G. Giorgi et al. / Tetrahedron 67 (2011) 1463e1467
1467
3H, CH2CH3), 0.79 (t, 3J¼7 Hz, 3H, CH2CH3), 1.46 (s, 9H, Boc), 1.59 (d,
2J¼14.4 Hz, 1H, H3), 1.77 (dt, J¼14.4, 7.4 Hz, 1H, H30), 2.49 (m, 1H,
CH2CH3), 2.60 (m,1H, CH2CH3), 2.85 (d, 3J¼8 Hz,1H, H4), 2.97 (m, 2H,
CH2CH3), 3.13 (s, 1H, H5), 3.48 (s, 1H, H1), 4.69 (t, 3J¼8.4 Hz, 1H, H2),
[MþH]þ, 415 [MþNa]þ. C19H24N2O7 (392.40): calcd C 58.16; H 6.16; N
7.14; found C 57.91; H 5.85; N 7.10.
4.2.4. (3aS,5R,6S,6aS) and (3aR,5S,6R,6aR) 6-hydroxy-2-oxo-N-phe-
nylhexahydro-2H-cyclopenta[d]oxazole-5-carboxamide (6d). Yellow
oil; yield¼93%; nmax(KBr) 3366, 3249, 2942, 2866, 1752, 1708, 1628,
7.08 (d, 3J¼8 Hz, 1H, NH). 13C NMR (400 MHz, C6D6)
d 12.9 (CH2CH3),
14.4 (CH2CH3), 28.5 (Boc), 32.3 (C3), 40.6 (C4), 41.9 (CH2CH3), 42.2
(CH2CH3), 51.0 (C2), 58.9 (C5), 58.9 (C1), 78.7 (Boc), 155.7 (CO car-
bamate), 172.1 (CO amide). MS(ESI): m/z¼299 [MþH]þ, 321
[MþNa]þ. C15H26N2O4 (298.38): calcd C 60.38; H 8.78; N 9.39; found
C 60.14; H 8.82; N 9.02.
1560, 1388, 1316, 1239, 1218, 1113, 1083, 1064 cmꢂ1 1H NMR
;
(400 MHz, CD3OD)
d
1.93 (dt, 3J¼7 Hz,1H, H4), 2.43 (dt, 3J¼7 Hz, 1H,
H40), 2.81 (m, 1H, H5), 4.26 (m, 1H, H3a), 4.43 (m, 1H, H6), 4.72 (m,
1H, H6a), 7.09 (t, 3J¼7.7 Hz, 1H, PheHpara), 7.29 (t, 3J¼7.7 Hz, 2H,
PheHmeta), 7.56 (d, 3J¼7.7 Hz, 2H, PheHortho). 13C NMR (400 MHz,
4.2. General procedure for the rearrangement of epoxides to
oxazolidinones
CD3OD) d 13.3 (CH2CH3), 14.7 (CH2CH3), 33.1 (C4), 37.0 (C5), 43.3
(CH2CH3), 43.8 (CH2CH3), 54.6 (C3a), 82.4 (C6), 88.7 (C6a), 160.6 (CO
carbamate), 172.9 (CO amide). MS(ESI): m/z¼263 [MþH]þ.
C13H14N2O4 (262.26): calcd C 59.54; H 5.38; N 10.68; found C 59.68;
H 5.16; N 10.43.
BF3$Et2O (120 mL, 1 mmol) was added with a micro-syringe to
a solution of epoxide 5aee (1.0 mmol) in dry THF (10 mL) and the
mixture was stirred in a sealed tube for 14 h. After this time the
solvent was removed under reduced pressure and the residue was
solubilized in CHCl3 (60 mL) and washed with saturated NaHCO3
(2ꢁ20 mL) and brine (1ꢁ20 mL). The organic phase was dried over
Na2SO4, filtered and concentrated under vacuum getting com-
pound 6 as a white solid after treatment with ether, except for
compound 6e, that is, a pale yellow oil.
