Reissert-type acylation with acylzirconocene chloride complexes

Article abstract of DOI:10.1002/ejoc.201301264

In the presence of ClCO₂Et, the use of CuI in MeNO₂ efficiently catalyzed the Reissert-type acylation of isoquinoline derivatives with acylzirconocene chlorides. In the reaction of quinolines with acylzirconocene chlorides, the choic

Full text of DOI:10.1002/ejoc.201301264

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201301264
Reissert-Type Acylation with Acylzirconocene Chloride Complexes
Akio Saito,*[a] Hikaru Sakurai,[b] Kohei Sudo,[b] Kosuke Murai,[a] and Yuji Hanzawa[b]
Keywords: Multicomponent reactions / Reissert reaction / Acylation / Nitrogen heterocycles / Zirconium
In the presence of ClCO2Et, the use of CuI in MeNO2 ef-
ficiently catalyzed the Reissert-type acylation of isoquinoline
derivatives with acylzirconocene chlorides. In the reaction of
adducts. The cationic RhI-catalyzed reaction in MeNO2 pref-
erentially afforded 1,2 adducts. On the other hand, the CuI-
catalyzed reaction in CH2Cl2 preferentially afforded 1,4 ad-
quinolines with acylzirconocene chlorides, the choice of cata- ducts.
lyst and solvent was crucial to the regioselective formation of
Introduction
The effective introduction of various carbon nucleophiles
into azaaromatic compounds such as isoquinolines and
quinolines has been developed because of the utility of the
functionalized N-heterocycles,[1] which are important syn-
thetic intermediates and structural units of alkaloids and
biologically active compounds.[2] Among them, the nucleo-
philic addition of cyanides to the N-acylisoquinolinium
and -quinolinium ions generated from azaaromatics and
acylating agents has been commonly known as the Reissert
reaction (Scheme 1a).[3] Reissert-type transformations using
organometallic compounds instead of the cyanides provide
us with a powerful strategy for alkynylation,[4] alkenyl-
ation,[5] arylation,[6] allylation,[7] and alkylation of azaarom-
atic compounds.[8,9] Although the incorporation of amide
groups into azaaromatics by Ugi-type reactions with isocya-
nides were reported,[10] to the best of our knowledge, the
direct nucleophilic acylation of azaaromatics has not been
investigated.[11]
Scheme 1. Reissert reaction and Reissert-type alkenylation.
by chloroformates (Scheme 1b).[5d,5e] Thus, we expected
that the nucleophilic acylation of azaaromatics with acylzir-
conocene chlorides would be achieved by Reissert-type
transformations using chloroformates. In this paper, we de-
scribe the Reissert-type acylation of isoquinolines and quin-
olines with acylzirconocene chlorides.
Our studies on easily accessible and stable acylzircono-
cene chloride complexes[12] have opened up the possibility
of their use as a donor of “unmasked” acyl anions in or- Results and Discussion
ganic syntheses.[13,14] As a part of these studies, we disclosed
Based on our previous studies of the Reissert-type alken-
a nucleophilic acylation of imine derivatives catalyzed by
Lewis or Brønsted acids.[15] These procedures, however,
could not be applied to azaaromatic compounds. Our re-
cent extensions to the reaction of azaaromatics with alken-
ylzirconocene chlorides (Cp = cyclopentadienyl) brought
about Reissert-type alkenylation of azaaromatics activated
ylation reaction,[5d,5e] our preliminary examinations focused
on the reaction of isoquinoline (2a) with acylzirconocene
chloride 1 (2 equiv.) in the presence of ClCO2Et (1.2 equiv.)
in CH2Cl2 or MeNO2 (Table 1, entry 1 or 2). It turned out
that the desired adduct 3a was obtained in low yield after
reaction at room temp. for 2 h. As the next step, we evalu-
ated various metal catalysts that have been known to pro-
mote a nucleophilic acylation of 1 by acyl group transfer of
Zr to the metal (transmetalation)[16] or by formation of the
cationic zirconocene species[17] for the Reissert-type acyl-
ation of 2a with 1 (Table 1, entries 3–13). Among the tried
catalysts, CuI catalysts showed a significant acceleration in
the rate of the desired reaction (entries 3–10).[18] In particu-
lar, by use of CuI (5 mol-%) in MeNO2, 2a was consumed
[a] Division of Applied Chemistry, Institute of Engineering, Tokyo
University of Agriculture and Technology,
2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan
E-mail: akio-sai@cc.tuat.ac.jp
https://kenkyu-db.tuat.ac.jp/tmp/4321/prof_e.html
[b] Showa Pharmaceutical University,
3-3165 Higashi-tamagawagakuen, Machida-shi, Tokyo
194-8543, Japan
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301264.
