Rhodium catalyzed synthesis of isoindolinones via C-H activation of N-benzoylsulfonamides

Article abstract of DOI:10.1016/j.tet.2012.08.095

An efficient approach to a wide range of isoindolinones, including 3-monosubstituted and 3,3-disubstituted isoindolinones, from the annulation of N-benzoylsulfonamides with olefins and diazoacetate has been developed. The transformation is broadly compatible with both terminal and internal olefins. Moreover, diazoacetate is for the first time incorporated into an amide-directed C-H functionalization reaction. Specifically, the rhodium complex [{RhCl ₂Cp*}₂] enables the in situ dimerization of diazoacetate in addition to its role in catalyzing C-H functionalization/cross- coupling.

Full text of DOI:10.1016/j.tet.2012.08.095

Tetrahedron 68 (2012) 9192e9199
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Rhodium catalyzed synthesis of isoindolinones via CeH activation of
N-benzoylsulfonamides
*
Chen Zhu , John R. Falck
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9038, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2012
Received in revised form 28 August 2012
Accepted 29 August 2012
Available online 4 September 2012
An efficient approach to
a wide range of isoindolinones, including 3-monosubstituted and
3,3-disubstituted isoindolinones, from the annulation of N-benzoylsulfonamides with olefins and diaz-
oacetate has been developed. The transformation is broadly compatible with both terminal and internal
olefins. Moreover, diazoacetate is for the first time incorporated into an amide-directed CeH function-
alization reaction. Specifically, the rhodium complex [{RhCl2Cp*}2] enables the in situ dimerization of
diazoacetate in addition to its role in catalyzing CeH functionalization/cross-coupling.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
N-Benzoylsulfonamide
CeH activation
Diazoacetate
Isoindolinone
Rhodium catalysis
1. Introduction
a variety of documented conventional methods,3 isoindolinone can
be readily prepared by the means of CeH activation. Our group,4
Transition-metal catalyzed direct transformations of CeH bonds
have become a promising strategy for the construction of complex
structures due to its undeniable synthetic efficiency and atom
the Lloyd-Jones/Booker-Milburn groups,5 and the Wang group6
recently revealed palladium-catalyzed sequences of CeH olefina-
tion/annulation to generate 3-monosubstituted isoindolinones; the
Li group,7 the Glorius group,8 and the Ackermann group9 also dis-
closed a similar process but accomplished by rhodium or ruthe-
nium catalysis. Regarding the broadly structural diversity of
isoindolinones, it is clear that it will continue to remain an area of
active investigations.
economy.1 Isoindolinone represents
a significant subunit of
nitrogen-containing heterocycles well represented amongst natu-
ral products and biologically active compounds (Fig. 1).2 Apart from
Amongst many efficient catalytic systems for CeH activation,
the utility of the rhodium complex [{RhCl2Cp*}2] has been cogently
demonstrated in numerous concise syntheses of oxygen- and
nitrogen-containing heterocycles.10,11 We recently developed an
efficient rhodium-catalyzed approach to
a wide range of
3,3-disubstituted isoindolinones from the annulation of N-ben-
zoylsulfonamides with internal olefins by means of CeH olefina-
tion.12 Two intriguing facts were referred in the preliminary study:
the internal olefins were the first time systematically investigated
in the CeH olefination and a new N-substituted quaternary center
was constructed during the reaction. Based on that, herein we wish
to report a full article about rhodium-catalyzed CeH activation of
N-benzoylsulfonamides, that N-benzoylsulfonamides are annu-
lated with a variety of olefins including terminal and internal ole-
fins to generate both 3-monosubstituted and 3,3-disubstituted
isoindolinones (Scheme 1). Moreover, the one-pot synthesis of 3,3-
disubstituted isoindolinones via the coupling with diazoacetate is
also described. It is noteworthy that, besides the known effect of
Fig. 1. Representative structures containing isoindolinone.
* Corresponding author. Tel.: þ1 214 648 8835; fax: þ1 214 648 6455; e-mail
address: chen.zhu@utsouthwestern.edu (C. Zhu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.095

C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
9193
Table 1
facilitating CeH bond cleavage, a novel function of the rhodium
complex [{RhCl2Cp*}2], i.e., in situ dimerization of methyl diazo-
acetate, is demonstrated in the transformation.
Substrate scope of reaction with tert-butyl acrylatea
Entry
1
Amide
Product
Yield (%)b
88
90
87
85
80
84
1a
3a
Scheme 1. Rhodium-catalyzed synthesis of isoindolinones.
2
3
4
5
2. Results and discussion
1b
3b
2.1. Annulation with olefins
For the initial survey of reaction conditions and optimization,
tert-butyl acrylate was selected as model substrate. Subsequent
screening experiments established some reaction parameters: (a)
toluene affords a better yield than other common solvents; (b) the
reaction at 130 ꢀC ensures the full conversions within 24 h.
With the optimized conditions in hand, we applied the method
to a variety of substituted N-benzoylsulfonamides (Table 1). The
tandem process readily provided 3-monosubstituted iso-
indolinones regardless of the electronic properties of the sub-
stituents. The electron-rich methyl (1b) and methoxy groups (1c) as
well as electron-deficient fluoro (1d) and trifluoromethyl groups
(1e) all furnished their respective products in high chemical yields
(entries 2e5). Even the ortho-substituted substrate 1f could afford
the corresponding adduct 3f in good yield with prolonged reaction
time (entry 6).
1c
3c
1d
3d
1e
3e
We next investigated the range of suitable alkenes (Table 2).
When subjected to the standard reaction conditions, the terminal
olefins (conjugated ketone 2b and amide 2c) smoothly evolved the
corresponding products (entries 1e2). Subsequently, we extended
the methodology into the annulation with internal olefins that
would result in the formation of 3,3-disubstituted isoindolinones.
The olefin configuration was observed to be unimportant to the
reaction, since either fumarate 2d or maleate 2e led to the similar
results (entries 3e4). E-1,2-Diketone conjugated olefin 2f was also
a suitable substrate and gave rise to the corresponding adduct 3j in
useful yield (entry 5). The transformation displayed excellent
electronic discrimination with respect to the unsymmetric olefin 2g
so that the regioisomeric product 3k was exclusively generated
(entry 6). Cyclic olefins were also compatible with the reaction
conditions (entry 7). Coupling with maleimide 2h offered a facile
access to the spiroisoindolinone 3l.
