J. M. Blanco et al. / Tetrahedron 58 (2002) 8843–8849
8847
2.58–2.49 (m, 1H), 2.34–2.24 (m, 3H), 1.94–1.84 (m, 1H).
13C NMR (CDCl3) d: 176.50 and 176.12 (2£CO), 167.21
(Ph–CO), 136.61 (C4arom), 130.24 (C1arom), 130.01 and
128.89 ((C2þC6þC3þC5)arom), 66.95 (CH2O), 52.41
(CH3), 49.04, 43.14 and 42.97 (C4þC1þC2), 34.54 and
32.87 (C5þC3). EIMS m/z (%): 306 (0.13, (Mþ1)þ), 305
(2, Mþ), 274 (4), 260 (0.23), 246 (5), 183 (15), 166 (10), 140
(18), 122 (3), 105 (100), 81 (28), 80 (22), 79 (23), 77 (50).
Anal. calcd for C16H19NO5 (305.33): C, 62.94; H, 6.27; N,
4.59. Found: C,63.16; H, 6.16; N, 4.73.
acetate (2.07 g, 4.66 mmol), t-BuOH (23 mL) and Et3N
(1.6 mL, 4.95 mmol) by a parallel procedure to that above
described for (^)-16. Once similarly purified by column
chromatography, (^)-17 (1.25 g, 88%) crystallized spon-
taneously. Mp 50–528C. IR (film) nmax: 3378, 2974, 1720,
1
1601, 1584, 1452, 1366, 1274 cm21. H NMR (CDCl3) d:
8.01 (d, 2H, J¼7.9 Hz, (2-Hþ6-H)arom), 7.55 (t, 1H, J¼
7.3 Hz, 4-Harom), 7.44 (t, 2H, J¼7.6 Hz, (3-Hþ5-H)arom),
5.05 (bs, 1H, D2O exch., NH), 4.37–4.25 (m, 2H, CH2O),
4.12–4.01 (m, 1H), 3.63 (s, 3H, OCH3), 2.83–2.70 (m, 2H),
2.35–2.31 (m, 1H), 1.93–1.89 (m, 1H), 1.86–1.77 (m, 2H),
1.44 (s, 9H, C(CH3)3). 13C NMR (CDCl3) d: 177.62 (1-CO),
166.67 (Ph–CO), 155.68 (N–CO–O), 133.46 (C4arom),
130.39 (C1arom), 129.97 and 128.78 ((C2þC6þC3þ
C5)arom), 79.97 [C(CH3)3], 67.40 (CH2O), 52.46 (OCH3),
51.92 (C4), 46.01 and 41.71 (C1þC3), 37.14 (C2þC5),
28.81 [C(CH3)3]. EIMS m/z (%): 321 (4, ((Mþ1)þ2
C(CH3)3)), 304 (2, Mþ2(OC(CH3)3)), 276 (15,
(Mþ2Boc)), 246 (2), 216 (2), 154 (28), 138 (8), 105 (90),
96 (21), 79 (11), 77 (36), 59 (16), 57 (100). Anal. calcd for
C20H27NO6 (377.43): C, 63.64; H, 7.21; N, 3.71. Found: C,
63.45; H, 7.43; N, 3.54.
(^)-15: mp 100–1028C (recrystallized from EtOAc/hexane
13:10). IR (KBr) nmax: 3393, 3198, 2951, 1727, 1656, 1450,
1
1431, 1378, 1317, 1266 cm21. H NMR (CDCl3) d: 7.99
(d, 2H, J¼7.2 Hz, (2-Hþ6-H)arom), 7.55 (t, 1H, J¼7.2 Hz,
4-Harom), 7.43 (t, 2H, J¼7.7 Hz, (3-Hþ5-H)arom), 5.92 (bs,
2H, D2O exch., NH2), 4.30 (d, 2H, J¼6.3 Hz, CH2O), 3.62
(s, 3H, OCH3), 2.90–2.77 (m, 2H), 2.75–2.66 (m, 1H),
2.35–2.14 (m, 3H), 1.96–1.79 (m, 1H). 13C NMR (CDCl3)
d: 176.79 and 175.03 (2£CO), 166.42 (Ph–CO), 133.08
(C4arom), 129.95 (C1arom), 129.54 and 128.39 ((C2þC6þ
C3þC5)arom), 66.71 (CH2O), 51.97 (CH3), 47.36, 43.97 and
42.00 (C4þC1þC3), 34.13 and 32.97 (C5þC2). EIMS m/z
(%): 306 (0.03, (Mþ1)þ), 305 (0.07, Mþ), 274 (2), 246
(0.11), 183 (15), 151 (8), 138 (27), 105 (100), 80 (17), 79
(20), 77 (42). Anal. calcd for C16H19NO5 (305.33): C,
62.94; H, 6.27; N, 4.59. Found: C, 63.17; H, 6.43; N, 4.38.