Eur. J. Org. Chem. 2013, 7295–7299
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7295

A. Saito, H. Sakurai, K. Sudo, K. Murai, Y. Hanzawa
SHORT COMMUNICATION
within 2 h at room temp., giving rise to 3a in 88% yield Table 3. Reissert-type acylation of 2 or 4 with 1.
(entry 7). The cationic RhI catalyst, which was prepared in
situ from [RhCl(coe)2]2 (coe = cyclooctene, 2.5 mol-%) and
AgBF4 (5 mol-%), also brought about a good result in the
formation of 3a (83%, entry 13).
Table 1. Evaluation of catalysts and solvents for the Reissert-type
acylation of 2a with 1.
Method Rh[a]
Method Cu[b]
8
R1
R2
9 [%][c] 10 [%][c]
9 [%][c] 10 [%][c]
8b
8c
8d
8e
H
Me
H
H
H
MeO
Br
58
71
51
42
24
17
30
36
9
51
56
41
54
44
20
10
H
[a] Catalyst: [RhCl(coe)2]2 (2.5 mol-%), AgBF4 (5 mol-%);
ClCO2Et: 1.2 equiv. (8b,c) or 2.4 equiv. (8d,e); solvent: MeNO2. [b]
Catalyst: CuI (10 mol-%); ClCO2Et: 2.4 equiv; solvent: CH2Cl2. [c]
Isolated yields.
Entry
Catalyst (mol-%)
Solvent
Yield [%][a]
1
2
3
4
–
–
CH2Cl2
MeNO2
CH2Cl2
THF
14
trace
72
CuBr (5)
CuBr (5)
13
5
6
7
8
CuBr (5)
CuBr (5)
CuI (5)
CuCl (5)
[Cu(MeCN)4]PF6(5)
CuBr (5), AgBF4(5)
AgBF4(5)
[RhCl(coe2]2(2.5)
MeCN
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
80
85[b]
88[b]
77[b]
73
9
10
11
12
13
78[b]
61
Scheme 2. Reissert-type acylation of 2a with 6.
9
[RhCl(coe2]2(2.5), AgBF4(5) MeNO2
83[b]
[a] The yield was determined by 1H NMR spectroscopic analysis
with toluene as internal standard. [b] Isolated yields.
The scope of the CuI- and/or cationic RhI-catalyzed
Reissert-type acylations of various azaaromatics with 1 in
the presence of ClCO2Et is summarized in Tables 2 and 3
and Schemes 2 and 3.
Scheme 3. Reissert reaction and Reissert-type alkenylation.
Table 2. Reissert-type acylation of 2 or 4 with 1.
after reaction for 2–4 h (Table 2). Even in the reactin of 1-
substituted isoquinoline 2e, the CuI/MeNO2 system af-
forded the desired product 5e in 71% yield by the use of
ClCO2Me (2.4 equiv.) instead of ClCO2Et (Table 2).
Furthermore, the CuI/MeNO2 catalytic system could be ap-
plied to the reaction of isoquinoline (2a) and α,β-unsatu-
rated acylzirconocene chloride 6 in the presence of ClCO2Et
(Scheme 2).
