Efficient Benzimidazolidinone Synthesis via Rhodium-Catalyzed Double-Decarbonylative C-C Activation/Cycloaddition between Isatins and Isocyanates

Article abstract of DOI:10.1021/acscatal.5b02532

The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins) with isocyanates is reported. Initiated by C-C activation, this distinct [5 - 2 + 2] transformation provides a rapid entry to access various benzimidazolidinone derivatives, and a wide range of isocyanates can be efficiently coupled with broad functional group tolerance. A modified one-pot process combining a Curtius rearrangement and C-C activation was also achieved by using acyl azides as the starting materials. A detailed mechanistic study revealed a surprising double-decarbonylative reaction pathway. The novel reactivity discovered in this basic research is expected to shed light on the development of new heterocycle formation methods through C-C/isocyanate coupling.

Full text of DOI:10.1021/acscatal.5b02532

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Article
Efficient Benzimidazolidinone Synthesis via Rhodium-
Catalyzed Double-Decarbonylative C-C Activation/
Cycloaddition between Isatins and Isocyanates
Rong Zeng, Peng-hao Chen, and Guangbin Dong
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b02532 • Publication Date (Web): 30 Dec 2015
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Page 1 of 6
ACS Catalysis
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9
Efficient Benzimidazolidinone Synthesis via Rhodium-
Catalyzed Double-Decarbonylative C−C Activa-
tion/Cycloaddition between Isatins and Isocyanates
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Rong Zeng, Peng-hao Chen, and Guangbin Dong*
Department of Chemistry, University of Texas at Austin, Austin, Texas, 78712, USA.
ABSTRACT: The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins) with isocyanates is reported. Initiated
by C−C activation, this distinct [5-2+2] transformation provides a rapid entry to access various benzimidazolidinone derivatives,
through which a wide range of isocyanates can be efficiently coupled with broad functional group tolerance. A modified one-pot
process, combining Curtius rearrangement and C−C activation, was also achieved by using acyl azides as the starting materials.
Detailed mechanistic study revealed a surprising double-decarbonylative reaction pathway. The novel reactivity discovered in this
basic research is expected to shed light on developing new heterocycle formation methods through a C−C/isocyanate coupling.
KEYWORDS: C−C activation, isocyanate, isatin, cycloaddition, rhodium
Transition metal-catalyzed C−H and C−C activations fol-
C_
a.
C/isocyanate coupling:
O
lowed by insertion of a 2π-unsaturated units have emerged as
N
R
O
M
R
C
C
C
C
M
C
N
C
attractive byproduct-free approaches for constructing complex
structures from readily available feedstock.1-2 Due to the ubiq-
uity and pivotal role of amide bonds in biologically important
molecules, isocyanates have been frequently employed as re-
action partners for amide synthesis;3 consequently, direct addi-
tion of a C−H or C−C bond across isocyanate C=N bonds
would offer unique atom-efficient methods to access various
nitrogen-containing compounds. In particular, cleavage of a
cyclic C−C bond accompanied by annulation with an isocya-
nate should offer an unusual approach to synthesize lactams
(Scheme 1a). While a number of elegant approaches have been
reported for coupling of isocyanates with unactivated C−H
bonds,4 the corresponding couplings involving C−C activation
are less common.
b. with donor-acceptor vinyl
cyclopropanes:
E
R1
R1
R1
R2
N
O
R2
E
E
E
Pd(0)
R
R2
Pd+
N
E
O
E
=
E
COOMe
L
L
R
c.
