The Journal of Organic Chemistry
NOTE
and hydrochloric acid (0.5 mL). The resulting mixture was stirred under
3 bar of hydrogen for 6 h. The catalyst was eliminated by filtration
through a pad of Celite, the filtrate was treated with 3 M HCl in
methanol, and the resulting solution was stirred at room temperature for
additional 10 min. The solvent was eliminated under reduced pressure to
afford pure 7 (0.1 g, quant) as a white solid: mp >150 °C dec; [R]26D =
þ10 (c 0.15, H2O); 1H NMR (400 MHz, D2O, 60 °C) δ 1.58 (dd, J =
14.0, 10.7 Hz, 1H, H2a), 1.68 (ddd, J = 14.3, 11.3, 3.2 Hz, 1H, H4a), 2.08
(ddd, J = 13.8, 6.0, 1.0 Hz, 1H, H2b), 2.27 (dddd, J = 5.7, 4.9, 3.0, 1.4 Hz,
1H, H4b), 3.60 (d, J = 12.9 Hz, 1H, CH2OH), 3.63 (d, J = 13.0 Hz, 1H,
CH2OH), 3.74 (t, J = 3.0 Hz, 1H, H5), 4.03ꢀ4.05 (m, 1H, H6),
4.05ꢀ4.11 (m, 2H, H3, H7); 13C NMR (100 MHz, D2O) δ 33.2 (C2),
34.0 (C4), 61.0 (C3), 61.4 (CH2OH), 61.7 (C5), 69.2 (C1), 78.1 (C7),
78.4 (C6). Anal. Calcd for C8H16ClNO4: C, 42.58; H, 7.15; N, 6.21.
Found: C, 42.76; H, 7.35; N, 6.10.
4.12 (s, 1H, H6), 4.19 (d, J = 11.8 Hz, 1H, CH2Ph), 4.35 (s, 1H, H7), 4.56
(d, J = 11.8 Hz, 1H, CH2Ph), 4.66 (d, J = 11.8 Hz, 1H, CH2Ph), 4.67 (d,
J = 12.0 Hz, 1H, CH2Ph), 4.84ꢀ4.89 (m, 2H, H5, CH2Ph),6.81 ꢀ 6.87
(m, 2H, Ar), 7.20ꢀ7.45 (m, 16H, Ar), 7.55 (d, J = 7.5 Hz, 2H, Ar); 13
C
NMR (125 MHz, CDCl3) δ 37.8 (C2), 47.3 (C4), 71.7 (CH2Ph), 72.1
(CH2Ph), 73.8 (CH2Ph), 74.7 (CH2OBn), 75.7 (C1), 79.0 (C5), 80.5
(C3), 84.4 (C7), 88.2 (C6), 126.5 (Ar), 127.4 (Ar), 127.5 (Ar), 127.6
(Ar), 127.7 (Ar), 127.8 (Ar), 127.9 (Ar), 128.0 (Ar), 128.1 (Ar), 128.4
(Ar), 128.4 (Ar), 137.7 (Ar), 138.2 (Ar), 138.5 (Ar), 143.2 (Ar). Anal.
Calcd for C35H35NO4: C, 78.77; H, 6.61; N, 2.62. Found: C, 78.83; H,
6.460; N, 2.78.
(2R,3R,4R)-2-Allyl-3,4-bis(benzyloxy)-2-(benzyloxymethyl)-
5-phenyl-3,4-dihydro-2H-pyrrole 1-Oxide (11) and (1R,3S,
5S,6S,7R)-6,7-Bis(benzyloxy)-1-benzyloxymethyl-3,8-epoxy-
5-phenyl-9-nortropane (12). A solution of nitrone 10 (0.533 g, 1
mmol) was dissolved in anhydrous toluene (25 mL), placed in a sealed
tube, and heated at 120 °C under an argon atmosphere for 14 h, at which
time the solvent was partially evaporated and the resulting solution was
filtered through a pad of silica gel. After the silica was washed with diethyl
ether, the resulting solution was evaporated under reduced pressure, and
the residue was purified by radial chromatography using hexaneꢀEtOAc
4:1 as an eluant to afford a 38:62 mixture of compounds 11 and 12,
respectively, in quantitative yield.