With the CuI/MeNO2 system, although the reaction of 4-
substituted quinoline 8a with 1 in the presence of ClCO2Et
(1.2 equiv.) gave only 1,2 adducts 9a in 71% yield, the case
of quinoline (8b) brought about a regioisomeric mixture of
adducts (9b: 43%, 10b: 32%, Scheme 3). The cationic RhI
catalyst prepared from [RhCl(coe)2]2 and AgBF4 in MeNO2
(Method Rh), however, led to the somewhat preferential
formation of 1,2 adducts 9b (9b: 58%, 10b: 24%,
Table 3).[19] On the other hand, 10b was preferentially ob-
tained under the catalytic conditions of Method Cu [CuI
(10 mol-%) in CH2Cl2], when 2.4 equiv. ClCO2Et was em-
2 or 4 R1
R2
R3
R4
3 or 5
R
Yield [%][a]
2a
2b
2c
2d
2e[b]
4
H
Me
H
H
H
H
H
Br
H
H
H
H
H
NO2
H
H
H
H
H
3a
3b
3c
3d
Et
Et
Et
Et
Me
88
90
70
68
71
72
CO2Me 3e
5
[a] Isolated yields. [b] Reaction time: 18 h; ClCO2Me: 2.4 equiv.
CuI was efficient (5 mol-%) in MeNO2 in the reaction ployed (9b: 9%, 10b: 51%, Table 3). By the similar choice
of isoquinolines 2a–d or 3,4-dihydroisoquinoline (4), and of the catalyst and solvent, regioselective formations of ad-
acylated products 3a–d and 5 were obtained in good yields ducts were observed in reactions of other quinolines 8c–e
7296
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 7295–7299

Reissert-Type Acylation with Acylzirconocene Chloride Complexes
with 1 (Table 3). Thus, Method Rh has a tendency to yield acylzirconocene chloride complexes. For the regioselective
1,2 adducts 9c–e, and Method Cu has a tendency to yield formation of adducts in the reactions of quinolines, it is
1,4 adducts 10c–e.[20]
critical to select catalyst and solvent appropriately. These
On the basis of these observations and previous reports findings indicate a new possibility for the use of acylzircon-
about Reissert-type transformations,[3–9] a plausible mecha- ocene chloride complexes in organic synthesis. Synthetic ap-
nism for the present Reissert-type acylation of isoquinolines plications and detailed mechanistic studies of the present
would consist of: (1) the generation of acyl Cu species by reaction are underway.
the acyl group transfer of acylzirconocene chloride 1 to Cu,
and (2) the addition of the acyl Cu species to active N-
Experimental Section
acylisoquinolinium intermediates 11, which are in equilib-
rium with isoquinolines 2 (Scheme 4).[21] The generation of
acyl Cu species would be supported by the detection of α-
ketols 12 (for 2a–d: 5–10%, for 2e: 29%) as byproducts in
all Reissert-type acylations of 2. As shown in Scheme 5, the
formation of 12 could be explained by the homocoupling
reaction of oxy Cu carbenes, which are derived from acyl
Cu species. A similar observation has been reported in the
Cu-catalyzed coupling reaction with acylzirconocene chlor-
ides.[15a]
Preparation of a CH2Cl2 Solution of Acylzirconocene Chloride 1: A
suspension of Schwartz reagent [Cp2Zr(H)Cl] (258 mg, 1.0 mmol)
and 1-octene (310 μL, 4.0 mmol) in CH2Cl2 (4.0 mL) was stirred at
ambient temperature for 30 min, and the mixture was treated with
carbon monoxide for 2 h (CO balloon, 1 atm). The resulting solu-
tion was used in the following experiments without any further
treatment.
Preparation of a MeNO2 Solution of Acylzirconocene Chloride 1:
After the CH2Cl2 was removed in vacuo from the solution of 1
in CH2Cl2 (4.0 mL), prepared according to the above procedure,
MeNO2 (4.0 mL) was added to the residue.
Typical Procedure for the Reissert-Type Acylation of Isoquinoline
(2a): A premixed solution (0 °C, 30 min) of 2a (59 μL, 0.5 mmol)
and ClCO2Et (57 μL, 0.6 mmol) in MeNO2 (3.0 mL), and then CuI
(4.8 mg, 25 μmol), were successively added to a solution of 1
(1.0 mmol) in MeNO2 (4.0 mL) at ambient temperature. After the
total consumption of 2a (by TLC analysis), the reaction mixture
was diluted with diethyl ether and filtered through a short alumina
column. After concentration of the filtrate to dryness, purification
by silica gel column chromatography (hexane/AcOEt = 30:1) gave
the corresponding adduct 3a (150.9 mg, 0.442 mmol, 88% yield;
Table 2, entry 1) as a colorless oil.