with
cyclobutanols:
O
O
R1 OH
X
R3
[Rh(cod)OH]2
dppf
O
R1
N
+
N
R2
H
R2
R3
X
via -C elimination
b
work:
d. This
with isatins
DG
DG
O
R
4
N
3
[Rh(cod)Cl]2
AsPh3
+
N
O
[5-2+2]
O
O
R
-
×
N
N
CO
2
Me
Me
via oxidative addition
In 1987, Tsuji and co-workers developed the first palladi-
um-catalyzed cycloaddition between vinyl cyclopropanes and
isocyanates,5a in which the highly reactive donor-acceptor cy-
clopropanes are needed (Scheme 1b). Later reports disclosed
that Lewis acids could also promote this transformation bene-
fiting from significant release of ring strain.5b-5c In 2013, a
novel rhodium(I)-catalyzed C−C cleavage of cyclobutanols via
β-carbon elimination followed by 1,2-addition with isocya-
nates was reported by Murakami for preparing linear amides
(Scheme 1c).6 While strain release offers an important ad-
vantage for C−C activation,2 to the best of our knowledge,
cycloaddition of isocyanates via activation of less strained
C−C bonds has not been reported previously. Herein, we de-
scribe a decarbonylative regioselective cycloaddition between
isatins and isocyanates, which involves a directed C−C activa-
tion of isatins with extrusion of two CO molecules (Scheme
1d).7-8 This formal [5-2+2] transformation provides a distinct
strategy to convert readily available isatins into various ben-
zimidazolidinone derivatives, a structural motif that has been
widely found in pharmaceutical compounds.
benzimidazolidinone
O
p-FC6H4
p-FC6H4
N
N
O
N
N
HN
NH
Ar
O
N
N
O
N
Pimozide
3-kinase
WO2012/101654 A2,
activation
2012
phosphoinositide
H
drug
antipsychotic
O
N
R'
N
H
Ph
Me
H
N
Me
R=
NH
O
Me
N
O
O
N
H
Me
N
N
R
Me
bromodomain inhibitor
2014
a
MAPK inhibitor /TNF- inhibitor
p38
2011
WO2011/21678 A1,
WO2014/160873 A1,
Scheme 1. Transition metal-catalyzed C−C cleavage and its cou-
pling with isocyanates
Pioneered by Suggs,9 Jun,2g-2i,10, Murai,11 Douglas,8d-8g Shi,12
and Wang,13a the use of directing groups (DGs)13b-13f has been
demonstrated as a successful strategy to assist C−C activation
of unstrained ketones. Our laboratory has been interested in
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 6
developing catalytic methods through activation of less- gardless of their electronic properties (entries 7-12). In addi-
1
2
3
4
5
6
7
8
strained cyclic ketones. For example, we recently reported a
formal [5+2-1] transformation involving a directed activation
of isatins and coupling with alkynes,14 in which the C3-C4
bond of isatins (e.g. 1a) was found to be efficiently cleaved by
a low valent rhodium complex even at room temperature.
Hence, this system provides an excellent platform to study the
insertion of isocyanates. Isatin 1a and isocyanate 2a were em-
ployed as the initial substrates. A variety of metal-ligand com-
binations were screened. To our surprise, the expected mono-
decarbonylative coupling product (4aa) was not observed;
instead, benzimidazolidinone 3aa was isolated as the dominat-
ing product under various rhodium-catalyzed conditions (Ta-
ble 1). This result indicated that double decarbonylation (two
CO extrusions) occurred when an isocyanate was used as the
coupling partner, and the corresponding 2π-insertion was
completely regioselective. It was also interesting that no C−H
activation coupling product4 was observed when 3-
methylpyridyl group was used as the DG.
tion, sterically hindered Xphos and NHC ligand (IMes) de-
creased the yield to 7% and 29%, respectively (entries 13-14).
All these observations suggested that the AsPh3 ligand played
a critical role for the high efficiency of this reaction. Besides
1,4-dioxane, PhCl also serves a competent solvent (entry 15).
Furthermore, decreasing the temperature resulted in lower
conversion (entry 16).
With the optimized conditions in hand, the reaction scope
was first tested using substrate 1a with different isocyanates 2
(Table 2). Both aryl and alkyl substituted isocyanates with
various electronic properties worked very well affording good
to excellent yields of the corresponding benzimidazolidinone
derivatives. A broad range of functional groups can be toler-
ated. Organic halides, such as aryl fluoride (2a), bromide (2c)
and trifluoromethyl groups (2f) were compatible; aryl and
alkyl substituted esters (2d and 2l) remained untouched due to
the near pH and redox neutral conditions. Sterically hindered
isocyanates, such as 2,5-dimethoxyl-isocyanate (2g) and 1-
naphthyl-isocyanate (2h), also provided high yields of prod-
ucts. When allylicisocyanate (2i) was used, the reaction un-
derwent chemoselective C=N insertion leaving the olefin moi-
ety intact. Furthermore, regular alkyl (2j), benzyl (2k) and α-
ester-isocyanate (2l) all gave high yields. X-ray crystal struc-
tures of products 3aa and 3al have also been obtained.15 At-
tempts to couple with other heterocumulenes, such as phenyl
isothiocyanates or N,N'-dicyclohexylcarbodiimide (DCC),
remained unsuccessful.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Control experiments.
