S. Arseniyadis et al.
FULL PAPER
solution, and worked up in the usual manner, and the residue was purified
by chromatography (eluent: heptane/EtOAc 20:1) to give 19a (5.67 g,
100%).
nÄ 3406, 2975, 2878, 1704, 1390 cmÀ1; 1H NMR (800 MHz, CDCl3): d 0.98
(s, 3H), 1.18 (s, 9H), 1.33 (dt, J 11.7, 13.8 Hz, 1H), 1.52 (dt, J 2.2,
14.5 Hz, 1H), 1.94 (dd, J 4.6, 14.5 Hz, 1H), 2.00 (d, J 19.0 Hz, 1H), 2.27
(ddt, J 1.5, 5.0, 13.8 Hz, 1H), 2.99 (dd, J 2.2, 19.0 Hz, 1H), 3.23 (dd, J
5.0, 11.2 Hz, 1H), 3.67 (ddd, J 2.1, 5.1, 12.0 Hz, 1H), 4.63 ppm (brs, 1H);
13C NMR (200 MHz, CDCl3): d 27.1, 29.0 (3C), 34.0, 34.3, 36.8, 36.9, 70.6,
5-tert-Butoxy-7-(tert-butyldimethylsilanyloxy)-4-methylbicyclo[2.2.2]oc-
tan-2-one (19a): M.p. 70 718C (heptane/diethyl ether); [a]2D0 41 (c
1.09 in chloroform); IR (film): nÄ 2929, 2857, 1728, 1462, 1387, 1372, 1361,
1256, 1168, 1095, 1052, 996, 837, 776 cmÀ1; 1H NMR (300 MHz, CDCl3): d
0.02 (s, 6H), 0.84 (s, 9H), 0.94 (s, 3H), 1.12 (s, 9H), 1.42 (d, J 14.5 Hz,
1H), 1.64 (ddd, J 2.2, 3.7, 5.9 Hz, 1H), 1.85 (ddd, J 2.9, 8.5, 14.5 Hz,
1H), 1.88 (d, J 18.0 Hz, 1H), 2.02 (ddd, J 2.5, 8.5, 11.0 Hz, 1H), 2.33 (m,
1H), 2.51 (dd, J 2.9, 18.0 Hz, 1H), 3.27 (brd, J 8.4 Hz, 1H), 4.04 ppm
(ddd, J 1.8, 4.1, 5.9 Hz, 1H); 13C NMR (75 MHz, CDCl3): d À4.9 (2C),
17.9, 23.7, 25.7 (3C), 28.6 (3C), 34.5, 36.6, 42.9, 43.8, 51.1, 69.1, 69.9, 73.2,
214.0 ppm; HRESIMS (MeOH): m/z calcd for C19H36O3NaSi: 363.2331;
found: 363.2333; elemental analysis calcd (%) for C19H36O3Si: C 67.01, H
10.65; found: C 67.03, H, 10.52.
72.3, 73.8, 78.4, 172 ppm; ESIMS (MeOH): m/z (%): 242.8 (25) [MH] ,
264.9 (100) [MNa] , 280.9 (46) [MK] ; elemental analysis calcd (%) for
C13H22O4: C 64.44, H 9.15; found: C 64.09, H 9.12.