Scheme 4. Proposed mechanism for Reissert-type acylation.
Typical Procedure for the Reissert-Type Acylation of Quinoline (8b)
[Method Rh]: A premixed solution (0 °C, 30 min) of 8b (59 μL,
0.5 mmol) and ClCO2Et (57 μL, 0.6 mmol) in MeNO2 (3.0 mL),
and then cationic RhI catalyst, which was generated by the treat-
ment of [RhCl(coe)2]2 (9.0 mg, 12.5 μmol) with AgBF4 (4.9 mg,
25 μmol) at ambient temperature. for 15 min, were successively
added to a solution of 1 (1.0 mmol) in MeNO2 (4.0 mL) at ambient
temperature. After the total consumption of 8b (by TLC analysis),
the reaction mixture was diluted with diethyl ether and filtered
through a short alumina column. After concentration of the filtrate
to dryness, purification by silica gel column chromatography (hex-
ane/AcOEt = 30:1) gave a regioisomeric mixture of adducts 9b and
10b. The regioisomeric mixture was separated by MPLC (hexane/
AcOEt = 50:1) to give 1,4 adduct 10b (50.0 mg, 0.146 mmol, 29%
yield) and 1,2 adduct 9b (99.0 mg, 0.288 mmol, 58% yield) in the
order of elution (Table 3).
Scheme 5. Reissert reaction and Reissert-type alkenylation.
Since α-ketols 12 were obtained in 4–9% yields in the
Reissert-type acylation of quinolines by CuI/CH2Cl2 cata-
lytic systems, the acyl Cu species might be involved in these
preferred 1,4-addition reactions. Such a preferential forma-
tion of 1,4 adducts has been reported in Reissert-type trans-
formations of quinolines and pyridines by using organocop-
per compounds[8a–8c] or organometallic compounds with
CuI additives.[5e,6d,8d,8e] Although details about the solvent
effect[22] and the role of the cationic RhI catalyst[23] for the
regioselectivity remain uncertain at present, the cationic
RhI catalyst might take part in promoting the generation of
N-acylquinolinium intermediates 13.[24]
[Method Cu]: A premixed solution (0 °C, 30 min) of 8b (59 μL,
0.5 mmol) and ClCO2Et (114 μL, 1.2 mmol) in CH2Cl2 (3.0 mL),
and then CuI (9.6 mg, 50 μmol), were successively added to a solu-
tion of 1 (1.0 mmol) in CH2Cl2 (4.0 mL) at ambient temperature.
After the total consumption of 8b (by TLC analysis), the reaction
mixture was diluted with diethyl ether and filtered through a short
alumina column. After concentration of the filtrate to dryness, pu-
rification by silica gel column chromatography (hexane/AcOEt =
30:1) gave a regioisomeric mixture of adducts 9b and 10b. The re-
gioisomeric mixture was separated by MPLC (hexane/AcOEt =
50:1) to give 1,4 adduct 10b (87.9 mg, 0.256 mmol, 51% yield) and
1,2 adduct 9b (15.5 mg, 45.1 μmol, 9% yield) in the order of elution
Conclusions
We have demonstrated the CuI- or RhI-catalyzed
Reissert-type acylation of azaaromatic compounds with (Table 3).
Eur. J. Org. Chem. 2013, 7295–7299
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7297

A. Saito, H. Sakurai, K. Sudo, K. Murai, Y. Hanzawa
SHORT COMMUNICATION
4315–4319; e) X. Wang, A. M. Kauppi, R. Olsson, F. Almqvist,
Eur. J. Org. Chem. 2003, 4586–4592; f) P. Mangeney, R. Gos-
mini, S. Raussou, M. Commerçon, A. Alexakis, J. Org. Chem.
1994, 59, 1877–1888; g) A. Alexakis, F. Amiot, Tetrahedron:
Asymmetry 2002, 13, 2117–2122.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and physical data for new com-
pounds (3a–e, 5, 7a, 9a–e, 10b–d).
[9]
Examples of enolate nucleophiles: a) K. Akiba, M. Nakatani,
M. Wada, Y. Yamamoto, J. Org. Chem. 1985, 50, 63–68; b) S.
Yamada, C. Morita, Chem. Lett. 2001, 1034–1035; c) Y.-M.
