974
J. E. Rodriguez-Borges et al.
PAPER
IR (NaCl): 3386, 3181, 2977, 1454, 1386, 1034, 761 cm–1.
1H NMR (CDCl3): d = 1.46 (d, J = 6.5 Hz, 3 H, CHCH3), 1.72 (br s,
2 H, H7syn, H7anti), 2.03 (d, J = 5.1 Hz, 1 H, H4), 2.18 (br s, 1 H, H3),
2.43 (dd, J = 10.4, 6.5 Hz, 1 H, CHaHOH), 2.75 (d, J = 10.4 Hz, 1
H, CHbHOH), 2.80 (br s, 3 H, D2O exch., 3 OH), 3.50 (br s, 1 H,
H1), 3.57 (q, J = 6.5 Hz, 1 H, CHCH3), 3.82 (d, J = 4.5 Hz, 1 H,
H5), 4.29 (d, J = 4.5 Hz, 1 H, H6), 7.20–7.35 (m, 5 H, ArH).
13C NMR (CDCl3): d = 22.1 (CHCH3), 29.5 (C7), 48.0 (C4), 60.2
(C3), 62.6 (CHCH3), 63.5 (CH2OH), 65.2 (C1), 67.7 (C5), 73.3
(C6), 127.9 (C4Ph), 127.5 (C3Ph, C5Ph), 128.6 (C2Ph, C6Ph), 127.3
(C1Ph).
(–)-(1S,3S)-3-[(tert-Butyldiphenylsiloxy)methyl]-2-[(1R)-1-phe-
nylethyl]-2-azabicyclo[2.2.1]hept-5-ene (6b); Typical Proce-
dure
To a soln of 5b (0.75 g, 3.27 mmol), DMAP (20 mg, 0.16 mmol,
ca. 0.05 equiv), and Et3N (0.91 mL, 0.66 g, 6.53 mmol) in anhyd
CH2Cl2 (30 mL) was added dropwise TBDPSCl (1.69 mL, 1.79 g,
6.51 mmol) under argon at 0 °C. The mixture was stirred at r.t. for
21 h and EtOAc (50 mL) and H2O (50 mL) were added. The aque-
ous layer was extracted with EtOAc (3 × 40 mL) and the combined
organic layers were washed with brine (60 mL) and dried (Na2SO4).
Removal of the solvent under reduced pressure left a yellow oil,
which was purified by chromatography (silica gel, hexane–EtOAc
6:1) to afford 6b (1.39 g, 91%) as a yellow oil; Rf = 0.3.
Anal. Calcd for C15H21NO3: C, 68.42; H, 8.04; N, 5.32. Found: C,
68.33; H, 8.24; N, 5.45.
[a]D25 –4.1 (c 1, CHCl3).
IR (NaCl): 2954, 2931, 2750, 1580, 1477, 1431, 1113, 818, 738
cm–1.
( )-(3-exo,5-exo,6-exo)-2-Benzyl-3-(hydroxymethyl)-2-azabicy-
clo[2.2.1]heptane-5,6-diol (7a)
Following the typical procedure for 7b using 5a. Flash chromatog-
raphy of the crude product (CH2Cl2–MeOH, 9:1) afforded pure 7a
(80%) as an oil; Rf = 0.2.
1H NMR (CDCl3): d = 0.89 [s, 9 H, C(CH3)3], 1.19–1.26 (m, 1 H,
H7anti), 1.32 [d, J = 6.6 Hz, 3 H, NCH(CH3)Ph], 1.60 (d, J = 8.3 Hz,
1 H, H7syn), 1.87–1.92 (m, 1 H, H3), 2.98–3.09 [m, 4 H,
NCH(CH3)Ph, CH2OSi, H4], 4.09 (br s, 1 H, H1), 6.16 (d, J = 5.4
Hz, 1 H, H5), 6.44–6.48 (m, 1 H, H6), 7.10–7.50 (m, 15 H, ArH).