6-tert-Butoxy-8-hydroxy-5-methyl-3-oxabicyclo[3.2.2]nonan-2-one (18a):
M.p. 94 958C (heptane); [a]2D0 62 (c 1.20 in chloroform); IR (film):
1
nÄ 3420, 2974, 2932, 1716, 1192, 1062 cmÀ1; H NMR (300 MHz, CDCl3):
d 0.90 (s, 3H), 1.16 (s, 9H), 1.70 (brs, 1H), 1.77 (dd, J 5.5, 14.7 Hz, 1H),
1.90 (ddd, J 1.3, 5.6, 15.2 Hz, 1H), 2.04 (ddd, J 1.4, 8.9, 14.7 Hz, 1H),
2.17 (ddd, J 7.7, 8.7, 15.2 Hz, 1H), 3.03 (m, 1H), 3.43 (dd, J 5.6, 7.7 Hz,
1H), 3.72 (dd, J 0.95, 11.8 Hz, 1H), 4.10 (dt, J 5.5, 8.7 Hz, 1H),
4.35 ppm (dd, J 1.4, 11.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 24.5,
28.8 (3C), 32.2, 39.2, 40.5, 49.2, 66.2, 69.1, 73,6, 73.7, 174 ppm; ESIMS
6-(tert-Butyldimethylsilanyloxy)-4-methylbicyclo[2.2.2]octan-2-one (19b):
Starting from 5b (R H) and following the procedure described above, the
TBS-protected bicyclic aldol 19b was obtained in 81% yield after
chromatography (eluent: heptane/EtOAc 20:1). [a]2D0 À3 (c 1.48 in
(MeOH): m/z (%): 243.1 (3) [MH] , 265.2 (100) [MNa] , 281.2 (18)
[MK] ; HRESIMS: m/z calcd for C13H22O4Na: 265.1416; found:
265.1425; elemental analysis calcd (%) for C13H22O4 ¥ 0.25CH2Cl2:
60.39, H 8.61; found: C 60.24, H 8.45.
C
chloroform); IR (film): nÄ 2952, 2858, 1732, 1471, 1257 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d 0.03 (s, 6H), 0.84 (s, 9H), 0.99 (s, 3H), 1.33 (m, 2H),
1.41 (d, J 13.7 Hz, 1H), 1.58 1.80 (m, 2H), 1.88 1.96 (m, 1H), 1.97 (d,
J 18.3 Hz, 1H), 2.18 (d, J 18.3 Hz, 1H), 2.36 (m, 1H), 4.12ppm (ddd,
J 1.6, 4.1, 5.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): d À5.0, À4.9, 17.8,
20.4, 25.6 (3C), 26.5, 31.1, 32.7, 44.5, 50.2, 50.3, 69.4, 214.3 ppm; ESIMS
Starting from 5b and following the procedure described above, 17b and
18b were obtained in 71% combined yield and 95:5 ratio after silica gel
chromatography (eluent: heptane/EtOAc 2:1), along with some unreacted
starting material.
(MeOH): m/z (%): 269.2 (6) [MH] , 291.1 (100) [MNa] , 307.0 (21)
8-Hydroxy-5-methyl-2-oxabicyclo[3.3.1]nonan-3-one (17b): M.p. 1348C
(heptane); [a]2D0 68 (c 0.8 in chloroform); IR (film): nÄ 3426, 2950,
2865, 1702, 1225 cmÀ1; 1H NMR (300 MHz, CDCl3): d 1.01 (s, 3H), 1.40
1.57 (m, 3H), 1.60 (dt, J 1.8, 14.1 Hz, 1H), 1.90 (ddd, J 3.0, 4.6, 14.1 Hz,
1H), 1.99 (m, 1H), 2.34 (d, J 18.6 Hz, 1H), 2.44 (dd, J 1.8, 18.6 Hz, 1H),
3.24 (brs, OH), 3.66 (m, 1H), 4.71 ppm (brs, 1H); 13C NMR (75 MHz,
CDCl3): d 26.8, 29.4, 29.7, 36.2, 36.9, 42.8, 71.1, 79.7, 171.9 ppm; ESIMS
[MK] ; elemental analysis calcd (%) for C15H28O2Si: C 67.11, H 10.51;
found: C 66.92, H 10.51.
