Palladium-catalyzed C-H oxidation of isoquinoline N-oxides: Selective alkylation with dialkyl sulfoxides and halogenation with dihalo sulfoxides

Article abstract of DOI:10.1002/adsc.201101009

A novel palladium-catalyzed C-H oxidation of isoquinoline N-oxides has been developed for regioselectively synthesizing substituted isoquinolines. The method represents the first example of using dialkyl sulfoxides as the alkyl sources for the construction of 1-alkylated isoquinolines. Moreover, the regioselective halogenation of isoquinoline N-oxides is also successful using dihalo sulfoxides as the halide sources. Copyright

Full text of DOI:10.1002/adsc.201101009

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DOI: 10.1002/adsc.201101009
À
Palladium-Catalyzed C H Oxidation of Isoquinoline N-Oxides:
Selective Alkylation with Dialkyl Sulfoxides and Halogenation
with Dihalo sulfoxides
Bo Yao,a Ren-Jie Song,b Yan Liu,a Ye-Xiang Xie,b Jin-Heng Li,b,* Meng-Ke Wang,a
Ri-Yuan Tang,a,b Xing-Guo Zhang,a and Chen-Liang Denga,*
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, Peopleꢀs Republic of China
College of Chemistry and Chemical Engineering, and State Key Laboratory of Chemo/Biosensing and Chemometrics,
b
Hunan University, Changsha 410082, Peopleꢀs Republic of China
Fax : (+86)-731-8887-2531; phone: (+86)-731-8887-2531; e-mail: jhli@hnu.edu.cn or dengchenliang78@tom.com
Received: December 24, 2011; Revised: February 20, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201101009.
À
Abstract: A novel palladium-catalyzed C H oxida-
tion of isoquinoline N-oxides has been developed
for regioselectively synthesizing substituted isoqui-
nolines. The method represents the first example of
using dialkyl sulfoxides as the alkyl sources for the
construction of 1-alkylated isoquinolines. Moreover,
the regioselective halogenation of isoquinoline N-
oxides is also successful using dihalo sulfoxides as
the halide sources.
groups encountered in organic molecules. Among the
numerous direct alkylation methods for aromatic mol-
ecules,[1–6] the most well-known is the Friedel–Crafts
alkylation.[1] However, the associated shortcomings of
the Friedel–Crafts alkylation are noticeable, as it in-
volves unsatisfactory regioselectivity and restriction
of substrates with electron-withdrawing or electron-
donating groups, associated with unnecessary eco-
nomic wastes and environmental pollution (often re-
quiring stoichiometric catalysts, such as AlCl3 or
strong acids). Recently, alternative alkylation
À
Keywords: alkylation; C H oxidation; halogena-
tion; isoquinoline N-oxides; palladium; sulfoxides
routes[2–6] were developed including C H bond func-
À
tionalization.[2,4–6] Despite these advances, examples
for the direct introduction of alkyl groups into aro-
matic molecules through the palladium-catalyzed
À
arene C H bond activation are much less abundant
The introduction of an alkyl group into an aromatic (Scheme 1).[5,6] Yu and co-workers have firstly report-
molecule (namely alkylation) is an important method- ed the alkylation of sp C H bonds and sp C H
2
3
À
À
ology in organic synthesis and the chemical industries bonds with alkyltins or alkylboronic acids using the
because the alkyl group is one of the most common Pd(II)/CuACTHNUTRGNEUNG
(OAc)2/benzoquinone catalytic system.[5]
À
Scheme 1. Routes to the Pd-catalyzed direct alkylation of the C H bond.
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Table 1. Screening for optimal conditions.[a]
Entry
[Pd] (mol%)
[O]
Yield [%][b]
3
4
1
2
3
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
G
ZnO
Bu3N
<5
<5
36
38
trace
17
36
37
31
30
5
<5
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
ZnO/Bu3N
19
12
trace
11
<5
19
42
25
22
22
76
0
4[c]
5[d]
6
7
8
9
10
11
12
13[e]
14[e,f]
PdCl2
Pd
Pd
Pd
–
35
29
<5
0
[a]
Reaction conditions: 1a (0.3 mmol, 0.067M), DMSO (2a), [Pd] (10 mol%), PTC (2 equiv.) and base/base (1:1; 4 equiv.) at
1208C for 16 h under an air atmosphere.
