Rh(III)-catalyzed olefination of N-sulfonyl imines: Synthesis of ortho -olefinated benzaldehydes

Article abstract of DOI:10.1021/ol403178a

Rh(III)-catalyzed olefination of N-sulfonyl imines using acrylates and styrenes has been achieved for the synthesis of ortho-olefinated benaldehydes. This reaction proceeds via a chelation assisted C-H olefination/in situ hydrolysis process.

Full text of DOI:10.1021/ol403178a

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Rh(III)-Catalyzed Olefination of N‑Sulfonyl
Imines: Synthesis of Ortho-Olefinated
Benzaldehydes
Tao Zhang,† Lamei Wu,*,† and Xingwei Li*,‡
College of Chemistry and Materials Science, South-Central University for Nationalities,
Wuhan 430074, China, and Dalian Institute of Chemical Physics, Chinese Academy of
Sciences, Dalian 116023, China
xwli@dicp.ac.cn; wlm52875@163.com
Received November 4, 2013
ABSTRACT
Rh(III)-catalyzed olefination of N-sulfonyl imines using acrylates and styrenes has been achieved for the synthesis of ortho-olefinated
benaldehydes. This reaction proceeds via a chelation assisted CÀH olefination/in situ hydrolysis process.
Direct functionalization of unreactive CÀH bonds has
been a dynamic research area in synthetic organic chemistry
in the past decades.1 This process takes advantage of the
ubiquity of CÀH bonds in organics and delivers products in
a step- and atom-economic fashion. Ever since the seminal
work by Fujiwara and Moritani on oxidative CÀH olefina-
tion of arenes,2 CÀH olefination has been extensively
explored using various transition metal catalysts such as
Pd,2,3 Ru,1h,4 and Rh,1c,j,m,f,g,5 among others. In most cases,
a chelating group was preinstalled that facilitates the CÀH
activation and olefination. Despite the significant progress,
the scope of the substrate still needs expansion.
† South-Central University for Nationalities.
‡ Chinese Academy of Sciences.
(1) Selected reviews: (a) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q.
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Rh(III)-catalyzed CÀH olefination has been achieved
with the assistance of a variety of nitrogen6 and oxygen
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r
10.1021/ol403178a
XXXX American Chemical Society