6c
1f
3f
a
Reaction conditions: 1 (0.10 mmol), 2a (0.12 mmol), [RhCl2Cp*]2 (0.002 mmol),
and Cu(OAc)2$H2O (0.20 mmol) in toluene, 130 ꢀC for 24 h.
b
Isolated yield.
c
48 h.
first incorporation of diazoacetate into the annulation reaction of
an amide and offered another efficient approach for the synthesis of
3,3-disubstituted isoindolinones.
Encouraged by the above results, we commenced to determine
the substrate scope (Table 3). The satisfactory results were obtained
with a wide range of N-benzoylsulfonamides in spite of their
electronic or steric properties. The electron-donating 4-methyl and
4-methoxy groups furnished their respective adducts in high yields
(entries 3e4). Weak or even strong electron-deficient substitution,
such as 4-fluoro and 4-trifluoromethyl groups, consistently resul-
ted in good outcomes (entries 5e6). The chemoselective trans-
formation in the presence of aryl bromide is noteworthy, as the
bromide could incur subsequently competitive cross coupling re-
actions (entry 7). Moreover, meta-substituted substrates delivered
not only good chemical yields but also excellent regioselectivities,
so that para-positional products were predominantly obtained
(entries 8e9). Even the ortho-fluoro group was tolerated and the
2.2. Annulation with diazoacetate
As part of our contribution to the construction of isoindolinones
from N-benzoylsulfonamides,4,12,13 we envisioned that if the rho-
dacycle a formed at the stage of CeH activation encounters diaz-
oacetate 4a, the rhodiumecarbene species b might be in situ
generated followed by carbene insertion, affording 3-carboxy iso-
indolinone adduct 5, a new type of isoindolinone, which could not
be produced via benzamide-directed CeH olefination (Scheme 2).
Under the previous reaction conditions, the proposed product 5
was not detected. But, an unexpected adduct 3i was alternatively
isolated in good yield. This finding intrigued us since it involved the

9194
C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
Table 2
Substrate scope of various alkenesa
Entry
Alkene
Product
Yield (%)b
Scheme 2. Proposed reaction pathway.
1
78
rhodium complex rather than copper acetate is essential to the
transformation. The experiment, that exposure of diazoacetate to
the complex [{RhCl2Cp*}2] rapidly generated the dimerization
product (a 2.5:1 mixture of fumarate and maleate), is noteworthy
(Eq. 3), as the decomposition of diazo compounds is prompted
generally by Rh(II),14 rarely by Rh(III) species.15,16 Based on these
observations, we speculate that at the beginning of the overall
transformations, the diazoacetate is quickly converted into the
corresponding internal olefin, which is the reactive species in the
subsequent CeH olefination and annulation (Table 2, entries 3e4).
2b
3g
2
82
2c
3h
(1)
(2)
3
4
5
82
80
51
2d
3i
3i
2e
2f
3j
(3)
The KIE value (kH/kD¼1) might suggest that the CeH cleavage is
fast, thus not involved as the rate-limiting step (Scheme 3). The
postulated mechanism is depicted in Fig. 2. Two roles of the rho-
dium complex [{RhCl2Cp*}2] were involved in the transformation.
At first, the diazoacetate 4a is rapidly converted into the corre-
sponding fumarate/maleate under the rhodium catalysis. Rapid
CeH functionalization of 1 generates five-membered rhodacycle
(I), which subsequently undergoes the insertion of fumarate/mal-
6
66
73
2g
3k
7c
eate and b-H elimination to generate RheH complex (III). Then, the
2h
following reductive elimination and Michael addition are proposed
to give rise to the annulated isoindolinone product 3. Meanwhile,
the rhodium catalyst is regenerated by copper oxidation.
3l
a
Reaction conditions: 1a (0.10 mmol), 2 (0.12 mmol), [RhCl2Cp*]2 (0.004 mmol),
and Cu(OAc)2$H2O (0.20 mmol) in toluene, 130 ꢀC for 24 h.
b
Isolated yield.
48 h.
c
3. Conclusion
We have described the rhodium catalyzed synthesis of iso-
indolinones from the annulation of N-benzoylsulfonamides with
a variety of olefins. The transformation is broadly compatible with
both terminally and internally electron-deficient olefins, efficiently
producing 3-monosubstituted and 3,3-disubstituted isoindolinones.
Moreover, diazoacetate is for the first time incorporated into an
amide-directed CeH functionalization reaction. The tandem pro-
cess, that dimerization of diazoacetate followed by subsequent
CeH olefination, offers another interesting approach to
reaction readily proceeded without compromising the chemical
yield (entry 10). However, significantly increasing the steric hin-
drance on either substrate hampered the reaction. For example,
conversions were sluggish when ethyl diazoacetate 2a was
replaced with tert-butyl diazoacetate 2b (entry 2), or possessed
a crowded spatial environment around the reaction site (entry 11).
Some control experiments were carried out to elucidate the
reaction pathways. The evidence in Eqs. 1 and 2 suggested that the

C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
9195
Table 3
Substrate scope of reaction with diazoacetatea
Entry
1
Amide
Diazoacetate
Product
Yield (%)b
80
1a
4a
3i
2
3
4
1a
<10
4b
3m
4a
81
75
1b
3n
4a
4a
1c
3o
5
82
1d
3p
6
7
4a
4a
74
66
76
1e
3q
1g
3r
8c,d
4a
4a
1h
3s
9c,e
70
(continued on next page)
1i
3t

9196
C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
Table 3 (continued )
Entry
Amide
Diazoacetate
Product
Yield (%)b
10c
4a
4a
78
1f
3u
11c
45
3v
1j
a
Reaction conditions: 1 (0.10 mmol), 4 (0.30 mmol), [RhCl2Cp*]2 (0.002 mmol), and Cu(OAc)2$H2O (0.20 mmol) in toluene, 130 ꢀC for 24 h.
Isolated yield.
48 h.
b
c
d
e
Regioisomeric ratio:
b/a>19:1.
Regioisomeric ratio: para/ortho¼15:1.
without further purification. Flash chromatography (FC) was per-
formed using E. Merck silica gel 60 (240e400 mesh). Thin layer
chromatography (TLC) was performed using pre-coated plates
purchased from E. Merck (silica gel 60 PF254, 0.25 mm). NMR
spectra were recorded in CDCl3, unless otherwise stated, on spec-
trometers at operating frequencies of 400/500 MHz (1H) or 100/
125 MHz (13C) as indicated in the individual spectrum.
4.1.1. Typical procedure for annulation of N-benzoylsulfonamide with
olefins. N-Benzoylsulfonamide 1a (27.5 mg, 0.1 mmol), [RhCl2Cp*]2
(1.2 mg, 0.002 mmol), and Cu(OAc)2$H2O (40.0 mg, 0.20 mmol)
were loaded in a dry vial, which was subjected to evacuation/
flushing with dry argon three times. Anhydrous toluene (1.0 mL)
Scheme 3. KIE experiment.
solution of tert-butyl acrylate 2a (17.4 mL, 0.12 mmol) was syringed
into the mixture, which was then stirred at 130 ꢀC for 24 h or until
the starting material had been consumed as determined by TLC.
