One-pot synthesis of isoquinolinium salts by rhodium-catalyzed C-H bond activation: Application to the total synthesis of oxychelerythrine

Article abstract of DOI:10.1002/anie.201105755

It's worth its salt: The title reaction leads to the synthesis of highly substituted isoquinolinium salts (see scheme; Cp=Me₅C ₅). The reaction proceeds through a C-H activation and a subsequent annulation in the presence of a rhodium catalyst. The reaction mechanism is discussed as well as its application to the synthesis of the natural product oxychelerythrine.

Full text of DOI:10.1002/anie.201105755

Angewandte
Chemie
DOI: 10.1002/anie.201105755
À
C H Activation
À
One-Pot Synthesis of Isoquinolinium Salts by Rhodium-Catalyzed C H
Bond Activation: Application to the Total Synthesis of
Oxychelerythrine**
Jayachandran Jayakumar, Kanniyappan Parthasarathy, and Chien-Hong Cheng*
Highly substituted isoquinolinium salts are valuable and
versatile intermediates for synthetic organic chemistry[1] and
are widely utilized for the construction of various natural
products and bioactive molecules.[2] The traditional methods
for the synthesis of isoquinolinium salts from isoquinolines
and alkyl halide derivatives is limited by the number of
substituted isoquinolines that are readily available. As a
result, the development of new versatile methods for the
synthesis of isoquinolinium salts has become an important
task in metal-catalyzed organic reactions. In this context,
Heck and co-workers reported the formation of isoquinoli-
nium salts from the reaction of cyclopalladated benzaldimines
and alkynes,[3] but they did not succeed in making the reaction
catalytic. Later, Larock and co-workers,[4a–b] and our group[4c]
independently reported a palladium- and nickel-catalyzed
synthesis of isoquinoline derivatives from N-tert-butyl o-
halobenzaldimines and alkynes. Recently, Fagnou et al.
developed a rhodium-catalyzed synthesis of isoquinolines
isoquinolinium salts from N-benzylidenemethylamine, 2-phe-
nylpyridine, and benzo[h]quinoline with DMAD (dimethyl
acetylenedicarboxylate) through C H bond activation.[8] The
À
method required a stoichiometric amount of [{RhCp*Cl2}2]
(Cp* = Me5C5), and DMAD was the only alkyne used. Our
[9]
À
continued interest in metal-catalyzed C H activation and
the reactions of isoquinolinium salts[7] prompted us to explore
À
the catalytic formation of isoquinolinium salts through C H
activation. Herein, we report an effective [RhCp*]-catalyzed
three-component reaction of aryl aldehydes, methylamines,
and alkynes to afford isoquinolinium salts regioselectively
À
through C H activation and annulation. Moreover, the
À
present rhodium-catalyzed C H activation reaction provides
a very convenient and useful method for the synthesis of
isoquinolinium salts under halide-free conditions.
The treatment of benzaldehyde (1a; 0.36 mmol) with
diphenyl acetylene (2a; 0.30 mmol) and methylamine 3a
(0.45 mmol in 35% aqueous solution) in the presence of
[{RhCp*Cl2}2] (2.0 mol%), AgBF4 (1.0 equiv), and Cu(OAc)2
(1.0 equiv) in tert-amyl alcohol at 1108C for 3 hours gave the
isoquinolinium salt 4a in 91% yield upon isolation (Table 1,
entry 1). The structure of 4a, containing an isoquinolinium
cation and a tetrafluoroborate anion, was confirmed by its 1H,
13C, 19F, and 11B NMR spectra, as well as MS data. The 19F and
11B NMR spectral data of the tetrafluoroborate anion are in
agreement with those reported previously.[10] To the best of
our knowledge, this is the first report for the synthesis of
À
from N-tert-butyl benzaldimines and alkynes through C H
activation and cyclization.[5a] Chiba and co-workers reported a
RhIII-catalyzed formation of isoquinolines from aryl ketone
O-acyloximes and alkynes.[5b–c] In 2009, Miura et al. reported
an efficient synthesis of polysubstituted isoquinoline deriva-
À
tives by rhodium-catalyzed C H bond activation of benzo-
phenone imines with alkynes.[5d] Previously, the formation of
dihydroisoquinolines through the catalytic electrophilic acti-
vation of the alkyne group in o-alknylbenzaldimines were
described.[6] In all of these reactions, isoquinolinium salts
were proposed as the intermediates but were never isolated.
