Synthesis of isoquinoline derivatives using ROM-RCM of cyclobutene-yne

Article abstract of DOI:10.1021/jo048214c

(Chemical Equation Presented) Isoquinoline derivatives were synthesized from cyclobutenylmethylamine derivatives having an alkyne moiety in a tether using a second-generation ruthenium carbene complex under ethylene gas in good yields.

Full text of DOI:10.1021/jo048214c

SCHEME 1. ROM-RCM of Cycloakene-yne
Synthesis of Isoquinoline Derivatives
Using ROM-RCM of Cyclobutene-yne
Miwako Mori,*,† Hideaki Wakamatsu,‡
Keisuke Tonogaki,† Reiko Fujita,‡
Tsuyoshi Kitamura,† and Yoshihiro Sato†
Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo 060-0812, Japan, and
Tohoku Pharmaceutical University, 4-4-1 Komatsushima,
Aoba-ku, Sendai 981-8558, Japan
mori@pharm.hokudai.ac.jp
Received October 9, 2004
we noticed that this reaction would be an attractive
method for the synthesis of bicyclic compound II.
The possible reaction course for the formation of
bicyclic compound II is shown in Scheme 1. The reaction
of terminal alkyne and ruthenium methylidene carbene
complex gives ruthenium carbene complex III, which
reacts with cycloalkene to give highly strained ruthena-
cyclobutane IV. Ring opening of this complex IV gives
ruthenium carbene complex V, which reacts with an
alkene part of a diene moiety to give ruthenacyclobutane
VI. Ring opening of this complex VI gives bicyclic
compound II. In this reaction, the initial n-membered
ring is converted into an (n + 2)-membered ring size. The
other ring size is (m + 2) and depends on the chain
lengths between the double bond and the triple bond.
To examine the feasibility of this reaction course, when
a CH2Cl2 solution of cyclopentenylmethylamine deriva-
tive 2 and 5 mol % second-generation ruthenium carbene
complex 13d was refluxed for 3 h under ethylene gas,4 7-6
fused bicyclic compound 3 was obtained in 76% yield
(Scheme 2). On the basis of this result, it was expected
that isoquinoline derivative5 IIa could be synthesized
using this procedure. For that purpose, cyclobutenyl-
methylamine derivative Ia (n ) 4, m ) 4 in I) was
required as a starting material.
Isoquinoline derivatives were synthesized from cyclobuten-
ylmethylamine derivatives having an alkyne moiety in a
tether using a second-generation ruthenium carbene com-
plex under ethylene gas in good yields.
Ring-opening metathesis (ROM)-ring-closing metath-
esis (RCM) is a very attractive reaction in synthetic
organic chemistry.1 We have already reported two types
of ROM-RCM of cycloalkyne-yne.2 During the course of
our investigation of ROM-RCM of cycloalkene-yne I,2b
† Hokkaido University.
‡ Tohoku Pharmaceutical University.
(1) Recent application of ROM-RCM: (a) Zuercher, W. J.; Hash-
imoto, M.; Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 6634. (b)
Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S. Organometallics
1996, 15, 901. (c) Fu¨rstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J.
Am. Chem. Soc. 1998, 120, 8305. (d) Burke, S. D.; Quinn, K. J.; Chen,
V. J. J. Org. Chem. 1998, 63, 8626. (e) Adams, J. A.; Ford, J. G.;
Stamatos, P. J.; Hoveyda, A. H. J. Org. Chem. 1999, 64, 9690. (f)
Voigtmann, U.; Blechert, S. Synthesis 2000, 893. (g) Trost, B. M.;
Doherty, G. A. J. Am. Chem. Soc. 2000, 122, 3801. (h) Ovaa, H.;
Stragies, R.; van der Malel, G. A.; van Boom, J. H.; Blechert, S. Chem.
Commun. 2000, 1501. (i) Fu¨rstner, A.; Szillat, H.; Stelzer, F. J. Am.
Chem. Soc. 2000, 122, 6785. (j) Stragies, R.; Blechert, S. J. Am. Chem.
Soc. 2000, 122, 9584. (k) Voigtmann, U.; Blechert, S. Org. Lett. 2000,
2, 3971. (l) Choi, T.-L.; Grubbs, R. H. Chem. Commun. 2001, 2648.