Upon cooling to room temperature, all volatiles were evaporated
and the residue was purified by preparative TLC (ethyl acetate/
hexane 1:2) to give isoindolinone 3a in 88% yield.
4.1.2. Typical procedure for annulation of N-benzoylsulfonamide with
ethyl diazoacetate. N-Benzoylsulfonamide 1a (27.5 mg, 0.1 mmol),
[RhCl2Cp*]2 (1.2 mg, 0.002 mmol), and Cu(OAc)2$H2O (40.0 mg,
0.20 mmol) were loaded in a dry vial, which was subjected to
evacuation/flushing with dry argon three times. An anhydrous tol-
uene (1.0 mL) solution of ethyl diazoacetate 4a (30 mL, 0.30 mmol)
was syringed into the mixture, which was then stirred at 130 ꢀC for
24 h or until the starting material had been consumed as determined
by TLC. Upon cooling to room temperature, all volatiles were evap-
orated and the residue was purified by preparative TLC (ethyl ace-
tate/hexane¼1:2) to give isoindolinone 3i in 80% yield.
Fig. 2. Plausible mechanism.
4.1.3. 3-tert-Butoxycarbonylmethyl-2-tosylisoindolin-1-one (3a). 1H
3,3-disubstituted isoindolinones. In addition to facilitating CeH
bond cleavage, the rhodium complex [{RhCl2Cp*}2] unexpectedly
dimerized diazoacetate in situ to a mixture of fumarate/maleate
that then participated in the annulation.
NMR (500 MHz, CDCl3)
d
1.24 (s, 9H), 2.42 (s, 3H), 3.01 (dd, J¼7.5,
16.5 Hz, 1H), 3.41 (dd, J¼3.5, 16.5 Hz, 1H), 5.55 (dd, J¼3.0, 7.5 Hz, 1H),
7.33 (d, J¼8.5Hz, 2H), 7.47 (dd, J¼7.5, 8.0Hz,1H), 7.50 (d, J¼8.0Hz,1H),
7.63 (dd, J¼7.5, 8.0 Hz, 1H), 7.79 (d, J¼7.5 Hz, 1H), 8.05 (d, J¼8.5 Hz,
4. Experimental section
4.1. General methods
2H); 13C NMR (125 MHz, CDCl3)
d 21.9, 28.0, 40.2, 58.8, 82.0, 123.2,
125.1, 128.7, 129.3, 129.8, 129.9, 134.4, 136.0, 145.4, 145.6, 166.8, 169.0.
FTIR (CH2Cl2) 2360, 1727, 1597, 1366, 1292, 1170, 1090, 668 cmꢁ1
.
HRMS calcd for C21H24NO5S [MþH]þ 402.1370, found 402.1358.
All reactions were maintained under an argon atmosphere un-
less otherwise stated. Anhydrous solvents (THF, DME) were freshly
distilled from sodium benzophenone ketyl or from CaH2 (CH2Cl2,
toluene) under argon. Commercially available reagents were used
4.1.4. 3-tert-Butoxycarbonylmethyl-5-methyl-2-tosylisoindolin-1-
one (3b). 1H NMR (500 MHz, CDCl3)
d
1.27 (s, 9H), 2.41 (s, 3H), 2.44 (s,
3H), 2.96(dd, J¼7.5,16.0 Hz,1H), 3.40 (dd, J¼3.5,16.5 Hz,1H), 5.50(dd,

C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
9197
J¼3.5, 7.5 Hz,1H), 7.27 (d, J¼7.5 Hz,1H), 7.29 (s,1H), 7.33 (d, J¼8.0 Hz,
2H), 7.66 (d, J¼8.0 Hz,1H), 8.04 (d, J¼7.5 Hz, 2H); 13C NMR (125 MHz,
1H), 5.77 (dd, J¼2.5, 10.0 Hz, 1H), 7.32 (d, J¼8.5 Hz, 2H), 7.43 (dd,
J¼7.5, 7.5 Hz, 1H), 7.58 (dd, J¼7.5, 8.0 Hz, 1H), 7.70 (d, J¼8.0 Hz,
1H), 7.75 (d, J¼7.5 Hz, 1H), 8.00 (d, J¼8.0 Hz, 2H); 13C NMR
CDCl3)
d 21.9, 22.4, 28.0, 40.5, 58.6, 81.9, 123.6, 124.9, 127.1, 128.6,
129.8, 130.4, 136.1, 145.3, 145.7, 146.0, 166.7, 169.1. FTIR (CH2Cl2) 2979,
1731, 1618, 1366, 1337, 1284, 1171, 1091, 815, 691, 659 cmꢁ1. HRMS
calcd for C22H26NO5S [MþH]þ 416.1526, found 416.1511.
(125 MHz, CDCl3) d 21.9, 35.7, 37.4, 39.9, 59.8, 124.7, 125.0, 128.5,
129.0, 129.2, 129.9, 134.6, 135.7, 145.5, 146.9, 166.9, 169.5; FTIR
(CH2Cl2) 2360, 1732, 1645, 1402, 1358, 1290, 1169, 1090, 695,
663 cmꢁ1. HRMS calcd for C19H21N2O4S [MþH]þ 373.1217, found
373.1217.
