1626
J. Szawkalo and Z. Czarnocki
The mixture was stirred at room temp for 3 h. Then 168.8 mg dihydroprotoberberine salt 3 (0.33 mmol)
in 10 cm3 of dry CH2Cl2 was added. The whole mixture was stirred for 12h and the solvent was evap-
orated followed by the addition of a solution of 25cm3 25% NaOH to the solid residue. The mixture
was stirred for 30 min and subsequently was extracted with ether (3ꢄ20 cm3). The combined organic
extracts were dried (MgSO4) and the solvent was removed. The residue was separated by flash column
chromatography (silica gel, CHCl3:CH3OH¼ 99:1) to give 48mg (93.9%) 5 and 6.
(8R,13aR)-2,3,10,11-Tetramethoxy-8-methyl-5,8,13,13a-tetrahydro-6H-
isoquino[3,2-a]isoquinoline (5)
The catalyst (S,S)-14 was prepared by stirring of 6 mg dichloro(ꢀ6-benzene)ruthenium(II) and 7.3mg
of (1S,2S)-1,2-diphenyl-N-(4-tolylsulfonyl)ethylenediamine in 5 cm3 of acetonitrile for 10min as de-
scribed in Ref. [13]. Formic acid=triethylamine mixture (1.01 cm3:1.49 cm3) and (S,S)-14 were added
to a solution of 0.5 g 3 in 10 cm3 of acetonitrile. After stirring at room temp for 12 h, the mixture was
made basic by addition of aqueous Na2CO3 solution and extracted with ether. The organic phase was
dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatog-
20
raphy to give 310 mg (85%) 5 as an oil; ½ꢁꢅD ¼ þ143.1ꢃ cm2 gꢁ1 (c ¼ 0.98, CHCl3) (Ref. [15]
20
½ꢁꢅD ¼ þ227ꢃ cm2 gꢁ1 (c ¼ 1, CHCl3)), 63% ee. All spectral data were identical with those reported
in Ref. [15].
Coralydine 5 was transformed into its HCl salt, which crystallized from acetone-diethyl ether
20
to give 20mg 5 ꢆ HCl; mp 247–250ꢃC; ½ꢁꢅD ¼ þ130.0ꢃ cm2 gꢁ1 (c ¼ 1.05, CHCl3) (Ref. [9] mp
20
246–250ꢃC, ½ꢁꢅD ¼ ꢁ130.4ꢃ cm2 gꢁ1 (c ¼ 1.27, CHCl3)).
6,7-Dimethoxy-1-[2-(3,4,5-trimethoxyphenyl)ethyl]-3,4-dihydroisoquinoline (15)
A mixture of 1.44g 3,4,5-trimethoxydihydrocinnamic acid (6mmol) and 1 g 3,4-dimethoxyphenethyl-
amine (5.5mmol) in 100 cm3 of anhydrous xylene that contained 10mg of p-toluenesulphonic acid
was refluxed under Ar with a Dean-Stark water trap. The solvent was evaporated and the oily residue
was quenched with 50 cm3 of ethanol to yield, after drying, the appropriate amide which was taken to
the next step without further purification. Thus, amide (1g, 2.5 mmol) was dissolved in 50 cm3 CH2Cl2
containing a suspended PCl5 (770mg, 3.7 mmol) and the mixture was stirred under Ar overnight at
room temp. The contents of the flask were then carefully poured onto a suspension of 2.5g NaHCO3 in
150 cm3 H2O. Extraction with CH2Cl2, drying, and evaporation afforded imine 15 as viscous syrup
(831 mg, 87%) [10].
(1S)-6,7-Dimethoxy-1-[2-(3,4,5-trimethoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline (16)
The catalyst (R,R)-14 was prepared as described for 5. Formic acid=triethylamine mixture
(1.01 cm3:1.49 cm3) and (R,R)-14 were added to a solution of 510 mg of imine 15 in 10 cm3 of
acetonitrile. After stirring at room temperature for 12h, the mixture was made basic by addition of
aqueous Na2CO3 solution and extracted with ether. The organic phase was dried (MgSO4) and con-
centrated under reduced pressure. The residue was separated by flash chromatography to give 470 mg
20
20
(91.7%) of compound 16 as an oil; ½ꢁꢅD ¼ ꢁ13.9ꢃ cm2 gꢁ1 (c ¼ 1.45, CHCl3) (Ref. [16] ½ꢁꢅD
¼
ꢁ14.1ꢃ cm2 gꢁ1 (c ¼ 0.34, CHCl3)), 98.6% ee. All spectral data were identical with those reported
in Ref. [16]. A small sample of 16 was subjected to the determination of stereomer composition by
1H NMR of its Mosher’s acid derivative according to the procedure of Ref. [14]. It confirmed the
optical purity value being >99% ee.
(14aS)-2,3,10,11,12-Pentamethoxy-5,6,8,13,14,14a-
hexahydroisoquino[2,1-b][2]benzazepine (17)
A 100 mg sample (S)-16 (0.26 mmol) was mixed with 1 drop conc. HCl in 3 cm3 H2O and then 1 cm3
37% aq. HCHO was added to the mixture. After refluxing for 2 h under Ar, the mixture was made basic
with 25% NaOH aq. solution and was extracted 4 times with benzene. The extract was washed
with saturated NaCl solution, dried, and evaporated to afford 98mg (95%) 17 as an oil;