(2S,3R,4R,5R)-2-Allyl-3,4-bis(benzyloxy)-5-(benzyloxymethyl)-
2-phenylpyrrolidin-1-ol (9). The reaction of 8 (0.987 g, 2 mmol)
with allylmagnesium bromide (6 mL of a solution 1.0 M in hexanes, 6
mmol), as described above for nitrone 1 to give 2, afforded pure 9 (1.07
1
g, quant): oil; [R]23 = ꢀ68 (c 0.60, CHCl3); H NMR (300 MHz,
D
CDCl3) δ 2.84 (ddt, J = 15.0, 7.5, 1.3 Hz, 1H, CH2CHCH2), 3.17 (ddt,
J = 15.0, 1.3 Hz, 1H, CH2CHdCH2), 3.64 (c, J = 5.4 Hz, 1H, H5), 3.74
(dd, J = 9.7, 5.2 Hz, 1H, CH2OBn), 3.81 (d, J = 5.6 Hz, 1H, H4), 3.82
(dd, J = 11.2, 5.6 Hz, 1H, CH2OBn), 3.98 (d, J = 2.0 Hz, 1H, H3), 4.02
(d, J = 11.5 Hz, 1H, CH2Ph), 4.11 (d, J = 11.5 Hz, 1H, CH2Ph), 4.55 (s,
1H, NOH), 4.61 (s, 2H, CH2Ph), 4.81 (s, 2H, CH2Ph), 5.00ꢀ5.14 (m,
2H, CH2CHdCH2), 5.95 (dddd, J = 16,9, 10.2, 7.4, 6.6 Hz, 1H,
CH2CHdCH2), 6.86 ꢀ 9.91 (m, 2H, Ar), 7.18ꢀ7.39 (m, 16H, Ar),
7.54ꢀ7.59 (m, 2H, Ar); 13C NMR (75 MHz, CDCl3) δ 36.7 (CH2CHd
CH2), 61.5 (C2), 69.1 (C5), 71.1 (CH2OBn), 71.8 (CH2Ph), 72.0
(CH2Ph), 73.4 (CH2Ph), 82.7 (C4), 86.4 (C3), 117.5 (CH2CHd
CH2), 126.5 (Ar), 127.6 (Ar), 127.6 (Ar), 127.6 (Ar), 127.7 (Ar),
127.8 (Ar), 128.1 (Ar), 128.1 (Ar), 128.4 (Ar), 128.6 (Ar), 136.2
(CH2CHdCH2), 137.5 (Ar), 138.1 (Ar), 138.3 (Ar), 140.9 (Ar). Anal.
Calcd for C35H37NO4: C, 78.48; H, 6.96; N, 2.61. Found: C, 78.52; H,
6.81; N, 2.87.
11 (0.202 g, 38%): oil; Rf (hexaneꢀEtOAc, 4:1) = 0.36; [R]23D = þ8
(c 0.35, CHCl3); 1H NMR (500 MHz, CDCl3) δ 2.54 (d, J = 7.1 Hz, 2H,
CH2CHdCH2), 3.53 (d, J = 10.2 Hz, 1H, CH2OBn), 4.22 (d, J = 10.2
Hz, 1H, CH2OBn), 4.33 (d, J = 11.5 Hz, 1H, CH2Ph), 4.50 (d, J = 11.7
Hz, 1H, CH2Ph), 4.51 (d, J = 11.5 Hz, 1H, CH2Ph), 4.67 (d, J = 11.2 Hz,
1H, CH2Ph), 4.69 (d, J = 11.5 Hz, 1H, CH2Ph), 4.74 (d, J = 11.8 Hz, 1H,
CH2Ph), 4.80 (d, J = 4.3 Hz, 1H, H3), 5.01 (dd, J = 10.2, 2.0 Hz, 1H,
CH2CHdCH2), 5.15 (ddt, J = 17.1, 2.1, 1.2 Hz, 1H, CH2CHdCH2),
5.33 (d, J = 4.3 Hz, 1H, H4), 5.82 (ddt, J = 17.4, 10.1, 7.3 Hz, 1H,
CH2CHdCH2), 7.10ꢀ7.13 (m, 2H, Ar), 7.26 ꢀ7.32 (m, 8H, Ar),
7.34ꢀ7.41 (m, 5H, Ar), 7.43ꢀ7.47 (m, 3H, Ar), 8.41ꢀ8.45 (m, 2H, Ar);
13C NMR (125 MHz, CDCl3) δ 34.9 (CH2CHdCH2), 68.5 (CH2Ph),
71.2 (CH2OBn), 72.8 (CH2Ph), 73.6 (CH2Ph), 78.5 (C3), 82.1 (C2),
83.7 (C4), 120.1 (CH2CH=CH2), 127.7 (Ar), 127.7 (Ar), 127.8 (Ar),
127.8 (Ar), 128.0 (Ar), 128.0 (Ar), 128.2 (Ar), 128.3 (Ar), 128.4 (Ar),
128.5 (Ar), 130.2 (Ar), 131.7 (CH2CHdCH2), 137.6 (Ar), 137.7 (Ar),
137.8 (Ar), 139.1 (C5). Anal. Calcd for C35H35NO4: C, 78.77; H, 6.61;
N, 2.62. Found: C, 78.54; H, 6.40; N, 2.45.