4.1.5. 3-tert-Butoxycarbonylmethyl-5-methoxy-2-tosylisoindolin-1-
one (3c). 1H NMR (500 MHz, CDCl3)
d 1.33 (s, 9H), 2.41 (s, 3H), 2.89
(dd, J¼8.0,16.5 Hz,1H), 3.46 (dd, J¼2.0,16.5 Hz,1H), 3.84 (s, 3H), 5.63
(dd, J¼2.0, 7.5 Hz, 1H), 6.96 (s, 1H), 6.97 (d, J¼9.0 Hz, 1H), 7.32 (d,
J¼8.0 Hz, 2H), 7.68 (d, J¼9.0 Hz, 1H), 8.03 (d, J¼8.0 Hz, 2H); 13C NMR
4.1.11. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-2-tosylisoindolin-
1-one (3i). 1H NMR (500 MHz, CDCl3)
d
0.79 (t, J¼7.0 Hz, 3H), 1.25
(t, J¼7.0 Hz, 3H), 2.42 (s, 3H), 3.52e3.64 (m, 2H), 3.70 (d,
J¼17.5 Hz, 1H), 3.94 (d, J¼17.5 Hz, 1H), 4.16e4.24 (m, 1H),
4.28e4.36 (m, 1H), 7.33 (d, J¼8.5 Hz, 2H), 7.44 (d, J¼7.5 Hz, 1H),
7.51 (dd, J¼7.5, 7.5 Hz, 1H), 7.63 (dd, J¼7.5, 7.5 Hz, 1H), 7.82 (d,
J¼7.5 Hz, 1H), 8.10 (d, J¼8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3)
(125 MHz, CDCl3) d 21.9, 28.1, 40.7, 56.0, 58.4, 82.0, 107.3, 116.8, 121.9,
126.8, 128.6, 129.8, 136.2, 145.3, 148.4, 165.0, 166.4, 169.4. FTIR
(CH2Cl2) 2978,1728,1608,1493,1366,1260,1170,1090, 693, 659 cmꢁ1
.
HRMS calcd for C22H26NO6S [MþH]þ 432.1475, found 432.1472.
d
13.7, 14.0, 21.9, 38.5, 60.8, 63.4, 70.5, 121.3, 125.1, 129.2, 129.4,
4.1.6. 3-tert-Butoxycarbonylmethyl-5-fluoro-2-tosylisoindolin-1-one
129.9, 130.1, 134.4, 136.1, 143.7, 145.4, 166.6, 167.9, 168.6. FTIR
(CH2Cl2) 2982, 1738, 1468, 1366, 1248, 1169, 1123, 1089, 1028, 693,
664 cmꢁ1. HRMS calcd for C22H24NO7S [MþH]þ 446.1268, found
446.1252.
(3d). 1H NMR (500 MHz, CDCl3)
d 1.31 (s, 9H), 2.42 (s, 3H), 2.93
(dd, J¼8.0, 16.5 Hz, 1H), 3.44 (dd, J¼3.5, 16.5 Hz, 1H), 5.52 (dd,
J¼3.0, 8.0 Hz, 1H), 7.15e7.19 (m, 1H), 7.21e7.23 (m, 1H), 7.34 (d,
J¼8.0 Hz, 2H), 7.76e7.80 (m, 1H), 8.04 (d, J¼8.5 Hz, 2H); 13C NMR
(125 MHz, CDCl3)
d
21.9, 28.1, 40.2, 58.4, 82.3, 110.9 (d,
4.1.12. 3-Ethylcarbonyl-3-ethylcarbonylmethyl-2-tosylisoindolin-1-
JCeF¼29.2 Hz), 117.5 (d, JCeF¼24.2 Hz), 125.7 (d, JCeF¼11.5 Hz), 127.5
(q, JCeF¼5.0 Hz), 128.6, 129.9, 135.8, 145.6, 148.3 (d, JCeF¼10.6 Hz),
165.6 (d, JCeF¼267 Hz), 167.7, 168.9. FTIR (CH2Cl2) 2981, 2360,
2342, 1733, 1624, 1603, 1485, 1358, 1245, 1173, 1105, 860, 813, 690,
668 cmꢁ1. HRMS calcd for C21H23FNO5S [MþH]þ 420.1275, found
420.1275.
one (3j). 1H NMR (400 MHz)
d
0.57 (t, J¼7.2 Hz, 3H), 0.95 (t,
J¼7.2 Hz, 3H), 2.06e2.16 (m, 3H), 2.41 (s, 3H), 2.80e2.92 (m, 1H),
3.70 (d, J¼19.2 Hz, 1H), 3.78 (d, J¼19.2 Hz, 1H), 7.14 (d, J¼7.6 Hz,
1H), 7.30 (d, J¼8.4 Hz, 2H), 7.51 (dd, J¼7.2, 7.6 Hz, 1H), 7.58 (dd,
J¼7.2, 7.6 Hz, 1H), 7.93 (d, J¼7.6 Hz, 1H), 8.02 (d, J¼8.4 Hz, 2H); 13C
NMR (100 MHz)
d 6.9, 8.5, 21.9, 28.6, 36.3, 42.5, 75.4, 121.1, 125.6,
128.3, 129.8, 130.0, 130.6, 134.6, 135.8, 143.1, 145.7, 167.0, 205.3,
205.6. FTIR (CH2Cl2) 1745, 1716, 1357, 1169, 1123, 1087, 1057, 822,
702, 658 cmꢁ1. HRMS calcd for C22H24NO5S [MþH]þ 414.1370,
found 414.1368.
4.1.7. 3-tert-Butoxycarbonylmethyl-5-trifluoromethyl-2-
tosylisoindolin-1-one (3e). 1H NMR (500 MHz, CDCl3)
d 1.30 (s, 9H),
2.43 (s, 3H), 2.92 (dd, J¼8.0, 16.5 Hz, 1H), 3.51 (dd, J¼3.5, 16.5 Hz,
1H), 5.62 (dd, J¼3.5, 8.0 Hz, 1H), 7.35 (d, J¼8.5 Hz, 2H), 7.74 (d,
J¼8.0 Hz, 1H), 7.82 (s, 1H), 7.91 (d, J¼8.0 Hz, 1H), 8.05 (d, J¼8.0 Hz,
4.1.13. 3-Ethoxycarbonyl-3-cyanomethyl-2-tosylisoindolin-1-one
2H); 13C NMR (100 MHz, CDCl3)
d
21.9, 28.0, 40.1, 58.8, 82.4, 120.9,
(3k). 1H NMR (400 MHz)
d
1.25 (t, J¼7.2 Hz, 3H), 2.43 (s, 3H), 3.78
122.1, 125.8, 126.5, 128.7, 130.0, 132.9, 135.9, 136.0 (q, JCeF¼32.3 Hz),
145.8,146.0,165.3,168.8. FTIR (CH2Cl2) 2980,1729,1598,1440,1367,
1312, 1171, 1131, 1092, 1061, 841, 696, 672 cmꢁ1. HRMS calcd for
C22H23F3NO5S [MþþH] 470.1244, found 470.1230.