Chang, Y.-S. Park, S.-H. Lee, C.-M. Yoon, Tetrahedron Lett.
2004, 45, 9049–9052; d) H. Rudler, B. Denise, Y. Xu, A. Parlier,
J. Vaissermann, Eur. J. Org. Chem. 2005, 3724–3749; e) J. S.
Yadav, B. V. S. Reddy, M. K. Gupta, U. Dash, D. C. Bhunia,
S. S. Hossain, Synlett 2007, 2801–2804; f) H. Huang, W. Hu,
Tetrahedron 2007, 63, 11850–11855; g) A. Schmidt, D. Mich-
alik, S. Rotzoll, E. Ullah, C. Fischer, H. Reinke, H. Goerls, P.
Langer, Org. Biomol. Chem. 2008, 6, 2804–2814.
a) J. L. Díaz, M. Miguel, R. Lavilla, J. Org. Chem. 2004, 69,
3550–3353; b) N. A. O. Williams, C. Masdeu, J. L. Díaz, R.
Lavilla, Org. Lett. 2006, 8, 5789–5792.
Additions of 2-lithio-1,3-dithianes as “masked” acyl anion
equivalents into azaaromatics have been known. See a) T. Tag-
uchi, M. Nishi, K. Watanabe, T. Mukaiyama, Chem. Lett.
1973, 1307–1308; b) D. Dirnberger, W. Wiegrebe, Arch. Pharm.
1990, 323, 323–330.
Acknowledgments
This work was partially supported by Japan Society for the Pro-
motion of Science (JSPS) Grants-in-Aid for Young Scientists (B)
(Grant No 24790024) and Japan Society for the Promotion of Sci-
ence (JSPS) Grants-in-Aid for Scientific Research (C) (Grant No
22590016).
[1] a) W. N. Speckamp, M. J. Moolenaar, Tetrahedron 2000, 56,
3817–3856; b) A. Yazici, S. G. Pyne, Synthesis 2009, 339–368;
c) A. Yazici, S. G. Pyne, Synthesis 2009, 513–541; d) W. Sliwa,
Heterocycles 1986, 24, 181–219; e) N. Kielland, R. Lavilla, Top.
Heterocycl. Chem. 2010, 25, 127–168; f) M. Ahamed, M. H.
Todd, Eur. J. Org. Chem. 2010, 5935–5942.
[2] a) C. Chen, Y.-F. Zhu, X.-J. Liu, Z.-X. Lu, Q. Xie, N. Ling, J.
Med. Chem. 2001, 44, 4001–4010; b) B. Reux, T. Nevalainen,
K. H. Raitio, A. M. P. Koskinen, Bioorg. Med. Chem. 2009, 17,
4441–4447; c) H.-Y. Lee, L.-W. Lee, C.-Y. Nien, C.-C. Kuo, P.-
Y. Lin, C.-Y. Chang, J.-Y. Chang, J.-P. Liou, Org. Biomol.
Chem. 2012, 10, 9593–9600; d) R. Nishikawa-Shimono, Y. Se-
kiguchi, T. Koami, M. Kawamura, D. Wakasugi, K. Watanabe,
S. Wakahara, K. Matsumoto, T. Takayama, Bioorg. Med.
Chem. Lett. 2012, 22, 3305–3310; e) Y.-N. Zhang, X.-G. Zhong,
Z.-P. Zheng, X.-D. Hu, J.-P. Zuo, L.-H. Hu, Bioorg. Med.
Chem. 2007, 15, 988–996.
[3] a) A. Reissert, Ber. Dtsch. Chem. Ges. 1905, 38, 1603–1614; b)
F. D. Popp, A. Soto, J. Chem. Soc. 1963, 1760–1763; c) R. H.
Reuss, N. G. Smith, L. J. Winters, J. Org. Chem. 1974, 39,
2027–2031; d) M. Takamura, K. Funabashi, M. Kanai, M. Shi-
basaki, J. Am. Chem. Soc. 2001, 123, 6801–6808; e) M. Pauvert,
S. C. Collet, M.-J. Bertrand, A. Y. Guingant, M. Evain, Tetra-
hedron Lett. 2005, 46, 2983–2987.
