Palladium-catalyzed intramolecular reductive cross-coupling of Csp 2-Csp3 bond formation

Article abstract of DOI:10.1002/chem.201403093

A Pd-catalyzed efficient reductive cross-coupling reaction without metallic reductant to construct a Csp²-Csp³ bond has been reported. A Pd^IV complex was proposed to be a key intermediate, which subsequently went through d

Full text of DOI:10.1002/chem.201403093

DOI: 10.1002/chem.201403093
Communication
&
Catalysis
Palladium-Catalyzed Intramolecular Reductive Cross-Coupling of
Csp2ÀCsp3 Bond Formation
Hui Liu,[a, b] Jianpeng Wei,[a] Zongjun Qiao,[a] Yana Fu,[a] and Xuefeng Jiang*[a, c, d]
to be an effective protocol in the preparation of the Csp2ÀCsp2
Abstract: A Pd-catalyzed efficient reductive cross-coupling
bond as well.[7] However, these products were restricted to ho-
reaction without metallic reductant to construct a Csp2À
mocoupling ones. The research on the formation of the Csp2À
Csp3 bond has been reported. A PdIV complex was pro-
Csp3 bond by the reductive cross-coupling reaction is relatively
posed to be a key intermediate, which subsequently went
rare due to the b-hydrogen elimination in palladium chemistry.
through double oxidative addition and double reductive
Since Fu’s pioneering work on cross-couplings involving the
elimination to produce the cross-coupling products by in-
Csp3ÀX bond,[8] the reductive cross-coupling of the Csp2ÀCsp3
volving Pd0/II/IV in one transformation. The oxidative addi-
bond has provoked more attention in the last decade. Efficient
tion from PdII to PdIV was partially demonstrated to be
nickel-catalyzed reductive cross-couplings between Csp2ÀX
a radical process by self-oxidation of substrate without
and Csp3ÀX using Zn or Mn as the reductant have been report-
additional oxidants. Furthermore, the solvent was proved
ed by Weix[9a–c] and others[9d–f] (Scheme 1a). The Lautens group
to be the reductant for this transformation through XPS
reported a series of palladium-catalyzed Csp2ÀCsp3 bond for-
analysis.
Transition-metal-catalyzed cross-coupling reactions
have emerged as a tremendously powerful synthetic
tool in organic chemistry.[1] According to coupling
partners, three types of coupling were classified: tra-
ditional coupling,[2] oxidative coupling,[3] and reduc-
tive coupling (Scheme 1), in which reductive cross-
coupling was less intensively studied. The Ullmann
reaction, initially reported in 1901, is one of the most
efficient reductive cross-coupling reactions used in
constructing carbon—carbon bonds between two
aryl halides using stoichiometric copper.[4] Much
milder conditions were obtained by combining Ni0
and reductant (such as zinc) or electrochemical re-
duction regenerating the catalytically active species.[5]
Scheme 1. Reductive cross-coupling protocols in the construction of the Csp2ÀCsp3
Palladium-catalyzed reductive coupling, which was
reported by Shimizu et al. in 1993,[6] has been proved bond.
mations by means of an original strategy of PdIV formation
with the help of norbornene (Scheme 1b).[10] In connection
[a] Dr. H. Liu, J. Wei, Z. Qiao, Y. Fu, Prof. Dr. X. Jiang
Shanghai Key Laboratory of Green Chemistry
with our goal in the transition-metal-catalyzed transformations
of Csp3ÀX,[11] we demonstrate a novel palladium-catalyzed in-
tramolecular cross-coupling of Csp2ÀI and Csp3ÀX bonds
through double oxidative addition and reductive elimination
via a PdIV intermediate (Scheme 1c).
and Chemical Process, Department of Chemistry
East China Normal University, 3663 North Zhongshan Road
Shanghai 200062 (P. R. China)
E-mail: xfjiang@chem.ecnu.edu.cn
[b] Dr. H. Liu
School of Chemical Engineering
We commenced with our study by investigating N-(2-io-
doethyl)-N-(2-iodophenyl)-4-methylbenzene-sulfonamide (1aa).