(d, J¼17.6 Hz, 1H), 3.90 (d, J¼17.6 Hz, 1H), 4.16e4.24 (m, 1H),
4.32e4.40 (m, 1H), 7.37 (d, J¼8.0 Hz, 2H), 7.52 (d, J¼7.6 Hz, 1H),
7.60 (dd, J¼7.6, 7.6 Hz, 1H), 7.73 (dd, J¼7.6, 7.6 Hz, 1H), 7.87 (d,
J¼7.6 Hz, 1H), 8.09 (d, J¼8.4 Hz, 2H); 13C NMR (100 MHz)
d 14.0,
22.0, 26.2, 64.1, 69.5, 114.7, 121.5, 126.0, 129.1, 129.2, 129.8, 131.3,
135.2, 135.3, 141.9, 146.2, 165.5, 167.3. FTIR (CH2Cl2) 2987, 1743,
1598, 1468, 1365, 1294, 1267, 1169, 1128, 1088, 815, 748, 698,
666 cmꢁ1. HRMS calcd for C20H19N2O5S [MþH]þ 399.1009, found
399.1009.
4.1.8. 3-tert-Butoxycarbonylmethyl-7-fluoro-2-tosylisoindolin-1-one
(3f). 1H NMR (500 MHz, CDCl3)
d 1.25 (s, 9H), 2.43 (s, 3H), 3.05 (dd,
J¼7.0,16.5 Hz,1H), 3.36 (dd, J¼3.5,16.5 Hz,1H), 5.55 (dd, J¼3.0, 7.0 Hz,
1H), 7.10 (dd, J¼8.5, 8.5 Hz,1H), 7.27 (d, J¼7.5Hz,1H), 7.34 (d, J¼8.0 Hz,
2H), 7.58e7.63 (m, 1H), 8.05 (d, J¼8.5 Hz, 2H); 13C NMR (125 MHz,
CDCl3)
d
21.9, 28.0, 40.1, 58.3, 82.1, 116.4, 116.5, 117.5, 117.6, 119.08,
4.1.14. 3,3-Spiro[30-N-methyl-20,40-dicarbonylpyrrolidine]-2-
119.12,128.8,129.9,135.7,136.4,136.5,145.6,147.9,158.6,160.7,163.4,
168.7; FTIR (CH2Cl2) 2979, 2360, 2341, 1731, 1626, 1599, 1482, 1366,
1313, 1292, 1252, 1207, 1172, 1102, 1036, 979, 684, 668 cmꢁ1. HRMS
calcd for C21H23FNO5S [MþH]þ 420.1275, found 420.1259.
tosylisoindolin-1-one (3l). 1H NMR (400 MHz)
d 2.44 (s, 3H), 3.21 (d,
J¼14.4 Hz, 1H), 3.27 (s, 3H), 3.89 (d, J¼14.4 Hz, 1H), 7.27 (d, J¼7.6 Hz,
1H), 7.36 (d, J¼8.4 Hz, 2H), 7.55 (dd, J¼7.6, 7.6 Hz, 1H), 7.68 (dd,
J¼7.6, 7.6 Hz, 1H), 7.81 (d, J¼7.6 Hz, 1H), 8.05 (d, J¼8.4 Hz, 2H); 13C
NMR (100 MHz)
d 22.0, 26.3, 41.6, 69.3, 120.5, 125.8, 128.6, 129.6,
4.1.9. 3-Ethylcarbonylmethyl-2-tosylisoindolin-1-one (3g). 1H NMR
129.7, 130.7, 134.8, 135.4, 144.6, 146.3, 165.4, 172.9, 173.4. FTIR
(CH2Cl2) 1791, 1738, 1715, 1597, 1436, 1382, 1359, 1286, 1263, 1168,
1123, 1091, 1059, 702, 665 cmꢁ1. HRMS calcd for C19H17N2O5S
[MþH]þ 385.0853, found 385.0827.
(500 MHz, CDCl3)
d
1.12 (t, J¼7.0 Hz, 3H), 2.41 (s, 3H), 2.41e2.46 (m,
1H), 2.56e2.62 (m, 1H), 2.90 (dd, J¼9.0,18.0 Hz,1H), 3.81 (dd, J¼3.0,
18.0 Hz, 1H), 5.69 (dd, J¼3.0, 9.0 Hz, 1H), 7.33 (d, J¼8.0 Hz, 2H),
7.42e7.46 (m, 2H), 7.59 (dd, J¼7.5, 7.5 Hz, 1H), 7.76 (d, J¼7.5 Hz, 1H),
7.99 (d, J¼8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d
7.83, 21.9, 36.8,
4.1.15. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-5-methyl-2-
48.0, 58.2, 123.7, 125.2, 128.5, 129.1, 129.3, 130.0, 134.6, 135.7, 145.6,
146.6, 166.7, 208.5. FTIR (CH2Cl2) 2938, 1729, 1597, 1358, 1290, 1169,
tosylisoindolin-1-one (3n). 1H NMR (400 MHz, CDCl3)
d 0.77 (t,
J¼7.2 Hz, 3H), 1.24 (t, J¼7.2 Hz, 3H), 2.40 (s, 3H), 2.43 (s, 3H),
3.52e3.62 (m, 2H), 3.66 (d, J¼17.6 Hz, 1H), 3.90 (d, J¼17.6 Hz, 1H),
4.12e4.22 (m, 1H), 4.28e4.36 (m, 1H), 7.20 (s, 1H), 7.28 (d, J¼8.0 Hz,
1H), 7.30 (d, J¼8.4 Hz, 2H), 7.68 (d, J¼8.0 Hz, 1H), 8.08 (d, J¼8.4 Hz,
1092, 694, 664 cmꢁ1
.
HRMS calcd For C19H20NO4S [MþH]þ
358.1108, found 358.1093.
4.1.10. 3-Dimethylaminocarbonylmethyl-2-tosylisoindolin-1-one
(3h). 1H NMR (500 MHz, CDCl3)
2.40 (s, 3H), 2.69 (dd, J¼10.0,
16.5 Hz, 1H), 2.99 (s, 3H), 3.04 (s, 3H), 3.78 (dd, J¼2.5, 16.5 Hz,
2H); 13C NMR (100 MHz, CDCl3)
d 13.7, 14.0, 21.9, 22.4, 38.5, 60.7,
d
63.4, 70.2, 121.6, 125.0, 127.4, 129.2, 129.4, 131.2, 136.2, 144.0, 145.3,
145.7, 166.6, 168.0, 168.8. FTIR (CH2Cl2) 2983, 1737, 1613, 1598, 1364,

9198
C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
1284, 1250, 1169, 1133, 1088, 1027, 853, 808, 704, 666 cmꢁ1. HRMS
1163, 1130, 1086, 1027, 764, 664 cmꢁ1. HRMS calcd for C26H26NO7S
calcd for C23H26NO7S [MþH]þ 460.1424, found 460.1413.
