2-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal
(7f).
4 : 1, 0.8 mL min-1.]: 28.2 min (major 1), 39.9 min (minor 1), ee =
85%; 46.4 min (major 2), 65.5 min (minor 2), ee = 93%.
The◦product was ob◦tained in 90% yield, white solid. Mp 163–
167 C; [a]2D6 = +77.7 (c = 1.00 in CH2Cl2); 1H NMR (400 MHz,
CDCl3): d (ppm) 9.80 (s, 1Hmin), 9.70 (s, 1Hmaj), 7.49–7.37 (m,
6Hmaj and 6Hmin), 7.30 (dd, J = 7.2 Hz, 2Hmaj and 2Hmin),
7.24 (d, J = 7.6 Hz, 2Hmin), 7.08 (d, J = 7.6 Hz, 2Hmaj), 3.84
(dd, J = 4.8, 9.6 Hz, 1Hmaj), 3.45 (dd, J = 5.6, 9.6 Hz, 1Hmin),
2.90 (dd, J = 9.6, 18.8 Hz, 1Hmaj), 2.73 (dd, J = 9.6, 18.4 Hz,
1Hmin), 2.60 (dd, J = 6.0, 18.8 Hz, 1Hmin), 2.54 (dd, J = 4.8,
19.2 Hz, 1Hmaj), 1.85 (s, 3Hmin), 1.79 (s, 3Hmaj). 13C NMR
(100 MHz, CDCl3): d (ppm) 201.0 (min), 199.1 (maj), 176.7 (min),
176.6 (maj), 174.7, 135.6, 131.6, 129.5 (maj), 129.4 (min), 129.1,
128.7 (maj), 128.7 (min), 128.6 (maj), 128.4 (min), 127.5 (maj),
127.2 (min), 126.6 (min), 126.4 (maj), 56.4 (min), 56.0 (maj), 46.5
(min), 45.0 (maj), 32.6 (min), 32.1 (maj), 19.4 (min), 16.5 (maj).
HRMS (EI): exact mass calculated for [M]+ (C19H17NO3) requires
m/z 307.1208, found m/z 307.1199. The enantiomeric excess was
determined by HPLC. [AS–H column, 240 nm, n-hexane–EtOH =
4 : 1, 0.8 mL min-1.]: 19.2 min (major 1), 25.2 min (minor 1), ee =
56%; 23.5 min (minor 2), 34.2 min (major 2), ee = 91%.
2-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal
(7i).
The◦product was ob◦tained in 93% yield, white solid. Mp 109–
113 C; [a]2D6 = +80.3 (c = 1.00 in CH2Cl2); 1H NMR (400 MHz,
CDCl3): d (ppm) 9.77 (s, 1Hmin), 9.68 (s, 1Hmaj), 7.48–7.36 (m,
5Hmaj and 5Hmin), 7.28 (d, J = 7.2 Hz, 2Hmaj and 2Hmin),
7.19–7.00 (m, 2Hmaj and 2Hmin), 3.81 (dd, J = 4.4, 9.6 Hz),
3.42 (dd, J = 6.0, 9.2 Hz, 1Hmin), 2.99 (dd, J = 9.2, 19.2 Hz),
2.70 (dd, J = 9.2, 18.8 Hz, 1Hmin), 2.58 (dd, J = 6.0, 19.2 Hz,
1Hmin), 2.55 (dd, J = 4.8, 19.2 Hz, 1Hmaj), 1.87 (s, 3Hmin), 1.79
(s, 3Hmaj). 13C NMR (100 MHz, CDCl3): d (ppm) 201.0 (min),
199.0 (maj), 176.2, 174.2, 135.4, 134.6, 133.0 (min), 132.6 (maj),
130.0, 129.5 (maj), 129.4 (min), 128.9 (maj), 128.8 (min), 128.7
(maj), 128.5 (min), 127.4 (maj), 127.1 (min), 126.9 (min), 126.7
(maj), 124.9 (min), 124.6 (maj), 56.5 (min), 55.9 (maj), 46.4 (min),
45.1 (maj), 32.7 (min), 32.1 (maj), 19.5 (min), 16.7 (maj). HRMS
(EI): exact mass calculated for [M]+ (C19H16ClNO3) requires m/z
341.0819, found m/z 341.0813. The enantiomeric excess was
determined by HPLC. [IA column, 220 nm, n-hexane–EtOH =
4 : 1, 1.0 mL min-1.]: 25.5 min (minor 1), 33.5 min (major 1), ee =
73%; 36.2 min (major 2), 53.4 min (minor), ee = 94%.