The reaction was first performed in the presence of [PdCl2-
(dppf)] and Cs2CO3 at 1108C in MeCN, which generated the de-
sired product 2a in 33% yield (Table 1, entry 1). Due partially
to starting material recovery, a higher temperature was used
(entries 2 and 3). To stabilize the catalyst, 10 mol% of addition-
al ligand TFP was added, which increased the yield to 70% (en-
Shandong University of Technology, Zibo, 255049 (P. R. China)
[c] Prof. Dr. X. Jiang
Beijing National Laboratory for Molecular Sciences (BNLMS)
Peking University (P. R. China)
[d] Prof. Dr. X. Jiang
State Key Laboratory of Elemento-Organic Chemistry
Nankai University (P. R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403093.
Chem. Eur. J. 2014, 20, 1 – 7
1
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
efficiently, but also substituted 2,3-dihydrobenzofuran, tetrahy-
dropyridine, and pyrrole derivatives could also be achieved.
The results shown in Table 2 demonstrate that the protocol
has a great functional-group tolerance. Both electron-rich and
-deficient substrates in the cases could be efficiently trans-
Table 1. Optimization of reaction conditions.[a]
Entry Ligand
[mol%]
Base
Solvent Additive
[equiv]
T
t
Yield[%][b]
[8C] [h]
Table 2. Pd-catalyzed cross-coupling of Csp2ÀI and Csp3ÀX bonds.[a]
1
2
3
4
5
6
7
8
–
–
–
Cs2CO3
Cs2CO3
Cs2CO3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
PhCl
PhMe
Dioxane
DMF
DMSO
DMA
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
110 16 33
130 16 35
150 16 45
150 16 49
150 16 36
150 16 64
150 16 70
150 16 68
150 24 26
dppf[c] (5) Cs2CO3
PPh3 (10)
PCy3 (10) Cs2CO3
TFP[e] (10) Cs2CO3
Cs2CO3
[d]
TFP (20)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
TFP (10)
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
150 12
8
150 12 12
150 12 15
150 10 trace
150
6
75
DMA
DMA
150 12 35
150 12 41
K3PO4
Ag2CO3 DMA
150
150
6
6
6
6
6
6
6
6
6
trace
ND
80
88
80
81
84
68
87
KOtBu
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
LiCl (2.0) 150
LiBr (2.0) 150
LiBr (0.3) 150
LiBr (1.0) 150
LiBr (3.0) 150
LiBr (2.0) 150
LiBr (2.0) 150
[f]
Cs2CO3
Cs2CO3
[g]
[a] Reaction Conditions: 1aa (0.1 mmol), [PdCl2(dppf)] (0.01 mmol), base
(0.3 mmol), solvent (1.0 mL). [b] Isolated yields. [c] dppf=1,1’-bis(diphe-
nylphosphino)ferrocene. [d] PCy3 =tricyclohexyl-phosphine. [e] TFP=tri(2-
furyl)phosphine. [f] 2.0 equiv of Cs2CO3 was used. [g] 4.0 equiv of Cs2CO3
was used.
tries 4–7). More TFP did not give a better result (entry 8). After
screening of the solvents, N,N-dimethylacetamide displayed an
irreplaceable role for providing the reductive atmosphere (en-
tries 9–14). Cs2CO3 is also a crucial base compared to others
(entries 15 and 16). Ag2CO3, which was supposed to accelerate
this transformation by precipitating iodide anion, however,
could not promote this reaction (entry 17). When KOtBu was
used, no desired product 2a was detected (entry 18). Notably,
the yield was increased to 88% by using two equivalents of
LiBr as an additive, which might further prohibit the b-hydro-
gen elimination of the Csp3ÀX bond (entries 19–23).[12] Com-
pound 2aa was obtained in 68% yield with 22% of 1aa recov-
ered when the amount of Cs2CO3 decreased to two equivalents
(entry 24). No big improvement was achieved when more
Cs2CO3 was launched (entry 25).
