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K. W. Glaeske et al. / Tetrahedron: Asymmetry 14 (2003) 917–920
10. Representative experimental procedures: Diazoacetoacetate
7b. Diketene (0.58 mL, 7.5 mmol) was added neat over a
period of 5 min to a 0°C solution of (S)-N-benzylprolinol
(2.65 g, 5.0 mmol) and Et3N (0.69 mL, 5.0 mmol) in 20
mL dry CH2Cl2. The reaction mixture was stirred at 0°C
for 3 h, then solvent and excess diketene were removed
under reduced pressure and the resulting orange liquid
was immediately dissolved in 20 mL CH3CN. To this
solution were added Et3N (0.69 mL, 5.0 mmol), H2O
(0.10 mL, 5.0 mmol) and MsN3 (0.56 mL, 6.5 mmol). The
reaction mixture was stirred at rt for 12 h, then most of
the solvent was removed and the residual oil was dis-
solved in Et2O (100 mL) and washed successively with 1
N NaOH (4×20 mL) and brine (25 mL). The organic
layer was dried (MgSO4), filtered and concentrated, and
the resulting yellow oil was purified by flash chromatog-
raphy (silica gel, 2 cm×15 cm column, 3:1 hexanes/
EtOAc) to give 1.16 g (77%) of 7b as a yellow oil:
[h]2D2=−43.4 (c=0.47, CH2Cl2); Rf 0.24 (7:3 hexanes/
hexanes/EtOAc) to afford 0.182 g (67%) of a 4.5:1 mix-
ture of 8b and 9b. Pure samples of each diastereomer 6b
could be obtained by iterative chromatography. 8b: white
solid (mp 103–105°C; [h]2D2=+62.8 (c=0.05, CH2Cl2); Rf
1
0.33 (7:3 hexanes/EtOAc); IR (KBr) 2977, 1731, cm−1; H
NMR (CDCl3, 300 MHz) l 7.29–7.20 (m, 5H), 4.28 (dd,
1H, J=10.0, 3.2 Hz), 4.04 (dd, 1H, J=10.5, 10.1 Hz),
3.43 (s, 2H), 3.13 (dt, 1H, J=8.6, 5.9 Hz), 2.78 (dt, 1H,
J=7.8, 5.3 Hz), 2.60–2.50 (m, 1H), 2.23 (s, 3H), 1.95–
1.63 (m, 4H); 13C NMR (CDCl3, 75 MHz) l 200.4, 168.3,
136.8, 130.3, 128.5, 126.8, 76.8, 75.3, 51.7, 45.0, 35.4,
27.1, 25.5, 23.4. Anal. calcd for C16H19NO3: C, 70.31; H,
7.01; N, 5.12. Found: C, 70.41; H, 7.07; N, 5.02%. 9b:
yellow oil; [h]2D2=−100.8 (c=0.03, CH2Cl2); Rf 0.31 (7:3
hexanes/EtOAc); IR (thin film) 2948, 1729, cm−1 1H
;
NMR (CDCl3, 300 MHz) l 7.29–7.14 (m, 5H), 4.06 (dd,
1H, J=10.2, 3.0 Hz), 3.36–3.26 (m, 1H), 3.22 (s, 2H),
3.18 (dt, 1H, J=8.1, 2.7 Hz), 3.07 (dd, 1H, J=10.2, 9.6
Hz), 2.65 (dt, 1H, J=8.4, 5.4 Hz), 2.20 (s, 3H), 2.05–1.81
(m, 4H); 13C NMR (CDCl3, 75 MHz) l 201.5, 169.1,
135.6, 130.4, 128.0, 126.9, 76.8, 72.5, 53.2, 45.6, 38.6,
28.6, 27.1, 23.5. Anal. calcd for C16H19NO3: C, 70.31; H,
7.01; N, 5.12. Found: C, 70.07; H, 6.95; N, 4.99%.
11. Crystallographic data (excluding structure factors) for
compound 9a have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publica-
tion number CCDC 200163. Copies of the data can be
obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK (fax: +44(0)-
1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
12. Vedejs, E.; Arco, M. J.; Powell, D. W.; Renga, J. M.;
Singer, S. P. J. Org. Chem. 1978, 43, 4831–4837. See also
Refs 5a,c and 6a–f.
1
EtOAc); IR (thin film) 2962, 2139, 1718, 1660 cm−1; H
NMR (CDCl3, 300 MHz) l 7.29–7.20 (m, 5H), 4.22 (d,
1H, J=2.1 Hz), 4.19 (d, 1H, J=2.1 Hz), 4.01 (d, 1H,
J=13.2 Hz), 3.41 (d, 1H, J=13.2 Hz), 2.97–2.82 (m, 2H),
2.48 (s, 3H), 2.27 (dd, 1H, J=17.1, 8.4 Hz), 2.00–1.91 (m,
1H), 1.77–1.63 (m, 3H); 13C NMR (CDCl3, 75 MHz) l
189.6, 161.0, 139.1, 128.3, 127.9, 126.6, 76.0, 66.9, 61.7,
59.1, 54.2, 28.1, 28.0, 22.9. Anal. calcd for C16H19N3O3:
C, 63.77; H, 6.36; N, 13.94. Found: C, 63.89; H, 6.41; N,
13.79%. Morpholinones 8b and 9b. A solution of 7b (0.301
g, 1.0 mmol) in dry PhCH3 (20 mL) was added dropwise
via cannula to a refluxing suspension of copper powder
(32 mg, 0.5 mmol) in dry PhCH3 (50 mL) over a period
of 45 min. The addition flask was rinsed with PhCH3 (5
mL) and this solution was added to the reaction mixture.
After an additional 2 h at reflux, the reaction mixture was
cooled, concentrated and the residue was purified by flash
chromatography (silica gel, 4 cm×15 cm column, 7:3
13. The radical–pair mechanism for [1,2]-shifts of ammonium
ylides is well-established. See: Ollis, W. D.; Rey, M.;
Sutherland, I. O. J. Chem. Soc., Perkin Trans. 1 1983,
1009–1027.