(2S,3R,4R)-2-Allyl-3,4-bis(benzyloxy)-5-(benzyloxymethyl)-
2-phenyl-3,4-dihydro-2H-pyrrole 1-Oxide (10). The oxidation
of 9 (1.07 g, 2 mmol), as described above for hydroxylamine 2 to give 3,
afforded pure 10 (1.07 g, quant) as an oil: [R]21 = ꢀ91 (c 0.16,
D
CHCl3); 1H NMR (500 MHz, CDCl3) δ 2.85 (dd, J = 14.3, 8.8 Hz, 1H,
CH2CHdCH2), 3.34 (ddt, J = 14.3, 5.1, 1.4 Hz, 1H, CH2CHdCH2),
4.31 (d, J = 4.5 Hz, 1H, H3), 4.37 (d, J = 0.9 Hz, 2H, CH2Ph), 4.41 (dd,
J = 13.4, 1.4 Hz, 1H, CH2OBn), 4.63 (d, J = 11.2 Hz, 1H, CH2Ph), 4.65
(d, J = 11.2 Hz, 1H, CH2Ph), 4.72 (d, J = 11.7 Hz, 1H, CH2Ph), 4.74 (d,
J = 11.5 Hz, 1H, CH2Ph), 4.81 (dd, J = 15.3, 4.5 Hz, 1H, H4), 4.87 (d, J =
13.8 Hz, 1H, CH2OBn), 5.14 (d, J = 17.0 Hz, 1H, CH2CHdCH2), 5.23
(d, J = 10.1 Hz, 1H, CH2CHdCH2), 5.78 (dddd, J = 17.1, 10.2, 8.8, 5.2
Hz, 1H, CH2CHdCH2), 7.01ꢀ7.06 (m, 2H, Ar), 7.26ꢀ7.46 (m, 18H,
Ar); 13C NMR (125 MHz, CDCl3) δ 39.7 (CH2CHdCH2), 61.5
(CH2OBn), 72.4 (CH2Ph), 73.2 (CH2Ph), 73.8 (CH2Ph), 82.7 (C3),
83.1 (C4), 83.7 (C2), 120.8 (CH2CHdCH2), 127.9 (Ar), 127.9 (Ar),
128.0 (Ar), 128.0 (Ar), 128.0 (Ar), 128.2 (Ar), 128.3 (Ar), 128.4 (Ar),
128.5 (Ar), 128.5 (Ar), 131.9 (CH2CHdCH2), 135.8 (Ar), 137.2, (Ar)
137.5 (Ar), 137.6 (Ar), 144.0 (C5). Anal. Calcd for C35H35NO4: C,
78.77; H, 6.61; N, 2.62. Found: C, 78.90; H, 6.70; N, 2.85.
12 (0.331 g, 62%). The physical and spectroscopic properties were
identical to those of the same compound obtained by heating at 120 °C
for 36 h as described above.
(3S,5S,6R)-1-(Hydroxymethyl)-5-phenyl-8-azabicyclo[3.2.1]-
octane-3,6,7-triol (13). The hydrogenation of 12 (0.533 g, 1 mmol),
as described above for cycloadduct 6 to give 8, afforded pure 13 (0.3 g,
quant) as a white solid: mp >150 °C dec; [R]27D = þ21 (c 0.34, H2O);
1H NMR (500 MHz, D2O) δ 1.77ꢀ1.86 (m, 2H, H2a, H4a), 2.24 (dd, J =
13.9, 5.9 Hz, 1H, H4b), 2.63 (dd, J = 14.1, 5.9 Hz, 1H, H2b), 3.81 (d, J =
12.9 Hz, 1H, CH2OH), 3.84 (d, J = 12.9 Hz, 1H, CH2OH), 4.15 (s, 1H,
H7), 4.41 (tt, J = 11.4, 6.0 Hz, 1H, H3), 4.50 (s, 1H, H6), 7.26 (d, 1H, J =
7.5 Hz, Ar), 7.39 (t, 1H, J = 7.4 Hz, Ar), 7.47 (t, 1H, J = 7.6 Hz, Ar); 13C
NMR (100 MHz, D2O) δ 32.6 (C4), 44.6 (C2), 61.2 (C3), 62.8
(CH2OH), 68.3, 71.8 (C5), 79.7 (C7), 80.4 (C6), 125.1 (Ar), 128.3
(Ar), 128.9 (Ar), 136.3 (Ar). Anal. Calcd for C14H20ClNO4: C, 55.72;
H, 6.68; N, 4.64. Found: C, 55.83; H, 6.45; N, 4.86.
(1R,3S,5S,6S,7R)-6,7-Bis(benzyloxy)-1-benzyloxymethyl-3,8-
epoxy-5-phenyl-9-nortropane (12). Heating of 10 (0.2 g, 0.36
mmol), as described above for nitrone 3 to give 6, but for 36 h, afforded
pure 12 (0.2 g, quant) as an oil: Rf (EtOAc) = 0.54; [R]26 = þ2
’ ASSOCIATED CONTENT
D
(c 0.416, CHCl3); 1H NMR (500 MHz, CDCl3) δ 1.61ꢀ1.66 (m, 1H,
H2a), 2.13 (d, J = 11.8 Hz, 1H, H4a), 2.30 (d, J = 11.9 Hz, 1H, H2b), 2.53
(ddd, J = 11.7, 4.7, 3.0 Hz, 1H, H1),3.59 (d, J = 10.2 Hz, 1H, CH2OBn),
3.77 (d, J = 10.2 Hz, 1H, CH2OBn), 4.07 (d, J = 11.8 Hz, 1H, CH2Ph),
Supporting Information. 1H and 13C NMR spectra of
S
b
compounds. This material is available free of charge via the
4142
dx.doi.org/10.1021/jo200315k |J. Org. Chem. 2011, 76, 4139–4143