[a] Reaction conditions: 1 (0.1 mmol), [PdCl2(dppf)] (0.01 mmol), TFP
(0.01 mmol), Cs2CO3 (0.3 mmol), LiBr (0.2 mmol), DMA (1.0 mL), 1508C,
6 h.
formed to the corresponding products in good to excellent
yields (2a–j). Notably, the sulfur-containing substrate 1e pro-
ceeds well in this system without poisoning the catalyst Pd.
Fluoro-, chloro-, and bromo-substituted substrates 1k, 1l, and
1m could survive in these conditions, leading to 2k (94%), 2l
(93%), and 2m (58%), respectively. Multisubstituted product 5-
fluoro-4-methyl-1-tosylindoline 2n could be obtained in 85%
yield. Substrates with different protecting groups on the nitro-
gen, such as N-(4-nitrobenzene-1-sulfonyl), COOEt, and Bn,
could offer the corresponding products in good yields as well
(2o–q). The oxygen-tethered substrate 1r provided 7-nitro-2,3-
dihydrobenzofuran in 76% yield.
Indolines are highly valuable building blocks for medicinal
chemistry and organic synthesis. Some elegant strategies have
been developed in the past, such as through the reduction of
indoles,[13a] CÀH bond activation,[13b,c] and cross-couplings.[13d,e]
The difficulties in the synthesis of substrates limits the applica-
tion of these strategies. However, the substrates in this novel
protocol could be obtained from substituted aniline efficiently.
Moreover, not only substituted indoline could be synthesized
It is noteworthy that the cross-coupling of vinyl iodide and
alkyl iodide were successfully achieved in moderate to good
yields (Scheme 2). The six-membered 1,2,3,6-tetrahydropyridine
derivate 2s could also be formed in excellent yield. The five-
membered hexahydro-1H-indole derivate 2t and hexahydrocy-
clopenta[b]pyrrole derivate 2u are both valuable cores in or-
&
&
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
2
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
intermediate 1q-B was detected, but the coupling product 2q
was formed in 79% yield after 5 h (there was no transforma-
tion under 1008C), which indicated the reductive elimination
of palladium(IV)
intermediate was a faster process than oxidative addition of
palladium(II).
The key PdIV intermediate 5, which was proposed in
Scheme 4,[10,17] was generated from intramolecular oxidative
addition of alkyl iodide to intermediate 4 according to the re-
search of Lautens[10] and Chen.[18] To investigate the mechanism
of the oxidative addition (OA) process of Csp3ÀI in this system,
the chiral substrate 1x was tested under the standard condi-
tions (Scheme 7, Eq. (1)). Substrate 1x (ee=98%) was convert-
Scheme 2. Reductive cross-coupling of vinyl iodide with Csp3ÀI.
ganic synthesis,[14] which could be achieved in mod-
erate yields by this protocol (2t and 2u).
To extend the application of reductive cross-cou-
pling in organic synthesis, two natural molecules
were examined. For example, l-phenylalanine deri-
vate 1v was converted to indoline 2v in 48% yield
(Scheme 3a). Notably, a more complex structure 1w,
based on natural product estradiol, was subjected
to standard conditions giving the corresponding
products 2w in 78% yield, which was hard to
achieve through late-stage modification strategies
(Scheme 3b).
Scheme 3. Modification of natural molecules by reductive cross-coupling.
To gain mechanistic insight into this reductive
cross-coupling, two possible pathways were taken
into consideration (Scheme 4). Though Csp2ÀI oxida-
tive addition exhibited superiority to Csp3ÀX, which
indicated that path b is a favorable route,[15] path a
which was initiated from the Csp3ÀI bond was still
a competitive route owing to the observation of
compounds 7 and 8 under the conditions listed in
Table 1, entry 8 (Scheme 4). To demonstrate this hy-
pothesis, compound 7 was subjected to the same
conditions, producing 8 in 89% yield; however, no
product 2a was observed (Scheme 5). On the other
hand, product 2a could not be converted to com-
pound 8 either, which indicated path a in Scheme 4
could be responsible for this side transformation
(Scheme 5). The above results showed the reductive
cross-coupling product 2a could not be obtained
through path a in Scheme 4.