6-tert-Butoxy-8-(tert-butyldimethylsilanyloxy)-5-methyl-2-oxabicyclo-
[3.3.1]nonan-3-one (17a-OTBS): Starting from 17a and following the
procedure described above, 17a-OTBS was obtained in 89% yield after
chromatography (eluent: heptane/EtOAc 10:1). M.p. 142 1438C (hep-
tane); [a]2D0 65 (c 1.08 in chloroform); IR (film): nÄ 2957, 2928, 2857,
1715, 1390 cmÀ1; 1H NMR (800 MHz, CDCl3): d 0.05 (2 Â s, 6H), 0.87 (s,
9H), 0.95 (s, 3H), 1.15 (s, 9H), 1.45 (m, 2H), 1.85 (dd, J 4.6, 14.4 Hz, 1H),
1.94 (dd, J 0.7, 19.0 Hz, 1H), 2.02 (dtd, J 1.2, 5.0, 14.0 Hz, 1H), 2.96 (dd,
J 2.3, 19.0 Hz, 1H), 3.19 (dd, J 4.9, 11.3 Hz, 1H), 3.68 (ddd, J 2.4, 5.0,
11.8 Hz, 1H), 4.46 ppm (brs, 1H); 13C NMR (200 MHz, CDCl3): d À4.5,
18.1, 25.7 (3C), 27.1, 28.9 (3C), 33.9, 34.4, 36.9, 71.2, 72.4, 73.6, 78.2,
(MeOH): m/z (%): 171.0 (12) [MH] , 192.8 (100) [MNa] , 208.8 (30)
[MK] , 362.8 (75) [2MNa] , 378.7 (2) [2MK] ; elemental analysis
calcd (%) for C9H14O3: C 63.51, H 8.29; found: C 63.48, H 8.51.
8-Hydroxy-5-methyl-3-oxabicyclo[3.2.2]nonan-2-one (18b): M.p. 94 958C
(diethyl ether); [a]2D0 À13 (c 0.6 in chloroform); IR (film): nÄ 3429,
2926, 2870, 1723, 1454, 1079 cmÀ1; 1H NMR (300 MHz, CDCl3): d 0.96 (s,
3H), 1.40 1.54 (m, 1H), 1.61 1.80 (m, 3H), 1.92 2.07 (m, 2H), 3.15 (td,
J 2.2, 5.6 Hz, 1H), 3.93 (dd, J 1.9, 11.6 Hz, 1H), 4.09 (dd, J 1.9,
11.6 Hz, 1H), 4.18 ppm (ddd, 3.9, 6.1, 8.2 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d 20.5, 26.7, 29.8, 34.4, 41.5, 48.3, 67.1, 79.3 (C4), 174.8 ppm (C2);
171 ppm; ESIMS (MeOH): m/z (%): 378.8 (100) [MNa] , 394.8 (21)
[MK] ; elemental analysis calcd (%) for C19H36O4Si: C 64.00, H 10.18;
found: C 63.91, H 10.21.
8-(tert-Butyldimethylsilanyloxy)-5-methyl-2-oxabicyclo[3.3.1]nonan-3-one
(17b-OTBS): Starting from 17b and following the procedure described
above, 17b-OTBS was obtained in 91% yield after chromatography
(eluent: heptane/EtOAc 20:1). M.p. 928C (heptane); [a]2D0 62 (c 0.8 in
chloroform); IR (film): nÄ 2952, 2854, 1722, 1463, 1217, 776 cmÀ1; 1H NMR
(300 MHz, CDCl3): d 0.05 (s, 6H), 0.89 (s, 9H), 1.00 (s, 3H), 1.39 1.60
(m, 4H), 1.77 (m, 1H), 1.85 (m, 1H), 2.32 (dd, J 1.0, 18.6 Hz, 1H), 2.41
(dd, J 2.0, 18.6 Hz, 1H), 3.67 (m, 1H), 4.55 ppm (brs, 1H); 13C NMR
(75 MHz, CDCl3): d À4.75, À4.59, 18.0, 25.7 (3C), 27.0, 29.5, 29.6, 36.5,
37.0, 42.8, 72.1, 79.4, 171.4 ppm; ESIMS (MeOH): m/z (%): 285.3 (40)
ESIMS (MeOH): m/z (%): 171.2 (27) [MH] , 193.1 (68) [MNa] , 209.0
(42) [MK] , 363.2 (100) [2MNa] , 379.1 (16) [2MK] ; elemental
analysis calcd (%) for C9H14O3 ¥ 0.15H2O: C 62.52, H 8.34; found: C 63.51,
H 8.29.
Starting from 19a and following the procedure described above, 20a and
24a were obtained in 56% combined yield and 30:70 ratio, along with
unreacted starting material (43%).
