¨
O. Sesenoglu et al. / Tetrahedron: Asymmetry 16 (2005) 995–1015
1009
dd, J = 4.3, 14.0), 2.04 (1H, m), 2.14 (3H, s), 2.49 (1H,
m), 2.51 (1H, dd, J = 6.50, 10.6), 3.08 (1H, d, J = 3.5,
H-5), 3.08 (1H, d, J = 10.1, H-10), 6.48 (1H, dd,
J = 1.7, 4.1, H-2), 6.60 (1H, d, J = 3.5, H-4), 7.42 (1H,
t, J = 7.8), 7.48 (1H, t, J = 7.8), 7.59 (1H, dt, J = 7.8,
8.0), 7.98 (1H, d, J = 8.0), 8.12 (1H, d, J = 8.0). 13C
NMR (150 MHz): 20.6, 21.2, 22.8, 28.8 (3C), 30.7,
35.3, 37.7, 45.5, 54.0, 73.9, 79.8, 89.1, 92.6, 128.4 (2C),
129.0, 129.8, 130.1, 133.5, 164.6, 169.4, 209.3. CIMS:
450 ([M+NH4]+, 100), 390 (8), 373 (19), 328 (98), 311
(31), 105 (53). Anal. Calcd for C24H32O7: C, 66.65; H,
7.46. Found: C, 66.58; H 7.41.
9b}: Me-10a, H-5, H-9a (NOE gem). 13C NMR
(75 MHz): 16.4 (MeCH), 16.7 (MeCH), 20.1 (Me-10a),
20.5 (CH3CO), 20.6 (CH3CO), 22.9 (C-8), 28.7 (tBu),
30.5 (C-9), 35.0 (C-1), 37.6 (Cq-10a), 45.5 (C-7), 53.2
(C-5), 68.3 (C H), 68.4 (C H), 73.9 (Cq–tBu), 80.0 (C-
*
*
10), 88.8 (C-4), 93.1 (C-2), 168.8 (2·C, MeCO), 170.2
(MeCO), 170.4 (MeCO), 208.7 (C-6). ESIMS (MeOH):
537 ([MNa]+, 100), 553 ([MK]+, 12), 1051 ([2MNa]+,
20).
4.4.3.2. (20S)-Acetoxy-propionic acid (1R)-[(20S)-acet-
oxy-propionyloxy]-(5R)-tert-butoxy-(4aR)-methyl-9-oxo-
deca hydro-cyclohepta[c]pyran-(3R)-yl ester d-ent-
20
4.4.2.3. Benzoic acid (1S)-acetoxy-(5S)-tert-butoxy-
(4aS)-methyl-9-oxo-decahydro-cyclohepta[c]pyran-(3S)-yl
16. ½aꢁ ¼ ꢀ4 (c 1.20, CHCl3). IR (film): 2975, 2941,
D
1747, 1716, 1583, 1455, 1372, 1344, 1303, 1237, 1189,
20
D
1
ester 18. ½aꢁ ¼ ꢀ49 (c 0.75, CHCl3), IR (film): 2977,
1174, 1127, 1097, 1049, 994, 941, 736 cmꢀ1. H NMR
2936, 1757, 1722, 1606, 1455, 1396, 1367, 1269, 1228,
1187, 1170, 1112, 1089, 1065, 1048, 1025, 996, 943,
(600 MHz): 1.13 (9H, s), 1.21–2.59 (9H, m), 1.29 (3H,
s), 1.49 (3H, d, J = 6.9), 1.53 (3H, d, J = 6.9), 2.09
(3H, s), 2.13 (3H, s), 2.96 (1H, t, J = 3.4), 5.07 (1H, q,
J = 6.9), 5.18 (1H, q, J = 6.9), 6.33 (1H, d, J = 3.2),
6.47 (1H, br s). 13C NMR (75 MHz): 16.7, 16.8, 20.5
(3C), 23.1, 28.8 (3C), 30.5, 35.1, 37.4, 45.6, 53.1, 68.5
(2C), 74.0, 80.2, 89.2, 93.7, 168.6, 168.9, 170.1, 170.5,
208.7. CIMS: 532 ([M+NH4]+, 97), 460 (47), 400 (100),
383 (6).
711 cmꢀ1 1H NMR (600 MHz): 1.15 (9H, s), 1.42
.
(3H, s), 1.55–2.11 (6H, m), 2.08 (3H, s), 2.40–2.60
(2H, m), 3.01 (1H, d, J = 3.4, H-5), 3.07 (1H, d,
J = 8.9, H-10), 6.46 (1H, d, J = 3.4, H-4), 6.67 (1H,
dd, J = 1.8, 4.1, H-2), 7.44–7.49 (2H, m), 7.56–7.63
(1H, m), 8.04–8.11 (2H, m). 13C NMR (150 MHz) 20.9
(2C), 22.8, 28.8 (3C), 30.7, 35.4, 37.5, 45.5, 53.7, 73.9,
79.8, 88.6, 93.1, 128.4 (2C), 128.9, 129.7 (2C), 133.2,
164.7, 168.9, 209.0. CIMS: 450 ([M+NH4]+, 75), 390
(100), 373 (26), 328 (27), 311 (27), 105 (19).
4.5. One pot fused to bridged ring system interchange:
preparation of bicyclo[3.2.2]nonane derivatives 20 and 21
4.4.3. Domino reactions in chiral solvent. A dry flask
was charged with 700 mg (2.92 mmol) of ( )-2 and
2.7 g (6.1 mmol) of Pb(OAc)4, vacuumed, flushed with
argon and then again vacuumed for 1 h. (S)-2-Acetoxy-
propionic acid (10 mL) was then added at room temper-
ature and stirring continued for 30 min under argon and
an additional 30 min under reduced pressure (ca.