To investigate path b in Scheme 4 initiated from
the Csp2ÀI bond,
a stoichiometric reaction of
Scheme 4. Proposed mechanism.
[Pd2(dba)3]/PPh3 with 1q was conducted under a N2
atmosphere in the absence of Cs2CO3 and LiBr
(Scheme 6). A palladium complex 1q-A was obtained
in 65% yield, which was confirmed by X-ray crystallography.
Treating the complex 1q-A with Cs2CO3 and LiBr in DMA at
1008C for 1 h gave the desired product 2q in 88% yield,
which indicated that the palladium complex 1q-A should be
a key intermediate in this transformation. According to path b
in Scheme 4, a palladium(IV) intermediate should be generat-
ed. When complex 1q-A was heated to 1008C in benzene, no
ed to 2x in 57% yield with only 5% ee remaining. This demon-
strated that the OA from PdII(1x-A) to PdIV(1x-B) might be
a radical mechanism in this process (Scheme 7, Eq. (1)). Then
the first reductive elimination of 5 led to the desired product
2a and complex [PdI2Ln] 6 through CÀC bond reductive elimi-
nation, which could produce Pd0 by the second reductive elim-
ination of [PdI2Ln] in the presence of Cs2CO3 and N,N-dimethy-
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
3
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
substrates 1y1 (X=Br, Cl) (Scheme 7, Eq. (2)) and 1y2 were con-
verted to 1y2-Br by SN2 replacement (Scheme 7, Eq. (3)), which
might be due to the difficulties of radical formation from the
Csp3ÀX (X=Br, Cl, OMs, OTs) compared to the Csp3ÀI bond.
When the substrate 1z (ee=93%) was examined, 2z was ob-
tained in 53% yield with 93% ee under the standard condi-
tions (Scheme 7, Eq. (4)), which indicated that no b-hydrogen
elimination occurred from the PdIV intermediate during this
transformation.[12]
As no additional reductant was added to this transforma-
tion, N,N-dimethylacetamide was supposed to act as a reduc-
tant to regenerate the Pd0 by sequent ligand exchange, b-hy-
drogen elimination, and reduc-
Scheme 5. Exclusion of the formation of 2a through path a (Scheme 4).
tive elimination from complex 6
(Scheme 4). The oxidative states
of the [Pd] under N,N-dimethyl-
acetamide conditions was in-
vestigated through X-ray photo-
electron spectroscopic (XPS)
techniques (Figure 1). Curve A
showed the identical binding
energy (Pd3d5/2 338.1 eV, Pd3d3/2
343.2 eV) of [PdCl2(dppf)], a char-
acteristic binding energy for the
PdII species. After [PdCl2(dppf)]
Scheme 6. Insight into path b (Scheme 4) through isolation, X-ray analysis, and transformation of the key
palladium intermediate 1q-A.[16]
was treated with N,N-dimethyl-
acetamide and Cs2CO3 in one
hour, the binding energy shifted
to Pd3d5/2 337.4 eV and Pd3d3/2 342.6 eV (62%),
which indicated that the PdII complex has been re-
duced to the Pd0 active species through N,N-dime-
thylacetamide.[20] Meanwhile, the binding energy of
the partial catalyst (38%) shifted to Pd3d5/2 336.2 eV
and Pd3d3/2 341.5 eV, which might be the palladium
black.[20c] Similar results were obtained when [PdCl2-
(dppf)] was treated with MeCN and Cs2CO3 (Pd3d5/2
337.4 eV and Pd3d3/2 342.6 eV for 67%), which dem-
onstrated the generation of the Pd0 active species
(See part V in the Supporting Information).
In conclusion, we have developed a Pd-catalyzed
efficient reductive cross-coupling reaction to con-
struct Csp2ÀCsp3 bonds without metallic reductant. A
PdIV complex was proposed to be a key intermediate,
which went through double oxidative addition and
double reductive elimination to produce the cross-
coupling products; this method utilized palladium
chemistry by involving Pd0/II/IV in one transformation.