4.2.5. (3aS,5R,6S,6aS) and (3aR,5S,6R,6aR) N,N-diethyl-6-hydroxy-2-
oxohexahydro-2H-cyclopenta[d]oxazole-5-carboxamide (6e). Yellow
oil; yield¼88%; nmax(KBr) 3306, 2940, 2858, 1741, 1616, 1465, 1456,
1383, 1367, 1249, 1218, 1112 cmꢂ1 1H NMR (400 MHz, CD3OD)
;
d
1.07 (t, 3J¼7 Hz, 3H, CH2CH3), 1.17 (t, 3J¼7 Hz, 3H, CH2CH3), 1.74 (m,
1H, H4), 2.30 (m, 1H, H40), 3.04 (m, 1H, H5), 3.24e3.37 (m, 2H,
CH2CH3), 3.38e3.51 (m, 2H, CH2CH3), 4.20 (m,1H, H3a), 4.34 (m,1H,
4.2.1. (3aS,5R,6S,6aS) and (3aR,5S,6R,6aR)-N-ethyl-6-hydroxy-2-
oxohexahydro-2H-cyclopenta[d]oxazole-5-carboxamide (6a). White
solid; yield¼78%; mp: 178e181 ꢀC; nmax(KBr) 3291, 2966, 2944,
2878, 1756, 1638, 1557, 1454, 1391, 1244, 1214, 1093 cmꢂ1; 1H NMR
H6), 4.64 (m, 1H, H6a). 13C NMR (400 MHz, CD3OD)
d 13.3 (CH2CH3),
15.0 (CH2CH3), 36.9 (C4), 42.1 (C5), 43.4 (CH2CH3), 45.9 (CH2CH3),
54.3 (C3a), 82.2 (C6), 87.8 (C6a), 161.1 (CO carbamate), 173.4 (CO
amide). MS (ESI): m/z¼243 [MþH]þ. C11H18N2O4 (242.27): calcd C
54.53; H 7.49; N 11.56; found C 54.26; H 7.82; N 11.67.
(200 MHz, CD3OD)
d
1.10 (t, 3J¼7.3 Hz, 3H, CH2CH3), 1.82 (dt,
3
3J¼6.8 Hz, 1H, H4), 2.29 (dt, J¼6.8 Hz, 1H, H40), 2.54 (m, 1H, H5),
3.20 (q, 3J¼7.3 Hz, 2H, CH2CH3), 4.18 (m, 1H, H3a), 4.29 (m, 1H, H6),
Acknowledgements
4.64 (m, 1H, H6a). 13C NMR (400 MHz, CD3OD)
d 14.8 (CH2CH3), 28.8
(C4), 35.4 (C5), 36.2 (CH2CH3), 54.9 (C3a), 82.2 (C6), 88.4 (C6a),
160.9 (CO carbamate), 173.8 (CO amide). MS (ESI): m/z¼215
[MþH]þ, 237 [MþNa]þ. C9H14N2O4 (214.22): calcd C 50.46; H 6.59;
N 13.08; found C 50.65; H 6.85; N 12.99.
This work was financially supported by the University of Siena
as a PAR Project 2007. The authors wish to thank the ‘Centro di
Analisi e Determinazioni Strutturali’ of the University of Siena for
MS spectra and X-ray data collections and Dr. Sara Draghi for
helpful collaborations.
4.2.2. (3aS,5R,6S,6aS) and (3aR,5S,6R,6aR)-6-hydroxy-N-(3-hydroxy-
propyl)-2-oxohexahydro-2H-cyclopenta[d]oxazole-5-carboxamide
(6b). White solid; yield¼87%; mp: 156e157 ꢀC; nmax(KBr) 3284,
2966, 2929, 2878, 1749, 1712, 1612, 1395, 1240, 1218, 1067,
Supplementery data
Spectroscopic data for compounds 5aee and 6aee. Supple-
mentary data related to this article can be found online at
1048 cmꢂ1; 1H NMR (400 MHz, CD3OD)
d 1.69 (m, 2H, CH2CH2CH2),
1.83 (dt, 3J¼6.9 Hz, 1H, H4), 2.29 (dt, 3J¼6.9 Hz, 1H, H40), 2.56 (m, 1H,
H5), 3.27 (t, 3J¼7.6 Hz, 2H, CH2NH), 3.57 (t, 3J¼7.6 Hz, 2H, CH2OH),
4.18 (q, 3J¼7 Hz, 1H, H3a), 4.29 (m, 1H, H6), 4.64 (m, 1H, H6a). 13
C
References and notes
NMR (200 MHz, CD3OD) d 33.1 (CH2CH2CH2), 36.2 (C4), 37.6 (CH2NH),
1. (a) Faith, W. C.; Booth, C. A.; Foxman, B. M.; Snider, B. B. J. Org. Chem. 1985, 50,
1983e1985; (b) Ober, M.; Muller, H.; Pieck, C.; Gierlich, J.; Carell, T. J. Am. Chem.
50.1 (C5), 54.3 (C3a), 60.3 (CH2OH), 81.2 (C6), 87.9 (C6a), 161.1 (CO
carbamate), 174.2 (CO amide). MS(ESI): m/z¼267 [MþNa]þ.
C10H16N2O5 (244.24): calcd C 49.17; H 6.60; N 11.47; found C 49.19; H
6.67; N 11.64.
