CDCl3): δ 1.08–1.14 (m; 1H), 1.28–1.31 (m; 1H), 1.41–1.50 (m;
1H), 1.57 (s; 9H), 1.68–1.71 (m; 1H), 1.77–1.83 (m; 3H),
1.93–1.96 (m; 1H), 3.16–3.22 (m; 1H), 3.88 (dd, J = 4.1,
13.8 Hz; 1H), 4.13 (dd, J = 7.1, 13.8 Hz; 1H), 4.95–4.96 (m;
1H), 6.20 (dd, J = 1.4, 6.2 Hz; 1H), 7.09 (dd, J = 1.6, 6.2 Hz;
1H); 13C NMR (100 MHz, CDCl3): δ 26.0, 28.0, 30.7, 30.8,
39.1, 42.8, 61.7, 73.3, 83.9, 129.2, 146.3, 148.9, 168.3; HRMS
7.10 (dd, J = 1.9, 6.2 Hz; 1H); 13C NMR (100 MHz, CDCl3):
δ 20.56, 20.64, 27.97, 29.49, 61.99, 73.53, 83.92, 129.24,
146.11, 148.89, 168.31. Spectral data are in agreement with the
+
literature.7 HRMS (ESI+): Calculated for C14H22N2NaO5
([M + Na]+): 321.1426, Found: 321.1428; [α]2D7 +120.3 (c 0.5,
CHCl3) for an enantiomerically enriched sample with 84 : 16 er
[Lit7: [α]2D4 −177 (c 1.0, CHCl3) for ent-3o]. Enantiomeric purity
was determined by HPLC analysis (Daicel Chiralpak-IC column,
(ESI+): Calculated for C17H26N2NaO5 ([M + Na]+): 361.1739,
+
Found: 361.1741; [α]2D4 −36.8 (c 0.1, CHCl3) for an enantiomeri-
cally enriched sample with 82.5 : 17.5 er. Enantiomeric purity
was determined by HPLC analysis (Daicel Chiralpak-IC column,
254 nm, EtOH, 0.7 mL min−1, τmajor = 8.19 min, τminor
=
11.64 min).
(3aR,9S,9aR)-tert-Butyl 9-(nitromethyl)-2-oxo-3,3a,9,9a-tetra-
hydrochromeno[3,2-b]pyrrole-1(2H)-carboxylate 4. Purified by
silica gel column chromatography (20% EtOAc in petroleum
ether) afforded pure 4 as a viscous oil (86 mg, 0.246 mmol; 82%
yield). Diastereomeric ratio was determined by 1H NMR analysis
of the crude product. FT-IR (neat): ν 2925 (m), 2852 (w), 1793
(s), 1654 (w), 1559 (m), 1475 (w), 1374 (w), 1282 (m), 1253
(m), 1202 (w), 1151 (s), 1113 (w), 1020 (s), 913 (w), 883 (w),
254 nm, EtOH, 0.7 mL min−1, τmajor = 8.99 min, τminor
=
13.25 min).
(R)-tert-Butyl 2-((R)-4-methyl-1-nitropentan-2-yl)-5-oxo-2,5-
dihydro-1H-pyrrole-1-carboxylate 3n (Table 2, entry 14). Purified
by silica gel column chromatography (10% EtOAc in toluene)
afforded pure 3n as a yellowish liquid (74 mg, 0.237 mmol;
1
79% yield). Diastereomeric ratio was determined by H NMR
1
841 (w), 766 (w), 707 (w) cm−1; H NMR (400 MHz, CDCl3):
analysis of the crude product. FT-IR (neat): ν 2961 (m), 2934
(m), 2873 (w), 1781 (s), 1743 (s), 1717 (w), 1557 (s), 1370 (s),
1339 (m), 1314 (s), 1282 (m), 1257 (m), 1159 (s), 1105 (m),
1048 (m), 1033 (m), 910 (w), 843 (m), 792 (w), 771 (w),
δ 1.60 (s; 9H), 2.88 (dd, J = 5.7, 18.9 Hz; 1H), 3.14 (dd, J = 9.2,
18.9 Hz; 1H), 4.37–4.42 (m; 1H), 4.48 (t, J = 10.3 Hz; 1H),
4.57 (dd, J = 4.5, 11.9 Hz; 1H), 4.65–4.76 (m; 2H), 7.02 (d, J =
7.9 Hz; 1H), 7.06 (t, J = 7.5 Hz; 1H), 7.18 (d, J = 7.2 Hz; 1H),
7.30 (t, J = 7.9 Hz; 1H); 13C NMR (100 MHz, CDCl3): δ 27.9,
38.4, 39.2, 59.9, 70.4, 84.9, 118.2, 124.2, 125.2, 129.4, 130.2,
149.2, 154.6, 170.2; HRMS (ESI+): Calculated for
750 (w) cm−1 1H NMR (400 MHz, CDCl3): δ 0.96 (t, J =
;
7.0 Hz; 6H), 1.27–1.41 (m; 2H), 1.54 (s; 9H), 1.65–1.75 (m;
1H), 3.33–3.41 (m; 1H), 3.96 (dd, J = 7.5, 13.0 Hz; 1H), 4.09
(dd, J = 5.2, 13.0 Hz; 1H), 4.74–4.75 (m; 1H), 6.19 (dd, J = 1.2,
6.2 Hz; 1H), 7.12 (dd, J = 1.6, 6.2 Hz; 1H); 13C NMR
(100 MHz, CDCl3): δ 22.2, 22.7, 25.3, 28.0, 35.9, 39.2, 63.1,
75.4, 83.9, 129.1, 145.9, 149.0, 168.4; HRMS (ESI+): Calcu-
+
C17H20N2NaO5 ([M + Na]+): 371.1219, Found: 371.1216;
28
[α]D −60.2 (c 0.1, CHCl3) for an enantiomerically enriched
sample with 84 : 16 er. Enantiomeric purity was determined by
HPLC analysis (Daicel Chiralpak-IC column, 254 nm, EtOH,
0.7 mL min−1, τminor = 7.93 min, τmajor = 14.94 min).