In 2009, we reported an efficient regioselective nickel-
catalyzed annulation of 2-halobenzaldimines with alkynes to
give isoquinolinium salts[7a–b] and the application of the
method to the synthesis of isoquinolinone alkaloids.[7b] How-
ever, this nickel-catalyzed reaction requires a halide source,
2-halobenzaldimine, as the substrate. To the best of our
knowledge, there is no report of the formation of isoquino-
À
isoquinolinium salts by catalytic C H activation.
It is noteworthy that in the reaction, if substrates 1a and
3a were replaced by the corresponding pre-synthesized imine,
the reactions also proceeded but with much lower yield
(19%). In the absence of AgBF4 4a is formed, but in the
absence of Cu(OAc)2 4a was observed in 53% yield. Thus, we
think that AgBF4 (1.0 equiv) provides an inert anion neces-
sary for the isolation of isoquinolinium salt and removes the
chloride on the rhodium complex to facilitate the catalytic
reaction. In addition, Ag+ also serves as an oxidant for the
reaction. Since the reaction requires two equivalents of the
oxidant, we added Cu(OAc)2 (1.0 equiv) to the reaction as the
second oxidant. In fact, if we used two equivalents of AgBF4
without any Cu(OAc)2, the catalytic reaction proceeded
smoothly to afford 92% of 4a (for detailed studies see the
Supporting Information).
À
linium salts catalytically involving C H bond activation as a
key step. Very recently, Jones et al. reported the formation of
[*] J. Jayakumar, Dr. K. Parthasarathy, Prof. Dr. C.-H. Cheng
Department of Chemistry, National Tsing Hua University
Hsinchu 30013 (Taiwan)
E-mail: chcheng@mx.nthu.edu.tw
The choice of silver salt is crucial for the success of the
present catalytic reaction. Various silver salts were examined
for the reaction of 1a with 2a and 3a. Among them, AgBF4
gave the best results, thus affording 4a in 91% yield. AgSbF6
was also effective in giving 4a in 67% yield. Other silver salts
Homepage: http://mx.nthu.edu.tw/~chcheng/
[**] We thank the National Science Council of Republic of China (NSC-
99-2811M-007-089) for support of this research.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201105755.
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Table 1: Results of rhodium-catalyzed C H activation and annulation of benzalde-
4a in 88 and 73% yield, respectively. Of the solvents
tested for the catalytic reaction, tert-amyl alcohol
afforded the highest product yield of 91%. Others
such as EtOH, tBuOH, 1,2-dichloroethane,
CH3CO2H and MeOH gave 4a in 90, 72, 64, 59, and
58% yield, respectively.
hydes, amines, and alkynes.[a]
Under similar reaction conditions, various sub-
stituted benzaldehydes (1b–j) reacted with diphenyl
acetylene (2a) and methylamine (3a) to give the
corresponding isoquinolinium salts. Thus, 4-ethyl-
benzaldehyde (1b) afforded 4b in 84% yield
(Table 1, entry 2). Benzaldehydes 1c–f with elec-
tron-rich groups reacted nicely with 2a and 3a to give
4c–f in good yield (entries 3–6). The catalytic reac-
tion is also compatible with halo substituents on the
aromatic ring of benzaldehyde 1. Thus, the reaction
of various halo-substituted benzaldehydes (1g–i)
with 2a and 3a gave isoquinolinium salts 4g–i in
good yield (entries 7–9). In addition, 4-phenylbenz-
aldehyde (1j) reacted with 2a and 3a to provide 4j in
83% yield (entry 10). The reaction of 4-methylester-
benzaldehyde (1k) with gave 4k in 58% yield
(entry 11), but the reaction of 4-nitrobenzaldehyde
did not give the expected isoquinolinium salt
(entry 12). To understand the regioselectivity of the
meta-substituted benzaldehyde with 2a and 3a, we
chose 3-chloro- (1m) and 3-bromobenzaldehyde
(1n) as the substrates. Thus, 1m gave the regioiso-
mers 4m and 4m’ in a 92:8 ratio in 78% combined
yield (entry 13), and 1n afforded the regioisomers 4n
and 4n’ in a 92:8 ratio and 81% combined yield
(entry 14).