The oxidative addition from PdII to PdIV was partially
demonstrated to be a radical process by self-oxida-
tion of substrate without additional oxidants. Fur-
thermore, the solvent was proved to be the reduc-
tant for this transformation through XPS analysis.
Meanwhile, this methodology could provide a remark-
ably straightforward means for the late-stage modifi-
cation of drugs. Synthetic applications will be reported in due
course.
Scheme 7. Investigation of the transformation from PdII to PdIV.
lacetamide (Scheme 4, path b).[19] The reaction of substrates
with chiral Csp3ÀBr, Cl, OMs, and OTs were also subjected to
the standard conditions; however, no reaction occurred for
&
&
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
4
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
Diederich, P. J. Stang), Wiley-VCH, Weinhein, 1998; c) T.-S.
Mei, L. Kou, S. Ma, K. M. Engle, J.-Q. Yu, Synthesis 2012, 44,
1778.
[2] a) P. Knochel, H. Leuser, L.-Z. Gong, S. Perrone, F. F. Kneisel,
Chem. Organozinc Comp. 2006, 287; b) G. R. Stephenson,
Polyfunctional Electrophilic Multihaptoorganometallics for Or-
ganic Synthesis, in Handbook of Functionalized Organometal-
lics: Applications in Synthesis, Vol. 2 (Ed.: P. Knochel), Wiley-
VCH, Weinheim, 2005.
[3] a) W. Shi, C. Liu, A. Lei, Chem. Soc. Rev. 2011, 40, 2761; b) C.
Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111, 1780;
c) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215; d) B.-
J. Li, Z.-J. Shi, Chem. Soc. Rev. 2012, 41, 5588.
[4] a) F. Ullmann, J. Bielecki, Ber. Dtsch. Chem. Ges. 1901, 34,
2174; b) E. Sperotto, G. P. M. van Klink, G. van Koten, J. G.
de Vries, Dalton Trans. 2010, 39, 10338; c) I. P. Beletskaya,
A. V. Cheprakov, Coord. Chem. Rev. 2004, 248, 2337; d) S. V.
Ley, A. W. Thomas, Angew. Chem. 2003, 115, 5558; Angew.
Chem. Int. Ed. 2003, 42, 5400; e) F. Monnier, M. Taillefer,
Angew. Chem. 2009, 121, 7088; Angew. Chem. Int. Ed. 2009,
48, 6954.
[5] a) M. F. Semmelhack, P. M. Helquist, L. D. Jones, J. Am. Chem.
Soc. 1971, 93, 5908; b) K. Tamao, K. Sumitani, M. Kumada, J.
Am. Chem. Soc. 1972, 94, 4374; c) M. Kumada, Pure Appl.
Chem. 1980, 52, 669; d) K. J. P. Corriu, J. P. Masse, J. Chem.
Soc. Chem. Commun. 1972, 144; e) T. D. Nelson, R. D.
Crouch, Org. React. 2004, 63, 265.
[6] N. Shimizu, T. Kitamura, K. Watanabe, T. Yamaguchi, Tetrahe-
dron Lett. 1993, 34, 3421. For earlier work, please see: W. J.
Thompson, J. Gaudino, J. Org. Chem. 1984, 49, 5237.
[7] J. Hassan, M. Sꢁvignon, C. Gozzi, E. Schulz, M. Lemaire,
Chem. Rev. 2002, 102, 1359.
[8] a) M. R. Netherton, C. Dai, K. Neuschꢂtz, G. C. Fu, J. Am.
Chem. Soc. 2001, 123, 10099; b) J. H. Kirchhoff, M. R. Nether-
ton, I. D. Hills, G. C. Fu, J. Am. Chem. Soc. 2002, 124, 13662;
c) K. Menzel, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 3718;
d) J.-Y. Lee, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 5616; e) J.
Zhou, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 12527; f) J. Zhou, G. C. Fu, J.
Am. Chem. Soc. 2004, 126, 1340; g) D. A. Powell, G. C. Fu, J. Am. Chem.