directing groups such as tertiary amide, ester, and ketones.6,7
Thus aryl ketones have been well-studied in CÀH olefination
reactions. However, benzaldehydes are more challenging
substrates,8 and occasionally the aldehyde group can act as
an efficient directing group for CÀH olefination reactions9
because of the low ligating ability of the aldehyde oxygen and
related competitive side reactions. Furthermore, the oxida-
tive conditions might not be compatible with the aldehyde
group. It has been reported that aldimines offer stronger
chelation assistance for CÀH activation and act as a surro-
gate of aldehydes.10 However, although imine-directed CÀH
olefination has been reported,11 a challenge remains since
the imine group is prone to hydrolysis prior to CÀH
activation. We now report usage of N-Ts imines as a re-
movable directing group in Rh(III)-catalyzed olefinationÀ
in situ hydrolysis of N-Ts aldimines.
the catalyst was simply switched to [RhCp*(MeCN)3](SbF6)2
(5 mol %) at a slightly lower temperature, with the selec-
tivity being retained (entry 11). Thus the following conditions
were eventually chosen for subsequent mono-olefination
studies: [RhCp*(MeCN)3](SbF6)2 (5 mol %), Cu(OAc)2
3
H2O (2.0 equiv) acrylate (1.2 equiv), AcOH (2.0 equiv),
1,4-dioxane, and 80 °C. In contrast to the high efficiency of
the N-Ts imine substrate, essentially no desired product
was generated when simple benzaldehyde was applied as a
more straightforward substrate, indicating that theimine is
a more efficient directing group. Furthermore, no desired
coupling occurred when the imine 1a was switched to
PhCHdNtBu,13 where significant hydrolysis took place,
highlighting the importance of the selection of a suitable
imine.
We recently reported metal-catalyzed CÀH activation
of N-Ts imines and subsequent redox-neutral functionali-
zation with alkynes for the synthesis of indenamines, a
process where the N-Ts group is retained.12 We reasoned
that under appropriate conditions, CÀH olefination may
also proceed. With this in mind, we initiated our studies by
screening conditions for the coupling of N-Ts benzalde-
hyde imine withtert-butylacrylate. We found that both the
coupling efficiency and selectivity are low when [RuCl2(p-
cymene)]2/AgSbF6 (5 mol %/20 mol %) was used as a
catalyst and AgOAc was used as an oxidant in the presence
of acetic acid (85 °C, Table 1, entry 1).4eÀi The coupled
product was identified as an ortho-olefinated aldehyde
(3aa) as a result of CÀH olefination followed by in situ
hydrolysis. Using anhydrous Cu(OAc)2 as an oxidant
slightly increased the yield (entry 2). In contrast, when
Table 1. Optimization Studies on Mono-olefinationa,b
temp
yieldc
(%)
entry
catalyst
oxidant
AgOAc
solvent
(°C)
1
A
A
A
A
A
A
A
A
A
B
B
B
dioxane
dioxane
dioxane
dioxane
dioxane
DCE
85
85
85
90
85
85
85
85
85
85
80
80
47
2
Cu(OAc)2
51
3
Cu(OAc)2 H2O
70
3
4
Cu(OAc)2 H2O
66
3
5d
6
Cu(OAc)2 H2O
65
3
Cu(OAc)2 H2O
trace
27
3
7
Cu(OAc)2 H2O
THF
3
8
Cu(OAc)2 H2O
DCM
trace
71
3
the oxidant was changed to Cu(OAc)2 H2O, the coupling
3
9
Cu(OAc)2 H2O
dioxane
dioxane
dioxane
dioxane
3
occurred with both good efficiency and high selectivity.
Under these conditions the amount of AcOH only margin-
ally affected the coupling efficiency. However, poor results
were obtained when the solvent was switched to DCE,
DCM, or THF (entries 6À8). To our delight, a slightly
higher yield of the olefination product was isolated when
10
11
12
Cu(OAc)2 H2O
73
3
Cu(OAc)2 H2O
75
3
Cu(OAc)2
68
a Reaction conditions: N-Ts imine (0.3 mmol), acrylate (0.36 mmol),
catalyst, oxidant (0.6 mmol), HOAc (0.6 mmol), solvent (3 mL),
80À90 °C, 14 h, under argon. b A = [RuCl2(p-cymene)]2 (5 mol %)/
AgSbF6 (20 mol %), B = [Cp*Rh(MeCN)3](SbF6)2 (5 mol %). c Isolated
yield. d No HOAc was used.
(7) (a) Shen, Y.; Liu, G.; Zhou, Z.; Lu, X. Org. Lett. 2013, 15, 3366.
(b) Park, S. H.; Kim, J. Y.; Chang, S. Org. Lett. 2011, 13, 2372. (c)
Patureau, F. W.; Besset, T.; Glorius, F. Angew. Chem., Int. Ed. 2011, 50,
1064. (d) Gong, T.-J.; Xiao, B.; Liu, Z.-J.; Wan, J.; Xu, J.; Luo, D.-F.;
Fu, Y.; Liu, L. Org. Lett. 2011, 13, 3235. (e) Feng, C.; Feng, D.; Loh,
T.-P. Org. Lett. 2013, 15, 3670.
(8) Gandeepan, P.; Parthasarathy, K.; Cheng, C.-H. J. Am. Chem.
Soc. 2010, 132, 8569.
(9) Padala, K.; Jeganmohan, M. Org. Lett. 2012, 14, 1134. This paper
reported a limited scope of aldehyde olefination reactions. When we
repeated the reactions under their conditions, the olefination products
were isolated in very low yield.
(10) (a) Jun, C.-H.; Lee, H.; Park, J.-B.; Lee, D.-Y. Org. Lett. 1999, 1,
2161. (b) Jun, C.-H.; Chung, K.-Y.; Hong, J.-B. Org. Lett. 2001, 3, 785. (c)
Lim, S.-G.; Lee, J. H.; Moon, C. W.; Hong, J.-B.; Jun, C.-H. Org. Lett.
2003, 5, 2759. (d) Parthasarathy, K.; Senthilkumar, N.; Jayakumar, J.;
Cheng, C.-H. Org. Lett. 2012, 14, 3478. (e) Chen, S.; Yu, J.; Jiang, Y.; Chen,
F.; Cheng, J. Org. Lett. 2013, 15, 4754. (f) Tan, P. W.; Juwaini, N. A. B.;
Seayad, J. Org. Lett. 2013, 15, 5166. (g) Lian, Y.; Hummel, J. R.; Bergman,
R. G.; Ellman, J. A. J. Am. Chem. Soc. 2013, 135, 12548.
With these optimal conditions in hand, we set out to
explore the scope and limitations of this system. A series of
acrylates underwent smooth coupling with 1a, and the
olefinated aldehydes were isolated in 71À79% yield. A
broad scope of N-Ts imines has also been defined. Thus
electron-donating, -withdrawing, and halogen groups at
the different positions of the benzene ring are well toler-
ated, including a para-nitro substituent which is usually
problematic in CÀH activation reactions. Moderate to
high yields of the coupled products were isolated although
electron-poor imines tend to give lower yields. The good to
(11) For selected examples, see: (a) Ding, S.; Shi, Z.; Jiao, N. Org.
Lett. 2010, 12, 1540. (b) Yamakawa, T.; Yoshikai, N. Org. Lett. 2013, 15,
196. (c) Shi, Z.; Koester, D. C.; Boultadakis-Arapinis, M.; Glorius, F.
J. Am. Chem. Soc. 2013, 135, 12204. (d) Yamakawa, T.; Yoshikai, N.
Tetrahedron 2013, 69, 4459.
(13) For selected examples on CÀH activation of this imine, see: (a)
Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2005, 127,
13498. (b) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. J. Am.
Chem. Soc. 2006, 128, 202. (c) Kuninobu, Y.; Ueda, H.; Kawata, A.;
Takai, K. J. Org. Chem. 2007, 72, 6749. (d) Guimond, N.; Fagnou, K.
J. Am. Chem. Soc. 2009, 131, 12050.
(12) Zhao, P.; Wang, F.; Han, K.; Li, X. Org. Lett. 2012, 14, 5506.
B
Org. Lett., Vol. XX, No. XX, XXXX