F
DG
O
N
F
Ar
O
=
DG
3-methyl-2-pyridinyl
N
DG
DG
O
5 mol%
[Rh(cod)Cl]2
20 mol% AsPh3
+
N
N
Me
O
160 o
C
O
N
1,4-dioxane,
N
Me
4aa
observed)
98%a
O
Me
(not
3.0
equiv
2a
x-ray
standard conditions 3aa
obtained
1a
(
)
a
conversion
entry
change from standard conditions
3aa
/ %
/ %
Table 2. The reaction scope of isocyanatesa
1
2
None
99
0
98
Without Rh catalyst
Without AsPh3
0
3
34
15
34
DG
DG
O
R
R
N
5 mol%
[Rh(cod)Cl]2
20 mol% AsPh3
4
5
6
7
RhC
instead of
14
l(PPh3)3
[Rh(cod)Cl]2
N
+
O
O
160 o
C
Ru
instead of
19
7
0
0
8
O
3(CO)12
[Rh(cod)Cl]2
N
1,4-dioxane,
N
2
instead of AsPh
Xantphos
3
Me
Me
3-methyl-2-pyridinyl
3.0
DG
equiv
1a
=
DG
Br
instead of AsPh
30
dppb
dppp
3
F
COOEt
8
9
instead of AsPh
16
28
9
3
PCy3 instead of AsPh3
16
10
11
12
13
H4-4-OMe)3 instead of AsPh3
H4-4-F)3 instead of AsPh3
28
91
10
22
41
13
78
10
7
DG
DG
N
DG
P(C6
P(C6
P(C6
Xphos
N
N
N
N
N
O
O
O
O
H -3,
instead of AsPh3
5-(CF3)2)3
2
N
N
instead of AsPh
Me
3
Me
Me
3ac 47%b
Me
98%
3aa
,
93%
3ab
93%
,
14
15
16
IMes instead of AsPh3
29
72
29
,
3ad
,
NO2
PhCl instead of
Temperature
96
31
1,4-Dioxane
F3C
MeO
150 oC
was
CF3
DG
DG
DG
DG
N
N
OMe
N
N
N
a Determined by crude 1H NMR using 1,1,2,2-tetrachloroethane as
the internal standard.
O
O
O
O
N
N
N
Me
Me
Me
Me
3ae
,
>99%
79%b
3ah
,
3ag
94%
,
3af
96%
,
After the reaction was carefully assayed, the benzimidazoli-
dinone (3aa) was almost exclusively formed in 98% yield
when 5 mol % [Rh(cod)Cl]2 and 20 mol% AsPh3 were discov-
ered as the optimal combination (Table 1, entry 1). Control
experiments were subsequently conducted to understand the
role of each reactant. In the absence of the rhodium catalyst,
no desired product was observed (entry 2). The conversion
decreased dramatically without the AsPh3 ligand, and only
34% of 3aa was obtained (entry 3). Use of Wilkinson’s cata-
lyst [Rh(PPh3)3Cl] instead gave only 14% of the desired prod-
uct together with a high recovery of the starting material (entry
4). Employment of other metal, such as Ru3(CO)12, didn’t af-
ford any desired product (entry 5). Bi- or monodentate phos-
phine ligands, like Xantphos, dppp, dppb, PCy3, and P(C6H2-
3,5-(CF3)2)3, which have been proven to be efficient ligands
for our previous C−C activation reactions, however, all inhib-
ited this reaction to various extents except P(C6H4-4-F)3, re-
DG
COOEt
DG
DG
Et
DG
N
N
N
N
N
N
O
O
O
O
N
N
Me
Me
Me
90%
Me
3al 74%
,
3aj
3ak 94%
,
,
3ai
98%
,
a
b
All the yields are isolated yields. The reaction was conducted
in PhCl.