13C NMR (CDCl3): d = 19.2 [C(CH3)3], 22.0 [NCH(CH3)Ph], 26.8
[C(CH3)3], 44.1 (C7), 44.6 (C4), 63.1 [NCH(CH3)Ph], 63.2 (C1),
64.3 (C3), 67.1 (CH2OSi), 127.0, 127.4, 127.9, 128.1, 129.2, 129.3,
131.6, 135.3, 135.4, 135.5, 137.0 (C5, C6, arom CH), 129.5 and
133.9 (2 Si-C1Ph), 135.2 (CHMe-C1Ph).
IR (NaCl): 3385 (OH), 3179, 2970, 1450, 1381, 1030 cm–1.
1H NMR (CDCl3): d = 1.65 (d, J = 11.3 Hz, 1 H, H7syn), 1.70 (d,
J = 11.3 Hz, 1 H, H7anti), 2.16 (d, J = 4.5 Hz, 1 H, H4), 2.23 (br s, 1
H, H3), 2.63 (br s, 3 H, D2O exch., 3 OH), 3.11 (br s, 1 H, H1), 3.31
(br s, 2 H, CH2OH), 3.73 (d, J = 13.3 Hz, 1 H, NCHaHPh), 3.80 (d,
J = 13.3 Hz, 1 H, NCHHbPh), 3.87 (d, J = 5.7 Hz, 1 H, H5), 4.31 (d,
J = 5.7 Hz, 1 H, H6), 7.20–7.35 (m, 5 H, ArH).
Anal. Calcd for C31H37NOSi: C, 79.61; H, 7.97; N, 2.99. Found: C,
79.83; H, 8.09; N, 2.77.
13C NMR (CDCl3): d = 30.4 (C7), 47.6 (C4), 55.1 (CH2Ph), 64.0
(C3), 64.6 (CH2OH), 66.2 (C1), 68.0 (C5), 73.6 (C6), 127.8 (C4Ph),
129.1 (C3Ph, C5Ph), 129.4 (C2Ph, C6Ph), 140.6 (C1Ph).
( )-(3-exo)-2-Benzyl-3-[(tert-butyldiphenylsiloxy)methyl]-2-
azabicyclo[2.2.1]hept-5-ene (6a)
Following the typical procedure for 6b using 5a. Flash chromatog-
raphy of the crude product (hexane–EtOAc, 1:1) afforded pure 6a
(89%) as an oil; Rf = 0.6.
Anal. Calcd for C14H19NO3: C, 67.45; H, 7.68; N, 5.62. Found: C,
67.62; H,, 7.55; N, 5.54.
( )-(3-exo,5-exo,6-exo)-2-Benzyl-3-[(tert-butyldiphenyl-
siloxy)methyl]-2-azabicyclo[2.2.1]heptane-5,6-diol (8a)
Following the typical procedure for 7b using 6a. Flash chromatog-
raphy of the crude product (hexane–EtOAc, 1:1) afforded pure 8a
(83%); Rf = 0.3.
IR (NaCl): 2956, 2936, 2748, 1583, 1479, 1436, 1118, 816, 737
cm–1.
1H NMR (CDCl3): d = 1.04 [s, 9 H, C(CH3)3], 1.27 (d, J = 8.4 Hz, 1
H, H7anti), 1.57 (d, J = 8.4 Hz, 1 H, H7syn), 1.87–1.92 (m, 1 H, H3),
2.97 (br s, 1 H, H4), 3.37 (s, 2 H, NCH2Ph), 3.39–3.47 (m, 1 H, H1),
3.60–3.65 (m, 2 H, OCH2), 6.14 (dd, J = 5.4, 1.8 Hz, 1 H, H5),
6.48–6.44 (m, 1 H, H6), 7.10–7.80 (m, 15 H, ArH).
13C NMR (CDCl3): d = 19.0 [C(CH3)3], 26.5 [C(CH3)3], 45.0 (C7),
45.2 (C4), 58.6 (NCH2Ph), 63.7 (C1), 65.0 (C3), 67.2 (CH2OSi),
127.3, 128.0, 128.6, 129.5, 129.8, 129.9 (Si-C1Ph), 132.4, 135.2,
136.0 (C5, C6, arom CH), 134.3 (NCH2-C1Ph).