In addition to 2a, symmetrical aliphatic alkynes
including oct-4-yne (2b) and 1,4-dimethoxy-2-butyne
(2c) reacted with 1a and 1d, respectively, in the
presence of 3a to give the corresponding products 4o
and 4p (entries 15 and 16). To understand the
regioselectivity of the present reaction, unsymmet-
rical alkynes were employed as the substrates for the
reaction with 1a and 3a. Thus, 1-phenyl-1-propyne
(2d) and the propargylic ether 2e gave 4q and 4r,
respectively (entries 17 and 18). No other regioiso-
meric product was detected in these two reactions.
The regiochemistry of products 4q and 4r was
confirmed by NOE experiments.
Entry
1
2
3
Product 4[b]
Yield [%][c]
1
2
3
4
5
6
7
8
1a 2a 3a
1b 2a 3a
1c 2a 3a
1d 2a 3a
1e 2a 3a
1 f 2a 3a
1g 2a 3a
1h 2a 3a
1i 2a 3a
1j 2a 3a
1k 2a 3a
1l 2a 3a
4a: R1, R2, R3, R4 =H
4b: R2 =Et
91
84
92
96
78
83
82
78
71
83
58
–
78
(92:8)
81
4c: R2 =OMe
4d: R2, R4 =OMe
4e: R1, R2, R3 =OMe
4 f: R1 =Br, R3, R4 =OMe
4g: R2 =F
4h: R2 =Cl
9
4i: R2 =Br
10
11
12
4j: R2 =Ph
4k: R2 =CO2Me
4l: R2 =NO2
4m: R3 =Cl
13
14
1m 2a 3a
1n 2a 3a
4m’: R1 =Cl
4n: R3 =Br
4n’: R1 =Br
(92:8)
15
16
1a 2b 3a
4o
4p
88
70
1d 2c 3a
17
18
19
20
21
22
1a 2d 3a
1a 2e 3a
1a 2a 3b
1a 2a 3c
1a 2a 3d
1a 2a 3e
4q: R5, R7 =Me
85
79
4r: R5 =CH2OMe, R7 =Me
4s: R5 =Ph, R7 =(CH2)2CH3 83
4t: R5 =Ph, R7 =CH2Ph
4u: R5, R7 =Ph
87
76
The scope of the amine used in the present
catalytic reaction was also tested. In addition to
methylamine, propyl- and benzylamine (3b,c)
reacted smoothly to afford 4s and 4t, respectively
(entries 19 and 20). Similarly, aromatic amines
including aniline (3d) and p-anisidine (3e) reacted
nicely to give 4u and 4v, respectively (entries 21 and
22).
4v: R5 =Ph, R7 =4-OMeC6H4 80
[a] Unless otherwise mentioned, all reactions were carried out using aryl aldehyde 1
(0.36 mmol), alkyne 2 (0.30 mmol), amine 3 (0.45 mmol in 35% aqueous solution),
[{RhCp*Cl2}2] (2.0 mol%), AgBF4 (0.3 mmol), Cu(OAc)2 (0.3 mmol), and tert-amyl
alcohol (2.5 mL) at 1108C for 3 h. [b] For 4b–n, H substituents are omitted. [c] Yield
of isolated product.