[MþH]þ 496.1424, found 496.1421.
4.1.16. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-5-methoxy-2-
4.1.21. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-6-methoxy-2-
tosylisoindolin-1-one (3o). 1H NMR (400 MHz, CDCl3)
d
0.80 (t,
tosylisoindolin-1-one (3t). 1H NMR (400 MHz, CDCl3)
d 0.81 (t,
J¼7.2 Hz, 3H), 1.26 (t, J¼7.2 Hz, 3H), 2.42 (s, 3H), 3.54e3.64 (m, 2H),
3.66 (d, J¼17.6 Hz, 1H), 3.86 (s, 3H), 3.92 (d, J¼17.6 Hz, 1H),
4.14e4.24 (m, 1H), 4.30e4.38 (m, 1H), 6.86 (d, J¼2.0 Hz, 1H), 6.99
(dd, J¼2.0, 8.8 Hz, 1H), 7.31 (d, J¼8.4 Hz, 2H), 7.73 (d, J¼8.4 Hz, 1H),
J¼7.2 Hz, 3H), 1.23 (t, J¼7.2 Hz, 3H), 2.40 (s, 3H), 3.55e3.65 (m, 2H),
3.64 (d, J¼17.2 Hz, 1H), 3.80 (s, 3H), 3.87 (d, J¼17.2 Hz, 1H),
4.14e4.22 (m, 1H), 4.26e4.34 (m, 1H), 7.14 (dd, J¼2.4, 8.4 Hz, 1H),
7.24 (d, J¼2.4 Hz, 1H), 7.30 (d, J¼8.4 Hz, 1H), 7.31 (d, J¼8.0 Hz, 2H),
8.09 (d, J¼8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
13.7, 14.0, 21.9,
8.08 (d, J¼8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 13.8, 14.0, 21.9,
38.7, 56.1, 60.8, 63.5, 70.0, 105.8, 116.9, 122.2, 126.8, 129.1, 129.4,
136.3, 145.2, 146.1, 164.9, 166.2, 167.9, 168.7. FTIR (CH2Cl2) 2982,
1738, 1604, 1495, 1362, 1343, 1291, 1254, 1168, 1126, 1085, 1026, 855,
659 cmꢁ1. HRMS calcd for C23H26NO8S [MþH]þ 476.1374, found
476.1376.
38.3, 56.0, 60.7, 63.4, 70.2, 107.6, 122.4, 122.7, 129.2, 129.4, 131.3,
135.8, 136.0, 145.3, 161.3, 166.6, 168.0, 168.7. FTIR (CH2Cl2) 2983,
1736, 1494, 1365, 1289, 1251, 1169, 1129, 1091, 1028, 664 cmꢁ1
.
HRMS calcd for C23H26NO8S [MþH]þ 476.1374, found 476.1382.
4.1.22. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-7-fluoro-2-
4.1.17. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-5-fluoro-2-
tosylisoindolin-1-one (3u). 1H NMR (400 MHz, CDCl3)
d 0.86 (t,
tosylisoindolin-1-one (3p). 1H NMR (400 MHz, CDCl3)
d
0.86 (t,
J¼7.2 Hz, 3H), 1.26 (t, J¼7.2 Hz, 3H), 2.43 (s, 3H), 3.56e3.68 (m, 2H),
3.67 (d, J¼17.6 Hz, 1H), 3.94 (d, J¼17.6 Hz, 1H), 4.16e4.26 (m, 1H),
4.30e4.38 (m, 1H), 7.14 (dd, J¼8.4, 8.4 Hz, 1H), 7.22 (d, J¼7.6 Hz, 1H),
7.32 (d, J¼8.4 Hz, 2H), 7.61 (ddd, J¼4.8, 7.6, 8.0 Hz, 1H), 8.09 (d,
J¼7.2 Hz, 3H), 1.27 (t, J¼7.2 Hz, 3H), 2.42 (s, 3H), 3.63 (q, J¼7.2 Hz,
2H), 3.65 (d, J¼17.6 Hz, 1H), 3.94 (d, J¼17.6 Hz, 1H), 4.18e4.26 (m,
1H), 4.30e4.39 (m, 1H), 7.12 (dd, J¼2.0, 7.6 Hz, 1H), 7.20 (ddd, J¼2.0,
8.4, 8.8 Hz, 1H), 7.33 (d, J¼8.4 Hz, 2H), 7.82 (dd, J¼4.8, 8.4 Hz, 1H),
J¼8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 13.7, 14.0, 21.9, 38.6,
8.08 (d, J¼8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
13.7, 14.0, 21.9,
60.9, 63.7, 70.1, 117.2 (d, JCeF¼4.2 Hz), 117.4 (d, JCeF¼18.8 Hz), 129.3,
129.5, 135.7, 136.4 (d, JCeF¼7.9 Hz), 145.6, 145.9 (d, JCeF¼2.3 Hz),
159.4 (d, JCeF¼274 Hz), 163.3 (d, JCeF¼2.6 Hz), 167.8, 168.2. FTIR
(CH2Cl2) 2984, 1740, 1622, 1483, 1367, 1256, 1236, 1196, 1171, 1122,
1090, 1073, 1035, 814, 691, 664 cmꢁ1. HRMS calcd for C22H23FNO7S
[MþH]þ 464.1174, found 464.1186.
38.4, 60.9, 63.7, 70.1, 109.0 (d, JCeF¼25.0 Hz), 118.1 (d, JCeF¼23.4 Hz),
126.1 (d, JCeF¼2.2 Hz), 127.5 (d, JCeF¼9.9 Hz), 129.2, 129.4, 135.9,
145.5, 146.3 (d, JCeF¼10.0 Hz), 165.2, 166.8 (d, JCeF¼267 Hz), 167.7,
167.8. FTIR (CH2Cl2) 2983, 1736, 1606, 1488, 1365, 1287, 1250, 1170,
1124,1084,1027, 853, 814, 655.2 cmꢁ1. HRMS calcd for C22H23FNO7S
[MþH]þ 464.1174, found 464.1158.
