E. Garc´ıa et al. / Tetrahedron Letters 42 (2001) 1511–1513
1513
In conclusion, a stereoselective synthesis of enantiomer-
ically pure pyrrolo[2,1-a]isoquinolones via tandem
organolithium addition–N-acyliminium ion cyclisation
has been achieved. Of particular interest is the stereo-
control in the cyclisation step that leads to the 5,10b-
trans diastereomers.
1996, 37, 6193–6196; (c) Collado, M. I.; Manteca, I.;
Sotomayor, N.; Villa, M. J.; Lete, E. J. Org. Chem. 1997,
62, 2080–2092.
6. Osante, I.; Collado, M. I.; Lete, E.; Sotomayor, N.
Synlett 2000, 101–103.
7. Determined by chiral phase HPLC using a Chiralcel OD
column, 7% hexane/2-propanol, 1 mL/min.
8. All compounds gave satisfactory spectroscopic and ana-
lytical data. Typical procedure for 7a: To a solution of
succinimide 5 (270 mg, 0.51 mmol) in dry THF (10 mL),
MeLi (2 mL of a 1.0 M solution in diethyl ether, 2 mmol)
was added at −78°C and the resulting solution was stirred
at this temperature for 6 h. The reaction was quenched
by the addition of H2O (5 mL) and allowed to warm to
20°C. Standard work-up afforded the corresponding
Acknowledgements
Financial support from Gobierno Vasco (PI-1999-165)
and Universidad del Pa´ıs Vasco is gratefully acknowl-
edged. We also thank the Departamento de Educacio´n,
Universidades e Investigacio´n (Gobierno Vasco) and
M.E.C. for grants.
1
oxoamide 6a as a yellowish oil. [6a: H NMR (l, ppm):
1.11 (s, 9H), 2.14 (s, 3H), 2.22–2.38 (m, 2H), 2.67–2.74
(m, 2H), 2.86 (d, J=7.1 Hz, 2H), 3.60–3.62 (m, 2H), 3.79
(s, 3H), 3.84 (s, 3H), 4.10–4.21 (m, 1H), 5.87 (d, J=8.7
Hz, 1H), 6.67–6.75 (m, 3H), 7.37–7.45 (m, 6H), 7.60–7.65
(m, 4H)]. Without further purification, 6a was dissolved
in dry CH2Cl2 (10 mL), BF3·Et2O (0.76 mL, 6.2 mmol)
and the reaction mixture was heated under reflux for 4
days. After addition of aqueous saturated NaHCO3 (5
mL), standard work-up followed by flash column chro-
matography (silica gel, AcOEt) afforded (5S,10bS)-5-
hydroxymethyl-8,9-dimethoxy-10b-methyl-1,5,6,10b-tetra-
hydropyrrolo[2,1-a]isoquinolin-3[2H]-one (7a) (54 mg,
36%): ee 99%; [h]D20 −203 (c=0.046, CH2Cl2); mp 124–
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126°C (n-pentane). IR (KBr): 3392, 1654 cm−1; H NMR
(l, ppm): 1.55 (s, 3H), 2.05–2.19 (m, 1H), 2.31–2.47 (m,
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