The scope of the isatins and DGs was next investigated and
compared (Table 3). Besides 3-methyl-2-pyridyl-based DGs,
other groups, such as 2-pyridyl (3bk and 3dk) and 1H-
indazol-1-yl (3ck), showed good reactivity for the transfor-
mation. Isatin substrates with a methyl group at the C-5 posi-
tion led to the corresponding product 3dk in 84% yield. In
addition, the N-benzyl protected isatin worked equally well
(3ek). Finally, the 7-aza-isatin compound was also found to be
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ACS Catalysis
a viable substrate, giving an interesting 1,3-dihydro-2H- cates that the transformation is likely initiated by directed C−C
1
imidazo[4,5-b]pyridin-2-one (3fk) as the product.
activation of isatins.
2
3
4
5
6
7
8
Table 3. The reaction scope of isatins
DG
2k
Bn
O
mol%
DG
DG CO
Rh
50
Bn
N
O
H4 2Cl]2
)
L
[Rh(C2
N
O
(1)
O
O
rt
toluene,
DG
1
Cl
N
Me
DG
200 mol% AsPh3
O
N
Me
5 mol%
20 mol% AsPh3
ref. 14
N
dioxane, 160 o
81%
C
[Rh(cod)Cl]2
N
N
R2
3ak
Me
R1
O
+
N
R1
O
1a
Int 1
PhCl, 160oC
N
R2
O
=
DG
3-methyl-2-pyridinyl
2k
3
3.0
equiv
Consequently, four possible reaction pathways are proposed
as depicted in Scheme 3: (i) the isocyanate inserts into the
aryl−Rh bond of Int 1 to give Int 2, which then undergoes a
second decarbonylation to give the benzimidazolidinone prod-
uct (path A); (ii) the isocyanate inserts into the acyl−Rh bond
of Int 1 to generate Int 3, which is followed by a second de-
carbonylation and reductive elimination (path B); (iii) direct
reductive elimination of Int 3, followed by a separate decar-
bonylative C−C activation sequence, would also give product
3 (path C); (iv) through Int 1, double-decarbonylative C−C
activation of the isatin can occur to generate a four-membered
rhodacycle Int 4, which then undergoes isocyanate insertion to
afford product 3 (path D).17
9
N
N
N
Me
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bn
N
Bn
Bn
N
N
N
O
O
O
N
Me
N
Me
Me
3ck 41%
,
3bk
73%
,
3ak
94%
,
N
N
N
Me
Me
Bn
Bn
Bn
Bn
N
N
Me
N
N
N
O
O
O
N
Me
N
Me
3fk 55%
,
3ek
90%
,
3dk
84%
,
DG
O
Acyl azides are well-known precursors for preparing isocy-
anates through Curtius rearrangement.3,16 Thus, a one-pot pro-
cess, which combines Curtius rearrangement and C−C activa-
tion, was further developed to access benzimidazolidinone
derivatives with a more complex substituent. Acyl azides were
DG
Lm
DG
O
Rh
CO
CO
Ln
N
Me
N
Rh
O
R
N
O
N
1
N
2
2
R
O
Me
Me
Int 1
Int 4
o
first transformed to the isocyanates after heating at 110 C in
A
path
D
path
DG
O
PhCl for 2-3 hours, which were then treated with isatin 1a
under the double-decarbonylation conditions (Scheme 2).
With this one-pot protocol, the ferrocene derivative (3am),
acetophenone derivative (3an), and Vitamin E derivative (3ao)
were efficiently synthesized from the corresponding acyl az-
ides. It is not surprising that 4-formyl-benzoyl azide was not a
suitable substrate due to the high reactivity of the aryl alde-
hyde moiety under the Rh catalysis conditions.
Rh
Rh-
L]
R
DG
[
O
N
N
R
Rh
N
DG
Lm
N
O
Me
N
Rh
R
Int 3
O
Me
Int 2
N
O
3-13C
C
B
path
path
and
3
Me
Int 5
=
DG
R
N
DG
DG
O
R
N
R
O
O
O
13C
N
O
DG
N
Me
C
-CO
1a
R
1.0
equiv
N
O
N
O
N
3-13
5 mol%
PhCl
110 o
3
N
[Rh(cod)Cl]2
Me
4
R
Me
O
R
N3
O
C
20 mol% AsPh3
1,4-dioxane,
N
160 o
C
3.0
equiv
DG
Me
Scheme 3: Possible reaction pathways
=
DG
3-methyl-2-pyridinyl
F
To examine the feasibility of each reaction mechanism, first,
1,3-dimethylquinazoline-2,4(1H,3H)-dione derivative 4 was
prepared and subjected to the standard reaction conditions (Eq.
