Rh2(OAc)4-AgOTf cooperative catalysis in cyclization/three-component reactions for concise synthesis of 1, 2-dihydroisoquinolines

Article abstract of DOI:10.1021/ol902409u

(Figure Presented) Dirhodium acetate and silve triflate cooperatively catalyzed tandem cyclization/three-component reactions of 2-alkynylarylaldimines with diazo compounds and water or alcohols are reported to afford 1, 2-dihydroisoquinolines bearing α-hy

Full text of DOI:10.1021/ol902409u

ORGANIC
LETTERS
2010
Vol. 12, No. 4
652-655
Rh2(OAc)4-AgOTf Cooperative Catalysis
in Cyclization/Three-Component
Reactions for Concise Synthesis of
1,2-Dihydroisoquinolines
Zhenqiu Guo, Mei Cai, Jun Jiang, Liping Yang, and Wenhao Hu*
Department of Chemistry, East China Normal UniVersity, Shanghai 200062,
People’s Republic of China
whu@chem.ecnu.edu.cn
Received October 20, 2009
ABSTRACT
Dirhodium acetate and silver triflate cooperatively catalyzed tandem cyclization/three-component reactions of 2-alkynylarylaldimines with diazo
compounds and water or alcohols are reported to afford 1,2-dihydroisoquinolines bearing r-hydroxyl-ꢀ-amino carboxylate skeleton in high yield.
Tandem or cascade reactions1 and multicomponent reactions2
offer significant advantages over traditional approaches for
the rapid construction of several bonds in a single synthetic
operation. In recent years, cooperative catalysis, including
dual-metal catalysis and metal-organo catalysis, has gained
much attention owing to its ability to enhance selectivity and
reactivity in the reactions.3 The appropriate combination of
compatible cocatalysts can affect the intrinsic reaction
kinetics in a designed way to activate the desired component
selectively. The 1,2-dihydroisoquinoline derivatives were
found in many natural products and pharmaceuticals with
remarkable biological activities.4 Various nucleophiles, such
as alkynes, allylstannanes, silyl enol ethers, and active
methylene compounds, have been employed in the Lewis
acid catalyzed reactions of 2-(1-alkynyl)arylaldimine, leading
to 1,2-dihydroisoquinoline derivatives through two possible
tandem routes (Scheme 1).5
The carbenoid chemistry of transformations through oxo-
nium ylides has received considerable attention in recent
years.6 Recently, we reported a new type of three-component
reaction in which ammonium or oxonium ylides generated
in situ from diazo compounds with amines or alcohols
underwent nucleophilic addition to aldehydes or imines.7 The
(1) For recent examples and reviews on tandem or cascade reactions,
see: (a) Mitchell, T. A.; Zhao, C.; Romo, D. Angew. Chem., Int. Ed. 2008,
47, 5026. (b) Chen, J.; Li, C.; An, X.; Zhang, J.; Zhu, X.; Xiao, W. Angew.
Chem., Int. Ed. 2008, 47, 2489. (c) Wang, Q.; Deng, X.; Zhu, B.; Ye, L.;
Sun, X.; Li, C.; Zhu, C.; Shen, Q.; Tang, Y. J. Am. Chem. Soc. 2008, 130,
5408. (d) Wang, J.; Xie, H.; Li, H.; Zu, L.; Wang, W. Angew. Chem., Int.
Ed. 2008, 47, 4177. (e) Wang, L.; Liu, Q.; Wang, D.; Li, X.; Han, X.;
Xiao, W.; Zhou, Y. Org. Lett. 2009, 11, 1119.
(3) For reviews of cooperative catalysis, see: (a) Lee, J. K.; Kung, M. C.;
Kung, H. H. Top Catal. 2008, 49, 136. (b) Park, Y. J.; Park, J. W.; Jun,
C. H. Acc. Chem. Res. 2008, 41, 222. (c) Ko, S.; Kang, B.; Chang, S. Angew.
Chem., Int. Ed. 2005, 44, 455. (d) Jeganmohan, M.; Bhuvaneswari, S.;
Cheng, C. H. Angew. Chem., Int. Ed. 2009, 48, 391. (e) Alexander, D.;
Stefan, F. K. Angew. Chem., Int. Ed. 2008, 47, 2.
(2) For recent examples and reviews on multicomponent reactions, see:
(a) Yue, T.; Wang, M.; Wang, D.; Zhu, J. Angew. Chem., Int. Ed. 2008,
47, 9454. (b) Jiang, J.; Yu, J.; Sun, X.; Rao, Q.; Gong, L. Angew. Chem.,
Int. Ed. 2008, 47, 2458. (c) Xiao, Y.; Zhang, J. Angew. Chem., Int. Ed.
2008, 47, 1903. (d) Yue, T.; Wang, M.; Wang, D.; Masson, G. Angew.
Chem., Int. Ed. 2009, 48, 6717. (e) Shu, W.; Jia, G.; Ma, S. Angew. Chem.,
Int. Ed. 2009, 48, 2788.
(4) For examples, see: (a) Zheng, S.; Chan, C.; Furuuchi, T.; Wright,
B. J. D.; Zhou, B.; Guo, J.; Danishefsky, S. D. Angew. Chem., Int. Ed.
2006, 45, 1754. (b) Vincent, G.; Williams, R. M. Angew. Chem., Int. Ed.
2007, 46, 1517. (c) Chen, J.; Chen, X.; Michele, B. C.; Zhu, J. J. Am. Chem.
Soc. 2006, 128, 87.
10.1021/ol902409u  2010 American Chemical Society
Published on Web 01/27/2010

