S.J. Czarnocki et al. / Tetrahedron 64 (2008) 3176e3182
3181
2H), 3.89 (s, 3H), 3.91 (s, 3H), 6.67 (s, 1H), 6.95 (s, 1H), 7.68e
7.72 (m, 2H), 7.80e7.84(m, 2H). 13C NMR (125 MHz,
CDCl3): d¼25.8, 32.9, 37.8, 46.8, 55.9, 56.2, 108.4, 110.3,
121.7, 123.1, 131.5, 132.1, 133.9, 147.5, 150.8, 165.4, 168.4.
HRMS (ESI) calcd for C22H23N2O4 ([MþH]þ) m/z 379.1658,
found 379.1668.
131.0, 147.3, 147.3, 153.3, 156.2, 163.6. HRMS (ESI) calcd
for C25H41N4O6 ([MþH]þ) m/z 493.3026, found 493.3027.
3.11. (R)-(þ)-Crispine E (3)
To a solution of 21 (370 mg, 0.75 mmol) in 20 mL
of CH2Cl2 was added 4 mL of TFA. The mixture was then
stirred at room temperature for 1 h, and concentrated under re-
duced pressure. The residue was treated with MeOH/HCl and
after evaporation to give product 3 as white solid, mp 132e
134 ꢁC (lit.21a mp 130e133 ꢁC), [a]2D3 þ22.6 (c 1, MeOH).
1H NMR (500 MHz, CD3OD): d¼1.82e1.86 (m, 2H), 2.01e
2.09 (m, 1H), 2.17e2.26 (m, 1H), 2.98e3.04 (m, 1H),
3.09e3.15 (m, 1H), 3.30e3.39 (m, 3H), 3.56e3.61 (m,
1H), 3.82 (s, 3H), 3.84 (s, 3H), 4.51e4.57 (m, 1H), 6.80 (s,
1H), 6.87 (s, 1H). 13C NMR (125 MHz, CD3OD): d¼25.8,
26.2, 32.3, 40.7, 42.0, 56.2, 56.5, 56.9, 111.1, 113.0, 125.1,
125.3, 149.8, 150.5, 158.6. IR (KBr, cmꢀ1): 3378, 3161,
2939, 1665, 1650, 1519, 1261. HRMS (ESI) calcd for
C15H25N4O2 ([MþH]þ) m/z 293.1978, found 293.1974.
3.9. 2-[3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)-
propyl]-1H-isoindole-1,3(2H)-dione (20)
The catalyst (R,R)-12 was pre-formed from [RuCl2(p-cym-
ene)]2 (3.7 mg, 6 mmol) and (1R,2R)-1,2-diphenyl-N-(p-tol-
uoylsulfonyl)ethylenediamine (4.4 mg, 12 mmol) in 4 mL
of CH3CN. To a solution of imine 19 (491 mg, 1.3 mmol) in
CH3CN (5 mL), a 5:2 formic acid/triethylamine mixture
(1.5 mL) was introduced, followed by the addition of the pre-
formed catalyst. The mixture was then stirred at room temper-
ature for 3 h and after evaporation of the solvents, the residue
was basified by the addition of aqueous Na2CO3 and extracted
with chloroform. The organic phase was washed with brine
(2ꢂ10 mL), dried over MgSO4, and concentrated under re-
duced pressure. The residue was purified by column chromatog-
raphy on silica gel using chloroform/methanol 30:1 to afford
444 mg (90% yield) of compound (þ)-(R)-20 as white solid,
mp 108e109 ꢁC, [a]D23 þ25.7 (c 1, CHCl3) (89% ee). Recrystal-
lization from ethyl acetate mixture gave pure enantiomer [a]D23
Acknowledgements
Financial support from grant PBZ-KBN-126/T09/2004/13
is gratefully acknowledged.
1
þ28.9 (c 1, CHCl3). H NMR (500 MHz, CDCl3): d¼1.71e
References and notes
1.94 (m, 4H), 2.61e2.74 (m, 2H), 2.92e2.97 (m, 1H), 3.15e
3.20 (m, 1H), 3.75e3.80 (m, 2H), 3.84 (s, 6H), 3.94e3.98
(m, 1H), 6.55 (s, 1H), 6.61 (s, 1H), 7.69e7.73 (m, 2H), 7.82e
7.85 (m, 2H). 13C NMR (125 MHz, CDCl3): d¼25.3, 29.5,
33.5, 37.9, 40.8, 54.8, 55.8, 56.0, 109.1, 111.7, 123.2, 127.2,
131.2, 132.1, 133.9, 147.2, 147.3, 168.4. HRMS (ESI) calcd
for C22H25N2O4 ([MþH]þ) m/z 381.1814, found 381.1815.
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3.10. N-[3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-
yl)propyl]-N0,N00-bis(Boc)guanidine (21)
To a solution of (1R)-(þ)-20 (1.37 g, 3.6 mmol) [a]2D3 þ28.9
(c 1, CHCl3) in 35 mL of ethanol 0.3 mL (8.19 mmol) of anhy-
drous hydrazine in ethanol (1.5 mL) was added. The mixture
was refluxed for 1.5 h, cooled to room temperature and concen-
trated under reduced pressure. The residue was dissolved in
DMF (20 mL) then N,N0-bis(Boc)-S-methylisothiourea
(1.57 g, 5.4 mmol) and DMAP (8.8 mg, 0.072 mmol) were
added. The mixture was stirred at room temperature for 3 h
and after evaporation of the solvents, the residue was purified
by column chromatography on silica gel using chloroform/
methanol 25:1 to afford 903 mg (51% yield) of compound
(þ)-(R)-21 as yellow solid, mp 108e109 ꢁC, [a]D23 þ13.7 (c
1, CHCl3). 1H NMR (500 MHz, CDCl3): d¼1.49 (s, 9H), 1.51
(s, 9H), 1.75e1.89 (m, 4H), 2.62e2.67 (m, 1H), 2.72e2.78
(m, 1H), 2.95e2.99 (m, 1H), 3.18e3.23 (m, 1H), 3.45e3.54
(m, 2H), 3.85 (s, 3H), 3.86 (s, 3H), 3.94e3.96 (m, 1H), 6.57
(s, 1H), 6.60 (s, 1H), 8.42 (t, J¼4.5 Hz, 1H), 11.51 (s, 1H).
13C NMR (125 MHz, CDCl3): d¼25.6, 28.1, 28.3, 29.5, 33.5,
40.8, 41.1, 54.9, 55.8, 56.0, 79.3, 83.0, 109.0, 111.8, 127.2,
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H. E.; Van Leeuwen, P. W. N. M. Chem.dEur. J. 2000, 6, 2818e2829;
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