2514
Scheme 5.
References
1. (a) Wasserman, H. H.; Ennis, D. S.; Blum, C. A.; Rotello, V. M. Tetrahedron Lett. 1992, 33, 6003; (b) Wasserman, H. H.;
Baldino, C. M.; Coats, S. J. J. Org. Chem. 1995, 60, 8231.
2. (a) Wasserman, H. H.; Chen, J.-H.; Xia, M. J. Am. Chem. Soc. 1999, 121, 1401; (b) Wasserman, H. H.; Rotello, V. M.;
Williams, D. R.; Benbow, J. W. J. Org. Chem. 1989, 54, 2785.
5
3. 3,4-Dioxo-4-piperidino-2-(1,1,1-triphenyl-λ -phosphanylidene)butanenitrile (2). (i) To a stirred, precooled (0°C)
solution of 2-oxo-2-piperidinoacetic acid (1.95 g, 12.4 mmol) in 50 mL of dry CH2Cl2 was added dry DMF (50 µl) and oxalyl
chloride (1.62 mL, 1.5 equiv.) by syringe and the resulting solution was stirred for 1 h at 0°C, then for 2 h at room temperature
under N2. Evaporation of the solvent and excess oxalyl chloride in vacuo and further drying of the residue under high vacuum
gave the crude acid chloride as a yellow solid, which was used directly in the next step. (ii) A precooled (0°C) solution of crude
acid chloride in dry CH2Cl2 (50 mL) was transferred to a precooled (0°C) solution of triphenylphosphoranylideneacetonitrile
(4.30 g, 1.15 equiv.) and BSA (3.68 mL, 1.2 equiv.) in 50 mL of dry CH2Cl2 via cannula and the resulting reaction mixture was
stirred for 1 h at 0°C, then overnight at room temperature under N2. The reaction mixture was diluted with 60 mL of H2O and
the two layers were separated. The aqueous layer was extracted further with 20 mL of CH2Cl2 (×3), and the combined organic
layers were washed with brine, dried over Na2SO4, filtered and evaporated. Flash chromatography of the crude product on
SiO2 (hexanes/EtOAc, 1/4.5 to 1/5) gave 4.75 g (87%) of pure compound 2 as an off-white solid: mp 247.0–248.5°C (dec);
Rf 0.21 (hexanes/EtOAc, 1/5); IR (CHCl3) 3014, 2947, 2869, 2184, 1636, 1579, 1570 cm−1; 1H NMR (CDCl3, 300 MHz) δ
1.61 (m, 6H), 3.37 (m, 2H), 3.57 (m, 2H), 7.49–7.68 (m, 15H); 13C NMR (CDCl3, 75 MHz) δ 24.7, 25.4, 26.4, 42.2, 47.0,
49.1 (d, J=120.9 Hz), 120.1 (d, J=14.5 Hz), 122.3 (d, J=9.3 Hz), 129.4 (d, J=12.9 Hz), 133.6 (d, J=2.9 Hz), 133.7 (d, J=10.4
Hz), 166.0 (d, J=11.5 Hz), 188.1 (d, J=3.6 Hz); HRMS FAB (m-NBA): calcd for C27H26N2O2P (MH)+: 441.1732, found:
441.1733. Anal. calcd for C27H25N2O2P: C, 73.62; H, 5.72; N, 6.36. Found: C, 73.88; H, 5.82; N, 6.14.
4. A typical procedure for preparation of oxomalondiamide: tert-Butyl (2S)-1-(2,3-dioxo-3-piperidinopropanoyl)tetrahydro-
1H-2-pyrrolecarboxylate (4a). 3,4-Dioxo-4-piperidino-2-(1,1,1-tripheyl-λ5-phosphanylidene)butanenitrile (2) (653.0 mg,
1.48 mmol, 1.5 equiv.) in 35 mL of dry CH2Cl2 containing a small amount of activated molecular sieves (4 Å) was treated
with O3 for 10–15 min at −78°C and the resulting deep green solution was purged with N2 for 20 min at −78°C. To this
yellow solution was transfered a precooled (−78°C) solution of L-proline t-butyl ester (169.2 mg, 1.0 equiv) in 10 mL of dry
CH2Cl2 via cannula and the mixture was stirred for 30 min at −78°C, then for 1 h at 0°C under N2. The reaction mixture
was filtered, concentrated in vacuo, and flash chromatographed on SiO2 (hexanes/EtOAc, 1.5/1 to 1/1) to give 296.6 mg
1
(89%) of pure compound 4a as a pale yellow solid, shown to be a mixture of two rotamers (ratio=ca. 3:2) by H and 13C
NMR: Rf 0.40 (hexanes/EtOAc, 1/1); mp 75.0–77.0°C; [α]2D2 −65.1 (c 0.57, CHCl3); IR (CHCl3) 2983, 2962, 1738, 1646
cm−1; 1H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H×2/5), 1.44 (s, 9H×3/5), 1.63 (m, 6H), 1.85–2.03 (m, 4H×3/5), 2.08–2.26
(m, 4H×2/5), 3.28–3.44 (m, 2H), 3.46–3.87 (m, 4H), 4.40 (dd, 1H×2/5, J=8.1, 3.6 Hz), 4.70 (dd, 1H×3/5, J=8.5, 2.9 Hz);
13C NMR (CDCl3, 75 MHz) δ 21.7, 24.40, 24.43, 24.8, 25.17, 25.22, 25.9, 26.1, 27.94, 27.97, 28.9, 31.6, 42.4, 42.5, 46.8,
47.0, 47.5, 60.0, 60.5, 81.8, 82.1, 160.5, 162.0, 164.5, 164.6, 170.0, 170.9, 184.5, 185.5; HRMS FAB (m-NBA): calcd for
C17H27N2O5 (MH)+: 339.1920, found: 339.1920. Anal. calcd for C17H26N2O5: C, 60.34; H, 7.74; N, 8.28. Found: C, 60.30;
H, 7.69; N, 8.33.
5. All new compounds gave satisfactory spectroscopic and analytical data.
6. Cui, C.-B.; Kakeya, H.; Osada, H. Tetrahedron 1997, 53, 59.