Scheme 1
.
Two Proposed Reaction Pathways for Tandem
Table 1. Screening for the Lewis acid Co-catalyst for the
Three-Component Reaction of 1a, 2a, and 3aa
Reactions of Various Nucleophiles with
2-(1-Alkynyl)arylaldimine
entry
Lewis acid
yield (%)b
drc
1
2
3
4
5
9
0
3
27
0
2
50:50
Pd(PPh3)4
PdCl2(PPh3)2
PdCl2
Cu(OTf)2
CuI
45:55
reaction afforded highly substituted amino acid frameworks
with quaternary stereogenic centers in one step. We envi-
sioned that the oxonium ylide, generated in situ from a diazo
compound with an alcohol or water, would serve as a
nucleophile to attack a Lews acid activated 2-alkynylaryla-
ldimine affording new functionalized 1,2-dihydroisoquino-
lines bearing an adjacent R-hydroxy-ꢀ-amino carboxylate
skeleton in one step (Scheme 2). In this multicomponent
6
7
8
Cu(CN)4PF6
AgOTf
AgOTf
AgOTf
In(OTf)3
28
83
29
0
46:54
60:40
60:40
9d
10e
11
0
a Reaction conditions: Unless otherwise noted, the reaction was carry
out in refluxing CH2Cl2 with 1a:2a:3a ) 1:1.2:1.2, catalyzed by 1 mol %
of Rh2(OAc)4 and 5 mol % of Lewis acid.. b Isolated yield based on 2-(1-
alkynyl)phenylaldimine 1a. c Determined by 1H NMR analysis. d 1 mol %
of catalyst was used. e In the absence of Rh2(OAc)4 catalyst, methyl 2-oxo-
2-phenylacetate was isolated.
Scheme 2
.
1,2-Dihydroisoquinoline Synthesis via Dual-Metal
Co-catalyzed Three-Component Reaction
To verify the practicability of the strategy shown in
Scheme 2, our studies commenced with screening of an
effective cocatalyst in a reaction of methyl phenyldiazoac-
etate (1a), H2O (2a), and 2-(1-alkynyl)phenylaldimine 3a and
the results are shown in Table 1. In the absence of a Lewis
acid cocatalyst, the reaction afforded only 9% yield of desired
product 4a with a significant amount of starting material 3a
recovered (Table 1, entry 1). Soft metal salts such as
palladium, copper, or silver with mild Lewis acidity were
examined to activate the triple bond functionality of 3a.5f
PdCl2 was found to be an effective cocatalyst among the Pd
catalysts screened, affording the desired product 4a in 27%
yield (entries 2-4). Similar results were observed with
reaction, two metal catalysts, Rh2(OAc)4 and a Lewis acid
catalyst, must be compatible and activate the desired
component selectively.
(5) (a) Obika, S.; Kono, H.; Yasui, Y.; Yanada, R.; Takemoto, Y. J.
Org. Chem. 2007, 72, 4462. (b) Asao, N.; Yudha, S. S.; Nogami, T.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2005, 44, 5526. (c) Yanada, R.;
Obika, S.; Kono, H.; Takemoto, Y. Angew. Chem., Int. Ed. 2006, 45, 3822.
(d) Asao, N.; Iso, K.; Yudha, S. S. Org. Lett. 2006, 8, 4149. (e) Mori, S.;
Uerdingen, M.; Krause, N.; Morokuma, K. Angew. Chem., Int. Ed. 2005,
44, 4715. (f) Ding, Q.; Wu, J. Org. Lett. 2007, 9, 4959. (g) Peng, C.; Cheng,
J.; Wang, J. AdV. Synth. Catal. 2008, 350, 2359. (h) Asao, N.; Iso, K.;
Yudha, S. S. Org. Lett. 2006, 8, 4149. (i) Chen, Z.; Yang, X.; Wu, J. Chem.
Commun. 2009, 3469.
(6) (a) Doyle, M.; Mckervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds; Wiley: New York, 1998.
(b) Padwa, A.; Weingarten, M. D. Chem. ReV. 1996, 96, 223. (c) Li, A.;
Dai, L.; Aggarwal, V. Chem. ReV. 1997, 97, 2341. (d) Ye, T.; Mckervey,
M. A. Chem. ReV. 1994, 94, 1091. (e) Davies, H. M. L.; DeMeese, J.
Tetrahedron Lett. 2001, 42, 6803. (f) Li, Z.; Davies, H. M. L. J. Am. Chem.
Soc. 2010, 132, 396. (g) Davies, H. M. L.; Coleman, M. G.; Ventura, D. L.
Org. Lett. 2007, 9, 4971. (h) Chen, C.; Zhu, S.-F.; Liu, B.; Wang, L.-X.;
Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 12616. (i) Liang, Y.; Zhou, H.;
Yu, Z.-X. J. Am. Chem. Soc. 2009, 131, 17783.
(7) (a) Wang, Y.; Zhu, Y.; Chen, Z.; Mi, A.; Hu, W.; Doyle, M. P.
Org. Lett. 2003, 5, 3923. (b) Wang, Y.; Chen, Z.; Mi, A.; Hu, W. Chem.
Commun. 2004, 2486. (c) Lu, C.; Liu, H.; Chen, Z.; Hu, W.; Mi, A. Org.
Lett. 2005, 7, 83. (d) Lu, C.; Liu, H.; Chen, Z.; Hu, W.; Mi, A. Chem.
Commun. 2005, 2624. (e) Huang, H.; Guo, X.; Hu, W. Angew. Chem., Int.
Ed. 2007, 46, 1337. (f) Guo, X.; Huang, H.; Yang, L.; Hu, W. Org. Lett.
2007, 9, 4721. (g) Zhang, X.; Huang, H.; Guo, X.; Guan, X.; Yang, L.;
Hu, W. Angew. Chem., Int. Ed. 2008, 47, 6647. (h) Hu, W.; Xu, X.; Zhou,
J.; Liu, W.; Huang, H.; Hu, J.; Yang, L.; Gong, L. J. Am. Chem. Soc. 2008,
130, 7782.
Figure 1
4t
.
ORTEP representation of the crystal structure of threo-
Org. Lett., Vol. 12, No. 4, 2010
653

