5716
S. M. Allin et al. / Tetrahedron Letters 47 (2006) 5713–5716
Ar
O
OMe
HO
O
N
TiCl4
O
N
H
OMe
DCM, Δ, 3 days
H
36%
H
MeO2C
16a
MeO2C
17
Scheme 6.
9. For compounds 7 and 14, a positive NOE effect was
observed between the proton at position 11b and a proton
of the newly added vinyl substituent. No positive NOE
effect was observed between the proton substituents at
positions 11b and 2.
substituted products 14 and 18 as single diastereoiso-
mers.12 The absolute stereochemistry of such products
can, if required, be tuned by the choice of appropriate
enantiomer of the b-aminoalcohol starting material.
´
10. Amat, M.; Bassas, O.; Canto, M.; Llor, N.; Santos, M. M.
M.; Bosch, J. Tetrahedron 2005, 61, 7693–7702.
Acknowledgements
11. X-ray data for 17: Data collected at 150 K on a Bruker
SMART 1000 diffractometer; solution by direct methods
and refinement by full-matrix least-squares on F2 using all
the data.13 Non-hydrogen atoms refined with anisotropic
atomic displacement parameters; hydrogen atoms inserted
at calculated positions using a riding model, except for the
alcohol proton which was located and refined with a fixed
isotropic displacement parameter. Crystal dimensions
0.36 · 0.24 · 0.22 mm3, monoclinic, P21, a = 5.1398(4),
The Loughborough group thanks the EPSRC and Charn-
wood Molecular for an industrial CASE award to L.J.D.
The Barcelona group thanks the Ministry of Science and
Technology (Spain)-FEDER through project BQU2003-
00505. Thanks are also due to DURSI, Generalitat de
Catalunya, for Grant 2005-SGR-00603, the Ministry of
Education and Science (Spain) for a fellowship to O.B.,
˚
b = 11.7652(8), c = 14.524(1) A, b = 94.274(1)ꢁ and V =
and the Fundac¸ao para a Cieˆncia e Tecnologia (Portugal)
˜
for a postdoctoral grant to M.M.M.S.
875.8(1) A , Z = 2, qcalcd = 1.378 M g/m3. 7592 Refl.,
3
˚
2156 independent (Rint = 0.0212), l = 0.102 mmꢀ1
,
F(000) = 388, 238 least-squares parameters, R1 =
0.0303, wR = 0.0777 (2r data). CCDC 297432 contains
supplementary crystallographic data in cif format. These
Road, Cambridge, CB2 1EZ, UK. Fax +44 1223 336033,
e-mail: deposit@ccdc.cam.ac.uk).
References and notes
1. Battersby, A. R.; Kapil, R. S.; Bhakuni, B. S.; Popli, S. P.;
Merchant, J. R.; Salgar, S. S. Tetrahedron Lett. 1965,
4965–4971.
2. Takacs, J. M.; Boito, S. C. Tetrahedron Lett. 1995, 36,
2941–2944, and references therein.
3. Itoh, A.; Ikuta, Y.; Tanahashi, T.; Nagakura, N. J. Nat.
Prod. 2000, 63, 723–725; Takayama, H.; Arai, M.;
Kitajima, M.; Aimi, N. Chem. Pharm. Bull. 2002, 50,
1141–1143.
4. Tan, G. T.; Kinghorn, A. D.; Hughes, S. H.; Pezzuto, J.
M. J. Biol. Chem. 1991, 266, 23529–23536.
5. For recent examples, see: (a) Allin, S. M.; Thomas, C. I.;
Doyle, K.; Elsegood, M. R. J. J. Org. Chem. 2005, 70,
357–359; (b) Bassas, O.; Llor, N.; Santos, M. M. M.;
Griera, R.; Molins, E.; Amat, M.; Bosch, J. Org. Lett.
2005, 7, 2817–2820.
6. Allin, S. M.; Khera, J. S.; Thomas, C. I.; Witherington, J.;
Doyle, K.; Elsegood, M. R. J.; Edgar, M. Tetrahedron
Lett. 2006, 47, 1961–1964.
22
12. Data for selected compounds: Compound 14: ½aꢁD +43.0
(c 1.0, CHCl3); dH (400 MHz; CDCl3) 2.02–2.08 (1H, m),
2.30–2.37 (1H, m), 2.54 (2H, t, J = 4), 2.63 (1H, dt,
J = 2.8, 15.2), 2.67–2.73 (1H, m), 2.78–2.85 (1H, m), 2.91–
2.90 (1H, m), 3.86 (3H, s), 3.87 (3H, s), 4.63–4.66 (1H, m),
4.83–4.88 (1H, m), 5.12–5.18 (2H, m), 5.91–6.00 (1H, m),
6.62 (1H, s), 6.64 (1H, s); dC (100 MHz; CDCl3) 28.5, 33.1,
34.8, 36.3, 40.1, 53.5, 55.9, 56.1, 107.8, 11.7, 115.4, 127.6,
129.0, 139.4, 146.8, 146.9, 169.0 (Found (EI): M+
288.15935. C17H21NO3 requires 288.15940). Compound
22
18: ½aꢁD +124.9 (c 1.6, CHCl3); dH (400 MHz; CDCl3)
1.34–1.43 (1H, m), 2.07 (1H, dd, J = 17, 12), 2.34–2.36
(2H, m), 2.43–2.49 (1H, m), 2.55–2.68 (3H, m), 2.74–2.92
(2H, m), 3.70 (3H, s), 3.83 (3H, s), 3.84 (3H, s), 4.65 (1H,
dd, J = 11, 4), 4.81–4.85 (1H, m), 6.59 (1H, s), 6.63 (1H,
s); dC (100 MHz; CDCl3) 28.4 (2C), 37.0, 38.1, 39.5, 39.9,
51.7, 55.8, 56.0, 56.1, 108.2, 111.5, 127.1, 128.6, 147.7,
147.8, 168.1, 172.1 (Found (EI): M+, 333.1576.
C18H23NO5 requires 333.1576).
´
7. For related conjugate additions, see: Amat, M.; Perez, M.;
Llor, N.; Escolano, C.; Luque, F. J.; Molins, E.; Bosch, J.
J. Org. Chem. 2004, 69, 8681–8693.
8. Allin, S. M.; Vaidya, D. G.; James, S. L.; Allard, J. E.;
Smith, T. A. D.; McKee, V.; Martin, W. P. Tetrahedron
Lett. 2002, 43, 3661–3663.
13. Sheldrick, G. M. SHELXTL version 6.12, Bruker-AXS,
Madison WI, 2001.