(m) Ru¨ckert, A.; Eisele, D.; Blechert, S. Tetrahedron Lett. 2001, 42,
5245. (n) Banti, D.; North, M. Tetrahedron Lett. 2002, 43, 1561. (o)
Lee, C. W.; Choi, T.-L.; Grubbs, R. H. J. Am. Chem. Soc. 2002, 124,
3224. (p) Randl, S.; Lucas, N.; Connon, J.; Blechert, S. Adv. Synth.
Catal. 2002, 344, 631. (q) Minger, T. L.; Phillips, A. J. Tetrahedron
Lett. 2002, 43, 5357. (r) Buschmann, N.; Ruckert, A.; Blechert, S. J.
Org. Chem. 2002, 67, 4325. (s) Imhof, S.; Blechert, S. Synlett 2003,
609. (t) Stapper, C.; Blechert, S. J. Org. Chem. 2002, 67, 6456. (u)
Schaudt, M.; Blechert, S. J. Org. Chem. 2003, 68, 2913. (v) van Otterlo,
W. A. L.; Ngidi, E. L.; de Koning, C. B.; Fernandes, M. A. Tetrahedron
Lett. 2004, 45, 659. (w) Arjona, O.; Csaky, A. G.; Leoon, V.; Medel, R.;
Plumet, J. Tetrahedron Lett. 2004, 45, 565. (x) Wrobleski, A.; Sahas-
rabudhe, K.; Aube, J. J. Am. Chem. Soc. 2004, 126, 5475. (y) Lesma,
G.; Crippa, S.; Danieli, B.; Sacchetti, A.; Silvani, A.; Virdis, A.
Tetrahedron, 2004, 60, 6437 and references therein.
When a CH2Cl2 solution of cyclobutenylmethylamine
derivative 4a and 5 mol % of second-generation ruthen-
ium carbene complex 1 was refluxed in CH2Cl2 for 3 h
(3) (a) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann,
W. A. Angew. Chem., Int. Ed. 1998, 37, 2490. (b) Huang, J.; Stevens,
E. D.; Nolan, S. P.; Peterson, J. L. J. Am. Chem. Soc. 1999, 121, 2674.
(c) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H. Tetrahedron
Lett. 1999, 40, 2247. (d) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H.
Org. Lett. 1999, 1, 953.
(4) In the metathesis of enyne having a terminal alkyne, ethylene
gas was very effective. See: Mori, M.; Sakakibara, N.; Kinoshita, A.
J. Org. Chem. 1998, 63, 6082.
(5) (a) Bentley, K. W. The Isoquinoline Alkaloids; Harwood Academic
Publishers: Australia, 1998; Vol. 1. (b) Coppola, G. M., Schuster, H.
F., Eds. The Chemistry of Heterocyclic Compounds, Isoquinolines Part
3; Wiley: New York, 1995; Vol. 38. (c) Chrzanowska, M.; Rozwadowska,
M. D. Chem. Rev. 2004, 104, 3341. (d) Xiang, Z.; Luo, T.; Lu, K.; Cui,
J.; Shi, X.; Fathi, R.; Chen, J.; Yang, Z. Org. Lett. 2004, 6, 3155 and
references cited therein.
(2) (a) Kitamura, T.; Mori, M. Org. Lett. 2001, 3, 1161. (b) Mori, M.;
Kuzuba, Y.; Kitamura, T.; Sato, Y. Org. Lett. 2002, 4, 3855. (c)
Kitamura, T.; Kuzuba, Y.; Sato, Y.; Wakamatsu, H.; Fujita, R.; Mori,
M. Tetrahedron, 2004, 60, 7375.
10.1021/jo048214c CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/08/2005
1066
J. Org. Chem. 2005, 70, 1066-1069

SCHEME 2. Synthesis of Fused 6,7-Membered
Ring Compound
SCHEME 4. Synthesis of Isoquinoline Derivatives
Using ROM-RCM of Cyclobutene-yne
SCHEME 3. Synthesis of Isoquinoline Derivative
SCHEME 5. Synthesis of Dihydroisoquinoline
Derivatives
toluene. Furthermore, cyclobutene derivative 8b (R )
Me) having a methyl group on an alkyne part provided
5-methyl-2-tosyl-3,4,7,8-tetrahydroisoquinolone 9b in 56%
yield. Various cyclobutene derivatives 8c-e were treated
in a similar manner to afford the expected isoquinolone
derivatives 9c-e having substituents at the 5-position
in good yields.