Isolated yield.
O2 (1 atm).
Under an N2 atmosphere.
1a (0.3 mmol, 0.2M) in DMSO (2a).
Another product, a reduction product 5, was isolated in 51% yield.
[b]
[c]
[d]
[e]
[f]
Recently, Li and co-workers described an unprece- cal synthesis of 1-substituted isoquinolines and deriva-
À
dented palladium-catalyzed methylation of the aryl tives by Pd-catalyzed C H oxidation of isoquinoline
C H bond employing peroxides as the methyl re- N-oxides with dialkyl sulfoxides or dihalo sulfoxides.
À
source. Subsequently, they have indicated a rutheni- It is noteworthy that this work represents the first ex-
À
um-catalyzed alkylation of arene C H bonds with al- ample of using dialkyl sulfoxides as the alkyl sources
kanes.[6] Thus, the development of new routes to for the synthesis of 1-alkyl-substituted isoquinolines
[12]
À
À
direct alkylation of the C H bond using common and through Pd-catalyzed C H oxidation/alkylation.
inexpensive alkylating reagents has remained a persis- Moreover, dihalo sulfoxides can also be employed as
tent challenge.
Recently, heteroaryl N-oxides were employed as (Scheme 1).
a class of fascinating intermediates for the synthesis We began our investigations by examining the C H
the halide sources for the regioselective halogenation
À
of substituted heterocycles by introducing various functionalization of 3-phenylisoquinoline 2-oxide (1a)
functional groups into the pre-existing skeleton via with DMSO (2a) (Table 1).[13] The reaction of 3-phe-
[7–11]
À
the N-oxide-induced C H bond functionalization.
nylisoquinoline 2-oxide (1a) and DMSO (2a),
(MeCN)2Cl2, (n-Bu)4NBr and base (ZnO or Bu3N)
These studies were prompted by the recent seminal Pd
U
work of Fagnou and co-workers, who discovered the was initially carried out in DMSO at 1208C under an
2
3
À
À
Pd-catalyzed sp C H and sp C H bond functionali- air atmosphere, affording a mixture of products, in-
zations of pyridine N-oxides with aryl halides giving cluding the desired 1-methyl-3-phenylisoquinoline 2-
rise to aryl-substituted pyridine N-oxides.[7] Related oxide (3) and 1-methyl-3-phenylisoquinoline (4), in
elegant studies on the functionalization of the ortho- low yields (entries 1 and 2). We were pleased to find
À
C H bond to the nitrogen atom of N-oxides with al- that ZnO combined with Bu3N could promote the
kynes, arenes or alkenes have also been reported re- methylation reaction: the yields of 1-methylated prod-
cently by the groups of Hiyama,[8] Chang,[9] Wu[10] and ucts 3 and 4 were thus enhanced to 36% and 19%, re-
several others.[11] To the best of our knowledge, how- spectively (entry 3). Notably, oxygen is necessary for
ever, the direct alkylation and halogenation reactions the reaction (entries 3–5): only a trace amount of the
À
of these heteroaryl N-oxides through the C H oxida- products was observed under an N2 atmosphere.
tion bond are rare.[6] Here, we report a novel, practi- Screening revealed that phase-transfer catalysts
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Palladium-Catalyzed C H Oxidation of Isoquinoline N-Oxides
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Table 2. Pd-catalyzed C H oxidation/alkylation of isoquinoline N-oxides (1) with dialkyl
sulfoxides (2).[a]
[a]
Reaction conditions: 1a (0.3 mmol, 0.2M) in 2, PdCl2ACHTNUTRGNE(UNG MeCN)2 (10 mol%), (n-Bu)4NOAc
(2 equiv.), ZnO (2 equiv.), and Bu3N (2 equiv.) at 1208C under an air atmosphere.
At 1408C.