[4] a) R. Yamaguchi, Y. Omoto, M. Miyake, K. Fujita, Chem.
Lett. 1998, 547–548; b) G. Guanti, S. Perrozzi, R. Riva, Tetra-
hedron: Asymmetry 1998, 9, 3923–3927; c) Y. Yamazaki, K.
Fujita, R. Yamaguchi, Chem. Lett. 2004, 33, 1316–1317; d) J. S.
Yadav, B. V. S. Reddy, M. Sreenivas, K. Sathaiah, Tetrahedron
Lett. 2005, 46, 8905–8908; e) D. A. Black, R. E. Beveridge,
B. A. Arndtsen, J. Org. Chem. 2008, 73, 1906–1910.
[5] a) Y. Yamaoka, H. Miyabe, Y. Takemoto, J. Am. Chem. Soc.
2007, 129, 6686–6687; b) T. Kodama, P. N. Moquist, S. E.
Schaus, Org. Lett. 2011, 13, 6316–6319; c) G. Signore, C. Mal-
anga, R. Menicagli, Tetrahedron 2008, 64, 197–203; d) A. Saito,
K. Iimura, M. Hayashi, Y. Hanzawa, Tetrahedron Lett. 2009,
50, 587–589; e) A. Saito, K. Sudo, K. Iimura, M. Hayashi, Y.
Hanzawa, Heterocycles 2012, 86, 267–280.
[6] a) D. L. Comins, N. B. Mantlo, Tetrahedron Lett. 1987, 28,
759–762; b) D. L. Comins, Y.-C. Myoung, J. Org. Chem. 1990,
55, 292–298; c) Y.-M. Chang, S.-H. Lee, M.-H. Nam, M.-Y.
Cho, Y.-S. Park, C.-M. Yoon, Tetrahedron Lett. 2005, 46, 3053–
3056; d) R. E. Beveridge, D. A. Black, B. A. Arndtsen, Eur. J.
Org. Chem. 2010, 3650–3656; e) T. J. A. Graham, J. D. Shields,
A. G. Doyle, Chem. Sci. 2011, 2, 980–984.
[7] a) R. Yamaguchi, M. Tanaka, T. Matsuda, T. Okano, T. Nag-
ura, K. Fujita, Tetrahedron Lett. 2002, 43, 8871–8874; b) S.-H.
Lee, Y.-S. Park, M.-H. Nam, C.-M. Yoon, Org. Biomol. Chem.
2004, 2, 2170–2172; c) J. S. Yadav, B. V. S. Reddy, M. Srinivas,
K. Sathaiah, Tetrahedron Lett. 2005, 46, 3489–3492; d) S. Yam-
ada, M. Inoue, Org. Lett. 2007, 9, 1477–1480.
[8] a) E. Piers, M. Soucy, Can. J. Chem. 1974, 52, 3563–3564; b)
K. Akiba, Y. Iseki, M. Wada, Bull. Chem. Soc. Jpn. 1984, 57,
1994–1999; c) R. Yamaguchi, Y. Nakazono, T. Matsuki, E.
Hata, M. Kawanishi, Bull. Chem. Soc. Jpn. 1987, 60, 215–222;
d) D. L. Comins, A. H. Abdullah, J. Org. Chem. 1982, 47,
[10]
[11]
[12]
[13]
[14]
C. A. Bertelo, J. Schwartz, J. Am. Chem. Soc. 1975, 97, 228–
230.
Comprehensive paper: Y. Hanzawa, T. Taguchi, J. Synth. Org.
Chem. Jpn. 2004, 62, 314–323.
a) A. Saito, Y. Oka, Y. Nozawa, Y. Hanzawa, Tetrahedron Lett.
2006, 47, 2201–2204; b) Y. Hanzawa, Y. Oka, M. Yabe, J. Or-
ganomet. Chem. 2007, 692, 4528–4534; c) Y. Hanzawa, Y. Tak-
ebe, A. Saito, A. Kakuuchi, H. Fukaya, Tetrahedron Lett. 2007,
48, 6471–6474.
a) A. Kakuuchi, T. Taguchi, Y. Hanzawa, Tetrahedron Lett.