Since this procedure is very attractive for the synthesis
of biaryl compounds, tetrahydroisoquinolone derivative
9e was treated with 2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone (DDQ) (Scheme 5). As a result, dihydroisoqui-
nolone derivative 10 was obtained in good yield.
In summary, ROM-RCM of cyclobutenylmethylamine
having an alkyne moiety in a tether afforded isoquinoline
derivatives in good yields in a one-step reaction.
under ethylene gas (1 atm), we were very pleased to find
that the desired isoquinoline derivative 5a was obtained
in 60% yield (Scheme 3). The reaction of cyclobutenyl-
methylamine derivative 4b having disubstituted alkyne
in a tether was treated in a similar manner under argon
gas to give isoquinoline derivative 5b having an ac-
etoxymethyl group at the 5-position in 36% yield along
with the starting material in 41% yield. Toluene can be
used for this reaction, and the desired isoquinoline
derivative 5b was obtained in 39% yield.
Next, synthesis of a cyclic amino acid using this method
was investigated. Condensation of cyclobutenylmethyl
alcohol 6 and amino acid derivative 7 using diethyl
azodicarboxylate (DEAD) and PPh3 gave cyclobutenyl-
methylamine derivative 4c, which was treated with 1 in
a similar manner to give cyclic amino acid 5c in 75%
yield.
Experimental Section
General Procedure for the Metathesis Reaction. A
catalytic amount of 1 (5-10 mol %) and cycloalkene-yne 2, 4, or
8 were dissolved in dry CH2Cl2 (or dry toluene) (0.02-0.03 M).
The solution was refluxed (or warmed at 80 °C) under ethylene
gas (1 atm) or argon gas (1 atm). When cycloalkene-yne having
a terminal alkyne was used as a substrate, the solution was
degassed and ethylene gas was introduced into the reaction
vessel. In the case of cycloalkene-yne having a disubstituted
alkyne, the reaction was carried out under argon gas. After the
Subsequently, an isoquinolone derivative was synthe-
sized. The starting cyclobutenecarboxamide 8a was
synthesized and treated with 10 mol % 1 in CH2Cl2 under
ethylene gas for 18 h to give the desired isoquinolone
derivative 9a in 41% yield (Scheme 4). The yield was
improved to 61% when the reaction was carried out in
J. Org. Chem, Vol. 70, No. 3, 2005 1067

spot of the starting material had disappeared on TLC, a few
drops of ethyl vinyl ether were added to this solution. The
volatiles were removed in vacuo, and the residue was purified
by column chromatography on silica gel to afford isoquinoline
derivative 3, 5, or 9.
and 1 (19.2 mg, 22.56 µmol, 10 mol %) in toluene (8 mL) by
warming at 80 °C for 0.5 h under ethylene, was purified by
column chromatography on silica gel (hexane/ethyl acetate, 3:2)
to give 9a (33.0 mg, 61%) as a pale yellow liquid: IR (neat) 1655
(s), 1621 (s), 1480 (m), 1441 (m) cm-1; 1H NMR (270 MHz, CDCl3)
δ 2.22-2.35 (m, 4 H), 2.47-2.55 (m, 2 H), 3.31 (t, J ) 7.1 Hz, 2
H), 4.64 (s, 2 H), 5.86 (d, J ) 9.4 Hz, 1 H), 6.11 (dt, J ) 9.4, 4.5
Hz, 1 H), 7.25-7.35 (m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ
20.0 (CH2), 23.2 (CH2), 27.2 (CH2), 44.3 (CH2), 50.0 (CH2), 123.8
(C), 126.2 (CH), 127.1 (CH), 127.8 (CH x 2), 128.4 (CH x 2), 132.7
(CH), 137.8 (C), 139.3 (C), 165.7 (C); EI-LRMS m/z 239 (M+),
160, 91, 77; EI-HRMS m/z calcd for C16H17ON (M+) 239.1310,
found 239.1295.
