822
K. Iso et al.
PRACTICAL SYNTHETIC PROCEDURES
mL, 1 mmol, 1.00 equiv) and CHCl3 (400 mL, 5 mmol, 5.00 equiv)
at 25 °C under argon. After stirring for 2 days at 25 °C, the resulting
dark brown mixture was filtered through a pad of Celite for removal
of 4A MS. The solvent was evaporated under reduced pressure to
leave the crude product, which was purified by basic silica gel col-
umn chromatography using a mixture of hexane and Et2O as an elu-
ent to give 2a; yield: 282 mg (87%); white needles; mp 132 °C.
corresponding products were obtained in high yields (en-
tries 12, 13).
In conclusion, we have reported an efficient and atom eco-
nomical synthetic method of 1,2-dihydroisoquinoline de-
rivatives from readily available starting materials. It is
obvious that the present reaction is simple and environ-
mentally benign preparation method because neither cata-
lysts nor any highly reactive reagents are needed. In
particular, the noncatalyzed self-construction was ob-
served in the reactions using 1a by just mixing three com-
ponents at room temperature. The obtained products are
known to be versatile intermediates for various kinds of
bioactive compounds, such as tetrahydroisoquinoline al-
kaloids.
IR (KBr): 3037, 1624, 1595, 1560, 1502, 1257, 1225, 1132, 945,
922, 862, 773, 752, 727, 692, 638 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 7.6 Hz, 1 H), 7.40–
7.33 (m, 3 H), 7.21–7.29 (m, 4 H), 7.05 (m, 1 H), 6.79 (dd, J = 7.3,
1.5 Hz, 1 H), 6.13 (d, J = 7.3 Hz, 1 H), 5.81 (d, J = 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 146.7, 133.1, 129.9, 129.2, 129.1,
129.0, 125.7, 124.1, 123.4, 122.5, 118.5, 108.7, 104.8, 74.6.
HRMS (ESI): m/z [M + H]+ calcd for C16H12Cl3N: 324.0108; found:
324.0108.
All reagents were used as supplied unless otherwise stated. Molec-
ular sieve beads (4A MS; ca. 2 mm) were purchased from Nacalai
Tesque, and were dried before use in an oven (140 °C) for 2 h. An-
alytical thin-layer chromatography (TLC) was performed using NH
TLC plates (Fuji Silysia Chemical LTD.). Column chromatography
was performed using 100–210 mm Silica Gel 60N (Kanto Chemical
Co., Inc.), 40–50 mm Silica Gel 60N (Kanto Chemical Co., Inc.),
and basic Chromatorex-NH 200–350 mesh (Fuji Silysia Chemical
References
(1) For reviews, see: (a) Chrzanowska, M.; Rozwadowska, M.
D. Chem. Rev. 2004, 104, 3341. (b) Bentley, K. W. Nat.
Prod. Rep. 2004, 21, 395. (c) Scott, J. D.; Williams, R. M.
Chem. Rev. 2002, 102, 1669.
(2) For the solid-supported synthesis of skeletally diverse
alkaloid-like compounds, see: Taylor, S. J.; Taylor, A. M.;
Schreiber, S. L. Angew. Chem. Int. Ed. 2004, 43, 1681.
(3) Asao, N.; Yudha, S. S.; Nogami, T.; Yamamoto, Y. Angew.
Chem. Int. Ed. 2005, 44, 5526.
(4) For other synthetic methods of 1,2-dihydroisoquinolines
from o-alkynylarylaldimines, see: (a) Ohtaka, M.;
Nakamura, H.; Yamamoto, Y. Tetrahedron Lett. 2004, 45,
7339. (b) Yanada, R.; Obika, S.; Kono, H.; Takemoto, Y.
Angew. Chem. Int. Ed. 2006, 45, 3822.
(5) Asao, N.; Iso, K.; Yudha, S. S. Org. Lett. 2006, 8, 4149.
(6) Addition of CHCl3 to quaternary protoberberine alkaloids
has been reported, see: Marek, R.; Sečkářová, P.; Hulová,
D.; Marek, J.; Dostál, J.; Sklenář, V. J. Nat. Prod. 2003, 66,
481.
1
LTD.). NMR spectra were measured at 400 MHz for H and 100
MHz for 13C on a JEOL JNM-AL 400 spectrometer. Chemical shifts
of 1H NMR were expressed in parts per million downfield from tet-
ramethylsilane with reference to internal residual CHCl3 (d = 7.26)
in CDCl3. Chemical shifts of 13C NMR were expressed in parts per
million downfield from CDCl3 as an internal standard (d = 77.0) in
CDCl3. Mass spectra were recorded on HITACHI M-2500S (EI,
HRMS) or Bruker APEX III (ESI-TOF MS, HRMS). Melting
points were measured on a Yanaco MP-S3 micro melting point ap-
paratus.
2-Phenyl-1-(trichloromethyl)-1,2-dihydroisoquinoline (2a);
Typical Procedure
To a mixture of 2-ethynylbenzaldehyde (1a; 130 mg, 1 mmol, 1.00
equiv) and 4A MS (1 g) in CH2Cl2 (5 mL) were added aniline (90
Synthesis 2008, No. 5, 820–822 © Thieme Stuttgart · New York