6-tert-Butoxy-8-(tert-butyldimethylsilanyloxy)-5-methyl-2-oxabicyclo-
[3.2.2]nonan-3-one (20a): M.p. 109 1108C (diethyl ether/heptane);
[a]2D0 9 (c 1.0 in chloroform); IR (film): nÄ 2928, 2856, 1715,
[MH] , 307.2 (100) [MNa] , 323.2 (25) [MK] ; elemental analysis
calcd (%) for C15H28O3Si ¥ 0.1CH2Cl2: C 61.91, H 9.70; found: C 61.83, H
9.95.
1082 cmÀ1
;
1H NMR: (800 MHz, CDCl3): d 0.08 (2s, 6H), 0.88 (s, 9H),
0.91 (s, 3H), 1.17 (s, 9H), 1.63 (dd, J 4.2, 14.6 Hz, 1H), 1.85 (ddd, J 2.6,
8.6, 14.6 Hz, 1H), 2.11 (m, 2H), 2.45 (dd, J 1.3, 18.3 Hz, 1H), 3.01 (dd, J
2.6, 18.3 Hz, 1H), 3.43 (ddd, J 1.0, 5.1, 7.4 Hz, 1H), 3.97 (ddd, J 4.2, 4.3,
8.6 Hz, 1H), 4.28 ppm (m, 1H); 13C NMR (200 MHz, CDCl3): d À4.8
(2C), 18.0, 25.7 (3C), 27.9, 28.8 (3C), 34.7, 36.8, 42.8, 43.7, 67.6, 70.2, 73.6,
Typical procedure for Baeyer Villiger oxidation: Sodium hydrogen
carbonate (5.3 mmol) and m-chloroperbenzoic acid (13.3 mmol) was added
to the appropriate bicyclic aldol (4.4 mmol) in methylene chloride (14 mL)
at 08C. The mixture was stirred at room temperature for approximately
17 h (TLC monitoring). The crude reaction mixture was diluted with
methylene chloride and filtered through a plug of Celite. The excess
peracid was decomposed by washing with aqueous 10% sodium sulfite.
Finally, the organic phase was washed with sat. NaHCO3, brine, dried over
MgSO4, and concentrated under reduced pressure.
77.2, 172.9 ppm; ESIMS (MeOH): m/z (%): 357.2 (54) [MH] , 379.1 (100)
[MNa] , 395.1 (19) [MK] ; elemental analysis calcd (%) for C19H36O4-
Si: C 64.00, H 10.18; found: C 63.97, H 10.22.
6-tert-Butoxy-8-(tert-butyldimethylsilanyloxy)-5-methyl-3-oxabicyclo-
[3.2.2]nonan-2-one (24a): M.p. 88 898C (heptane); [a]2D0 36 (c 1.1 in
chloroform); IR (film): nÄ 2934, 1715, 1070 cmÀ1
;
1H NMR (300 MHz,
Starting from 5a and following the procedure described above, 17a and 18a
were obtained in 66% combined yield and 94:6 ratio after silica gel
chromatography (eluent: heptane/EtOAc 1.5:1).
CDCl3): d 0.06 (s, 6H), 0.88 (s, 12H), 1.16 (s, 9H), 1.70 (dd, J 4.2,
14.6 Hz, 1H), 1.87 (m, 2H), 2.06 (m, 1H), 2.95 (m, 1H), 3.41 (dd, J 4.6,
8.3 Hz, 1H), 3.74 (d, J 11.6 Hz, 1H), 4.00 (m, 1H), 4.35 ppm (dd, J 1.7,
11.6 Hz, 1H); 13C NMR (75 MHz, CDCl3): d À4.8, À4.9, 18.0, 24.5, 25.7
(3C), 28.8 (3C), 32.3, 39.2, 42.3, 49.0, 66.7, 69.6, 73.4, 73.5, 174 ppm; ESIMS
6-tert-Butoxy-8-hydroxy-5-methyl-2-oxabicyclo[3.3.1]nonan-3-one (17a):
M.p. 170 1728C (heptane); [a]2D0 81 (c 0.8 in chloroform); IR (film):
3818
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2003, 9, 3813 3820