2001, 42, 1547–1549; b) A. Kakuuchi, T. Taguchi, Y. Hanzawa,
Eur. J. Org. Chem. 2003, 116–122.
a) Y. Hanzawa, K. Narita, M. Yabe, T. Taguchi, Tetrahedron
2002, 58, 10429–10435; b) P. Wipf, W. Xu, J. H. Smitrovich, R.
Lehmann, L. M. Venanzi, Tetrahedron 1994, 50, 1935–1954; c)
A. El-Batta, T. R. Hage, S. Plotkin, M. Bergdahl, Org. Lett.
2004, 6, 107–110.
a) S. Harada, T. Taguchi, N. Tabuchi, K. Narita, Y. Hanzawa,
Angew. Chem. 1998, 110, 1796; Angew. Chem. Int. Ed. 1998,
37, 1696–1698; b) P. Wipf, W. Xu, Tetrahedron 1995, 51, 4551–
4562; c) K. Suzuki, T. Hasegawa, T. Imai, H. Maeta, S. Obata,
Tetrahedron 1995, 51, 4483–4494.
Other metal catalysts, such as Pd(OAc)2, (Ph3P)2PdCl2, (Ph3P)
2NiCl2, [RhCl(cod)]2 (cod = cyclooctadiene), (Ph3P)AuCl,
PtCl2, ZnCl2, BF3·OEt2, Yb(OTf)3, or Cu(OTf)2, did not pro-
mote the Reissert-type acylation.
[15]
[16]
[17]
[18]
[19]
Other AgI additives, such as AgSbF6, AgAsF6, AgPF6,
AgNTf2, or AgOTf, instead of AgBF4, showed inferior results
in both yields and regioselectivities of the acylated adducts 9b
and 10b. See Supporting Information for results of attempted
catalytic reactions.
1
[20]
[21]
Rh- and Cu-catalyzed reactions of 3-bromoquinoline (R = Br,
R2 = H) did not take place; only the starting material was
recovered.
We confirmed the generation of acylisoquinolinium ion 11a by
1
the H NMR spectroscopic measurement of a mixture of iso-
quinoline (2a) and ClCO2Et (1.2 equiv.) in CD3NO2 at room
1
temperature. The H NMR spectrum shows new peaks for the
C-1 proton (δ = 10.59 ppm) and the Et protons [CH3 (δ =
1.61 ppm), CH2 (δ = 4.91 ppm)] of 11a along with the C-1 pro-
ton of 2a. The ratio of 11a to 2a depends on the amounts of
ClCO2Et (1.2 equiv: 11a/2a = 1.1:1, 2.4 equiv: 11a/2a = 2:1),
which indicates the equilibrium between 11a and 2a (see the
Supporting Information).
7298
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 7295–7299

Reissert-Type Acylation with Acylzirconocene Chloride Complexes
[22] In the Reissert-type reaction of quinolines with alkenylzircono-
cene chlorides, MeNO2 brought about an improvement of 1,2-
regioselectivities relative to CH2Cl2 as solvent (see ref.[5e]).
[23] In the RhI-catalyzed addition of alkenylzirconocene chlorides
to imines, an alkenyl rhodium species, formed by the transmet-
alation from Zr to Rh, was postulated as an intermediate. See:
A. Kakuuchi, T. Taguchi, Y. Hanzawa, Tetrahedron Lett. 2003,
44, 923–926.
ClCO2Et (1.2 equiv.) in CD3NO2 at room temperature. Ad-
dition of the cationic rhodium (0.25 equiv.) derived from
[RhCl(coe)2]2 and AgBF4, however, brought about the signifi-
cant peaks (C-2: 9.68 ppm, CH2: 4.95 ppm, CH3:1.62 ppm)
corresponding to 13a (13a/8a = 1:2.8; see the Supporting Infor-
mation). AgOTf also works as a promoter of the generation of
acylquinolinium ions (see also ref.[7a]).
Received: August 22, 2013
Published Online: October 9, 2013
[24] Only a trace amount of acylquinolinium ion 13a was observed
in the 1H NMR spectrum after mixing quinoline (8a) and
Eur. J. Org. Chem. 2013, 7295–7299
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7299