high yield synthesis of 3ba, 3ja, and 3la (Scheme 1)
indicates that steric hindrance of a relatively bulky aryl
ring induced by ortho substitution can be tolerated. In the
case of meta-substituted imines, the CÀH activation oc-
curred selectively and consistently at the less hindered site.
These olefinated aldehydes are known as important pre-
cursors for the synthesis of a variety of complex struc-
tures.14 The preinstalled halogen, nitro, and cyano groups
in the coupled products are typically encountered in
organic synthesis and should allow further chemical ma-
nipulation. In contrast to the efficient coupling of these
imines of benzadehydes, subjection of the N-Ts imines of
2-furaldehyde and 2-picolinaldehyde to the standard con-
ditions mostly returned the starting materials, with <10%
formation of the desired product.
product could be isolated in 78% yield with a ratio of 1:6
for the mono- to diolefination. HOAc has a miminal effect
on the reaction selectivity and efficiency.
Table 2. Optimization Studies of Diolefinationa
temp
yieldb
(%)
entry
oxidant
additive
(°C)
mono/di
1
2
3
4
5
6
Cu(OAc)2 H2O
HOAc
HOAc
HOAc
HOAc
HOAc
none
90
70
73
76
76
75
78
1:3
1:4
1:5
1:5
1:5
1:6
3
Cu(OAc)2 H2O
95
3
Cu(OAc)2 H2O
100
105
100
100
3
Cu(OAc)2 H2O
3
Scheme 1. Scope of Mono-Olefination with Acrylatesa,b
Cu(OAc)2
Cu(OAc)2
a Reaction conditions: N-Ts imine (0.3 mmol), acrylate (0.9 mmol),
[RhCp*(MeCN)3](SbF6)2 (5 mol %), copper salt (1.2 mmol), HOAc
(0.6 mmol), 1,4-dioxane (3 mL), 100 °C, 24 h, under argon. b Isolated
yield.
Under these diolefination conditions, the coupling part-
ner to imine 1a was extended to a series of acrylates to
afford the diene product in high yields (Scheme 2). In
addition, variation of the para substituent to methyl and
halogens is well tolerated, and the coupled products were
isolated in consistently high yields.
Scheme 2. Diolefination Using Acrylatesa,b
a Reaction conditions: N-Ts imine (0.3 mmol), acrylate (0.36 mmol),
[Cp*Rh(MeCN)3](SbF6)2 (5 mol %),Cu(OAc)2 H2O (0.6 mmol),
3
HOAc (0.6 mmol), 1,4-dioxane (3 mL), 80 °C, 12 h, under argon.
b Isolated yield.
To achieve the complementary diolefination of these
imines, the reaction conditions of the coupling of 1a with
tert-butyl acrylate were further optimized (Table 2). Using
anexcess of the acrylate (3 equiv) and anhydrousCu(OAc)2
(4 equiv) at 100 °C, we found that although the mono-
olefination product was still generated, the diolefination
(14) (a) Xia, W.; Shao, Y.; Gui, W.; Yang, C. Chem. Commun. 2011,
47, 11098. (b) Jagdale, A. R.; Youn, S. W. Eur. J. Org. Chem. 2011, 2011,
3904. (c) Das, B. G.; Ghorai, P. Chem. Commun. 2012, 48, 8276. (d)
Kundu, K.; McCullagh, J. V.; Morehead, A. T. J. Am. Chem. Soc. 2005,
127, 16042.
a Reaction conditions: N-Ts imine (0.3 mmol), acrylate (0.9 mmol),
[RhCp*(MeCN)3](SbF6)2 (5 mol %), Cu(OAc)2 (1.2 mmol), 1,4-dioxane
(3 mL), 100 °C, 24 h, under argon. b Isolated yield.
Org. Lett., Vol. XX, No. XX, XXXX
C