4.1.23. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-4,6-dimethoxy-2-
4.1.18. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-5-
tosylisoindolin-1-one (3v). 1H NMR (400 MHz, CDCl3)
d 0.84 (t,
trifluoromethyl-2-tosylisoindolin-1-one (3q). 1H NMR (400 MHz,
J¼7.2 Hz, 3H), 1.24 (t, J¼7.2 Hz, 3H), 2.42 (s, 3H), 3.57e3.65 (m, 2H),
3.79 (d, J¼17.2 Hz, 1H), 3.81 (s, 3H), 3.83 (s, 3H), 3.90 (d, J¼17.2 Hz,
1H), 4.16e4.24 (m, 1H), 4.26e4.34 (m, 1H), 6.61 (d, J¼2.0 Hz, 1H),
6.87 (d, J¼2.0 Hz, 1H), 7.31 (d, J¼8.4 Hz, 2H), 8.07 (d, J¼8.4 Hz, 2H);
CDCl3)
d
0.87 (t, J¼7.2 Hz, 3H), 1.27 (t, J¼7.2 Hz, 3H), 2.43 (s, 3H),
3.63 (q, J¼7.2 Hz, 2H), 3.72 (d, J¼17.6 Hz, 1H), 3.98 (d, J¼17.6 Hz,
1H), 4.18e4.27 (m, 1H), 4.33e4.42 (m, 1H), 7.34 (d, J¼8.4 Hz, 2H),
7.69 (s, 1H), 7.78 (d, J¼8.0 Hz, 1H), 7.95 (d, J¼8.0 Hz, 1H), 8.10 (d,
13C NMR (100 MHz, CDCl3)
d 13.8, 14.1, 21.9, 36.0, 56.0, 56.1, 60.5,
J¼8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
13.8, 14.0, 21.9, 38.2,
62.9, 69.3, 98.7, 105.1, 124.3, 129.1, 129.4, 132.5, 136.1, 145.3, 155.1,
162.9, 166.7, 167.8, 168.6. FTIR (CH2Cl2) 2982, 1741, 1625, 1598, 1503,
61.0, 63.9, 70.6, 118.6 (q, JCeF¼3.8 Hz), 123.3 (q, JCeF¼272 Hz),
125.8, 127.3 (q, JCeF¼3.5 Hz), 129.2, 129.5, 133.3, 135.6, 136.0 (q,
JCeF¼32.9 Hz), 144.2, 145.8, 165.3, 167.7, 167.9. FTIR (CH2Cl2)
2986, 1739, 1369, 1329, 1259, 1171, 1133, 1099, 1028, 846, 696,
659 cmꢁ1. HRMS calcd for C23H23F3NO7S [MþH]þ 514.1142, found
514.1158.
1459, 1356, 1323, 1244, 1169, 1151, 1090, 1068, 1031, 827, 664 cmꢁ1
.
HRMS calcd for C24H28NO9S [MþH]þ 506.1479, found 506.1458.
Acknowledgements
We thank the NIH (GM31278) and the Robert A. Welch Foun-
4.1.19. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-5-bromo-2-
dation (GL625910) for financial support.
tosylisoindolin-1-one (3r). 1H NMR (400 MHz, CDCl3)
d 0.87 (t,
J¼7.2 Hz, 3H), 1.28 (t, J¼7.2 Hz, 3H), 2.42 (s, 3H), 3.63 (q, J¼7.2 Hz,
2H), 3.65 (d, J¼17.6 Hz, 1H), 3.93 (d, J¼17.6 Hz, 1H), 4.16e4.26 (m,
1H), 4.32e4.42 (m, 1H), 7.33 (d, J¼8.4 Hz, 2H), 7.59 (s, 1H), 7.66 (dd,
J¼8.0, 16.8 Hz, 2H), 8.08 (d, J¼8.4 Hz, 2H); 13C NMR (100 MHz,
Supplementary data
NMR spectra. Supplementary data related to this article can be
found online at http://dx.doi.org/10.1016/j.tet.2012.08.095.
CDCl3)
d 13.8, 14.0, 21.9, 38.3, 61.0, 63.8, 70.0, 124.7, 126.4, 129.0,
129.1, 129.2, 129.5, 133.6, 135.8, 145.3, 145.6, 165.7, 167.7, 168.1. FTIR
(CH2Cl2) 2983, 1737, 1605, 1593, 1367, 1278, 1247, 1170, 1131, 1090,
1028, 839, 664 cmꢁ1. HRMS calcd for C22H23BrNO7S [MþH]þ
524.0373, found 524.0378.
References and notes
1. For recent reviews about CeH activation, see: (a) Lewis, J. C.; Bergman, R. G.;
Ellman, J. A. Acc. Chem. Res. 2008, 41, 1013; (b) Li, B.-J.; Yang, S.-D.; Shi, Z.-J.
Synlett 2008, 949; (c) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2009, 48, 5094; (d) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem.,
Int. Ed. 2009, 48, 9792; (e) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res.
2009, 42, 1074; (f) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Chem. Soc.
Rev. 2009, 38, 3242; (g) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev.
2010, 110, 624; (h) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. Chem. Rev. 2010, 110, 890; (i) Lyons, T. W.; Sanford, M. S. Chem. Rev.
2010, 110, 1147; (j) Ackermann, L. Chem. Commun. 2010, 4866; (k) Jazzar, R.;
Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem.dEur. J. 2010, 16,
2654; (l) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215; (m) McMurry, L.;
O’Hara, F.; Gaunt, M. J. Chem. Soc. Rev. 2011, 40, 1885; (n) Gutekunst, W. R.;
Baran, P. S. Chem. Soc. Rev. 2011, 40, 1976; (o) Hartwig, J. F. Chem. Soc. Rev. 2011,
4.1.20. 3-Ethoxycarbonyl-3-ethoxycarbonylmethyl-2-tosyl-5,6-benzo
isoindolin-1-one (3s). 1H NMR (400 MHz, CDCl3)
d
0.74 (t, J¼7.2 Hz,
3H), 1.24 (t, J¼7.2 Hz, 3H), 2.41 (s, 3H), 3.51 (q, J¼7.2, 2H), 3.82 (d,
J¼18.0 Hz,1H), 4.01 (d, J¼18.0 Hz,1H), 4.14e4.20 (m,1H), 4.30e4.38
(m, 1H), 7.32 (d, J¼8.4 Hz, 2H), 7.57 (dd, J¼7.6, 7.6 Hz, 1H), 7.62 (dd,
J¼7.6, 7.6 Hz, 1H), 7.84 (s, 1H), 7.89 (d, J¼8.0 Hz, 1H), 7.99 (d,
J¼8.0 Hz, 1H), 8.12 (d, J¼8.4 Hz, 2H), 8.36 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 13.7,14.0, 21.9, 39.1, 60.8, 63.5, 70.2,120.5, 126.3,
€
40, 1992; (p) Wencel-Derord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011,
40, 4740; (q) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651; (r) Zhu, C.;
Wang, R.; Falck, J. R. Chem.dAsian J. 2012, 7, 1502.