[b]
(PTC) played important role in the reaction, and (n- ated well (products 6–12). Importantly, the fluoro and
Bu)4NOAc was the most effective (entries 3 and 6-9). chloro substituents can be tolerated in this reaction,
While 28% total yield of products 3 and 4 was ob- thereby facilitating additional modifications at the
tained without PTC (entry 6), the total yield was en- halogenated positions (products 6 and 7). Treatment
hanced to 73% in the presence of (n-Bu)4NOAc of an F-substituted substrate, for instance, with
(entry 9). The results demonstrated that other Pd cat- DMSO (2a), Pd
alysts, PdCl2, Pd(OAc)2 and Pd(PPh3)4, display high Bu3N afford the desired 1-methylated product 6, 7-
catalytic activity for the reaction, although they were fluoro-1-methyl-3-phenylisoquinoline, in 68% yield. A
inferior to Pd(MeCN)2Cl2 (entries 10–12). Interesting- substrate with an electron-withdrawing CF3 group was
ACHTNUGRTEN(NNUG MeCN)2Cl2, (n-Bu)4NOAc, ZnO and
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ly, the substrate concentration affected the selectivity: also suitable for the 1-methylation reaction in good
product 4 was selective furnished in 76% yield along yield (product 9). It was noted that some heterocycles
with only <5% yield of product 3 when the concen- could be introduced into this system, which also
tration of substrate 1a was enhanced from 0.067M to makes this methodology more useful for the prepara-
0.2M (entry 13). It is noteworthy that the desired tion of pharmaceuticals and natural products (prod-
products 3 and 4 cannot be observed without Pd cata- ucts 12 and 13). A moderate yield was found to be
lysts: a reduction product 5 is obtained in 51% yield still achievable from a substrate with an alkyl group
(entry 14).
on the 3-position of the isoquinoline 2-oxide under
The scope was explored for the alkylation reaction the optimal conditions (product 14). Screening dis-
under the optimal reaction conditions, and the results closed that either electron-rich or electron-deficient
are summarized in Table 2. Initially, substituents on aryl groups on the 1-position of isoquinoline 2-oxide
the isoquinoline moiety of 3-phenylisoquinolines were were perfectly compatible with the optimal condi-
investigated: a number of functional groups, including tions, providing the target methylated products (15–
F, Cl, MeO, CF3, Me and OCH2O groups, were toler- 18) in good yields. Using quinoline 1-oxide, the 2-
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Table 3. Palladium-catalyzed C H oxidation/halogenation of isoquinoline N-oxides (1)
with dihalo sulfoxides (2).[a]
[a]
Reaction conditions: 1a (0.3 mmol, 0.2M) in 2, PdCl2ACTHNUTRGNEU(NG MeCN)2 (10 mol%), (n-
Bu)4NOAc (2 equiv.), ZnO (2 equiv.), and Bu3N (2 equiv.) at 1208C under an air at-
mosphere.
methylation reaction proceeded smoothly at 1408C, noline 2-oxides, bearing either an electron-withdraw-
and the corresponding 2-methylquinoline (19) was ob- ing group or an electron-donating group on the aro-
tained in 51% yield. Subsequently, dibutyl sulfoxide matic ring, were also suitable substrates for the diha-
was tested as the n-butyl source (products 20–22). In logenation reaction under the same conditions (prod-
the presence of Pd
and Bu3N, dibutyl sulfoxide underwent the reaction
with three isoquinoline 2-oxides, respectively, leading (1a) was treated with DMSO (2a) PdAHCUTNGTRENNUNG
ACHTUNGTRENNUNG
to the desired 1-butylated isoquinolines 20–22 in good Bu)4NOAc, ZnO and Bu3N at 1208C under an air at-
yields. However, pyridine 1-oxide, pyridine, quinoline mosphere for 16 h, followed by reduction with PCl3 in
and isoquinoline could not undergo the alkylation re- DMSO/toluene it afforded the target product 4 exclu-
action with DMSO under the optimal conditions.