2). However, no desired benzimidazolidinone 3ap was ob-
served even after 2 days, which excluded the ‘second separate
decarbonylative C−C activation’ mechanism (path C). Second,
when 13C-labeled isocyanate 2b-13C, was subjected to the reac-
tion with 2a under the standard conditions, the benzimidazoli-
dinone 3ab-13C was isolated in 87% yield with more than 99%
of 13C incorporation at the carbonyl group (Eq. 3). This result
strongly disfavoured both paths A and B, in which partial or
no 13C-labeled product should be observed (Scheme 3). Thus,
path D, involving double decarbonylation first and then isocy-
anate insertion, should be the most reasonable reaction path-
way.
O
Me
Fe
O
DG
N
N
DG
N
N
O
N
N
O
3aa
3am
43%
,
69%
O
,
Me
Me
3an
68%
,
Me
Me
DG
N
N
O
O
Me
O
Me
Me
Me
Me
Me
3ao
85%
,
Scheme 2: Curtius Rearrangement/C−C activation/isocyanate
insertion
To have a better understanding of this transformation, the
reaction mechanism was first explored with stoichiometric
rhodium. According to our previously reported procedure,
treatment of isatin 1a with [Rh(C2H4)2Cl]2 led to the cleavage
of C3−C4 bond and formation of rhodacycle Int 1,14 which
was subsequently examined in the reaction with isocyanate 2k.
Unsurprisingly, the reaction proceeded smoothly and afforded
the desired product 3ak in 81% yield (Eq. 1). This study indi-
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Page 4 of 6
DG
DG
O
N
2002, 189, 157-168. (e) Van der Boom, M. E.; Milstein, D. Chem.
Me
N
5 mol%
20 mol% AsPh3
[Rh(cod)Cl]2
Me
O
Rev. 2003, 103, 1759-1792. (f) Satoh, T.; Miura, M. Top. Organomet.
Chem. 2005, 14, 1-20. (g) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610-
618. (h) Jun, C.-H.; Park, J. W. Top. Organomet.Chem. 2007, 24,
117-143. (i) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008,
41, 222-234. (j) Necas, D.; Kotora, M. Curr. Org. Chem. 2007, 11,
1566-1591. (k) Crabtree, R. H. Chem. Rev. 1985, 85, 245-269. (l)
Kondo, T.; Mitsudo, T. A. Chem. Lett. 2005, 34, 1462-1467. (m)
Ruhland, K. Eur. J. Org. Chem. 2012, 2683-2706. (n) Korotvicka, A.;
Necas, D.; Kotora, M. Curr. Org. Chem. 2012, 16, 1170-1214. (o)
Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Angew. Chem. Int. Ed.
2011, 50, 7740-7752. (p) Murakami, M.; Matsuda, T. Chem. Com-
mun. 2011, 47, 1100-1105. (q) Dermenci, A.; Coe, P. W.; Dong, G.
Org. Chem. Front. 2014, 1, 567-584. (r) Dong, G. ed. C−C bond
activation in Topics in Current Chemistry, Springer-Verlag, Berlin
Heidelberg, 2014, vol. 346. (s) Dermenci, A.; Dong, G. Sci. China,
Chem. 2013, 685-701. (t) Souillart, L.; Cramer, N. Chem. Rev. 2015,
115, 9410-9464. (u) Chen, F.; Wang, T.; Jiao, N. Chem. Rev. 2014,
114, 8613-8661.