2-(p-Toluenesulfonyl)-2,3,4,7,8,9-hexahydro-1H-cyclo-
hepta[c]pyridine (3). A crude product, which was prepared
from 2 (91.9 mg, 0.30 mmol) and 1 (13.2 mg, 15 µmol, 5 mol %)
by refluxing in CH2Cl2 (10 mL) for 3 h under ethylene, was
purified by column chromatography on silica gel (hexane/ethyl
acetate, 5:1) to give 3 (69.5 mg, 76%) as a colorless oil: IR (neat)
2924, 2856, 1597, 1346, 1164 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.81 (m, 2 H), 2.06 (m, 2 H), 2.25 (m, 4 H), 2.43 (s, 3 H), 3.11
(dd, J ) 5.6, 6.0 Hz, 2 H), 3.51 (s, 2 H), 5.53 (d, J ) 12.0 Hz, 1
H), 5.75 (dt, J ) 12.0, 4.8 Hz, 1 H), 7.32 (d, J ) 8.2 Hz, 2 H),
7.68 (d, J ) 8.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 21.6
(CH3), 27.3 (CH2), 30.8 (CH2), 31.4 (CH2), 32.7 (CH2), 43.0 (CH2),
49.1 (CH2), 125.7 (C), 127.1 (C), 127.7 (CH x 2), 128.8 (CH), 129.5
(CH x 2), 131.3 (C), 132.5 (CH), 143.4 (C); LRMS m/z 303 (M+),
288, 275, 262, 249, 236, 223, 155, 147, 91. Anal. Calcd for C17H21-
NO2S: C, 67.29; H, 6.98; N, 4.62; S, 10.57. Found: C, 67.13; H,
6.97; N, 4.44; S, 10.41.
2-(p-Toluenesulfonyl)-1,2,3,4,7,8-hexahydroisoquino-
line (5a). A crude product, which was prepared from 4a (111.4
mg, 0.38 mmol) and 1 (16.3 mg, 19.25 µmol, 5 mol %) by refluxing
in CH2Cl2 (15 mL) for 3 h under ethylene, was purified by column
chromatography on silica gel (hexane/ethyl acetate, 20:1) to give
5a (66.3 mg, 60%) as an amorphous solid: IR (KBr) 1596 (w),
1346 (s), 1163 (s) cm-1; 1H NMR (400 MHz, CDCl3) δ 1.94-2.02
(m, 2 H), 2.10-2.23 (m, 4 H), 2.43 (s, 3 H), 3.19 (t, J ) 5.7 Hz,
2 H), 3.51 (s, 2 H), 5.64-5.73 (m, 2 H), 7.33 (d, J ) 8.2 Hz, 2 H),
7.68 (d, J ) 8.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 21.5
(CH3), 22.6 (CH2), 24.9 (CH2), 27.9 (CH2), 43.2 (CH2), 47.7 (CH2),
124.3 (C), 124.8 (C), 124.9 (CH), 126.4 (CH), 127.6 (CH x 2), 129.5
(CH x 2), 133.0 (C), 143.4 (C); EI-LRMS m/z 289 (M+), 133, 107,
91; EI-HRMS m/z calcd for C16H19O2NS (M+) 289.1136, found
289.1138.