Table 2. Reactions of Diazoacetates 1, Water or Alcohols 2,
and 2-(1-Alkynyl)phenylaldimines 3 Catalyzed by Silver Triflate
and Dirhodium Acetatea
Scheme 3
.
Reaction of Diazo Compound 1i, Water 2, and
2-(1-Alkynyl)phenylaldimine 3a
in the reactions of tandem nucleophilic addition and cycliza-
tion of 2-alkynylarylaldimines,5a was ineffective in the
current reaction (entry 11).
To demonstrate the generality of this method, the substrate
scope of the reaction was investigated under optimized
conditions [AgOTf (5 mol %), Rh2(OAc)4 (1 mol %),
CH2Cl2, rt, 1 h], and the results are summarized in Table 2.
The chemo- and stereoselectivities of the reactions were
found to be dependent on electronic and steric features of
the substrates used. In the reactions of methyl aryldiazoac-
etates 1a-g with H2O and 2-(1-alkynyl)phenylaldimines
3a-f, electron-rich substrates 1 and 3 gave a higher yield
of the product (Table 2, entries 1-12). For example, the use
of methyl p-MeO-phenyldiazoacetate (1b) furnished the
reaction in 90% yield (entry 2), while electron-deficient
methyl p-NO2-phenyldiazoacetate (1g) or N-p-NO2-phenyl
2-(1-alkynyl)phenylaldimine (3e) gave no desired three-
component product (entries 7 and 11). The reaction was not
limited to aryldiazoacetates, as good yields of the desired
entry
1
2
3
4
yield(%)b
drc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20d
21d
22d
23d
24d
1a
1b
1c
1d
1e
1f
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
3a
3g
3b
3d
3c
3e
3f
4a
4b
4c
4d
4e
4f
83
90
84
80
85
65
0
65
67
60
0
60:40
56:44
58:42
52:48
53:47
57:43
1g
1a
1a
1a
1a
1a
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
4g
4h
4i
56:44
56:44
59:41
0
4j
4k
4l
4m
4n
4o
92
93
73
71
72
65
0
60
55
51
43
34
49:51
54:46
55:45
76:24
68:32
61:39
Scheme 4. Plausible Reaction Mechanism of Rh2(OAc)4 and
AgOTf Co-catalyzed Tandem Cyclization/Three-Component
Reaction
3a
3a
3a
3a
3a
4p
4q
4r
4s
4t
46:54
50:50
61:39
50:50
N.D.e
a All reactions were carried out in CH2Cl2 at rt in the presence of 1 mol
% of Rh2(OAc)4 and 5 mol % of AgOTf with 1:2:3 ) 1.2:1.2:1.0 mmol.
b Isolated yield based on 2-(1-alkynyl)phenylaldimine 1. c Determined by
1H NMR analysis of crude products. d 4 Å MS (100 mg) was added. e Only
one diastereomer was isolated after chromatography purification.
copper catalysts (entries 5-7). Gratifyingly, AgOTf was
found to be the best cocatalyst to give 4a in 83% islolated
yield (entry 8). The yield dramatically decreased to 29%
while decreasing the catalyst loading of AgOTf from 5 mol
% to 1 mol % (entry 9). Silver salts were reported to
effectively catalyze diazo decomposition of donor/acceptor
diazo compounds.8 In this study, by using AgOTf catalyst
alone in the absence of Rh2(OAc)4, we isolated methyl 2-oxo-
2-phenylacetate together with a significant amount of unre-
acted starting material 3a (entry 10). Another Lewis acid
In(OTf)3, which was demonstrated as an effective catalyst
(8) (a) Thompson, J. L.; Davies, H. M. L. J. Am. Chem. Soc. 2007,
129, 6090. (b) Yue, Y.; Guo, X.; Chen, Z.; Yang, L.; Hu, W. Tetrahedron
Lett. 2008, 49, 6862.
654
Org. Lett., Vol. 12, No. 4, 2010