2-(1-(4-Bromophenyl)-2,5-dioxopyrrolidin-3-yl)-2-phenylpropa-
nal (7g). Th◦e product was obtained in 92% yield, white solid.
Mp 157–160 C; [a]D26 = +74.1◦ (c = 1.00 in CH2Cl2); H NMR
1
(400 MHz, CDCl3): d (ppm) 9.78 (s, 1Hmin), 9.68 (s, 1Hmaj), 7.60
(dd, J = 8.8 Hz, 2Hmin), 7.56 (dd, J = 8.8 Hz, 2Hmaj), 7.47–7.38
(m, 3Hmaj and 3Hmin), 7.28 (d, J = 8.8 Hz, 2Hmaj and 2Hmin),
7.15 (d, J = 8.4 Hz, 2Hmin), 6.98 (d, J = 8.4 Hz, 2Hmaj), 3.81
(q, J = 4.8 Hz, 1Hmaj), 3.41 (dd, J = 6.0, 9.6 Hz, 1Hmin), 2.90
(dd, J = 9.6, 18.8 Hz, 1Hmaj), 2.69 (dd, J = 9.6, 18.8 Hz, 1Hmin),
2.54 (dd, J = 4.4, 18.8 Hz, 1Hmaj and 1Hmin), 1.79 (s, 3Hmaj),
1.60 (s, 3Hmin). 13C NMR (100 MHz, CDCl3): d (ppm) 201.0
(min), 199.0 (maj), 176.4 (min), 176.3 (maj), 174.2, 135.5, 132.3,
130.5, 129.5, 128.7, 128.2 (min), 127.9 (maj), 127.4 (maj), 127.1
(min), 122.6, 56.5 (min), 56.0 (maj), 46.4 (min), 45.0 (maj), 32.6
(min), 32.1 (maj), 19.6 (min), 19.7 (maj). HRMS (EI): exact mass
calculated for [M]+ (C19H16BrNO3) requires m/z 385.0314, found
m/z 385.0315. The enantiomeric excess was determined by HPLC.
[AS–H column, 240 nm, n-hexane–EtOH = 4 : 1, 0.8 mL min-1.]:
18.9 min (major 1), 27.0 min (minor 1), ee = 73%; 25.1 min (minor
2), 32.4 min (major 2), ee = 95%.
Acknowledgements
We are grateful for the financial support from National Natural
Science Foundation of China (20902018), Shanghai Pujiang
Program (08PJ1403300), the Fundamental Research Funds for
the Central Universities and 111 Project (B07023),
Notes and references
1 For examples of studies on substituted succinimides and functional
pyrrolidines see: (a) S. Ahmed, Drug Des. Discovery, 1996, 14, 77;
(b) M. L. Curtin, R. B. Garland, H. R. Heyman, R. R. Frey, M. R.
Michaelides, J. Li, L. J. Pease, K. B. Glaser, P. A. Marcotte and S. K.
Davidsen, Bioorg. Med. Chem. Lett., 2002, 12, 2919; (c) R. Ballini, G.
Bosica, G. Cioci, D. Fiorini and M. Petrini, Tetrahedron, 2003, 59, 3603;
(d) J. Pohlmann, T. Lampe, M. Shimada, P. G. Nell, J. Pernerstorfer,
N. Svenstrup, N. A. Brunner, G. Schiffer and C. Freiberg, Bioorg. Med.
Chem. Lett., 2005, 15, 1189.
2 For recent books, see: (a) A. Berkessel and H. Gro¨ger, Asymmetric
Organocatalysis, Wiley-VCH, Weinheim, Germany, 2004; (b) P. I.
Dalko, Enantioselective Organo-catalysis, Wiley-VCH, Weinheim, Ger-
many, 2007.