Soc. 2004, 126, 7788; h) F. O. Arp, G. C. Fu, J. Am. Chem. Soc. 2005, 127,
10482; i) F. Gonzꢃlez-Bobes, G. C. Fu, J. Am. Chem. Soc. 2006, 128, 5360;
j) B. Saito, G. C. Fu, J. Am. Chem. Soc. 2008, 130, 6694; k) S. L. Zultanski,
G. C. Fu, J. Am. Chem. Soc. 2011, 133, 15362; l) A. Wilsily, F. Tramutola,
N. A. Owston, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 5794; m) A. S.
Dudnik, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 10693; n) S. L. Zultanski,
G. C. Fu, J. Am. Chem. Soc. 2013, 135, 624.
Figure 1. X-ray photoelectron spectra of [Pd]. Conditions for A: [PdCl2(dppf)]; conditions
for B: [PdCl2(dppf)] in N,N-dimethylacetamide at 1508C for 1.0 h.
Experimental Section
General method
In a 25 mL sealed tube, the air was exchanged with N2 for three
times. Then the mixture of substrate 1 (0.1 mmol), [PdCl2(dppf)]
(0.01 mmol), TFP (0.01 mmol), Cs2CO3 (0.3 mmol), and LiBr
(0.2 mmol) was dissolved in DMA (1 mL). The system was heated
to 1508C for 6 h. When the reaction was finished, the mixture was
[9] a) D. A. Everson, R. Shrestha, D. J. Weix, J. Am. Chem. Soc. 2010, 132,
920; b) D. A. Everson, B. A. Jones, D. J. Weix, J. Am. Chem. Soc. 2012,
134, 6146; c) A. C. Wotal, D. J. Weix, Org. Lett. 2012, 14, 1476; d) X. Yu, T.
Yang, S. Wang, H. Xu, H. Gong, Org. Lett. 2011, 13, 2138; e) S. Wang, Q.
Qian, H. Gong, Org. Lett. 2012, 14, 3352; f) C.-S. Yan, Y. Peng, X.-B. Xu, Y.-
W. Wang, Chem. Eur. J. 2012, 18, 6039.
cooled to RT. and directly subjected to silica gel column chroma-
tography to give product 2.
Acknowledgements
[10] a) H. Liu, M. El-Salfiti, D. I. Chai, J. Auffret, M. Lautens, Org. Lett. 2012,
14, 3648; b) H. Liu, M. El-Salfiti, M. Lautens, Angew. Chem. 2012, 124,
9984; Angew. Chem. Int. Ed. 2012, 51, 9846; c) H. Weinstabl, M. Suharto-
no, Z. Qureshi, M. Lautens, Angew. Chem. 2013, 125, 5413; Angew.
Chem. Int. Ed. 2013, 52, 5305; d) K. M. Gericke, D. I. Chai, N. Bieler, M.
Lautens, Angew. Chem. 2009, 121, 1475; Angew. Chem. Int. Ed. 2009, 48,
1447; e) A. Rudolph, N. Rackelmann, M. Lautens, Angew. Chem. 2007,
119, 1507; Angew. Chem. Int. Ed. 2007, 46, 1485; f) B. Mariampillai, J.
Alliot, M. Li, M. Lautens, J. Am. Chem. Soc. 2007, 129, 15372.
[11] a) H. Liu, Z. Qiao, X. Jiang, Org. Biomol. Chem. 2012, 10, 7274; b) Z. Qiao,
H. Liu, X. Xiao, Y. Fu, J. Wei, Y. Li, X. Jiang, Org. Lett. 2013, 15, 2594. For
review see: c) X. Jiang, H. Liu, Z. Gu, Asian J. Org. Chem. 2012, 1, 16.
[12] Z. Zhang, X. Lu, Z. Xu, Q. Zhang, X. Han, Organometallics 2001, 20,
3724.
Financial support was provided by NSFC (21272075,
21302057), NCET (120178), DFMEC (20130076110023), Fok Ying
Tung Education Foundation (141011), “Shanghai Pujiang Pro-
gram” (12J1402500), program for Professor of Special Appoint-
ment (Eastern Scholar) at Shanghai Institutions of Higher
Learning, and program for Changjiang Scholar and Innovative
Research Team in University.