products were also obtained by using ethyl diazoacetate (1h)
(entries 13-18 and 20-24). Sterically hindered N-aryl 2-(1-
alkynyl)phenylaldimine 3f bearing an ortho substituent on
the N-aryl group gave no desired product both in the reactions
with aryldiazoacetate 1a or ethyl diazoacetate (1h) (entries
12 and 19). Diastereoselectivity was generally poor in the
reaction. The highest dr of 76:24 was observed in the reaction
of ethyl diazoacetate, H2O, and N-p-Br-phenyl 2-(1-alky-
nyl)phenylaldimine 3d (entry 16). Interestingly, electron-
deficient substrate 3e, which was inactive toward methyl
phenyldiazoacetate, reacted well with ethyl diazoacetate and
H2O affording the corresponding product 4o in 65% yield
with a dr of 61:39 (entry 18). Alcohols 2b-f were also used
to replace H2O in the reaction to give the corresponding
products 4p-t in moderate yield (entries 20-24). The
structure and relative configuration of isomer threo-4t was
confirmed by single-crystal X-ray analysis (Figure 1).
The reaction was extended to additional diazo compounds.
Diazo ketone 1i was employed in the reaction with H2O and
3a to afford the desired product 4u in 74% yield (Scheme
3).
the AgOTf-coordinated alkyne 5. The existence of the
isoquinolinium intermediate 6 has been reported by Yama-
moto in the reaction of 3a with AgOTf in the absence of
any pronucleophiles.5b,9 In another catalytic cycle, an oxo-
nium ylide intermediate 7 is formed,7c which undergoes a
Mannich-type reaction via a proposed intermediate 8 to
afford the desired product 4.
In summary, we have reported a cooperative catalyst
combination, Rh2(OAc)4 and AgOTf, which is effective for
a tandem cyclization/three-component reaction of 2-alkyny-
larylaldimines, diazo compounds, and water or alcohols to
afford functionalized 1,2-dihydroisoquinolines in moderate
to high yield. Further investigation to improve diastereose-
lectivity and to study an asymmetric version of the current
reaction is in progress in our laboratory.
Acknowledgment. Financial support from National Natu-
ral Science Foundation of China (Grant Nos. 20932003 and
20772033) and Science and Technology Commission of
Shanghai Municipality (Nos. 09JC1404901 and 07dz22005)
is gratefully acknowledged.
The exact reaction pathway leading to the three-component
adducts is unclear yet, but we prefer a reaction pathway
shown in Scheme 4. The isoquinolinium intermediate 6 is
formed by nucleophilic attack of the imine nitrogen atom to
Supporting Information Available: Experimental pro-
cedures, characterization data, and copies of 1H and 13C NMR
of new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
(9) A less soluble solid was formed prior to the last addition of a diazo
compound, suggesting the formation of 6.
OL902409U
Org. Lett., Vol. 12, No. 4, 2010
655