sively in 80% yield [Eq. (4) in Scheme 2). To eluci-
As shown in Table 3, the selective halogenation of date the mechanism, some other control experiments
isoquinoline N-oxides (1) with dihalo sulfoxides (2) were carried out [Eqs. (5)–(7)]. It was found that the
were carried out smoothly in the presence of reaction
of
substrate
1a
with
(CD3)2SO,
Pd(MeCN)2Cl2, (n-Bu)4NOAc, ZnO and Bu3N. Treat- Pd(MeCN)2Cl2, (n-Bu)4NOAc, ZnO and Bu3N afford-
A
ACHTUNGTRENNUNG
ment of 3-hexylisoquinoline 2-oxide or isoquinoline 2- ed the CD3-substituted product 4-D3 in 60% yield. It
oxide with sulfurous dichloride (2c) furnished the cor- is noteworthy that the carbon peak of CD3S(O)OÀ
responding 1-chloro-substituted isoquinolines 23 and was observed in the 13C NMR spectrum [Eq. (5)].[12,14]
24 in 60% and 79% yields, respectively. Interestingly, Notably, the reaction between substrate 1a with dieth-
selective dihalogenation of 3-arylisoquinoline 2-oxides yl sulfane (2e) could not form the target product 29
took place at the 1-position of the isoquinoline 2- under the optimal conditions [Eq. (6)]: the reduction
oxide moiety and the 2-position of the 3-aryl moiety product 5 from substrate 1a was isolated in 75%
(products 25–28). 3-Phenylisoquinoline 2-oxide, for yield.[12] The results of Eq. (7) and entry 9 in Table 1
instance, successfully underwent the dihalogenation indicated that the presence of (n-Bu)4NOAc favored
reaction with sulfurous dichloride (2c) or sulfurous di- the reduction of isoquinoline 2-oxides into isoquino-
bromide (2d), PdACHTUNGTRNEUNG(MeCN)2Cl2, (n-Bu)4NOAc, ZnO lines. Notably, ZnO combined with Bu3N as a mixture
À
and Bu3N, affording the corresponding 1-chloro-3-(2- of bases could also improve the cleavage of the N O
chlorophenyl)isoquinoline (25) and 1-bromo-3-(2-bro- bonds in isoquinoline N-oxides. Thus, we deduce that
mophenyl)isoquinoline (28), respectively, in moderate there are two roles of (n-Bu)4NOAc in the reaction
to good yields. The results demonstrated that isoqui- including: (i) a phase-transfer catalyst to improve the
4
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Palladium-Catalyzed C H Oxidation of Isoquinoline N-Oxides
Scheme 2. Control experiments.
À
reaction, and (ii) a base to reduce the N O bond. It is
noted that in the absence of Pd catalysts substrate 1a
can be reduced to isoquinoline 5, not the desired
methylation products 3 and 4 (entry 14 in Table 1).
Moreover, the present reaction is not consistent with
the SEAr mechanism because electron-deficient
arenes (products 9, 18 and 22) have the same reactivi-
ty with electron-rich arenes (Table 2 and Table 3). It
is noteworthy that PdACHTNUGTRNEUG(N PPh3)4, a Pd(0) species, can
also catalyze the reaction (entry 12 in Table 1), and
oxygen plays a crucial role in this process (entries 3–5
in Table 1).
Consequently, a possible mechanism is illustrated in
Scheme 3.[2,7–12,14,15] Initially, [PdLn] coordinates with
oxygen in substrate 1a to yield intermediate A.[2,7–12]
À
The initial step makes the C H bond more reactive
À
and instantaneously triggers C H oxidation–carbopal-
lation–complexation to form intermediate B with the
aid of bases and air, in which substrate 1a may be
used as an internal oxidant[15] to improve this path-
[12]
À
way. Oxidative cleavage of the C S bond in DMSO
and methyl insertion takes place to furnish intermedi-
ate C and MeS(O)OÀ.[14] Finally, reductive elimination
of intermediate C gives rise to the formation of prod-
uct 3 and the active [PdLn] species. Product 3 is re-
duced by the [PdLn]/PTC/bases system to afford the
target product 4. For the halogenation reaction, inter-
mediate D is first generated, followed by halogena-
À
Scheme 3. Possible mechanisms.
In summary, we have described
tion and chelation assistance with the N O group of PdACHTNUGTRNENUG(MeCN)2Cl2/ACHUTNGTRNE(NUGN n-Bu)4NOAc/ZnO/Bu3N/air system
intermediate D affords intermediate E. Sequentially for the regioselective alkylation and halogenation of
a
new
the second halogenation and reductive elimination of isoquinoline N-oxide and its derivatives with sulfox-
À
intermediate E lead to 1-halo-3-(2-haloaryl)isoquino- ides. The present method proceeds using the N O
lines.
group as the directing moiety, which provides a new
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339; g) M. Bandini, A. Melloni, A. Umani-Ronchi,
Angew. Chem. 2004, 116, 560; Angew. Chem. Int. Ed.
2004, 43, 550; h) M. Bandini, E. Emer, S. Tommasi, A.
Umani-Ronchi, Eur. J. Org. Chem. 2006, 3527; i) K. A.