N
1
2
3
4
5
6
7
8
(2)
160 o
C
N
O
1,4-dioxane,
Me
Me
no
4
3ap
product
DG
Ph
N
13C
Ph
13C >99%
O
5 mol%
DG
[Rh(cod)Cl]2
N
O
N
20 mol% AsPh3
+
13C
O
(3)
160 o
C
O
1,4-dioxane,
87%
N
Me
3ab-13
2b-13
C
Me
1a
C
9
In summary, we have developed a unique Rh-catalyzed [5-
2+2] transformation through directed C−C activation of isatins
followed by “double decarbonylative cycloaddition” with iso-
cyanates. A broad range of isocyanates can be coupled with
high efficiency, and the corresponding benzimidazolidinone
derivatives can be obtained in good to excellent yields with
high functional group tolerance. In addition, a modified one-
pot process combining a Curtius rearrangement and C−C acti-
vation was also realized. Furthermore, the mechanistic study
disclosed a new mode of reactivity of isatins and strongly sup-
ported the proposed double decarbonylation pathway. The
novel mode of reactivity discovered here is expected to shed
light on developing new heterocycle formation methods
through a C−C/isocyanate coupling. Efforts on extending to
other systems (e.g. use of a temporary DG) are ongoing.
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25
26
27
28
29
30
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35
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(3) For books and reviews on isocyanates, see: (a) Ulrich, H. in
Chemistry and Technology of Isocyanates, John Wiley & Son, Chich-
ester, 1997. (b) Braunstein, P.; Nobel, D. Chem. Rev. 1989, 89, 1927-
1945. (c) Allen, A. D.; Tidwell, T. T. Chem. Rev. 2013, 113, 7287-
7342.
(4) For selected reports on C−H coupling with isocyanates, see: (a)
Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. J. Am. Chem.
Soc. 2006, 128, 202-209. (b) Kuninobu, Y.; Kikuchi, K.; Tokunaga,
Y.; Nishina, Y.; Takai, K. Tetrahedron, 2008, 64, 5974-5981. (c)
Hesp, K. D.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2011,
133, 11430-11433. (d) Muralirajan, K.; Parthasarathy, K.; Cheng, C.-
H. Org. Lett. 2012, 14, 4262-4265. (e) Hou, W.; Zhou, B.; Yang, Y.;
Feng, H.; Li, Y. Org. Lett. 2013, 15, 1814-1817. (f) De Sarkar, S.;
Ackermann, L. Chem. Eur. J. 2014, 20, 13932-13936. (g) Shi, X.-Y.;
Renzetti, A.; Kundu, S.; Li, C.-J. Adv. Synth. Catal. 2014, 356, 723-
728. (h) Hummel, J. R.; Ellman, J. A. Org. Lett. 2015, 17, 2400-2403.
(i) Li, J.; Ackermann, L. Angew. Chem. Int. Ed. 2015, 54, 8551-8554.
(j) Han, S.; Mishra, N. K.; Sharma, S.; Park, J.; Choi, M.; Lee, S.-Y.;
Oh, J. S.; Jung, Y. H.; Kim, I. S. J. Org. Chem. 2015, 80, 8026-8035.
(k) Geng, X.; Wang, C. Org. Biomol. Chem., 2015, 13, 7619-7623.
(5) (a) Yamamoto, K.; Ishida, T.; Tsuji, J. Chem. Lett. 1987, 1157-
1158. (b) Goldberg, A. F. G.; O’Connor, N. R.; Craig II, R. A.; Stoltz,
B. M. Org. Lett. 2012, 14, 5314-5317. (c) Tsunoi, S.; Maruoka, Y.;
Suzuki, I.; Shibata, I. Org. Lett. 2015, 17, 4010-4013.
ASSOCIATED CONTENT
Supporting Information is available free of charge via the Inter-
net at http://pubs.acs.org.
Detailed experimental procedures, characterization of products,
and the X-ray analysis.
AUTHOR INFORMATION
Corresponding Author
* Email: gbdong@cm.utexas.edu
Notes
The authors declare no competing financial interest.
(6) Ishida, N.; Nakanishi, Y.; Murakami, M. Angew. Chem. Int. Ed.
2013, 52, 11875-11878.
ACKNOWLEDGMENT
(7) For a recent review on decarbonylative cross couplings, see: ref
2s. For representative works of catalytic C−C activation with subse-
quent insertion of olefins or alkynes with decarbonylation, see: (a)
Kondo, T.; Nakamura, A.; Okada, T.; Suzuki, N.; Wada, K.; Mitsudo,
T. A. J. Am. Chem. Soc. 2000, 122, 6319-6320. (b) Kondo, T.;
Taguchi, Y.; Kaneko, Y.; Niimi, M.; Mitsudo, T.-A. Angew. Chem.
