Regio- and stereoselective α-allylation of quinolines activated by chloroformate and triflate ion by means of chiral allylsilane: A synthesis of chiral 2-substituted 1,2-dihydroquinolines

Article abstract of DOI:10.1016/S0040-4039(02)02201-3

Addition reactions of a chiral allylsilane to a variety of quinolines activated by phenyl chloroformate and triflate ion proceed with high regio- and stereoselectivities to afford various chiral 2-allylated 1,2-dihydroquinolines in good yields.

Full text of DOI:10.1016/S0040-4039(02)02201-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8871–8874
Regio- and stereoselective a-allylation of quinolines activated by
chloroformate and triflate ion by means of chiral allylsilane: a
synthesis of chiral 2-substituted 1,2-dihydroquinolines
Ryohei Yamaguchi,a,* Masato Tanaka,a Tomohiko Matsuda,a Toshihiko Okano,a Teruno Naguraa
and Ken-ichi Fujitab
aGraduate School of Human and Environmental Studies, Kyoto University, Yoshida, Kyoto 606-8501, Japan
bGraduate School of Global Environmental Studies, Kyoto University, Yoshida, Kyoto 606-8501, Japan
Received 9 September 2002; revised 30 September 2002; accepted 3 October 2002
Abstract—Addition reactions of a chiral allylsilane to a variety of quinolines activated by phenyl chloroformate and triflate ion
proceed with high regio- and stereoselectivities to afford various chiral 2-allylated 1,2-dihydroquinolines in good yields. © 2002
Elsevier Science Ltd. All rights reserved.
Hydroquinoline derivatives have attracted great atten-
tion as biological active nitrogen compounds,1 and
regio- and/or stereoselective nucleophilic addition of
organometallic reagents to quinolinium ion have been
widely investigated.2,3 All of the methods so far
reported have exploited diastereoselective additions of
achiral organometallic reagents to quinolinium ion with
a chiral auxiliary in the activating group or on the
quinoline ring. Stereoselective addition reaction of chi-
ral organometallic reagent to an achiral quinolinium
ion has been rarely reported.4 In view of great interest
in allylation reactions,5 we have recently revealed that
allylsilanes, which are less toxic but less reactive than
allyltins, can readily react with quinolines and isoquino-
lines activated by phenyl chloroformate and triflate ion
to give allylated products.6,7 We have also reported
stereoselective addition of a chiral allylsilane to iso-
quinolines.8 We wish to disclose here that a chiral
allylsilane can differentiated the ring-face of N-acylated
quinolinium ion to afford chiral 2-allylated 1,2-dihy-
droquinolines in highly regio- and stereoselective
manners.
(R)-3-phenyl-3-trimethylsilyl-1-propene (3)9 (83% ee by
a chiral GLC analysis) at room temperature, the 2-allyl-
ated 1,2-dihydroquinoline adduct 410 was obtained
regioselectively in 94% yield (Scheme 1). No formation
of the 1,4-adduct was observed by NMR. The exclusive
formation of E geometry (J=16 Hz) of the allylic
double bond was observed, supposing the high anti-SE2%
manner of the present allylation reaction.5 The chiral
HPLC analysis showed 77% ee of 4, indicating 93% of
the stereoselectivity (Table 1, entry 1). The results of
the reactions using other triflate ions are summarized in
Table 1.
As shown in Table 1, the stereoselectivity of the present
reactions is as high as 90%. Zn(OTf)2 gave the very
high selectivity (96%), although the yield was very low
When quinoline (1) was activated by phenyl chlorofor-
mate (1.2 equiv.) and AgOTf (1.2 equiv.) in CH3CN to
generate a quinolinium ion 2 and, then, reacted with
Keywords: N-acylquinolinium ion; regio- and stereoselective allyla-
tion; chiral allylsilane; chiral 2-substituted 1,2-dihydroquinoline.
* Corresponding author. Tel.: +81-75-753-6840; fax: +81-75-753-7861;
e-mail: yama@kagaku.mbox.media.kyoto-u.ac.jp
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02201-3