Keywords: catalysis · C–C bond formation · cross-coupling ·
Csp3ÀX bond · palladium
[13] a) S. Chandrasekhar, D. Basu, C. R. Reddy, Synthesis 2007, 1509; b) T.-S.
Mei, X. Wang, J.-Q. Yu, J. Am. Chem. Soc. 2009, 131, 10806; c) G. He, C.
Lu, Y. Zhao, W. A. Nack, G. Chen, Org. Lett. 2012, 14, 2936; d) C. E. Houl-
den, C. D. Bailey, J. G. Ford, M. R. Gagnꢁ, G. C. Lloyd-Jones, K. I. Booker-
[1] a) Metal-Catalyzed Cross Coupling Reactions, 2nd Completely Revised and
Enlarged Edition, Vol. 2 (Eds.: A. de Meijere, F. Diederich), Wiley-VCH,
Weinheim, 2004; b) Metal-Catalyzed Cross Coupling Reactions (Eds.: F.
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
ˇ
Milburn, J. Am. Chem. Soc. 2008, 130, 10066; e) R. Omar-Amrani, R.
Schneider, Y. Fort, Synthesis 2004, 2257.
[17] For PdIV reviews, please see: a) K. Muniz, Angew. Chem. 2009, 121, 9576;
Angew. Chem. Int. Ed. 2009, 48, 9412; b) P. Sehnal, R. J. K. Taylor, I. J. S.
Fairlamb, Chem. Rev. 2010, 110, 824.
[14] a) J. LabraÇa, G. Choy, X. Solans, M. Font-Bardia, G. de La Fuente, F. Vila-
domat, C. Codinaa, J. Bastida, Phytochemistry 1999, 50, 183; b) Y.-H.
Wang, Z.-K. Zhang, F.-M. Yang, Q.-Y. Sun, H.-P. He, Y.-T. Di, S.-Z. Mu, Y. Lu,
Y. Chang, Q.-T. Zheng, M. Ding, J.-H. Dong, X.-J. Hao, J. Nat. Prod. 2007,
70, 1458; c) G. Schmeda-Hirschmann, J. A. Rodriguez, J. I. Loyola, L. As-
tudillo, J. Bastida, F. Viladomat, C. Codina, Pharm. Pharmacol. Comm.
2000, 6, 309; d) D. C. Smith, P. L. Fuchs, J. Org. Chem. 1995, 60, 2692.
[15] A. Ariafard, Z. Lin, Organometallics 2006, 25, 4030.
[16] CCDC-968870 (1q-A) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[18] S.-Y. Zhang, G. He, W. A. Nack, Y. Zhao, Q. Li, G. Chen, J. Am. Chem. Soc.
2013, 135, 2124.
[19] W. Yang, C. Liu, J. Qiu, Chem. Commun. 2010, 46, 2659.
[20] For XPS data of palladium, please see: a) P. G. Tsyrul’nikov, T. N. Afona-
senko, S. V. Koshcheev, A. I. Boronin, Kinet. Catal. 2007, 48, 728; b) K. S.
Kim, A. F. Gossmann, N. Winograd, Anal. Chem. 1974, 46, 197; c) C. Qi, X.
Sun, C. Lu, J. Yang, Y. Du, H. Wu, X.-M. Zhang, J. Organomet. Chem.
2009, 694, 2912.
Received: April 14, 2014
Published online on && &&, 0000
&
&
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
COMMUNICATION
&
Catalysis
H. Liu, J. Wei, Z. Qiao, Y. Fu, X. Jiang*
&& – &&
Palladium-Catalyzed Intramolecular
Reductive Cross-Coupling of Csp2À
Csp3 Bond Formation
Radical chemistry: A palladium-cata-
lyzed reductive cross-coupling reaction
to construct Csp2ÀCsp3 bonds was de-
veloped (see scheme). Palladium (Pd0/II/
IV) was involved in one transformation,
in which the oxidative addition from
PdII to PdIV by Csp3ÀX was proved to be
a radical process. Solvent N,N-dimethy-
lacetamide (DMA) was proved to be the
reductant in this catalytic cycle by XPS
examination.
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
7
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