PAPER
Use of Bis(oxazoline) in the Synthesis of Grenadamide
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1
H NMR (400 MHz, CDCl ): d = 0.15–0.24 (m, 2 H), 0.37–0.49 (m,
(4) Al Dulayymi, J. R.; Baird, M. S.; Jones, K. Tetrahedron
2004, 60, 341.
(5) Green, R.; Cheeseman, M.; Duffill, S.; Merritt, A.; Bull, S.
D. Tetrahedron Lett. 2005, 46, 7931.
3
2
1
H), 0.86 (t, J = 6.9 Hz, 3 H), 1.08–1.14 (m, 1 H), 1.16–1.35 (m,
2 H), 1.49–1.54 (m, 2 H), 2.41 (t, J = 7.5 Hz, 2 H).
1
3
C NMR (100 MHz, CDCl ): d = 11.7, 14.1, 18.0, 18.9, 22.6, 29.3,
3
(6) Avery, T. D.; Culbert, J. A.; Taylor, D. K. Org. Biomol.
2
9.41, 29.47, 29.5, 31.9, 34.0, 34.2, 180.1.
Chem. 2006, 4, 323.
(7) Salim, H.; Piva, O. Tetrahedron Lett. 2007, 48, 2059.
+
HRMS (ESI+): m/z [M + Na] calcd for C H NaO : 235.1669;
found: 235.1661.
1
3
24
2
(
8) For reviews on stereoselective cyclopropanation reactions,
see: (a) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A.
B. Chem. Rev. 2003, 103, 977. (b) Pellissier, H.
Tetrahedron 2008, 64, 7041.
(
+)-Grenadamide (ent-3)
DIPEA (421 mg, 540 mL, 3.26 mmol) and EDC (625 mg, 3.26
mmol) were added to a solution of acid ent-5 (460 mg, 2.17 mmol),
phenethylamine (4; 395 mg, 411 mL, 3.26 mmol) and 1-hydroxy-
benzotriazole (441 mg, 3.26 mmol) in CH Cl (25 mL) at 0 °C. The
reaction mixture was warmed to r.t. and stirred for 16 h. The reac-
tion mixture was partitioned between aq HCl (0.1 M, 12 mL) and
(
9) Cullen, W. R.; Sugi, Y. Tetrahedron Lett. 1978, 19, 1635.
(
10) Jackson, R.; Thompson, D. J. J. Organomet. Chem. 1978,
2
2
159, C29.
(
(
11) Selke, R. React. Kinet. Catal. Lett. 1979, 10, 135.
12) Sinou, D.; Descotes, G. React. Kinet. Catal. Lett. 1980, 14,
463.
(13) For reviews, see: (a) Hale, K. J. In Rodd’s Chemistry of
Carbon Compounds, 2nd ed., 2nd Suppl., Vol. 1E/F/G;
Sainsbury, M., Ed.; Elsevier: Amsterdam, 1993, Chap. 23b,
CH Cl (12 mL). The organic layer was washed with sat. aq NH Cl
(
2
2
4
12 mL), dried over Na SO and concentrated under reduced pres-
2 4
sure. Flash chromatography on silica gel (PE–EtOAc, 2:1) yielded
+)-grenadamide (ent-3).
(
2
73. (b) Diéguez, M.; Pàmies, O.; Claver, C. Chem. Rev.
Yield: 664 mg (2.11 mmol, 97%); colourless solid; mp 54.5–
20
2004, 104, 3189. (c) Diéguez, M.; Claver, C.; Pàmies, O.
Eur. J. Org. Chem. 2007, 4621. (d) Boysen, M. M. K.
Chem. Eur. J. 2007, 13, 8648. (e) Benessere, V.; Del Litto,
R.; De Roma, A.; Ruffo, F. Coord. Chem. Rev. 2010, 254,
5
5.8 °C; [a]D +12.6 (c 1.02, CHCl ) [for (–)-grenadamide (3) Lit
D 3
3
[
a] –11.0 (c 0.1, CHCl )].
1
H NMR (400 MHz, CDCl ): d = 0.10–0.19 (m, 2 H), 0.30–0.44 (m,
3
2
1
7
H), 0.86 (t, J = 6.9 Hz, 3 H), 1.06–1.19 (m, 2 H), 1.21–1.32 (m,
0 H), 1.43–1.54 (m, 2 H), 2.20 (t, J = 7.6 Hz, 2 H), 2.80 (t, J =
.0 Hz, 2 H), 3.49 (q, J = 6.9 Hz, 2 H), 5.74 (s, 1 H, NH), 7.13–7.25
3
90.
14) (a) Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev.
006, 106, 3561. (b) McManus, H. A.; Guiry, P. F. Chem.
(
2
(
m, 3 H, Ph), 7.26–7.31 (m, 2 H, Ph).
Rev. 2004, 104, 4151. (c) Ghosh, A. K.; Mathivanan, P.;
Capiello, J. Tetrahedron: Asymmetry 1998, 9, 1.
1
3
C NMR (100 MHz, CDCl ): d = 11.7, 14.0, 18.1, 18.8, 22.6, 29.3,
3
2
1
9.4, 29.6, 30.3, 31.8, 34.0, 35.6, 36.7, 40.5, 126.4, 128.5, 128.7,
38.8, 173.2.
(15) Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103,
119.
+
(16) (a) Irmak, M.; Groschner, A.; Boysen, M. M. K. Chem.
Commun. 2007, 177. (b) Irmak, M.; Boysen, M. M. K. Adv.
Synth. Catal. 2008, 350, 403. (c) Minuth, T.; Boysen, M. M.
K. Synlett 2008, 1483. (d) Minuth, T.; Irmak, M.;
Groschner, A.; Lehnert, T.; Boysen, M. M. K. Eur. J. Org.
Chem. 2009, 997. (e) Minuth, T.; Boysen, M. M. K.
Beilstein J. Org. Chem. 2010, 6, doi:10.3762/bjoc.6.23.
HRMS (ESI+): m/z [M + Na] calcd for C H NaNO: 338.2454;
found: 338.2433.
2
1
33
Acknowledgment
We thank the German Research Foundation (DFG) and the Volks-
wagen Foundation for generous financial support.
(
17) (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M.
M. J. Am. Chem. Soc. 1991, 113, 726. (b) Loewenthal, R.
E.; Abiko, A.; Masamune, S. Tetrahedron Lett. 1990, 31,
References
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18) (a) With semicorrin ligands, see: Fritschi, H.; Leutenegger,
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(
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(
(
(
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(
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(
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(
(
Synthesis 2010, No. 16, 2799–2803 © Thieme Stuttgart · New York