4 mmHg). The reaction mixture was then diluted with
ether (200 mL), washed with water (3 · 20 mL), 6 N
NaOH (3 · 10 mL), and water again (2 · 20 mL). The
organic layer was dried over magnesium sulfate and
the solvent evaporated under reduced pressure. The res-
idue was purified on silica gel (toluene–ether 4:1) to yield
536 mg of 16 (36%), 506 mg of d-ent-16 (34%) along with
62 mg of lactone 9 (8%).
To a stirred solution of 16 (1.0 g, 2.7 mmol) in a mixture
of methanol (40 mL) and water (5 mL), was added
potassium carbonate (2.1 g, 15 mmol). The resulting
mixture was stirred at room temperature for 15 h, di-
luted with water, and extracted with methylene chloride.
Following usual work up the residue was purified by
flash chromatography on silica gel affording 550 mg
(2.29 mmol, 85%) of a diastereomeric mixture of 20
and 21 in a nearly 1:1 ratio. Elution with ethyl ace-
tate–heptane–methanol (1:1:0.01) allowed separation;
higher eluting isomer (2S)-tert-butoxy-(9R)-a-hydroxy-
20
D
(1S)-methyl-bicyclo[3.2.2]nonane-6-one
21:
½aꢁ ¼
þ70 (c 1.12, CHCl3). IR (film): 3422, 2971, 2934, 2871,
1705, 1458, 1387, 1364, 1189, 1057, 1024, 991 cmꢀ1
.
1H NMR (400 MHz): 1.02 (3H, s, Me-1), 1.15 (9H, s,
tBu), 1.45 (1H, m, H-3aax), 1.55–1.75 (2H, m, H-4),
1.66 (1H, dd, J = 3.9, 14.7, H8a), 1.68 (1H, d,
J = 18.7, H-7b), 1.93 (1H, m, H-4), 2.06 (1H, dd,
J = 9.5, 14.7, H-8b), 2.07 (1H, m, H-4), 2.60 (1H, m,
H-5), 2.63 (1H, dd, J = 2.6, 18.7, H-7a), 3.44 (1H, t,
J = 5.7, H-2), 4.20 (1H, ddd, J = 3.9, 6.7, 9.5, H-9).
Diagnostic NOEs: {Me-1}: H-8b, H-7a, H-7b, H-2;
{H-9}: H-5, H8b; {H-2}: H-8a; {H-5}: H-9, H-4, 40;
{H-8a}: H-2. 13C NMR (75 MHz): 19.8 (CH2), 29.1
(tBu), 29.3 (Me-1), 30.4 (CH2), 37.6 (Cq-1), 41.6 (C-8),
45.2 (C-7), 54.1 (C-5), 66.6 (C-9), 73.2 (Cq–tBu), 77.6
(C-2), 214.6 (C-6). EIMS: 240 (M+Æ, 89), 184 (100), 166
(34), 57 (89). HREIMS: calcd for C14H24O3: m/z
240.1725, found: 240.1729.
4.4.3.1. (20S)-Acetoxy-propionic acid (1S)-[(20S)-acet-
oxy-propionyloxy]-(5S)-tert-butoxy-(4aS)-methyl-9-oxo-
20
D
deca hydro-cyclohepta[c]pyran-(3S)-yl ester 16. ½aꢁ
¼
ꢀ80 (c 1.70, CHCl3). IR (film): 2982, 2943, 1746, 1456,
1371, 1345, 1312, 1246, 1187, 1127, 1101, 1062, 1049,
989, 943, 910, 737 cmꢀ1 1H NMR (600 MHz): 1.14
.
(9H, s, tBu), 1.30 (3H, s, Me-10a), 1.48 (3H, d,
J = 7.2), 1.55 (3H, d, J = 6.7), 1.62 (1H, m, H-8a),
1.72 (1H, dt, J = 4.3, 14.9, H-9a), 1.84 (1H, dd,
J = 1.4, 14.8, H-1b), 1.88 (1H, dd, J = 4.2, 14.8, H-1a),
1.93 (1H, m, H-8b), 2.00 (1H, dq, J = 2.6, 14.9, H-9b),
2.08 (3H, s, MeCO), 2.11 (3H, s, MeCO), 2.42 (1H, m,
H-7), 2.54 (1H, m, H-70), 2.93 (1H, d, J = 3.4, H-5),
2.95 (1H, d, J = 8.9, H-10), 4.92 (1H, q, J = 7.2), 5.08
(1H, q, J = 7.2), 6.30 (1H, d, J = 3.4, H-4), 6.47 (1H,
dd, J = 1.4, 3.8, H-2). Diagnostic NOEs: {Me-10a}: H-
4, H-1beq, H-5, H-9bax; {H-4}: H-5, Me-10a; {H-10}:
H1aax, H-8a; {H-5}: H-4, H7b, H-9b, Me-10a; {H-
Lower eluting isomer (2S)-tert-butoxy-(9S)-b-hydroxy-
(1S)-methyl-bicyclo[3.2.2]nonane-6-one 20: mp 76–
20
D
(film): 3422, 2957, 2871, 1705, 1458, 1392, 1361, 1235,
78 ꢁC (ether–heptane). ½aꢁ ¼ þ92 (c 1.10, CHCl3). IR