Olefinic C-H bond addition to aryl aldehyde and its N-sulfonylimine via Rh catalysis

Article abstract of DOI:10.1021/ol301989n

The first example of olefinic C-H addition to N-sulfonylaldimines and aryl aldehydes is reported. This strategy offered a concise and high atom-economic approach to vinyl amines and vinyl alcohols.

Full text of DOI:10.1021/ol301989n

ORGANIC
LETTERS
2012
Vol. 14, No. 17
4498–4501
Olefinic CÀHBondAdditiontoArylAldehyde
and Its N‑Sulfonylimine via Rh Catalysis
Yang Li,†,§ Xi-Sha Zhang,†,§ Qi-Lei Zhu,† and Zhang-Jie Shi*,‡
Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of
Chemistry, Peking University, Beijing 100871, China, and State Key Laboratory of
Organometallic Chemistry, SIOC, CAS, Shanghai 200032, China
zshi@pku.edu.cn
Received July 18, 2012
ABSTRACT
The first example of olefinic CÀH addition to N-sulfonylaldimines and aryl aldehydes is reported. This strategy offered a concise and high atom-
economic approach to vinyl amines and vinyl alcohols.
Transition-metal catalyzed CÀH functionalization has
aldehyde via Rh catalysis with the assistance of a proper
directing group. This strategy offered a concise and high
atom-economic approach to allylic amines and alcohols.
Containing the double bond,8 the designed products
show potential transformations. Herein, we wish to
report our recent research on the first direct alkene
CÀH bond addition to N-sulfonyl aldimines and aryl
aldehydes (eq 2).
been demonstrated as one of the most popular methods in
We first examined the alkenyl CÀH addition to imines.
The olefin substrate 1a was synthesized and selected as a
model substrate. After the systematic studies we found that
organic synthesis.1 Although hydroarylation of alkenes
and alkynes has been well developed,2 only a few exam-
ples of CÀH addition to polar multiple bonds have been
reported, the overwhelming majority of which were fo-
cused on the aromatic CÀH bonds.3 In recent decades,
Rh complexes played active roles in the catalysis of direct
CÀH transformations.4 Recently, Ellman and Bergman’s
group and ours independently reported the rhodium
catalyzed aryl CÀH addition to imines.5 Subsequently,
Ellman and Bergman’s group reported aryl and vinyl
CÀH addition to N-isocyanates.6 Li’s group and ours
also extended aryl CÀH addition to aryl aldehydes.7
Inspired by these developments (eq 1), we envisioned that
the addition of olefinic CÀH bonds to aldimines and
(1) For reviews on CÀH activation, see: (a) Jia, C.; Kitamura, T.;
Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. (b) Miura, M.; Nomura, M.
Top. Curr. Chem. 2002, 219, 211. (c) Ritleng, V.; Sirlin, C.; Pfeffer, M.
Chem. Rev. 2002, 102, 1731. (d) Kakiuchi, F.; Chatani, N. Adv. Synth.
Catal. 2003, 345, 1077. (e) Godula, K.; Sames, D. Science 2006, 312, 67.
(f) Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev. 2007, 36, 1173.
(g) Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (h) Chen,
M. S.; White, M. C. Science 2007, 318, 783. (i) Chen, X.; Engle, K. M.;
Wang, D. H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094.
(j) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42,
1074. (k) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int.
Ed. 2009, 48, 9792. (l) Li, C.-J. Acc. Chem. Res. 2009, 42, 335. (m) Colby,
D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624.
(n) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (o) Sun,
C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 46, 677. (p) Jazzar, R.;
Julien, H.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem.;Eur.
J. 2010, 16, 2654. (q) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.;
Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890. (r) Gutekunst,
W. R.; Baran, P. S. Chem. Soc. Rev. 2011, 40, 1976. (s) Wencel-Delord,
€
J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740.
(t) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (u) Cho, S. H.;
Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068.
(v) Ackermann, L. Chem. Rev. 2011, 111, 1315. (w) Liu, C.; Zhang,
H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780.
† Peking University.
‡ CAS.
§ These authors contributed equally.
r
10.1021/ol301989n
Published on Web 08/14/2012
2012 American Chemical Society

the catalyst loading was increased to 10 mol % (Scheme 1,
3c). This result might be attributed to torsional effects.