mono-olefinated benzaldehyde 3aa to the reaction condi-
tions for diolefination with tert-butyl acrylate only re-
turned the starting material. This result suggests that the
(di)olefination should occur prior to hydrolysis. To further
probe this CÀH activation process, the intermolecular
KIE has been measured on the basis of the competitive
coupling of tert-butyl acrylate with an equimolar mixture
of 1a and 1a-d5 (eq 2). 1H NMR analysis revealed a rather
large value of kH/kD = 6.1, and this large value indicates
that the reaction proceeds via a CÀH activation pathway.
Scheme 3. Mono-olefination Using Styrenesa,b
1
In addition, on the basis of H NMR spectroscopy, no
H/D exchange was detected at the ortho position of prod-
ucts 3aa and 3aa-d4, suggesting that the CÀH activation is
irreversible under the catalytic conditions.
a Reaction conditions: N-Ts imine (0.3 mmol), styrene (0.36 mmol),
[RhCp*(MeCN)3](SbF6)2 (5 mol %), Cu(OAc)2 (0.6 mmol), 1,4-dioxane
(3 mL), 90 °C, 18 h, under argon. b Isolated yield.
Extension of the olefin substrate to styrenes met with
failure when we directly applied the conditions of mono-
olefination adopted for acrylates, but modified conditions
for acrylates turned out to be applicable. Thus high effi-
ciency was reached for the coupling of 1a with simple styrene
using anhydrous Cu(OAc)2 as an oxidant (2.0 equiv) at
90 °C in the absence of AcOH. However, an inseparable
mixture of the mono- and diolefination products was
obtained in a 6:1 ratio and in 78% total yield (eq 1), even
though an equimolar amount of styrene was provided.
Further attempts to effectively improve the reaction
selectivity met with failure. Hence a blocking group was
introduced to the ortho and meta position of the benzene
ring to ensure high regioselectivity. Indeed, good isolated
yields were consistently achieved when methyl, halogen,
and methoxy groups were introduced as blocking groups
(Scheme 3). In addition to simple styrenes, 4-chloro- and
naphthylstyrene also coupled efficiently.
In summary, we have successfully applied N-Ts imine as
a removable directing group for the olefination of imines,
leading to an efficient synthesis of olefinated benzalde-
hydes. This coupling occurs via a CÀH oxidative olefination/
hydrolysis process, and it circumvents the poor directing
effectof aldehydes. Under different conditions, both acrylates
and styrenes are viable olefin substrates. In addition, efficient
diolefination using acrylates was also achieved under control
of the condition. These olefinated aldehydes are important
building blocks in organic synthesis. Thissynthetic method
demonstrated the removable directing effect of N-Ts im-
ines and may find useful applications in the synthesis of
related structures.
Acknowledgment. Financial support from the Dalian
Institute of Chemical Physics, Chinese Academy of
Sciences, and the NSFC (No. 21272231) is acknowledged.
X.L. conceived and designed all the experiments.
Supporting Information Available. Standard experi-
mental procedure, characterization data of the products,
and copies of the NMR spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
Several experiments have been performed to obtain
insight into the reaction mechanism. Subjection of the
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX