References
1 Current address: Novo Nordisk A/S,
Medicinal Chemistry Research, 2760 Måløv, Denmark.
2
Derwick PM.
Medicinal Natural Products
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Nadin A.
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6 Fürstner A.; Angew. Chem. Int. Ed.; 2000, 39: 3012
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Lindsay KB.
Tang M.
Pyne SG.
Synlett
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731 ; for the application of RCM reaction to the
synthesis of pyrrolines see references cited therein
8 Compound 3 was
synthesized in ˜20 g scale from allylamine and 2,3-dibromopropene
followed by Boc protection using the procedure described by: Shi L.
Narula CK.
Mak KT.
Kao L.
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Typical Procedure:
To a stirred solution of allyl-(2-bromoallyl)-carbamic acid tert-butyl ester (3)
(1.49 g, 5.4 mmol) and Fe(acac)3 (38 mg, 2 mol%)
in THF (7.5 mL) and NMP (5.4 mL) at 0 °C was added
a THF solution of i-PrMgCl (6.0 mL, 1.8
M, 10.8 mmol) drop wise over a period of 30 min. After stirring
for 1 h the reaction mixture was quenched with sat. NH4Cl
(20 mL) followed by extraction with CH2Cl2 (3 × 20
mL). Drying of the organic layers (Na2SO4)
and removal of the solvents in vacuo gave crude 5. An
analytically sample was purified on silica gel (heptane/EtOAc
20:1). Data for 5: 1H
NMR: δ = 5.84-5.68 (m, 1 H), 5.16-5.03
(m, 2 H), 4.86 (br s, 1 H), 4.73 (br s, 1 H), 3.88-3.68
(m, 4 H), 2.26-2.14 (m, 1 H), 1.46 (s, 9 H), 1.06 (d, J = 7 Hz,
6 H). 13C NMR: δ = 151.0
(s), 144.4 (s), 133.9 (d), 116.5 and 116.2 (t), 108.0 and 107.5
(t), 49.4 and 48.3 (t), 31.2 (d), 28.4 (q), 21.7 (q). HRMS calcd
for C14H25NO2: 239.1886. Found:
239.1877. The crude residue was dissolved in degassed CH2Cl2 (270
mL) and 2 (229 mg, 5 mol%) were
added. After stirring for 24 h at r.t. under nitrogen the solvent
was removed in vacuo. The mixture was redissolved in MeOH (20 mL)
and 10 wt% Pd/C (400 mg) was added. The mixture
was stirred in a hydrogen atmosphere (3 bar) for 24 h and then filtered
through celite and gently concentrated in vacuo. Purification on
silica gel (heptane/EtOAc 20:1) provided 630 mg (52%)
of 11 as a clear oil. Data for 11: 1H NMR: δ = 3.59-3.44
(m, 2 H), 3.26-3.15 (m, 1 H), 2.91-2.82 (m, 1
H), 2.03-1.92 (m, 1 H), 1.87-1.71 (m, 1 H), 1.54-1.35
(m, 11 H), 0.96-0.89 (m, 6 H). 13C
NMR: δ = 154.7, 78.7, 50.1, 46.1, 45.9, 31.8,
29.9, 28.3, 21.2, 20.9. HRMS calcd for C12H23NO2:
213.1729. Found: 213.1724.