127.4, 127.6, 128.7, 129.1, 129.2, 129.5, 130.1, 133.6, 136.1, 136.2, 138.3,
145.4, 166.6, 168.1, 169.1. FTIR (CH2Cl2) 2983, 1736, 1365, 1252, 1180,

C. Zhu, J.R. Falck / Tetrahedron 68 (2012) 9192e9199
9199
2. (a) Wrobel, J.; Dietrich, A.; Woolson, S. A.; Millen, J.; McCaleb, M.; Harrison, M.
C.; Hohman, T. C.; Sredy, J.; Sullivan, D. J. Med. Chem. 1992, 35, 4613; (b) Anzini,
M.; Capelli, A.; Vomero, S.; Giorgi, G.; Langer, T.; Bruni, G.; Romero, M. R.; Basile,
A. S. J. Med. Chem. 1996, 39, 4275; (c) Chang, L. C.; Bhat, K. P. L.; Pisha, E.;
Kennelly, E. J.; Fong, H. H. S.; Pezzuto, J. M.; Kinghorn, A. D. J. Nat. Prod. 1998, 61,
1257; (d) Belliotti, T. R.; Brink, W. A.; Kesten, S. R.; Rubin, J. R.; Wustrow, D. J.;
Zoski, K. T.; Whetzel, S. Z.; Corbin, A. E.; Pugsley, T. A.; Heffner, T. G.; Wise, L. D.
Bioorg. Med. Chem. Lett. 1998, 8, 1499; (e) Honma, T.; Hayashi, K.; Aoyama, T.;
Hashimoto, N.; Machida, T.; Fukasawa, K.; Iwama, T.; Ikeura, C.; Ikuta, M.;
Suzuki-Takahashi, I.; Iwasawa, Y.; Hayama, T.; Nishimura, S.; Morishima, H. J.
Med. Chem. 2001, 44, 4615; (f) Sorbera, L. A.; Leeson, P. A.; Silvestre, J.; Castaner,
J. Drugs Future 2001, 26, 651; (g) Stuk, T. L.; Assink, B. K.; Bates, R. C., Jr.; Erdman,
D. T.; Fedij, V.; Jennings, S. M.; Lassig, J. A.; Smith, R. J.; Smith, T. L. Org. Process
Res. Dev. 2003, 7, 851; (h) Riedinger, C.; Endicott, J. A.; Kemp, S. J.; Smyth, L. A.;
Watson, A.; Valeur, E.; Golding, B. T.; Griffin, R. J.; Hardcastle, I. R.; Noble, M. E.;
McDonnell, J. M. J. Am. Chem. Soc. 2008, 130, 16038.
3. For selected examples, see: (a) Pin, F.; Comesse, S.; Garrigues, B.; Marchalin, S.;
Daich, A. J. Org. Chem. 2007, 72, 1181; (b) Klumpp, D. A.; Zhang, Y.; O’Connor, M. J.;
Esteves, P. M.; de Almeida, L. S. Org. Lett. 2007, 9, 3085; (c) Guo, S.;
Xie, Y.; Hu, X.; Xia, C.; Huang, H. Angew. Chem., Int. Ed. 2010, 49, 2728;
(d) Sai, K. K. S.; O’Connor, M. J.; Klumpp, D. A. Tetrahedron Lett. 2010, 52, 2195; (e)
Campbell, J. B.; Dedinas, R. F.; Trumbower-Walsh, S. Synlett 2010, 3008;
(f) Shacklady-McAtee, D. M.; Dasgupta, S.; Watson, M. P. Org. Lett. 2011, 13, 3490.
4. Zhu, C.; Falck, J. R. Org. Lett. 2011, 13, 1214.
9. Ackermann, L.; Wang, L.; Wolfram, R.; Lygin, A. V. Org. Lett. 2012, 14, 728.
10. For a special review about [RhCl2Cp*]2, see: Satoh, T.; Miura, M. Chem.dEur. J.
2010, 16, 11212.
11. For selected examples, see: (a) Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007,
72, 5362; (b) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407; (c) Stuart, D.
R.; Bertrand-Laperle, M.; Burgess, K. M. N.; Fagnou, K. J. Am. Chem. Soc. 2008,
130, 16474; (d) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009,
74, 3478; (e) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74,
6295; (f) Fukutani, T.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. Chem. Com-
mun. 2009, 5141; (g) Mochida, S.; Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M.
Chem.dAsian J. 2010, 5, 847; (h) Guimond, N.; Gouliaras, C.; Fagnou, K. J. Am.
Chem. Soc. 2010, 132, 6908; (i) Hyster, T. K.; Rovis, T. J. Am. Chem. Soc. 2010, 132,
10565; (j) Mochida, S.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. Chem. Lett.
2010, 39, 744; (k) Song, G.; Chen, D.; Pan, C.-L.; Crabtree, R. H.; Li, X. J. Org. Chem.
2010, 75, 7487; (l) Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010,
132, 9585; (m) Su, Y.; Zhao, M.; Han, K.; Song, G.; Li, X. Org. Lett. 2010, 12, 5462;
(n) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc. 2011, 133,
2350; (o) Li, X.; Gong, X.; Zhao, M.; Song, G.; Deng, J.; Li, X. Org. Lett. 2011, 13,
5808; (p) Willwacher, J.; Rakshit, S.; Glorius, F. Org. Biomol. Chem. 2011, 9, 4736.
12. Zhu, C.; Falck, J. R. Chem. Commun. 2012, 48, 1674.
13. Zhu, C.; Xie, W.; Falck, J. R. Chem.dEur. J. 2011, 17, 12591.
14. For selected reviews, see: (a) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911;
(b) Lebel, H.; Marcoux, J.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977;
(c) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861.
5. Wrigglesworth, J. W.; Cox, B.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. Org. Lett.
2011, 13, 5326.
6. Li, D.-D.; Yuan, T.-T.; Wang, G.-W. Chem. Commun. 2011, 12789.
7. Wang, F.; Song, G.; Li, X. Org. Lett. 2010, 12, 5430.
15. Callot, H. J.; Metz, F.; Piechocki, C. Tetrahedron 1982, 38, 2365.
16. During the review process of this manuscript, a transformation of CeH acti-
vation incorporating with diazo compounds in the use of same rhodium (III)
catalyst has been reported. See: Chan, W. W.; Lo, S. F.; Zhou, Z.; Yu, W. Y. J. Am.
Chem. Soc. 2012, 134, 13565.
8. Patureau, F. W.; Besset, T.; Glorius, F. Angew. Chem., Int. Ed. 2011, 50, 1064.