Unfortunately, no desired products were detected when
2-vinylpyridne, 2-(prop-1-en-2-yl)pyridine, and (E)-2-
(prop-1-enyl)pyridine were submitted. To our delight,
heterocyclic substrate 1d was surveyed and the desired
product 3d was obtained in an acceptable yield. Moreover,
various imines were investigated with 1a as a standard
substrate. The following observations were made: (1) An
electron-withdrawing substituent on the phenyl group of
the imine moiety is beneficial, which arises from enhance-
ment of the electrophilicity of the corresponding N-
tosylaldimine (3f, 3g). (2) A meta-substituted group slightly
decreases the efficiency (3h). In comparison with the
electronic effect, the steric hindrance highly affected this
transformation and the ortho-methyl substituted N-tosy-
laldimine only exhibited poor efficiency (Scheme 1, 3k). (3)
The heterocyclic N-tosylaldimine also showed credible
reactivity and the desired product was obtained in an
acceptable yield, keeping the heterocyclic ring untouched
(Scheme 1, 3l). (4) With Boc as the protecting group
instead of the tosyl group, the desired product was ob-
tainedalbeitina muchloweryieldintheabsence oftheacid
additive by using dichloromethane (DCM) as the solvent,
caused by the lower stability of Boc-imine under the
optimized conditions (Scheme 1, 3e).
Table 1. Conditions Screening for Alkene CÀHAdditiontoIminea
catalyst
(%)
temp reaction isolated
entry
additive
(°C) time (h) yield (%)
1b
2
10
5
À
À
90
110
110
110
110
72
48
48
48
48
48
48
62
65
63
62
64
69
57
3
5
HOAc (5 mol %)
HOAc (20 mol %)
PivOH (5 mol %)
4
5
5
5
6
5
PivOH (20 mol %) 110
PivOH (50 mol %) 110
7
5
a 1a (0.25 mmol), 2a (0.50 mmol) in t-BuOH (0.25 M) under a N2
atmosphere in a sealed reaction tube. b t-BuOH (0.50 M). See ORTEP
drawing of 3a below. Thermal ellipsoids are drawn at 30% probability,
and H-atoms are omitted for clarity.
Next, the alkenyl CÀH addition to aldehydes was
investigated (Table 2). Due to the high reactivity of alkene
1b in the above reaction, it was selected as a model
substrate to perform the addition with aldehyde 4a.7b
Unfortunately, no desired product 5a was detected when
the reported conditions were applied (Table 2, entry 1). To
the desired addition product 3a was obtained in 62%
isolated yield in the presence of 10 mol % [Cp*Rh-
(CH3CN)3][SbF6]2 as the catalyst in 72 h (Table 1, entry 1).
The structure of the desired compound 3a was confirmed
by the X-ray crystallography of its single crystal. With an
increase in temperature to 110 °C, a comparable yield
(65%) was obtained with a lower catalyst loading (5.0 mol %)
in a much shorter time (48 h) (Table 1, entry 2). Further
increasing the temperature to 130 °C induced the partial
decomposition of sulfonylaldimine 2a, which resulted in a
difficult separation of the desired product 3a from the
decomposed byproduct. Many other conditions were
tested, and we finally found that 20 mol % of PivOH
slightly promoted the efficiency (Table 1, entry 6).
(3) For the addition of CÀH bonds to a carbonyl group, see:
(a) Fukumoto, Y.; Sawada, K.; Hagihara, M.; Chatani, N.; Murai, S.
Angew. Chem., Int. Ed. 2002, 41, 2779. (b) Kuninobu, Y.; Nishina, Y.;
Nakagawa, C.; Takai, K. J. Am. Chem. Soc. 2006, 128, 12376. (c) Zhao,
B.; Lu, X. Org. Lett. 2006, 8, 5987. (d) Kuninobu, Y.; Nishina, Y.;
Takeuchi, T.; Takai, K. Angew. Chem., Int. Ed. 2007, 46, 6518.
(e) Kuninobu, Y.; Nishina, Y.; Takai, K. Tetrahedron 2007, 63, 8463.
(f) Kuninobu, Y.; Fujii, Y.; Matsuki, T.; Nishina, Y.; Takai, K. Org.
Lett. 2009, 11, 2711. (g) Tsuchikama, K.; Hashimoto, Y.; Endo, K.;
Shibata, T. Adv. Synth. Catal. 2009, 351, 2850. (h) Li, B.-J.; Shi, Z.-J.
Chem. Sci. 2011, 2, 488. For the addition of CÀH bonds to other polar
bonds: (i) Jones, W. D.; Foster, G. P.; Putinas, J. M. J. Am. Chem. Soc.