2-(p-Toluenesulfonyl)-1,2,3,4,7,8-hexahydroisoquinolin-
5-ylmethyl Acetate (5b). A crude product, which was prepared
from 4b (44.7 mg, 0.12 mmol) and 1 (10.5 mg, 12.37 µmol, 10
mol %) in toluene (6 mL) by warming for 22 h under Ar, was
purified by column chromatography on silica gel (hexane/ethyl
acetate, 2:1) to give 5b (17.6 mg, 39%) as a colorless liquid and
recovered 4b (11.7 mg, 26%): IR (neat) 1739 (s), 1599 (w), 1346
(m), 1245 (s), 1165 (s) cm-1; 1H NMR (270 MHz, CDCl3) δ 1.92-
2.18 (m, 4 H), 2.04 (s, 3 H), 2.24-2.33 (m, 2 H), 2.42 (s, 3 H),
3.19 (t, J ) 5.7 Hz, 2 H), 3.52 (s, 2 H), 4.52 (s, 2 H), 5.79 (t, J )
4.3 Hz, 1 H), 7.32 (d, J ) 8.2 Hz, 2 H), 7.68 (d, J ) 8.2 Hz, 2 H);
13C NMR (67.8 MHz, CDCl3) δ 21.0 (CH3), 21.5 (CH3), 22.2 (CH2),
24.8 (CH2), 25.0 (CH2), 43.2 (CH2), 47.8 (CH2), 64.8 (CH2), 124.7
(C), 126.6 (CH), 126.9 (C), 127.7 (CH x 2), 129.6 (CH x 2), 131.4
(C), 133.0 (C), 143.6 (C), 170.7 (C); EI-LRMS m/z 361 (M+), 301,
146, 91; EI-HRMS m/z calcd for C19H23O4NS (M+) 361.1348,
found 361.1328.
N-Benzyl-5-methyl-3,4,7,8-tetrahydro-1(2H)-isoquino-
lone (9b). A crude product, which was prepared from 8b (39.9
mg, 0.16 mmol) and 1 (13.4 mg, 15.75 µmol, 10 mol %) in toluene
(8 mL) by warming at 80 °C for 0.5 h under ethylene, was
purified by column chromatography on silica gel (hexane/ethyl
acetate, 2:1) to give 9b (22.2 mg, 56%) as a pale yellow liquid:
IR (neat) 1659 (s), 1622 (s), 1479 (m), 1442 (m), 1242 (m) cm-1
;
1H NMR (270 MHz, CDCl3) δ 1.77 (dt, J ) 1.8, 1.8 Hz, 3 H),
2.09-2.20 (m, 2 H), 2.28-2.50 (m, 4 H), 3.31 (t, J ) 7.0 Hz, 2
H), 4.65 (s, 2 H), 5.86 (tq, J ) 5.0, 1.8 Hz, 1 H), 7.25-7.35 (m,
5 H); 13C NMR (67.8 MHz, CDCl3) δ 18.5 (CH3), 20.9 (CH2), 22.9
(CH2), 24.6 (CH2), 44.1 (CH2), 50.0 (CH2), 125.4 (C), 127.2 (CH
x 2), 128.0 (CH), 128.3 (CH), 128.5 (CH x 2), 131.8 (C), 138.0
(C), 141.7 (C), 166.1 (C); EI-LRMS m/z 252 (M+ - 1), 174, 160,
91; EI-HRMS m/z calcd for C17H19ON (M+) 253.1467, found
253.1451.
N-Benzyl-5-phenyl-3,4,7,8-tetrahydro-1(2H)-isoquino-
lone (9c). A crude product, which was prepared from 8c (50.7
mg, 0.16 mmol) and 1 (13.6 mg, 16.07 µmol, 10 mol %) in toluene
(8 mL) by warming at 80 °C for 0.5 h under ethylene, was
purified by column chromatography on silica gel (hexane/ethyl
acetate, 2:1) to give 9c (41.8 mg, 82%) as a pale yellow liquid:
IR (neat) 1652 (s), 1620 (s), 1478 (m), 1443 (m), 1223 (m) cm-1
;
1H NMR (270 MHz, CDCl3) δ 2.14-2.22 (m, 2 H), 2.29-2.39 (m,
2 H), 2.53-2.63 (m, 2 H), 3.24 (t, J ) 7.0 Hz, 2 H), 4.66 (s, 2 H),
6.13 (t, J ) 4.5 Hz, 1 H), 7.11-7.36 (m, 10 H); 13C NMR (67.8
MHz, CDCl3) δ 20.7 (CH2), 23.3 (CH2), 26.2 (CH2), 44.5 (CH2),
50.0 (CH2), 126.5 (C), 127.2 (CH), 127.3 (CH), 128.0 (CH x 2),
128.2 (CH x 2), 128.2 (CH x 2), 128.2 (C), 128.6 (CH x 2), 131.2
(CH), 137.9 (C), 139.4 (C), 140.3 (C), 166.0 (C); EI-LRMS m/z
314 (M+ - 1), 91; EI-HRMS m/z calcd for C22H21ON (M+)
315.1623, found 315.1642.
