van All-
en, D. Venkataraman, J. Org. Chem. 2003, 68, 4590; c) S. Thielges, P. Bis-
seret, J. Eustache, Org. Lett. 2005, 7, 681; d) H. Rao, Y. Jin, H. Fu, Y. Jiang,
Y. Zhao, Chem. Eur. J. 2006, 12, 3636; e) C. Huang, X. Tang, H. Fu, Y.
Jiang, Y. Zhao, J. Org. Chem. 2006, 71, 5020.
[23] A. A. Kamel, A. Geronikaki, W. M. Abdou, Eur. J. Med. Chem. 2012, 51,
239.
[24] a) T. Hatakeyama, M. Nakamura, S. Hashimoto, PCT Int. Appl. WO
2012121398; b) Y. Yuan, J. Zhao, S. Liu, Y. Zhu, Y. Liu, CN 102775638.
[6] For a recent review, see: S. V. D. Jeught, C. V. Stevens, Chem. Rev. 2009,
109, 2672.
Received: August 2, 2013
Published online on February 23, 2014
Chem. Eur. J. 2014, 20, 3301 – 3305
www.chemeurj.org
3305
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