1987, 109, 5047. (j) Zhou, C.; Larock, R. C. J. Am. Chem. Soc. 2004, 126,
2302. (k) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. J. Am.
Chem. Soc. 2006, 128, 202. (l) Kuninobu, Y.; Inoue, Y.; Takai, K. Chem.
Lett. 2006, 35, 1376. (m) Kuninobu, Y.; Kikuchi, K.; Takai, K. Chem.
Lett. 2008, 37, 740. (n) Qian, B.; Guo, S.; Shao, J.; Zhu, Q.; Yang, L.;
Xia, C.; Huang, H. J. Am. Chem. Soc. 2010, 132, 3650. (o) Boogaerts,
I. I. F.; Nolan, S. P. J. Am. Chem. Soc. 2010, 132, 8858. (p) Zhang, L.;
Cheng, J.; Ohishi, T.; Hou, Z. Angew. Chem., Int. Ed. 2010, 50, 8670.
(q) Boogaerts, I. I. F.; Fortman, G. C.; Furst, M. R. L.; Cazin, C. S. J.;
Nolan, S. P. Angew. Chem., Int. Ed. 2011, 50, 8674.
With the optimized conditions, the ring size of vinyl
substrates was investigated with N-tosyl benzaldimine 2a.
To our delight, the five-membered substrate gave an 84%
isolated yield (Scheme 1, 3b). Comparably, the seven-
memberedsubstrate gavea muchlower efficiencyalthough
(4) For recent reviews, see: (a) Bouffard, J.; Itami, K. Top. Curr.
Chem. 2010, 292, 231. (b) Colby, D. A.; Tsai, A.-S.; Bergman, R. G.;
Ellman, J. A. Acc. Chem. Res. 2012, 45, 814.
(5) (a) Tsai, A. S.; Tauchert, M. E.; Bergman, R. G.; Ellman, J. A.
J. Am. Chem. Soc. 2011, 133, 1248. (b) Li, Y.; Li, B.-J.; Wang, W.-H.;
Huang, W.-P.; Zhang, X.-S.; Chen, K.; Shi., Z.-J. Angew. Chem., Int. Ed.
2011, 50, 2115.
(6) Hesp, K. D.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc.
2011, 133, 11430.
(7) (a) Yang, L.; Correia, C. A.; Li, C.-J. Adv. Synth. Catal. 2011, 353,
1269. (b) Li, Y.; Zhang, X.-S.; Chen, K.; He, K.-H.; Pan, F.; Li, B.-J.;
Shi, Z.-J. Org. Lett. 2012, 14, 636.
(2) For recent repesentative samples, see: (a) Muralirajan, K.;
Parthasarathy, K.; Cheng, C.-H. Angew. Chem., Int. Ed. 2011, 50,
4169. (b) Gao, K.; Yoshikai, N. Angew. Chem., Int. Ed. 2011, 50,
6888. (c) Gao, K.; Yoshikai, N. J. Am. Chem. Soc. 2011, 133, 400.
(d) Patureau, F. W.; Besset, T.; Kuhl, N.; Glorius, F. J. Am. Chem. Soc.
2011, 133, 2154. (e) Lee, P.-S.; Fujita, T.; Yoshikai, N. J. Am. Chem. Soc.
2011, 133, 5221. (f) Ilies, L.; Chen, Q.; Zeng, X.; Nakamura, E. J. Am.
Chem. Soc. 2011, 133, 17283. (g) Li, X.; Gong, X.; Zhao, M.; Song, G.;
Deng, J.; Li, X. Org. Lett. 2011, 13, 5808. (h) Padala, K.; Jeganmohan,
M. Org. Lett. 2011, 13, 6144. (i) Li, B.; Ma, J.; Wang, N.; Feng, H.; Xu,
S.; Wang, B. Org. Lett. 2012, 14, 736. (j) Li, B.-J.; Wang, H.-Y.; Zhu,
Q.-L.; Shi, Z.-J. Angew. Chem. Int. Ed 2012, 51, 3948. For recent reivews,
see: (k) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731.
(l) Satoh, T.; Miura, M. Chem.;Eur. J. 2010, 16, 11212.
(8) Larock, R. C. Comprehensive Organic Transformations, a Guide to
Functional Group Preparations, 2nd ed.; Wiley-VCH: 1999; pp 215À562.