Ethyl 4-(2-Benzyl-1-oxo-1,2,3,4,7,8-hexahydroisoquino-
lin-5-yl)-benzoate (9d). A crude product, which was prepared
from 8d (25.5 mg, 0.07 mmol) and 1 (5.6 mg, 6.58 µmol, 10 mol
%) in toluene (3.3 mL) by warming at 80 °C for 0.5 h under
ethylene, was purified by column chromatography on silica gel
(hexane/ethyl acetate, 3:2) to give 9d (21.2 mg, 83%) as a pale
yellow liquid: IR (neat) 1716 (s), 1652 (s), 1622 (s), 1609 (s),
1274 (s), 755 (s) cm-1; 1H NMR (270 MHz, CDCl3) δ 1.39 (t, J )
7.1 Hz, 3 H), 2.12-2.20 (m, 2 H), 2.32-2.42 (m, 2 H), 2.55-2.64
(m, 2 H), 3.25 (t, J ) 7.0 Hz, 2 H), 4.37 (q, J ) 7.1 Hz, 2 H), 4.66
(s, 2 H), 6.19 (t, J ) 4.6 Hz, 1 H), 7.21 (d, J ) 8.3 Hz, 2 H),
7.24-7.35 (m, 5 H), 7.99 (d, J ) 8.3 Hz, 2 H); 13C NMR (67.8
MHz, CDCl3) δ 14.3 (CH3), 20.7 (CH2), 23.3 (CH2), 26.1 (CH2),
44.5 (CH2), 50.1 (CH2), 61.0 (CH2), 127.0 (C), 127.4 (CH), 128.1
(CH x 2), 128.2 (CH x 2), 128.6 (CH x 2), 129.4 (C), 129.5 (CH x
2), 132.3 (CH), 137.8 (C), 138.7 (C), 139.5 (C), 143.9 (C), 165.8
(C), 166.3 (C); EI-LRMS m/z 386 (M+ - 1), 342, 91; EI-HRMS
m/z calcd for C25H25O3N (M+) 387.1834, found 387.1859.
N-Benzyl-5-naphthalen-1-yl-3,4,7,8-tetrahydro-1(2H)-iso-
quinolone (9e). A crude product, which was prepared from 8e
(61.6 mg, 0.17 mmol) and 1 (14.3 mg, 16.86 µmol, 10 mol %) in
toluene (8.5 mL) by warming at 80 °C for 1 h under ethylene,
was purified by column chromatography on silica gel (hexane/
ethyl acetate, 3:1) 9e (43.9 mg, 71%) as a pale yellow liquid: IR
Ethyl 2-(p-Toluenesulfonyl)-1,2,3,4,7,8-hexahydroiso-
quinoline-3-carboxylate (5c). A crude product, which was
prepared from 4c (88.4 mg, 0.24 mmol) and 1 (10.4 mg, 12.23
µmol, 5 mol %) in CH2Cl2 (8 mL) by refluxing for 2 h under
ethylene, was purified by column chromatography on silica gel
(hexane/ethyl acetate, 5:1) to afford 5c (66.4 mg, 75%) as an
amorphous solid: IR (KBr) 1728 (s), 1598 (m), 1346 (s), 1163 (s)
cm-1 1H NMR (400 MHz, CDCl3) δ 1.06 (t, J ) 7.0 Hz, 3 H),
;
1.93-2.01 (m, 2 H), 2.04-2.19 (m, 2 H), 2.41 (s, 3 H), 2.47 (d, J
) 10.6 Hz, 1 H), 2.62 (m, 1 H), 3.79 (d, J ) 17.0 Hz, 1 H), 3.86
(m, 1 H), 3.95-4.04 (m, 2 H), 4.87 (dd, J ) 1.6, 6.6 Hz, 1 H),
5.62-5.72 (m, 2 H), 7.28 (d, J ) 8.2 Hz, 2 H), 7.69 (d, J ) 8.2
Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 13.9 (CH3), 21.5 (CH3),
22.5 (CH2), 24.6 (CH2), 30.9 (CH2), 45.0 (CH2), 53.4 (CH), 61.1
(CH2), 122.3 (C), 124.8 (C), 125.1 (CH), 126.3 (CH), 127.1 (CH x
2), 129.3 (CH x 2), 136.1 (C), 143.1 (C), 170.2 (C); EI-LRMS m/z
361 (M+), 288, 206, 132, 91; EI-HRMS m/z calcd for C19H23O4-
NS (M+) 361.1348, found 361.1352.