IR (NaCl): 3240 (OH), 2920, 2850, 1470, 1380, 1080, 690 cm–1.
1H NMR (CDCl3): d = 1.02 [s, 9 H, C(CH3)3], 1.48 (d, J = 10.5 Hz,
1 H, H7anti), 1.61 (d, J = 10.5 Hz, 1 H, H7syn), 2.14 (t, J = 6.3 Hz, 1
H, H4), 2.38 (br s, 1 H, H3), 2.51, 2.75 (2 br s, 2 H, D2O exch.,
2 OH), 2.93 (br s, 1 H, H1), 3.28, 3.31 (2 br s, 2 H, NCH2Ph), 3.58–
3.63 (m, 2 H, CH2OSi), 3.84 (d, J = 6.0 Hz, 1 H, H5), 4.23 (d,
J = 6.0 Hz, 1 H, H6), 7.18–7.69 (m, 15 H, ArH).
13C NMR (CDCl3): d = 19.6 [C(CH3)3], 27.3 [C(CH3)3], 29.6 (C7),
46.5 (C4), 54.7 (CH2Ph), 63.3 (C3), 66.0 (C1), 66.1 (CH2OSi), 68.3
(C5), 73.6 (C6), 127.7, 128.7, 128.6, 128.7, 129.3, 130.6, 130.7,
136.4, 136.5 (arom CH), 133.9, 133.7 (2 Si-C1Ph), 140.0 (C1Bn).
Anal. Calcd for C30H35NOSi: C, 79.42; H, 7.78; N, 3.09. Found C
79.33; H, 7.65; N, 3.21.
(+)-(1S,3S,4S,5S,6R)-3-(Hydroxymethyl)-2-[(1R)-1-phenyleth-
yl]-2-azabicyclo[2.2.1]heptane-5,6-diol (7b); Typical Procedure
To a soln of 5b (0.39 g, 1.71 mmol) in t-BuOH (5 mL), THF (5 mL),
and H2O (1 mL), kept under magnetic stirring for 30 min, was slow-
ly added NMO (0.27 g, 2.30 mmol) and OsO4 (5 mM in dioxane–
H2O (3:1); 5.4 mL, 0.015 equiv). After stirring the mixture at r.t. for
18 h, EtOAc (20 mL) and H2O (20 mL) were added and the resulting
mixture was filtered through a pad of Celite and silica gel. The
aqueous layer was extracted with EtOAc (2 × 20 mL); the combined
organic phases were washed with H2O (50 mL) and brine (60 mL)
and dried (Na2SO4). Removal of the solvent under reduced pressure
yielded a brown oil, that was subjected to column chromatography
(silica gel, CH2Cl2–MeOH, 9:2) affording 7b (0.35 g, 78%) as a yel-
low oil; Rf = 0.5.
Anal. Calcd for C30H37NO3Si: C, 73.88; H, 7.65; N, 2.87. Found: C,
74.03; H, 7.44; N, 2.99.
(–)-(1S,3S,4S,5S,6R)-3-[(tert-Butyldiphenylsiloxy)methyl]-2-
[(1R)-1-phenylethyl]-2-azabicyclo[2.2.1]heptane-5,6-diol (8b)
Following the typical procedure for 7b using 6b. Flash chromatog-
raphy of the crude product (hexane–EtOAc, 1:1) afforded pure 8b
(81%); Rf = 0.5.
[a]D25 –1.1 (c 1, CHCl3).
IR (NaCl): 3363 (OH), 2932, 2750, 1460, 1420, 1369, 1102, 750
cm–1.
1H NMR (CDCl3): d = 0.88 [s, 9 H, C(CH3)3], 1.34 (d, J = 6.6 Hz, 3
H, CHCH3), 1.49 (d, J = 10.1 Hz, 1 H, H7syn), 1.69 (d, J = 10.1 Hz,
1 H, H7anti), 2.14 (dd, J = 9.9, 4.2 Hz, 1 H, CHaHOSi), 2.47 (s, 1 H,
[a]D25 +6.5 (c 1, CHCl3).
Synthesis 2008, No. 6, 971–977 © Thieme Stuttgart · New York