Jørgensen, Synthesis 2003, 1117; j) T. B. Poulsen, K. A.
Jørgensen Chem. Rev. 2008, 108, 2903; k) G. Stefanida-
kis, J. E. Gwyn, Alkylation, in: Chemical Processing
Handbook, (Ed.: J. J. McKetta), CRC Press, Boca
Raton, 1993, pp 80–138.
approach to regioselective modification of isoquino-
line N-oxides. Moreover, the mechanism was dis-
cussed according to the 13C NMR experiments and
the results presented. Applications of this C H oxida-
tion method in organic synthesis are underway.
À
Experimental Section
À
[2] For selected reviews on the C H functionalization, see:
Typical Experimental Procedure for the Palladium-
Catalyzed C H Oxidation of Isoquinoline N-Oxides
a) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002,
102, 1731; b) D. Alberico, M. E. Scott, M. Lautens,
Chem. Rev. 2007, 107, 174; c) B.-J. Li, S.-D. Yang, Z.-J.
Shi, Synlett 2008, 949; d) O. Daugulis, H.-Q. Do, D.
Shabashov, Acc. Chem. Res. 2009, 42, 1074; e) X. Chen,
K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem.
2009, 121, 5196; Angew. Chem. Int. Ed. 2009, 48, 5094;
f) L. Ackermann, R. Vicente, A. R. Kapdi, Angew.
Chem. 2009, 121, 9976; Angew. Chem. Int. Ed. 2009, 48,
9792; g) Topics in Current Chemistry, (Eds.: J.-Q. Yu,
Z. Shi), Springer-Verlag, Berlin, 2010, Vol. 292; h) K.
MuÇiz, Angew. Chem. 2009, 121, 9576; Angew. Chem.
Int. Ed. 2009, 48, 9412; i) T. W. Lyons, M. S. Sanford,
Chem. Rev. 2010, 110, 1147.
À
To a Schlenk tube were added isoquinoline N-oxide 1a
(0.3 mmol), PdCl2ACHTNUTRGNE(UGN MeCN)2 (10 mol%), (n-Bu)4NOAc
(2 equiv.), ZnO (2 equiv.), Bu3N (2 equiv.) and DMSO (2a,
1 mL). Then the tube was stirred at 1208C (oil bath temper-
ature) under the air atmosphere for the indicated time until
complete consumption of starting material as monitored by
TLC and GC-MS analysis. After the reaction was finished,
the reaction mixture was cooled to room temperature, dilut-
ed in ethyl acetate, and washed with brine. The aqueous
phase was re-extracted with ethyl acetate. The combined or-
ganic extracts were dried over Na2SO4 and concentrated in
vacuum. The residue was then purified by silica gel column
chromatography (hexane/ethyl acetate) to afford the corre-
sponding methylation product 4.
[3] For selected papers on the other alkylations, see for
cross-coupling reactions: a) Metal-Catalyzed Cross-
Coupling Reactions, 2nd edn., (Eds.: F. Diederich, A.
de Meijere), Wiley-VCH, Weinheim, 2004; b) A. C.
Frisch, M. Beller, Angew. Chem. 2005, 117, 680;
Angew. Chem. Int. Ed. 2005, 44, 674; c) M. R. Nether-
ton, G. C. Fu, Adv. Synth. Catal. 2004, 346, 1525; d) F.
Glorius, Angew. Chem. 2008, 120, 846; Angew. Chem.
Int. Ed. 2008, 47, 834; e) A. Rudolph, M. Lautens,
Angew. Chem. 2009, 121, 2694; Angew. Chem. Int. Ed.
2009, 48, 2656; for Wibaut–Arens alkylation: f) J. P.
Wibaut, J. F. Arens, Recl. Trav. Chim. Pay-Bas 1941, 60,
119; g) J. P. Wibaut, J. F. Arens, Recl. Trav. Chim. Pays-
Bas 1942, 61, 59.