Int. Ed. 2004, 43, 5369-5372. (c) Yamamoto, Y.; Kuwabara, S.;
Hayashi, H.; Nishiyama, H. Adv. Synth. Catal. 2006, 348, 2493-2500.
(d) Chen, P.-H.; Xu, T.; Dong, G. Angew. Chem., Int. Ed. 2014, 53,
1674-1678.
(8) For representative works of catalytic C−C activation with sub-
sequent insertion of olefins or alkynes without decarbonylation, see:
(a) Edelbach, B. L.; Lachicotte, R. J.; Jones, W. D. Organometallics
1999, 18, 4040-4049. (b) Murakami, M.; Itahashi, T.; Ito, Y. J. Am.
Chem. Soc. 2002, 124, 13976-13977. (c) Ko, H. M.; Dong, G. Nat.
Chem. 2014, 6, 739-744. (d) Wentzel, M. T.; Reddy, V. J.; Hyster, T.
K.; Douglas, C. J. Angew. Chem. Int. Ed. 2009, 48, 6121-6123. (e)
Dreis, A. M.; Douglas, C. J. J. Am. Chem. Soc. 2009, 131, 412-413.
(f) Lutz, J. P.; Rathbun, C. M.; Stevenson, S. M.; Powell, B.
M.; Boman, T. S.; Baxter, C. E.; Zona, J. M.; Johnson, J. B. J. Am.
Chem. Soc. 2012, 134, 715-722. (g) Rathbun, C. M.; Johnson, J. B. J.
Am. Chem. Soc. 2011, 133, 2031-2033. (h) Narasaka, K.; Koga, Y.
Chem. Lett. 1999, 28, 705-706. (i) Li, C.; Zhang, H.; Feng, J.; Zhang,
Y.; Wang, J. Org. Lett. 2010, 12, 3082-3085. (j) Jiao, L.; Lin, M.;
Zhuo, L.-G.; Yu, Z.-X. Org. Lett. 2010, 12, 2528-2531. (k) Wender,
P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc. 1995, 117, 4720-
We thank CPRIT for startup funds, NIGMS (R01GM109054) and
the Welch Foundation (F 1781) for research grants. GD is a Searle
Scholar. We thank Dr. Ying Xia for checking the reproducibility
of the experiments. We thank Dr. M. C. Young for X-ray crystal-
lographic analysis and proofreading of the manuscript. We are
also grateful to Johnson Matthey for a donation of Rh salts.
REFERENCES
(1) For selected reviews on C−H functionalization coupling with
unsaturated units, see: (a) Kakiuchi, F.; Murai, S. Acc. Chem. Res.
2002, 35, 826-834. (b) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev.
2002, 102, 1731-1770. (c) Kakiuchi, F.; Kochi, T. Synthesis, 2008,
3013-3039. (d) Foley, N. A.; Lee, J. P.; Ke, Z.; Gunnoe, T. B.; Cunda-
ri, T. R. Acc. Chem. Res. 2009, 42, 585-597. (e) Kitamura, T. Eur. J.
Org. Chem. 2009, 1111-1125. (f) Colby, D. A.; Bergman, R. G.;
Ellman, J. A. Chem. Rev. 2010, 110, 624-655. (g) Yoshikai, N. Syn-
lett, 2011, 1047-1051. (h) Colby, D. A.; Tsai, A. S.; Bergman, R. G.;
Ellman, J. A. Acc. Chem. Res., 2012, 45, 814-825.
(2) For selected reviews on transition-metal-mediated C−C bond
activations, see: (a) Jones, W. D. Nature 1993, 364, 676-677. (b)
Murakami, M.; Ito, Y. Top. Organomet. Chem. 1999, 3, 97-129. (c)
Rybtchinski, B.; Milstein, D. Angew. Chem. Int. Ed. 1999, 38, 870-
883. (d) Perthuisot, C.; Edelbach, B. L.; Zubris, D. L.; Simhai, N.;
Iverson, C. N.; Müller, C.; Satoh, T.; Jones, W. D. J. Mol. Catal. A
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4721. (l) Shaw, M. H.; Melikhova, E. Y.; Kloer, D. P.; Whittingham,
W. G.; Bower, J. F. J. Am. Chem. Soc. 2013, 135, 4992-4995. (m)
Weintz, H.-J.; Binger, P. Tetrahedron Lett. 1985, 26, 4075-4078. For
C−CN bond cleavage: (n) Nakao, Y.; Oda, S.; Hiyama, T. J. Am.