3.1.9. (6)-(1b,3a,4b)-tert-Butyl N-[3,4-bis(hydroxy-
methyl)cyclopent-1-yl]carbamate (18). A solution of
(^)-16 (0.48 g, 1.30 mmol) in dry toluene (5 mL) was
added dropwise under argon to a commercial 1.5 M solution
of DIBAL-H in the same solvent (6.24 mL, 9.36 mmol) at
2788C, the mixture was stirred at this temperature for 3 h,
and the reaction was quenched by cautious and successive
addition of toluene/MeOH (9:1; 2 mL), MeOH (1 mL) and
water (4 mL), then leaving the mixture to reach room
temperature. The solid precipitate was filtered out and
washed with EtOAc (4£40 mL). The combined liquid
filtrate and washings were dried over anhydrous Na2SO4,
the solvents were evaporated at low pressure, and the
residue left was chromatographed on silica gel (15 g) with
EtOAc as eluent to afford (^)-18 (0.27 g, 86%), as a white
solid. Mp 129–130.58C (recrystallized from EtOAc/hexane
2:1). IR (KBr) nmax: 3649, 3303, 2977, 2940, 1702, 1681,
1543, 1457, 1363, 1291 cm21. 1H NMR (DMSO-d6) d: 6.73
(d, 1H, J¼7.8 Hz, D2O exch., NH), 4.44 (t, 1H, J¼5.2 Hz,
D2O exch., OH), 4.36 (t, 1H, J¼5.1 Hz, D2O exch., OH),
3.45–3.37 (m, 2H), 3.31–3.15 (m, 3H), 1.95–1.88 (m, 2H),
1.78–1.75 (m, 1H), 1.48–1.43 (m, 2H), 1.36 (s, 9H,
C(CH3)3), 1.09–1.05 (m, 1H). 13C NMR (CDCl3) d: 156.01
(CO), 80.77 [C(CH3)3], 67.15 and 64.23 (2£CH2O), 54.65
(C1), 49.01 and 38.36 (C3þC4), 36.11 and 30.22 (C2þC5),
28.75 [C(CH3)3]. EIMS m/z (%): 189 (2, (Mþ1)þ2
(C(CH3)3)), 172 (1, (Mþ2OC(CH3)3)), 144 (7,
(Mþ2Boc)), 126 (4), 114 (21), 93 (8), 80 (17), 79 (11),
59 (13), 58 (11), 57 (100). Anal. calcd for C12H23NO4
(245.32): C, 58.75; H, 9.45; N, 5.71. Found: C, 58.98; H,
9.32; N, 5.91.
3.1.7. (6)-(1b,2a,4b)-Methyl-2-benzoyloxymethyl-4-
tert-butoxycarbonylamino-1-cyclopentanecarboxylate
(16). Lead tetraacetate (3.55 g, 8.00 mmol) was added under
argon to a solution of carbamoyl ester (^)-14 (1.97 g,
6.46 mmol) in t-BuOH (40 mL), the mixture was heated to
708C, Et3N (2.74 mL, 8.48 mmol) was added dropwise, and
the mixture was refluxed for 8 h. Concentration under
reduced pressure by azeotropic codistillation with toluene
afforded a yellow solid that upon chromatographic frac-
tionation on silica gel (114 g) with hexane/EtOAc 10:3 as
eluent gave (^)-16 (2.21 g, 91%), as a solid. Mp 100.5–
101.58C. IR (KBr) nmax: 3367, 2972, 1727, 1716, 1681,
1525, 1452, 1429, 1365, 1316, 1284 cm21 1H NMR
.
(CDCl3) d: 8.02 (d, 2H, J¼7.4 Hz, (2-Hþ6-H)arom), 7.55
(t, 1H, J¼7.4 Hz, 4-Harom), 7.43 (t, 2H, J¼7.6 Hz, (3Hþ
5H)arom), 4.91 (bs, 1H, D2O exch., NH), 4.40 and 4.27 (the
AB part of an ABX system, 2H, JAB¼11.1 Hz, JAX¼6.6 Hz,
JBX¼5.4 Hz, OCH2), 4.01–3.91 (m, 1H, 4-H), 3.68 (s, 3H,
OCH3), 2.93–2.89 (m, 1H), 2.42–2.32 (m, 2H), 2.30–2.18
(m, 1H), 1.84–1.76 (m, 2H), 1.41 (s, 9H, C(CH3)3). 13C
NMR (CDCl3) d: 177.51 (1-CO), 166.88 (Ph–CO), 155.79
(N–CO–O), 133.38 (C4arom), 130.50 (C1arom), 130.01 and
128.77 ((C2þC6þC3þC5)arom), 79.91 [C(CH3)3], 66.54
(CH2O), 54.59 (C4), 52.42 (OCH3), 45.32 and 40.91 (C1þ
C2), 36.88 and 31.80 (C5þC3), 28.76 [C(CH3)3]. EIMS m/z
(%): 321 (0.37, ((Mþ1)þ2C(CH3)3)), 304 (0.81, (Mþ2
OC(CH3)3)), 276 (0.09, Mþ2Boc), 246 (1.37), 198 (7), 154
(49), 140 (12), 105 (60), 96 (40), 77 (35), 57 (100). Anal.
calcd for C20H27NO6 (377.43): C, 63.64; H, 7.21; N, 3.71.
Found: C, 63.82; H, 7.42; N, 3.49.
3.1.10. (6)-(1b,2a,4b)-tert-Butyl N-[2,4-bis(hydroxy-
methyl)cyclopent-1-yl]carbamate (19). From carbamate
(^)-17 (0.34 g, 0.90 mmol) in dry toluene (4 mL) and
commercial 1.5 M DIBAL-H in the same solvent (4.5 mL,
6.75 mmol), crude (^)-19 was obtained as a viscous liquid
by a parallel procedure to that above described for (^)-18.
Once similarly purified by column chromatography, (^)-19
(0.21 g, 95%) was isolated as a white solid. Mp 59.5–628C.
3.1.8. (6)-(1b,3a,4b)-Methyl-3-benzoyloxymethyl-4-
tert-butyloxycarbonylamino-1-cyclopentanecarboxylate
(17). Crude (^)-17 was obtained as a thick liquid from
carbamoyl ester (^)-15 (1.15 g, 3.77 mmol), lead tetra-