+
lated for C15H24N2NaO5 ([M + Na]+): 335.1583, Found:
335.1586; [α]2D7 +109.2 (c 0.1, CHCl3) for an enantiomerically
enriched sample with 87 : 13 er. Enantiomeric purity was deter-
mined by HPLC analysis (Daicel Chiralpak-IC column, 254 nm,
EtOH, 0.7 mL min−1, τmajor = 7.87 min, τminor = 10.71 min).
Acknowledgements
Generous financial support from Indian Institute of Science,
Bangalore, in the form of start-up grant is gratefully acknowl-
edged. We thank the Department of Science and Technology
(DST), New Delhi (Grant No. SR/FT/CS-90/2010) and the
Council of Scientific and Industrial Research (CSIR), New Delhi
(Grant No. 01(2505)/11/EMR-II) for funding this research
program. A. R. C. thanks CSIR for a doctoral fellowship.
(S)-tert-Butyl
2-((S)-4-methyl-1-nitropentan-2-yl)-5-oxo-2,5-
dihydro-1H-pyrrole-1-carboxylate ent-3n (Table 3, entry 7). Purified
by silica gel column chromatography (10% EtOAc in toluene)
afforded pure ent-3n as a yellowish viscous oil (82 mg,
0.264 mmol; 88% yield). Diastereomeric ratio was determined
1
by H NMR analysis of the crude product. [α]2D7 −79.7 (c 0.1,
CHCl3) for an enantiomerically enriched sample with 77 : 23 er.
Enantiomeric purity was determined by HPLC analysis (Daicel
Chiralpak-IC column, 254 nm, EtOH, 0.7 mL min−1, τminor
7.84 min, τmajor = 10.61 min).
=
Notes and references
1 (a) G. Casiraghi, L. Battistini, C. Curti, G. Rassu and F. Zanardi, Chem.
Rev., 2011, 111, 3076; (b) S. E. Denmark, J. R. Heemstra, Jr. and
G. L. Beutner, Angew. Chem., Int. Ed., 2005, 44, 4682; (c) R. C. Fuson,
Chem. Rev., 1935, 16, 1.
2 (a) B. Schetter and R. Mahrwald, Angew. Chem., Int. Ed., 2006, 45,
7506; (b) G. Casiraghi, F. Zanardi, G. Appendino and G. Rassu, Chem.
Rev., 2000, 100, 1929; (c) J. L. Herrmann, G. R. Kieczykowski and R.
H. Schlessinger, Tetrahedron Lett., 1973, 14, 2433; (d) M. W. Rathke and
D. Sullivan, Tetrahedron Lett., 1972, 13, 4249.
3 For reviews, see: (a) S. V. Pansare and E. K. Paul, Chem.–Eur. J., 2011,
17, 8770; (b) G. Casiraghi, L. Battistini, C. Curti, G. Rassu and
F. Zanardi, Chem. Rev., 2011, 111, 3076; (c) G. Casiraghi, F. Zanardi,
L. Battistini and G. Rassu, Synlett, 2009, 1525; (d) G. Casiraghi and
G. Rassu, Synthesis, 1995, 607.
4 For selected examples, see: (a) J. Luo, H. Wang, X. Han, L.-W. Xu,
J. Kwiatkowski, K.-W. Huang and Y. Lu, Angew. Chem., Int. Ed., 2011,
50, 1861; (b) M. Terada and K. Ando, Org. Lett., 2011, 13, 2026;
(c) H. Ube, N. Shimada and M. Terada, Angew. Chem., Int. Ed., 2010,
(R)-tert-Butyl
2-((R)-3-methyl-1-nitrobutan-2-yl)-5-oxo-2,5-
dihydro-1H-pyrrole-1-carboxylate 3o (Table 2, entry 15). Purified
by silica gel column chromatography (10% EtOAc in toluene)
afforded 3o as a viscous oil (68 mg, 0.228 mmol; 76% yield).
1
Diastereomeric ratio was determined by H NMR analysis of the
crude product. FT-IR (neat): ν 2975 (m), 2934 (m), 2879 (w),
1780 (s), 1746 (s), 1717 (m), 1557 (s), 1370 (s), 1338 (m), 1314
(m), 1285 (m), 1257 (m), 1160 (s), 1048 (m), 1033 (m), 902
(w), 844 (w), 825 (w), 771 (w), 751 (w), 705 (w) cm−1
;
1H NMR (400 MHz, CDCl3): δ 1.06 (d, J = 6.7 Hz; 3H), 1.14
(d, J = 6.7 Hz; 3H), 1.57 (s; 9H), 1.75–1.84 (m; 1H), 3.10–3.16
(m; 1H), 3.91 (dd, J = 4.2, 13.8 Hz; 1H), 4.13 (dd, J = 6.9, 13.8
Hz; 1H), 4.92–4.93 (m; 1H), 6.21 (dd, J = 1.4, 6.2 Hz; 1H),
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 7313–7320 | 7319