Chem. Soc. 2004, 126, 13904-13905. (o) Xu, T.; Dong, G. Angew.
Chem., Int. Ed. 2012, 51, 7567-7571.
(9) (a) Suggs, J. W.; Cox, S. D. J. Organomet. Chem. 1981, 221,
199-201. (b) Suggs, J. W.; Jun, C.-H. J. Am. Chem. Soc. 1984, 106,
3054-3056. (c) Suggs, J. W.; Jun, C.-H. J. Am. Chem. Soc. 1986, 108,
4679-4681. (d) Suggs, J. W.; Jun, C.-H. J. Chem. Soc., Chem. Com-
mun., 1985, 92-93.
1
2
3
4
5
6
7
8
9
(10) (a) Lee, H.; Jun, C. -H. J. Am. Chem. Soc. 1999, 121, 880-881.
(b) Jun, C. -H.; Lee, H.; Lim, S.-G. J. Am. Chem. Soc. 2001, 123,
751-752.
10
11
12
13
14
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21
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23
24
25
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27
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48
49
50
51
52
53
54
55
56
57
58
59
60
(11) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc.
1999, 121, 8645-8646.
(12) (a) Lei, Z.-Q.; Pan, F.; Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.;
Wang, X.; Li, Y.-X.; Sun, J.; Shi, Z.-J. J. Am. Chem. Soc. 2015, 137,
5012-5020. (b) Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Shi,
Z.-J. J. Am. Chem. Soc. 2011, 133, 15244-15247. (c) Chen, K.; Li, H.;
Lei, Z.-Q.; Li, Y.; Ye, W.-H.; Zhang, L.-S.; Sun, J.; Shi, Z.-J. An-
gew.Chem. Int. Ed. 2012, 51, 9851-9855. (d) Lei, Z.-Q.; Li, H.; Li,
Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Sun, J.; Shi, Z.-J. Angew.
Chem. Int. Ed. 2012, 51, 2690-2694.
(13) (a) Wang, J.; Chen, W.; Zuo, S.; Liu, L.; Zhang, X.; Wang, J.
Angew. Chem. Int. Ed. 2012, 51, 12334-12338. For other reports us-
ing a directing group for C−C cleavage, see: (b) Gozin, M.; Weisman,
A.; Ben-David, Y.; Milstein, D. Nature 1993, 364, 699-701. (c) Liou,
S.-Y.; Gozin, M.; Milstein, D. J. Am. Chem. Soc. 1995, 117, 9774-
9775. (d) Rybtchinski, B.; Vigalok, A.; Ben-David, Y.; Milstein, D. J.
Am. Chem. Soc. 1996, 118, 12406-12415. (e) Ozkal, E.; Cacherat, B.;
Morandi, B. ACS Catal. 2015, 5, 6458-6462. (f) Tashiro, S.; Yamada,
M.; Shionoya, M. Angew. Chem. Int. Ed. 2015, 54, 5351-5354.
(14) Zeng, R.; Dong, G. J. Am. Chem. Soc.2015, 137, 1408-1411.
(15) CCDC numbers of 3aa and 3al are 1430588 and 1430589, re-
spectively. For more information on the crystal structures, please see
SI.
(16) For reviews on Curtius rearrangement, see: (a) Smith, P. A.
Org. React. 1946, 337-449. (b) Banthorpe, D. V. ed. Rearrangements
Involving Azido Groups in The Chemistry of the Azide Group, Patai,
S., Wiley, New York, 1971, 397-440.
(17) For a review on migratory insertion of unsaturated units into
metal-oxygen and metal nitrogen bonds, see: (a) Hanley, P. S.; Hart-
wig, J. F. Angew, Chem. Int. Ed. 2013, 52, 8510-8525. For example
on migratory insertion of isocyanate into Rh−N bond, see: (b) Whited,
M. T.; Qiu, L.; Kosanovich, A. J.; Janzen, D. E. Inorg. Chem. 2015,
54, 3670-3679.
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DG
DG
DG
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Rh
[Rh(cod)Cl]2
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[5-2+2]
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