€
ꢁ
€€
€ €
Soc. 2005, 127, 18143e18149; (c) Kiss, L.; Forro, E.; Sillanpaa, R.; Fulop, F. Syn-
thesis 2010, 1, 153e160; (d) Zhang, H.; Schinazi, R. F.; Chu, C. K. Bioorg. Med.
Chem. 2006, 14, 8314e8322; (e) Kothandaraman, S.; Vicario, P. P. Bioorg. Med.
Chem. Lett. 2009, 19, 1830e1834.
2. (a) Smith, M. E. B.; Derrien, N.; Lloyd, M. C.; Taylor, S. J. C.; Chaplin, D. A.;
4.2.3. (2S,3R)-Methyl 3-(benzyloxy)-2-((3aS,5R,6S,6aS)-6-hydroxy-2-
oxohexahydro-2H-cyclopenta[d]oxazole-5-carboxamido)butanoate
ꢁ
McCague, R. Tetrahedron Lett. 2001, 42, 1347e1350; (b) Kiss, L.; Forro, E.;
€€
€ €
Sillanpaa, R.; Fulop, F. Nucleic Acids Symp. Ser. 2008, 52, 551e552.
3. (a) Katagiri, N.; Yamatoya, Y.; Ishikura, M. Tetrahedron Lett. 1999, 40, 9069e9072;
(b) Bhushan, R. G.; Vince, R. Bioorg. Med. Chem. 2002, 10, 2325e2333.
4. Ishikura, M.; Hasunuma, M.; Yamada, K.; Yanada, R. Heterocycles 2006, 68,
2253e2257.
(6c). White solid; yield¼88%; mp: 134e135 ꢀC; [
a]
D
20 þ30.48 (c 0.01,
MeOH); nmax(KBr) 3343, 3062, 2937, 1767, 1725, 1707, 1655, 1542,
1238, 1063 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.25 (d, 3J¼6.4 Hz, 3H,
CH3CH), 2.06 (m, 1H, H4), 2.42 (m, 1H, H40), 2.72 (m, 1H, H5), 3.68 (s,
3H, COOCH3), 4.13e4.21 (m, 2H, H3aþCH3CH), 4.38 (AB system, d,
2J¼12 Hz, 1H, OCH2Ph), 4.46 (m, 1H, H6), 4.59 (AB system, d,
2J¼12 Hz, 1H, OCH2Ph), 4.69 (d, 3J¼9.2 Hz, 1H, NHCHCOOMe), 4.74
(m, 1H, H6a), 5.53 (br s, 1H, OH), 6.73 (d, J¼9.2 Hz, 1H, NH amide),
7.24e7.30 (m, 2H, Ph), 7.30e7.39 (m, 3H, Ph). 13C NMR (200 MHz,
5. (a) Palmer, C. F.; Bannister, R. M.; McCague, R. Tetrahedron Lett. 1999, 40,
6109e6112; (b) Rommel, M.; Ernst, A.; Koert, U. Eur. J. Org. Chem. 2007,
4408e4430.
6. Papandrea, G.; Ponticelli, F. Synth. Commun. 2008, 38, 858e865.
7. Palmer, C. F.; McCague, R.; Ruecroft, G.; Savage, S.; Taylor, S. J. C.; Ries, C.
Tetrahedron Lett. 1996, 37, 4601e4604.
8. Katagiri, N.; Matsuhashi, Y.; Kokufuda, H.; Takebayashi, M.; Kaneko, C. Tetra-
hedron Lett. 1997, 38, 1961e1964.
9. Dominguez, B. M.; Cullis, P. M. Tetrahedron Lett. 1999, 40, 5783e5786.
10. (a) Kiss, L.; Forro, E.; Sillanpaa, R.; Fulop, F. J. Org. Chem. 2007, 72, 8786e8790;
CDCl3) d 16.2 (CH3CH), 33.7 (C4), 48.2 (C5), 52.4 (COOCH3), 52.7 (C3a),
ꢁ
€€
€ €
56.7 (NHCHCOOMe), 70.8 (OCH2Ph), 74.2 (CH3CH), 79.9 (C6), 86.3
(C6a), 127.8 (o-Ph, p-Ph), 128.4 (m-Ph), 137.7 (q-Ph), 158.6 (CO car-
bamate), 171.1 (CO ester), 172.0 (CO amide). MS(ESI): m/z¼393
ꢁ
€€ € €
(b) Kiss, L.; Forro, E.; Sillanpaa, R.; Fulop, F. Tetrahedron 2010, 66, 3599e3607.
~
ꢁ
11. Leitao, A. J. L.; Salvador, J. A. R.; Pinto, R. M. A.; Sa e Melo, M. L. Tetrahedron Lett.
2008, 49, 1694e1697.