On the basis of the chemistry of known metal-
[7–9,11]
À
including AgOAc, Ag2CO3, and Ag2O did not give the
expected isoquinolinium product. Various oxidants were also
tested for the reaction. Among these Cu(OAc)2 was found to
be most effective, thus giving 4a in 91% yield. Other oxidants
including Cu(OTf)2 and oxygen are also effective delivering
catalyzed C H bond activation/annulation reactions,
a
possible mechanism to account for the present catalytic
reaction is proposed (Scheme 1). The catalytic cycle is likely
initiated by the removal of chloride from [{RhCp*Cl2}2] by
Ag+, coordination of the imine nitrogen atom (in situ
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Scheme 1. Proposed mechanistic pathway for the formation of isoqui-
nolinium salt.
generation of imine from 1a and 3a) to the rhodium species,
À
and subsequent ortho C H bond activation to form the five-
membered rhodacycle A. Regioselective insertion of the
alkyne 2d into the rhodium–carbon bond of intermediate B
gives the seven-membered rhodacycle C. Reductive elimina-
tion of C affords the final isoquinolinium salt 4q and RhI. The
rhodium species is reoxidized by Cu(OAc)2 or Ag+ to
regenerate the active RhIII species for the next cycle.
To support the proposed mechanism, we tried to isolate
the intermediate A shown in Scheme 1. Thus, heating 1a and
3a in the presence of 0.1 equivalents of [{RhCp*Cl2}2] and
1 equivalent of AgBF4 in tert-amyl alcohol at 1108C for 1 hour
led to the isolation of the five-membered rhodacycle A in
Scheme 2. Total synthesis of oxychelerythrine. a) [{RhCp*Cl2}2]
1
86% yield. This complex was characterized by its H and
(2.0 mol%), AgBF4 (1.0 mmol), Cu(OAc)2 (1.0 mmol) and tert-amyl
alcohol (5.0 mL) at 1108C for 3 h; b) K3[Fe(CN)6] (2.0 mmol), CsOH
(1.2 mmol) and MeOH/H2O (1:1; 10mL) at 808C for 12 h.
13C NMR spectra, as well as IR data. In addition, the structure
was determined by single-crystal X-ray diffraction (see the
Supporting Information). Surprisingly, the amine coordinated
to the rhodium center in A is dimethylamine, not the original
methylamine. This is likely to be a result of a partial
conversion of methylamine into dimethylamine under the
reaction conditions. A similar conversion was reported and
such a mechanism has been proposed before.[12] The reaction
of A with 1-phenyl-1-propyne (2d) in tert-amyl alcohol at
1108C for 0.15 hours regioselectively gave the isoquinolinium
salt 4q in 90% yield [Eq. (1)].
following the procedure we employed before.[7b] First, 4w
was treated with K3[Fe(CN)6] and CsOH[13a] in a mixture of
H2O and MeOH (1:1) to give the isoquinolone 5a in 90%
yield. Compound 5a was then transformed into the corre-
sponding aldehyde derivative 6a in 88% yield by PCC
(pyridinium chlorochromate) oxidation.[13b] After a successful
acid-catalyzed ring-closing and a dehydration reaction, 7[14]
was obtained in 95% yield. The overall yield of 7 from 1p, 2e,
and 3a was 62%, which is much higher than those reported
earlier.[14b–c] The alkyne 2e can be easily prepared from the
Sonogashira reaction of commercially available 5-
bromobenzo[d][1,3]dioxole and 3-butyn-1-ol.[7] It is interest-
ing to note that 7 has exhibited antitumor properties,[15a] and
the ability to stimulate GSH transport[15b] and inhibit the
BclXL function.[15c] There are a large number of isoquinoli-
none alkaloids existing in the nature that have a core structure
similar to that of oxychelerythrine (7). As a result, the
methodology shown in Scheme 2 should be very useful for the
synthesis of these alkaloids.
À
The significance of this rhodium-catalyzed C H activa-
tion/annulation reaction is additionally demonstrated by its
application to the total synthesis of the isoquinolinone
alkaloid oxychelerythrine (7). The synthesis of this natural
product using the present methodology is shown in Scheme 2.
First, the reaction of the aldehyde 1p, alkyne 2e, and 3a in the
presence of [{RhCp*Cl2}2], AgBF4, and Cu(OAc)2 in tert-amyl
alcohol at 1108C for 3 hours gave the isoquinolinium salt 4w
in 82% yield (isolated) in a highly regioselective manner. No
other regioisomer was detected in this catalytic reaction. The
regiochemistry was confirmed by the NOE experiments. This
isoquinolinium salt was eventually converted into 7 by
In conclusion, we have successfully developed a new
highly regioselective rhodium-catalyzed synthesis of substi-
tuted isoquinolinium salts from the reaction of benzalde-
À
hydes, amines, and alkynes through C H bond activation and
annulation. The protocol was successfully applied to the total
synthesis of oxychelerythrine (7) with excellent yield. The
proposed mechanism is strongly supported by the isolation of
a five-membered rhodacycle and an intermediate organic
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c) P. C. Too, S. H. Chua, S. H. Wong, S. Chiba, J. Org. Chem.