1-Methyl-3-phenylisoquinoline (4):[16] Yellow liquid;
1H NMR (500 MHz, CDCl3): d=8.08–8.05 (m, 3H), 7.85 (s,
1H), 7.79 (d, J=8.0 Hz, 1H), 7.62 (t, J=7.5 Hz, 1H), 7.51
(t, J=7.5 Hz, 1H), 7.43 (t, J=7.5 Hz, 2H), 7.33 (t, J=
7.5 Hz, 1H), 3.01 (s, 3H); 13C NMR (125 MHz, CDCl3): d=
158.7, 149.7, 136.9, 130.9, 130.5, 128.8, 128.5, 127.7, 127.2,
127.0, 126.6, 125.8, 115.7, 22.3; LR-MS (EI 70 eV): m/z
(%)=219 (M+, 100), 218 (18), 217 (9), 115 (8), 69 (15); HR-
MS (ESI): m/z=220.1048, calcd. for C16H14N (M+H)+:
220.1052.
[4] For pioneering papers on Au-catalyzed direct alkyla-
À
tion of electron-rich arene C H bonds with epoxides,
Acknowledgements
see: a) Z. Shi, C. He, J. Am. Chem. Soc. 2004, 126,
5964; with alkylsulfonate esters: b) Z. Shi, C. He, J.
Am. Chem. Soc. 2004, 126, 13596.
We thank the Natural Science Foundation of China (Nos.
21102104 and 21172060) and Fundamental Research Funds
for the Central Universities (Hunan University) for financial
support. Mr Yao also thanks the Emerging Talent Program
of Zhejiang Province (No. 2011R424051).
[5] a) X. Chen, J.-J. Li, X.-S. Hao, C. E. Goodhue, J.-Q.
Yu, J. Am. Chem. Soc. 2006, 128, 78; b) X. Chen, C. E.
Goodhue, J.-Q. Yu, J. Am. Chem. Soc. 2006, 128,
12634; c) R. Giri, N. Maugel, J.-J. Li, D.-H. Wang, S. P.
Breazzano, L. B. Saunders, J.-Q. Yu, J. Am. Chem. Soc.
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[6] a) Y. Zhang, J. Feng, C.-J. Li, J. Am. Chem. Soc. 2008,
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[7] Pd/aryl halides: a) L. C. Campeau, S. Rousseaux, K.
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clerc, K. Fagnou, Angew. Chem. 2006, 118, 7945;
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[13] See Table S1 in the Supporting Information for detailed
data.
[9] Pd/alkenes or arenes: S. H. Cho, S. J. Hwang, S. Chang,
[14] The mixture was directly determined by the NMR anal-
ysis after the reaction was finished without purification
(see spectra in the Supporting Information). The
carbon peak of CD3S(O)OÀ was assigned according to
the authoritative 13C NMR spectra literature. See: a) F.
Freeman, C. N. Angeletakis, J. Am. Chem. Soc. 1983,
105, 4039; b) F. Freeman, C. N. Angeletakis, Org.
Magn. Reson. 1983, 21, 86; c) Structure Determination
of Organic Compounds, Tables of Spectral Data, 4th
edn., (Eds.: E. Pretsch, P. Bꢂhlmannn, C. Affolter),
Springer-Verlag, Berlin, Heidelberg, 2009, p 69.
[15] F. W. Patureau, F. Glorius, Angew. Chem. 2011, 123,
2021; Angew. Chem. Int. Ed. 2011, 50, 1977.
J. Am. Chem. Soc. 2008, 130, 9254.
[10] Pd/alkenes: J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J.
Am. Chem. Soc. 2009, 131, 13888.
[11] Cu/aryl halides: a) H.-Q. Do, O. Daugulis, J. Am.
Chem. Soc. 2007, 129, 12404; b) H.-Q. Do, R. M. K.
Khan, O. Daugulis, J. Am. Chem. Soc. 2008, 130, 15185;
Pd/heteroarenes: c) P. Xi, F. Yang, S. Qin, D. Zhao, J.
Lan, G. Gao, C. Hu, J. You, J. Am. Chem. Soc. 2010,
132, 1822; d) X. Gong, G. Song, H. Zhang, X. Li, Org.
Lett. 2011, 13, 1766.
[12] For selected papers on the use of DMSO as a reactant,
see: a) A. H. Fenselau, J. G. Moffatt, J. Am. Chem. Soc.
1966, 88, 1762; b) G. A. Russell, S. A. Weiner, J. Org.
Chem. 1966, 31, 248; c) R. Xu, J.-P Wang, H. Mao, Y.
Pan, J. Am. Chem. Soc. 2010, 132, 15531; d) L. Chu, X.
[16] E. V. Kuznetsov, I. V. Shcherbakova, V. I. Ushakov,
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