3 For selected reviews, see: (a) P. I. Dalko and L. Moisan, Angew. Chem.,
Int. Ed., 2001, 40, 3726; (b) J. Christoffers and A. Baro, Angew. Chem.,
Int. Ed., 2003, 42, 1688; (c) K. Fagnou and M. Lautens, Chem. Rev.,
2003, 103, 169; (d) P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed.,
2004, 43, 5138; (e) Special issue on asymmetric organocatalysis: Acc.
Chem. Res., 2004, 37, 487; (f) R. Ballini, G. Bosica, D. Fiorini, A.
Palmieri and M. Petrini, Chem. Rev., 2005, 105, 933; (g) B. List, Chem.
Commun., 2006, 819; (h) M. S. Taylor and E. N. Jacobsen, Angew.
Chem., Int. Ed., 2006, 45, 1520; (i) S. J. Connon, Chem.–Eur. J., 2006,
12, 5418; (j) D. Almas¸i, D. A. Alonso and C. Na´jera, Tetrahedron:
Asymmetry, 2007, 18, 299; (k) P. Melchiorre, M. Marigao, A. Carlone
and G. Bartoli, Angew. Chem., Int. Ed., 2008, 47, 6138; (l) S. Bertelsen
and K. A. Jørgensen, Chem. Soc. Rev., 2009, 38, 2178.
4 (a) R. Shintani, K. Ueyama, I. Yamada and T. Hayashi, Org. Lett.,
2004, 6, 3425; (b) R. Shintani, W.-L. Duan, T. Nagano, A. Okada and
T. Hayashi, Angew. Chem., Int. Ed., 2005, 44, 4611; (c) R. Shintani,
W.-L. Duan and T. Hayashi, J. Am. Chem. Soc., 2006, 128, 5628.
5 J. K. Myers and E. N. Jacobsen, J. Am. Chem. Soc., 1999, 121, 8959.
6 S. Harada, N. Kumagai, T. Kinoshita, S. Matsunaga and M. Shibasaki,
J. Am. Chem. Soc., 2003, 125, 2582.
2-(1-(4-Methoxyphenyl)-2,5-dioxopyrrolidin-3-yl)-2-phenylpro-
panal (7h). The product was obtained in 85% yield, white solid.
◦
Mp 150–153 C; [a]D26 = +96.5◦ (c = 1.00 in CH2Cl2); H NMR
1
(400 MHz, CDCl3): d (ppm) 9.80 (s, 1Hmin), 9.69 (s, 1Hmaj),
7.44 (q, J = 7.2 Hz, 3Hmaj), 7.40 (q, J = 7.2 Hz, 3Hmin), 7.29
(d, J = 8.8 Hz, 2Hmaj), 7.14 (d, J = 8.8 Hz, 2Hmin), 6.98 (q,
J = 9.2 Hz, 4Hmaj and 4Hmin), 3.84–3.80 (m, 1Hmaj), 3.82 (s,
3Hmaj and 3Hmin), 3.44 (dd, J = 6.0, 9.6 Hz, 1Hmin), 2.96 (dd,
J = 9.6, 18.8 Hz, 1Hmaj), 2.71 (dd, J = 9.2, 18.4 Hz, 1Hmin),
2.57 (dd, J = 5.6, 18.8 Hz, 1Hmin), 2.52 (dd, J = 4.8, 19.2 Hz,
1Hmaj), 1.84 (s, 3Hmin), 1.78 (s, 3Hmaj). 13C NMR (100 MHz,
CDCl3): d (ppm) 201.0 (min), 199.0 (maj), 176.4 (min), 176.3
(maj), 174.2, 135.5, 132.3, 130.5, 129.5, 128.7, 128.2 (min), 127.9
(maj), 127.4 (maj), 127.1 (min), 122.6, 56.5 (min), 56.0 (maj), 46.4
(min), 45.0 (maj), 32.6 (min), 32.1 (maj), 19.6 (min), 19.7 (maj).
HRMS (EI): exact mass calculated for [M]+(C20H19NO4) requires
m/z 337.1314, found m/z 337.1313. The enantiomeric excess was
determined by HPLC. [AS–H column, 240 nm, n-hexane–EtOH =
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 4767–4774 | 4773
©