2144
D. Craig et al.
LETTER
(13) For previous syntheses of (–)-trachelanthamidine see:
manipulations of the major cyclisation product have been
used in a successful total synthesis of the pyrrolizidine
natural product (–)-trachelanthamidine.14,15
(a) Nagao, Y.; Dai, W.-M.; Ochiai, M.; Tsukagoshi, S.;
Fujita, E. J. Org. Chem. 1990, 55, 1148. (b) Robins, D. J.;
Sakdarat, S. J. Chem. Soc., Perkin Trans. 1 1981, 909.
(c) Rüeger, H.; Benn, M. Heterocycles 1982, 19, 1677.
(d) Moriwake, T.; Hamano, S.; Saito, S. Heterocycles 1988,
27, 1135.
Acknowledgment
(14) Data for 4: Rf = 0.51 (10% MeOH–CH2Cl2); [a]D22 –104.6 (c
1.0, CHCl3). IR (film): nmax = 2956, 1747, 1649, 1439, 1269,
1269, 1153, 1086, 941, 793, 729 cm–1. 1H NMR (300 MHz,
CDCl3): d = 7.78–7.76 (2 H, m, ortho Ts), 7.38–7.28 (2 H,
m, meta Ts), 5.83–5.61 (2 H, m, CH=CH), 4.78–4.62 (3 H,
m, CHN and CH2OCO2Me), 4.28–3.47 (4 H, m, CH2Ts and
CH2N), 3.81–3.80 (3 H, m, OMe), 2.45 (3 H, s, Me of Ts),
2.21–1.69 (4 H, m, CH2CH2CHN). 13C NMR (75 MHz,
CDCl3): d = 160.4, 159.8, 155.6, 155.5, 145.3, 145.2, 136.2,
135.7, 134.3, 133.4, 129.8, 128.7, 125.3, 123.0, 67.7, 66.9,
61.7, 61.4, 59.1, 58.0, 55.0, 54.8, 48.1, 46.8, 32.6, 30.4, 23.7,
21.8. MS (CI): m/z = 382 [M + H]+, 306, 228, 152. HRMS:
m/z calcd for C18H23NO6S [M + H]+: 382.1324; found [M +
H]+: 382.1328. Anal. Calcd for C18H23NO6S (%): C, 56.68;
H, 6.08; N, 3.67. Found: C, 56.53; H, 6.08; N, 3.53.
(15) Preparation of 9a,b.
The authors thank EPSRC and Knoll Pharmaceuticals (CASE
studentship to C.J.T.H.) and GlaxoSmithKline for support.
References and Notes
(1) Craig, D.; Hyland, C. J. T.; Ward, S. E. Chem. Commun.
2005, 3439.
(2) Liddell, J. R. Nat. Prod. Rep. 2002, 19, 773.
(3) Kennewell, P. D.; Miles, N. J.; Sammes, P. G.; Westwood,
R. J. Chem. Soc., Perkin Trans. 1 1985, 11, 2299.
(4) Moriwake, T.; Hamano, S.; Miki, D.; Saito, S.; Torii, S.
Chem. Lett. 1986, 815.
(5) (a) PyBOP = (Benzotriazol-1-yloxy)tripyrrolidinophospho-
nium hexafluorophosphate (b) Castro, B.; Dormoy, J. R.;
Evin, G.; Selve, C. Tetrahedron Lett. 1975, 1219.
(6) TTMPP = tris(2,4,6-trimethoxyphenyl)phosphine.
(7) Wada, M.; Higashizaki, S. Chem. Commun. 1984, 482.
(8) For a review on steric and electronic effects of phosphorus
ligands, see: Tollman, C. A. Chem. Rev. 1977, 3, 313.
(9) Broeker, J. L.; Reinhard, W. H.; Houk, K. N. J. Am. Chem.
Soc. 1991, 113, 5006.
(10) A referee has made the reasonable suggestion that in the
cyclisations of 1, the same conformation is adopted as for
cyclisation of 4, but that for 1 Pd approaches the p-bond
from the opposite face due to the absence of the constraining
ring and the consequent ability of the N-acyl moiety to
rotate. This would necessitate a subsequent change in the
conformation of the p-allyl complex to allow cyclisation to
take place.
To a solution of allylic carbonate 4 (59.0 mg, 0.156 mmol,
1.0 equiv) in MeCN (2 mL) was added Pd2(dba)3 (7.30 mg,
0.008 mmol, 0.05 equiv) and triisopropyl phosphite (20.0
mL, 0.078 mmol, 0.5 equiv) at r.t. After 12 h the reaction was
concentrated under reduced pressure and the residue purified
by chromatography (Et2O) to yield an inseparable 94:6
mixture of the pyrrolizidinones 9a and 9b (34 mg, 72%) as a
colourless oil; Rf = 0.2 (Et2O). IR (film): nmax = 2972, 1703,
1421, 1317, 1177, 1086, 910, 814, cm–1. 1H NMR (400 MHz,
CDCl3): d (major isomer) = 7.83 (2 H, d, J = 8.0 Hz), 7.34 (2
H, d, J = 8.0 Hz), 5.96 (1 H, ddd, J = 16.0, 10.0, 7.0 Hz), 5.26
(1 H, d, J = 17.0 Hz), 5.21 (1 H, d, J = 9.0 Hz), 4.16 (d, J =
9.0 Hz, 1 H), 3.64–3.55 (m, 2 H), 3.47 (q, J = 7.0 Hz, 1 H),
3.09–3.03 (m, 1 H), 2.44 (s, 3 H), 2.27–1.97 (m, 3 H), 1.56–
1.46 (m, 1 H). 13C NMR (100 MHz, CDCl3): d (major
isomer) = 163.9, 145.1, 135.1, 136.0, 129.7, 129.4, 118.0,
73.5, 63.7, 45.5, 41.8, 30.6, 26.2, 21.7. MS (CI): m/z calcd
for C16H19NO3S [M + H]+: 306.1164; found [M + H]+:
306.1174.
(11) We thank Dr. A. J. P. White (Imperial College) for the X-ray
structure determination. Full details will be reported
elsewhere.
(12) For desulfonylation of a structurally similar substrate, see:
Chang, M.-Y.; Hsu, R.-T.; Tseng, T.-W.; Sun, P.-P.; Chang,
N.-C. Tetrahedron 2004, 60, 5545.
Synlett 2006, No. 13, 2142–2144 © Thieme Stuttgart · New York