(neat) 1653 (s), 1620 (s), 1478 (s), 1226 (m), 756 (s) cm-1 1H
;
NMR (270 MHz, CDCl3) δ 1.88 (t, J ) 7.1 Hz, 2 H), 2.32-2.69
(m, 3 H), 2.86 (m, 1 H), 3.02-3.22 (m, 2 H), 4.58 (d, J ) 14.8
Hz, 1 H), 4.66 (d, J ) 14.8 Hz, 1 H), 6.18 (dd, J ) 4.0, 4.9 Hz, 1
H), 7.18-7.32 (m, 6 H), 7.40-7.50 (m, 3 H), 7.70-7.85 (m, 3 H);
N-Benzyl-3,4,7,8-tetrahydro-1(2H)-isoquinolone (9a). A
crude product, which was prepared from 8a (54.0 mg, 0.23 mmol)
1068 J. Org. Chem., Vol. 70, No. 3, 2005

13C NMR (67.8 MHz, CDCl3) δ 20.6 (CH2), 23.3 (CH2), 25.1 (CH2),
44.4 (CH2), 50.1 (CH2), 125.3 (C), 125.3 (CH), 125.4 (CH), 125.9
(CH), 126.2 (CH), 126.6 (CH), 127.2 (CH), 127.8 (CH), 128.0 (CH
x 2), 128.3 (CH), 128.4 (CH x 2), 132.0 (C), 132.3 (CH), 133.3
(C), 137.3 (C), 137.6 (C x 2), 141.4 (C), 166.0 (C); EI-LRMS m/z
364 (M+ - 1), 215, 91; EI-HRMS m/z calcd for C26H23ON (M+)
365.1779, found 365.1769.
(s, 2 H), 7.14-7.45 (m, 12 H), 7.80 (t, J ) 7.5 Hz, 2 H), 8.20 (dd,
J ) 2.0, 7.1 Hz, 1 H); 13C NMR (67.8 MHz, CDCl3) δ 25.9 (CH2),
45.1 (CH2), 50.5 (CH2), 125.3 (CH), 125.6 (CH), 125.9 (CH), 126.3
(CH), 126.7 (CH), 126.9 (CH), 127.4 (CH), 128.0 (CH), 128.0 (CH
x 2), 128.3 (CH), 128.3 (CH), 128.6 (CH x 2), 129.7 (C), 131.9
(C), 133.5 (C), 133.7 (CH), 137.0 (C), 137.3 (C), 137.7 (C), 138.4
(C), 164.7 (C); EI-LRMS m/z 363 (M+), 272, 259, 243, 229, 215,
91; EI-HRMS m/z calcd for C26H21ON (M+) 363.1623, found
363.1642.
N-Benzyl-5-naphthalen-1-yl-3,4-dihydro-1(2H)-isoqui-
nolone (10). To a solution of 9e (42.6 mg, 0.12 mmol) in toluene
(2 mL) was added DDQ (79.4 mg, 0.35 mmol) at room temper-
ature, and the solution was stirred at 80 °C for 3 h. The solution
was filtered, and the filtrate was concentrated. The residue was
purified by column chromatography on silica gel (hexane/ethyl
acetate, 2:1) to afford 10 (32.1 mg, 76%) as an amorphous solid:
Supporting Information Available: Information on
experimental procedures and spectral data of 2, 4a-c, 8a-e,
14, and 15. This material is available free of charge via the
Internet at http://pubs.acs.org.
IR (KBr) 1650 (s), 782 (m), 755 (m) cm-1 1H NMR (270 MHz,
;
CDCl3) δ 2.44 (t, J ) 6.6 Hz, 2 H), 3.21 (t, J ) 6.6 Hz, 2 H), 4.69
JO048214C
J. Org. Chem, Vol. 70, No. 3, 2005 1069