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R. Yamaguchi et al. / Tetrahedron Letters 43 (2002) 8871–8874
Table 1. Additions of (R)-3 to quinoline activated with ClCO2Ph and promoter
Entry
Promoter (equiv.)
Time (h)
Yield of 4 (%)a
ee of 3 (%)b
ee of 4 (%)c
Select. (%)d
1
2
3
4
AgOTf (1.2)
Zn(OTf)2 (1.0)
TMSOTf (1.0)
AgOTf (0.1)
5
5
5
94
24
72
65
83
83
76
76
77
80
69
68
93
96
90
89
24
a Isolated yield.
b Determined by a chiral GLC (Chiral-DEX CB) analysis.
c Determined by a chiral HPLC (SUMICHIRAL OA-2000) analysis.
d Stereoselectivity.
AgOTf (Scheme 3). The results are summarized in
Table 2.
As is shown in Table 2, the present reaction tolerates a
variety of functional groups. The stereoselectivities are
also higher than 90%, except for 3-methoxycar-
bonylquinoline (entry 3). The best result (96% yield,
96% stereoselectivity) was obtained in the reaction of
6-nitroquinoline (entry 6). The absolute configurations
of the adducts 11 are deduced to be S, because all of
them show levorotatory optical rotations.
In order to clarify the origin of the high stereoselectiv-
ity of the present reactions, it is inevitable to know the
conformation of the reactive intermediate, N-phenoxy-
carbonylquinolinium triflate (2). Then, we have been
able to prepare 2 by reaction of 1 with equimolar
amounts of ClCO2Ph and AgOTf as moisture sensitive
solids. A single crystal of 2 could be obtained by
recrystallization from CH2Cl2 and a X-ray structure of
2 is shown in Fig. 1.13,14 It is apparent that the carbonyl
group directs to the inside of the aromatic ring and that
the dihedral angle between the carbonyl and the aro-
matic planes is about 36 degrees probably due to
reducing the steric repulsion between them. This
slightly twisted conformation is contrasted with the
almost coplanar conformations observed for N-acyl-
pyridinium15 and -isoquinolinium ions.16
Scheme 2. Reagents and conditions: (i) H2, Pd–C, 92%; (ii)
KOH, i-PrOH–H2O, 92%; (iii) LiAlH4, 94%; (iv) I2, PPh3,
imidazole, 91%; (v) PhCH2MgCl, CuI (cat.), 46%.
(entry 2). TMSOTf gave the high selectivity and the
moderate yield (entry 3). Among the promoters, AgOTf
seems preferable in views of the yield and selectivity.
The use of catalytic amount (0.1 equiv.) of AgOTf
worked as well (entry 4), though the yield was lower.
The absolute configuration of 4 was determined to be S
by the following experiments (Scheme 2). The adduct 4
(70% ee) was hydrogenated and deprotected11 to give
2-(3-phenylpropyl)-1,2,3,4-tetrahydroquinoline
(6),
As mentioned above, it is highly likely that the present
addition reaction proceeds via the generally proposed
anti-SE2% mode, in which antiperiplanar and synclinal
non-chelation transition states are possible.5 Consider-
ing the conformation of the intermediate 2 revealed by
the X-ray analysis, three possible transition state (A, B,
and C) in the present reaction are depicted in Fig. 2.
The transition states A and B are antiperplanar and the
transition state B is synclinal. It is apparent that,
among the two antiperplanar transition states, B is
more congested than A. It is also probable that the
which showed a levorotatory optical rotation ([h]D=
−46). On the other hand, (R)-6 (95% ee) was prepared
from (S)-712 through the three step operations (Scheme
2) and showed a dextorotatory optical rotation ([h]D=
+65). Thus, it is evident that the present addition
reaction afforded the (S)-adduct 4.
We next examined the stereoselective addition reaction
of (R)-3 to various functionalized quinolines activated
by ClCO2Ph and a catalytic amount (0.1 equiv.) of
Scheme 3.

R. Yamaguchi et al. / Tetrahedron Letters 43 (2002) 8871–8874
8873
Table 2. Additions of (R)-3 to a variety of quinolines activated with ClCO2Ph and a catalytic amount of AgOTf
Entry
R1
R2
R3
Product
Yield (%)a
Select. (%)b,c
1
2
3
4
5
6
Br
H
H
H
CO2Me
H
H
H
H
H
H
OMe
NO2
11a
11b
11c
11d
11e
11f
76
71
64
58
62
96
96
90
84
97
96
96
Me
CO2Me
H
H
H
a Isolated yield.
b Stereoselectivity.
c Calculated on the basis of enantiomeric purities of (R)-3 and the products 11a–11f.
synclinal transition states C leading to (R)-4 would be
subjected to the steric repulsion between the allylic
moiety and phenoxy group as indicated in Fig. 2 and,
therefore, less stable than the transition state A. Thus,
the chiral allylsilane could preferably attack to the
si-face of quinoline ring through the most favorable
transition state A to afford the adduct (S)-4 selec-
tively.
In summary, we have demonstrated regio- and stereose-
lective addition reactions of a chiral allylsilane to
quinolines activated with chloroformate and triflate ion
to afford chiral 2-allylated 1,2-dihydroquinolines. A
variety of functional groups can be tolerated. The
present reaction provide a new straightforward method
for synthesis of chiral 2-substituted 1,2-dihydroquinoli-
nes, which may be valuable synthetic intermediates
for alkaloids and related nitrogen heterocyclic com-
pounds.
Figure 1. A single-crystal X-ray structure of 2. The hydrogen
atoms are omitted for clarity.
Figure 2. Three possible transition states.

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R. Yamaguchi et al. / Tetrahedron Letters 43 (2002) 8871–8874
Nakayasu, T.; Hatano, B.; Nagura, T.; Kozima, S.;
Acknowledgements
Fujita, K. Tetrahedron 2001, 57, 109 and references cited
therein.
We thank Dr. Ryu Nagata of Sumitomo Pharmaceuti-
cal Research Center for kindly providing us (S)-7. This
work is partially supported by a Grant-in-Aid from
Ministry of Education, Science, Sports, and Culture of
Japan (No. 10650832).
7. For alkynylation reactions of quinolines, see: Yamaguchi,
R.; Omoto, Y.; Miyake, M.; Fujita, K. Chem. Lett. 1998,
1, 547.
8. Yamaguchi, R.; Tanaka, M.; Matsuda, T.; Fujita, K.
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Kumada, M. J. Org. Chem. 1986, 51, 3772; (b) Hayashi,
T.; Iwamura, T.; Uozumi, Y. Tetrahedron Lett. 1994, 35,
4813.
10. All new compounds gave satisfactory spectral and analyt-
ical data.
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