N. Le Carrer-Le Goff et al. / Tetrahedron Letters 43 (2002) 6325–6328
6327
CH3
Bn2N
CH3
8. Reetz, M. T.; Lauterbach, E. H. Tetrahedron Lett. 1991,
32, 4477–4480.
NBn2
4
O
H
1
H3C
5
3
2
9. (a) Lehr, P.; Billich, A.; Charpiot, B.; Ettmayer, P.;
Scholz, D.; Rosenwirth, B.; Gstach, H. J. Med. Chem.
1996, 39, 2060–2067; (b) Travins, J. M.; Bursavich, M.
G.; Veber, D. F.; Rich, D. H. Org. Lett. 2001, 3, 2725–
2728.
CH3
OH
BrZn
H
A
4c (3,4-anti-4,5-anti)
10. Piveteau, N.; Audin, P.; Paris, J. Synlett 1997, 1269–1270.
11. Jurczack, J.; Golebiowski, A. Chem. Rev. 1989, 89, 149–
164.
12. Reetz, M. T. Chem. Rev. 1999, 99, 1121–1162.
13. Reetz, M. T.; Drewes, M. W.; Schmitz, A. Angew. Chem.,
Int. Ed. Engl. 1987, 26, 1141–1143.
14. Brinkmann, H.; Hoffmann, R. W. Chem. Ber. 1990, 123,
2395–2401.
15. Hanessian, S.; Park, H.; Yang, R.-Y. Synlett 1997, 353–
354.
H
O
Bn2N
H3C
CH3
CH3
BrZn
Bn2N
OH
CH3
H
B
4c (3,4-syn-4,5-syn)
Scheme 2.
one and resulted from the chairlike transition state A
where both the g-methyl group of the crotyl reagent
and the chiral residue of the aminoaldehyde 3a are in
pseudo-equatorial position.18 The minor one should
emerge from the less favored transition state B in which
the latter group is in the axial position (Scheme 2). The
subsequent ozonolysis gave the statine 5c as a mixture
from which the major diastereomer could be obtained
pure by chromatography.24
16. Ciapetti, P.; Falorni, M.; Taddei, M. Tetrahedron 1996,
52, 7379–7390.
17. Paquette, L. A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C.
F.; Schomer, W. W. J. Org. Chem. 1997, 62, 4293–4301.
18. For reviews on the stereodifferentiated addition of allylic
organometallic compounds to carbonyl group, see: (a)
Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1982, 21,
555–566; (b) Yamamoto, Y. Acc. Chem. Res. 1987, 20,
243–249.
19. (a) Pe´trier, C.; Luche, J.-L. J. Org. Chem. 1985, 50,
910–912; (b) Pe´trier, C.; Einhorn, J.; Luche, J.-L. Tetra-
hedron Lett. 1985, 26, 1449–1452; (c) Wilson, S. R.;
Guazzaroni, M. E. J. Org. Chem. 1989, 54, 3087–3091.
20. Gryko, D.; Urbanczyck-Lipkowska, Z.; Jurczak, J. Tet-
rahedron 1997, 53, 13373–13382.
21. (a) Marshall, J. A.; Garofalo, A. W.; Sedrani, R. C.
Synlett 1992, 643–645; (b) Marshall, J. A.; Garofalo, A.
W. J. Org. Chem. 1993, 58, 3675–3680.
Crotylzinc bromide reacted likewise with a-aminoalde-
hyde 3c (entry 4). It gave the homoallylic alcohol 4d
also as a mixture of two diastereomers (ratio 80:20;
supposed to be the anti–anti and syn–syn diastereomers
by analogy with alcohol 4c) as shown by analysis of its
1H and 13C NMR spectra. The corresponding b-
hydroxyester 5d was further obtained by ozonolysis of
the terminal double bond.
22. (a) Che´rest, M.; Felkin, H.; Prudent, N. Tetrahedron
Lett. 1968, 2199–2204; (b) Anh, N. T. Top. Curr. Chem.
1980, 88, 145–162.
In summary, we have demonstrated that a-substituted
statine derivatives can be obtained by the diastereose-
lective zinc-mediated condensation of allylic bromides
to N,N-dibenzyl a-aminoaldehydes followed by ozono-
lysis of the intermediate homoallylic alcohols.
23. Typical procedure (entry 3). Crotyl bromide (1.4 g, 10.4
mmol, 2 equiv.) was slowly added to a suspension of
N,N-dibenzylaminoaldehyde 3a (1.31 g, 5.2 mmol) and
Zn (1.37 g, 20.8 mmol, 4 equiv.) in THF (15 mL)/satu-
rated aqueous NH4Cl (3 mL) maintained at 0°C. After
stirring for 6 h, another equivalent of crotyl bromide was
added. The mixture was stirred at room temperature
overnight, diluted with water and extracted with AcOEt.
The solvents were evaporated to afford a crude residue
that was purified by flash-chromatography on silica gel
with hexane/AcOEt (90/10). 5-Dibenzylamino-3-methyl-
hexen-4-ol 4c (908 mg, 57%) was obtained as a mixture
78/22 of two diastereomers. Rf (SiO2, PE/Et2O: 50/50)=
0.72. IR (neat), cm−1: 3452, 3063, 2965, 2803, 1635, 1602,
1494, 1453, 1377, 1242, 1111, 1073, 1028, 998, 970, 913,
828. Spectral data for 4c (anti–anti): 1H NMR (200 MHz,
CDCl3) l ppm: 0.95 (d, J=7.0 Hz, 3H, 3-C-CH3); 1.14
(d, J=6.7 Hz, 3H, 6-CH3); 1.45 (br.s, 1H, OH); 2.74
(quint, J=6.7 Hz, 5-CH-N); 3.4–3.5 (m, 1H, 4-CH-O);
3.51 and 3.78 (syst. AB, J=13.7 Hz, 4H, 2×CH2-N); 4.90
(dd, J=17.3 and 1.9 Hz, 1H, 1-CH); 5.0 (m, 1H, 1-CH);
5.43 (ddd, J=17.3, 10.6 and 7.1 Hz, 1H, 2-CH); 7.2–7.4
(m, 10H, ArH). 13C NMR (50 MHz, CDCl3) l ppm: 8.6
(6-C); 16.6 (3-C-CH3); 39.3 (3-C); 54.6 (2×CH2-N); 55.0
(5-CH-N); 76.8 (4-CH-O); 116.8 (1-C); 126.9, 128.3 and
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