2011, 76, 6159; d) T. Fukutani, N. Umeda, K. Hirano, T. Satoh,
M. Miura, Chem. Commun. 2009, 5141.
compound. Additional applications of this methodology to
natural product syntheses and investigations into the detailed
mechanism are in progress.
[6] a) D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil, Y. Yama-
moto, Angew. Chem. 2007, 119, 4848; Angew. Chem. Int. Ed.
2007, 46, 4764; b) N. Asao, S. Yudha, S. T. Nogami, Y.
Yamamoto, Angew. Chem. 2005, 117, 5662; Angew. Chem. Int.
Ed. 2005, 44, 5526; c) R. Yanada, S. Obika, H. Kono, Y.
Takemoto, Angew. Chem. 2006, 118, 3906; Angew. Chem. Int.
Ed. 2006, 45, 3822; d) S. Obika, H. Kono, Y. Yasui, R. Yanda, Y.
Takemoto, J. Org. Chem. 2007, 72, 4462.
[7] a) R. P. Korivi, W.-J. Wu, C.-H. Cheng, Chem. Eur. J. 2009, 15,
10727; b) R. P. Korivi, W.-J. Wu, C.-H. Cheng, Chem. Eur. J.
2010, 16, 282.
[8] L. Li, W. W. Brennessel, W. D. Jones, J. Am. Chem. Soc. 2008,
130, 12414.
[9] a) K. Parthasarathy, M. Jeganmohan, C.-H. Cheng, Org. Lett.
2008, 10, 325; b) K. Parthasarathy, C.-H. Cheng, Synthesis 2009,
1400; c) K. Parthasarathy, C.-H. Cheng, J. Org. Chem. 2009, 74,
9359; d) V. S. Thirunavukkarasu, K. Parthasarathy, C.-H. Cheng,
Angew. Chem. 2008, 120, 9604; Angew. Chem. Int. Ed. 2008, 47,
9462; e) V. S. Thirunavukkarasu, K. Parthasarathy, C.-H. Cheng,
Chem. Eur. J. 2010, 16, 1436; f) P. Gandeepan, K. Parthasarathy,
C.-H. Cheng, J. Am. Chem. Soc. 2010, 132, 8569; g) K.
Muralirajan, K. Parthasarathy, C.-H. Cheng, Angew. Chem.
2011, 123, 4255; Angew. Chem. Int. Ed. 2011, 50, 4169.
[10] H-J. Frohn, A. Wenda, U. Florke, Z. Anorg. Allg. Chem. 2008,
634, 764.
[11] a) C.-H. Jun, C. W. Moon, D.-Y. Lee, Chem. Eur. J. 2002, 8, 2422;
b) Y. J. Park, C.-H. Jun, Bull. Korean Chem. Soc. 2005, 26, 877;
c) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010,
110, 624; d) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110,
1147; e) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16, 11212.
[12] a) N. F. P. Ribeiroa, C. A. Henriquesb, M. Schmala, Catal. Lett.
2005, 104, 111; b) D. R. Corbin, S. Schwarz, G. C. Sonnichsen,
Catal. Today 1997, 37, 71; c) G. E. Dobereiner, R. H. Crabtree,
Chem. Rev. 2010, 110, 681.
[13] a) D. Gnecco, C. Marazano, R. G. Enriquez, J. L. Teran, M. R.
Sanchez, S. A. Galindo, Tetrahedron: Asymmetry 1998, 9, 2027;
b) S. D. Burke, R. L. Danheiser, Oxidizing and Reducing Agents,
Wiley, New York, 2000, p. 154.
[14] a) M. Hanaoka, T. Motonishi, C. Mukai, J. Chem. Soc. Perkin
Trans. 1 1986, 2253; b) T. Harayama, T. Akiyama, K. Kawano,
Chem. Pharm. Bull. 1996, 44, 1634; c) T. N. Le, W.-J. Cho, Chem.