Org. Lett., Vol. 14, No. 17, 2012
4499

Scheme 1. Substrate Scope of Alkene CÀH Addition to Iminesa
Table 2. Conditions Screening for Alkene CÀH Addition to
Aldehydesa
temp
time 1H NMR
(h) yield (%)
entry
solvent
(°C)
additive
1b
2b
3
Et2O/Me0H (2:1)
DCM
90 H2O (30 equiv) 48
À
75
75
À
À
À
À
À
À
À
À
À
12
12
12
12
12
12
12
12
12
12
12
12
8
28
DCM
46
4
DCM
90
62
5
CHCl3
90
63
6
DCE
90
63
7
t-BuOH
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
CCl3CH3
90
65
8
90
56
9
120
130
57 (60c)
58c
60
10
11
12
13
14
15
16
17
120 PivOH (5%)
120 PivOH (10%)
120 PivOH (20%)
120 PivOH (10%)
120 PivOH (10%)
120 PivOH (10%)
120 PivOH (10%)
65 (68c)
57
a 1a (0.25 mmol), 2 (0.50 mmol) in t-BuOH (0.25 M) under a N2
atmosphere in a sealed reaction tube at 110 °C for 48 h, and isolated
yields were reported. b10 mol % catalyst was used. cDCM was used as
solvent. d 1HNMR yield was reported.
64
4
68 (73c)
63
2
1
51
our delight, a 28% 1H NMR yield was observed when the
reaction was conducted in DCM (Table 2, entry 2).
Compared with catalyst [Cp*Rh(CH3CN)3][BF4]2, the
reaction gave a higher yield with [Cp*Rh(CH3CN)3]-
[SbF6]2 as the catalyst (Table 2, entry 3). When the
temperature was increased from 75 to 90 °C, the yield
increased correspondingly (Table 2, entry 4). Solvent
screening revealed CHCl3, DCE, and t-BuOH resulted in
similar reaction efficiencies to that using DCM (Table 2,
entries 5À7). Although the reaction gave a slightly lower
yield using 1,1,1-trichloroethane as solvent, it was selected
for the following experiments because the formation of the
inseparable byproduct (2-chloro-5-nitrophenyl)methanol
was inhibited (Table 2, entry 8). When the reaction tem-
perature was increased to 120 °C, the yield improved
slightly (Table 2, entry 9). Higher temperatures did not
enhance the yield (Table 2, entry 10). Screening of the
amount of PivOH showed that the reaction can reach a
better yield (68% isolated yield, Table 2, entry 12) with
10 mol % PivOH. Notably, higher efficiency was ob-
tained when the reaction time was reduced to 4 h
(Table 2, entry 15).
a 1b (0.25 mmol), 4a (0.75 mmol) in solvent (0.25 M) under an air
atmosphere in a sealed reaction tube. b [Cp*Rh(CH3CN)3][BF4]2 was
used as the catalyst. c Isolated yield.
electron-withdrawing groups on the phenyl part of alde-
hyde were investigated. The reactions showed moderate
efficiency with cyano (Scheme 2, 5e), trifluoromethyl
(Scheme 2, 5f), and ester (Scheme 2, 5g) substituents. An
acceptable yield was also obtained with dibromo substi-
tuted benzaldehyde (Scheme 2, 5h), which could under-
go further transformations to diversify the product.9
With benzaldehyde as a partner, the reaction gave a low
yield (17%), accompanied by a 50% recovery of starting
material alkene 1b (Scheme 2, 5i). Although the yield of
this transformation is relatively lower, this observation
is important to show the potential of the vinyl CÀH
addition to normal aldehyde. Based on the good reac-
tivity of 2-chloro-5-nitrobenzaldehyde and the poten-
tial for further transformation of the nitro group, other
halides were introduced to nitrobenzaldehyde at dif-
ferent substituted positions. When a nitro group was
present on the meta- or para-position, substrates 5j to
5p showed good yields. Notably, in the presence of an
Similar to the alkene CÀH addition to N-Ts imines, the
six-membered substrate exhibited a much lower efficiency
(Scheme 2, 5b, 43% yield) compared to the five-membered
substrate (Scheme 2, 5a). However, the desired product
was not detected with a seven-membered ring substrate.
Different aryl aldehydes were further explored with 1b as a
substrate. First, 4-nitrobenzaldehyde was used and the
reaction gave a moderate yield (Scheme 2, 5c). When a
nitro group was introduced at the m-position, the reaction
exhibited better efficiency (Scheme 2, 5d). Other different
(9) Katritzky, A. R.; Taylor, R. J. K. Comprehensive Organic Func-
tional Group Transformations II; Elsevier: Dordrecht, 2004; Chapter 2, pp
561À593.