Pharm. Bull. 2005, 53, 118.
[15] a) T. K. Hoffmann, K. Leenen, D. Hafner, V. Balz, C. Gerharz,
A. Grund, H. Ballo, U. Hauser, H. Bier, Anti-Cancer Drugs 2002,
13, 93; b) H. Lou, M. Ookhtens, A. Stolz, N. Kaplowitz, Am. J.
Physiol. Gastrointest. Liver Physiol. 2003, 285, G1335; c) S.-L.
Chan, M. C. Lee, K. O. Tan, L.-K. Yang, A. S. Y. Lee, H. Flotow,
N. Y. Fu, M. S. Butler, D. D. Soejarto, A. D. Buss, V. C. Yu, J.
Biol. Chem. 2003, 278, 20453.
Experimental Section
General procedure for the rhodium-catalyzed synthesis of isoquino-
linium salt: A sealed tube containing [{RhCp*Cl2}2] (2.0 mol%),
AgBF4 (0.30 mmol), and Cu(OAc)2 (0.30 mmol) was evacuated and
purged with nitrogen gas three times. Then, t-amyl alcohol (2.5 mL),
aryl aldehyde 1 (0.36 mmol), alkyne 2 (0.30 mmol), and methylamine
3 (0.45 mmol in 35% aqueous solution) were sequentially added to
the mixture via syringe under a nitrogen atmosphere, and the reaction
mixture was stirred at 1108C for 3 h. The mixture was cooled to RT
and diluted with CH2Cl2 (10 mL). The mixture was then filtered
through a Celite pad and the Celite pad was washed with CH2Cl2
(50 mL). The combined filtrate fractions were concentrated under
vacuum and the residue was carefully washed with ethyl acetate and
n-hexane to afford the desired pure product 4.
Received: August 15, 2011
Revised: September 29, 2011
Published online: November 15, 2011
À
Keywords: alkynes · annulation · C H activation · heterocycles ·
rhodium
.
[1] a) B. D. Krane, M. O. Fagbule, M. Shamma, J. Nat. Prod. 1984,
47, 1; b) B. Gerhard, T. Gulder, U. Hentschel, F. Meyer, H. Moll,
J. Morschhauser, D. V. A. Ponte-Sucre, W. Ziebuhr, A. Stich, R.
Brun, W. E. G. Muller, V. Mudogu, Int. Patent, WO 2008/
037482A1, 2008; c) M. S. Cushman, A. S. Ioanoviciu, Y. G.
Pommier, WO 2005/089294A2, 2005; d) N-laurylisoquinolinium
bromide, hexadecamethylenediisoquinolium dichloride, and
quinapril are popular drug molecules.
[2] a) R. M. Scarborough, K. A. Kane-Maguire, C. K. Marlowe,
M. S. Smyth, X. Zhang, US Patent, US 2005/0113399A1, 2005;
b) N. I. Alun, P. K. Mark, B. P Allen, Int. Patent, WO 2006/
067444A1, 2006; c) M. Barrie, W. Paul, Int. Patent, WO 2007/
149031A1, 2007; d) L. J. Adams, Int. Patent, WO 2004/
108682A2, 2004.
[3] a) G. Wu, A. L. Rheingold, S. J. Geib, R. F. Heck, Organo-
metallics 1987, 6, 1941; b) G. Wu, S. J. Geib, A. L. Rheingold,
R. F. Heck, J. Org. Chem. 1988, 53, 3238.
[4] a) Q. Huang, J. A. Hunter, R. C. Larock, Org. Lett. 2001, 3, 2973;
b) K. R. Roesch, H. Zhang, R. C. Larock, J. Org. Chem. 2001, 66,
8042, and references therein; c) R. P. Korivi, C.-H. Cheng, Org.
Lett. 2005, 7, 5179.
[5] a) N. Guimond, K. Fagnou, J. Am. Chem. Soc. 2009, 131, 12050;
b) P. C. Too, Y.-F. Wang, S. Chiba, Org. Lett. 2010, 12, 5688;
200
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