(10) (a) Li, Y.; Zhang, X.-S.; Li, H.; Wang, W.-H.; Chen, K.; Li, B.-J.;
Shi, Z.-J. Chem. Sci. 2012, 3, 1634. (b) Tauchert, M. E.; Incarvito, C. D.;
Rheingold, A. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2012,
134, 1482.
(11) (a) Scheeren, C.; Maasarani, F.; Hijazi, A.; Djukic, J.-P.; Pfeffer,
M. Organometallics 2007, 26, 3336. (b) Li, L.; Brennessel, W. W.; Jones,
W. D. J. Am. Chem. Soc. 2008, 130, 12414. (c) Li, L.; Brennessel, W. W.;
Jones, W. D. Organometallics 2009, 28, 3492.
4500
Org. Lett., Vol. 14, No. 17, 2012

Scheme 2. Substrate Scope of Alkene CÀH Addition to Alde-
hydesa
Meanwhile, we also detected the catalytic reactions
by ESI-MS. In both the catalytic olefinic CÀH addi-
tion to N-sulfonyl aldimine 2a and the catalytic ole-
finic CÀH addition to 4a, the same two peaks were
observed. One peak (527.1933) can be assigned to species
I (Figure 1). Compared with 6, the ligand is changed from
acetonitrile to 1b in spieces I. The other peak (382.1043) can
be assigned to species II (Figure 1). Compared with 6, the
acetonitrile is dissociated in species II. At the same time, in
the catalytic olefinic CÀH addition to 4a, another peak
(567.0917) can be assigned to species III and/or IV
(Figure 1). Species III is speculated as the coordination
of species II with 4a. Species IV is speculated as the
precursor of product 5a without protonlysis.
a 1 (0.25 mmol), 4 (0.75 mmol) in CCl3CH3 (0.25 M) under an air
atmosphere in a sealed reaction tube. b The reaction was performed in
10 h. c The reaction was performed on a 1 mmol scale in 1 mL of solvent.
d The reaction was performed for 8 h. e The reaction was performed on a
1 mmol scale in CH2Cl2 for 12 h. f This reaction was performed in 1 mL
of CH2Cl2 on a 1 mmol scale for 14.5 h; 50% of 1b was recovered.
i
g 1HNMR yield. h 7% catalyst was used. The reaction was performed
with 20 mol % PivOH in 8 h.
electron-donating methoxyl group accompanied by the
nitro group, the desired product was isolated in an
acceptable yield (Scheme 2, 5q).
To highlight the synthetic value of this new strategy, we
conducted our model reaction (the reaction between 1b
and 4a) on a 5 mmol scale; the same good yield (73%) as
that from the standard conditions was obtained, and up to
1.2 g of product was isolated.
Figure 1. Observed possible intermediates by ESI-MS.
In summary, we developed the first example of direct
alkenyl CÀH addition to N-sulfonyl aldimines and aryl
aldehydes. These studies show their significance in enriching
the reactivity of broadly existing alkenes. The reactions can
occur under mild conditions with high atom-economic
efficiency. Further efforts to make this transformation
potentially applicable and to find the proper chiral ligand
to approach the efficient asymmetric version are underway.
The catalytic pathway was considered as a similar
catalytic cycle with aryl CÀH addition to imines.10 To give
more evidence, one of the possible key intermediates 6 was
synthesized and separated in 56% isolated yield (eq 3).10,11
It can also be observed under a similar condition with our
catalytic system (eq 4). Then the activity of intermediate 6
was invesitgated. Because the lower solubilityof intermedi-
ate 6 in tBuOH, DCM was added when it was used in the
catalytic olefinic CÀH addition to N-sulfonyl aldimines
(eq 5). The desired product was obtained with lower
efficiency (62% yield) compared with the precatalyst
(75% yield). A similar lower efficiency was also observed in
the catalytic olefinic CÀH addition to aryl aldehydes (eq 6).
These lower reactivities might be attributed to the instability
of intermediate 6 at high temperature because of the ob-
servation of black precipitation under these reaction con-
ditions. Although lower yields occur when using 6 instead
of [Cp*Rh(CH3CN)3][SbF6]2, these results still indicated
that 6 is a possible intermediate.
Acknowledgment. Support of this work by grants from
the “973” program from MOST of China (2009CB825300)
and NSFC (Nos. 20821062, 20925207, and 21002001) are
gratefully acknowledged.
Supporting Information Available. Brief experimental
details and other spectral data for products. This material is
available free of charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 17, 2012
4501