Total Synthesis of (+)-Muconin
as a single isomer and 12 along with inseparable minor
isomers (0.475 g, 59%) as a colorless oil. Alcoh ol 11: [R]D +10.1
(c 0.57, CHCl3); IR (neat) νmax 3580, 3468, 2928 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.36-7.24 (m, 5H), 4.52 (s, 2H), 3.92-
3.77 (m, 3H), 3.55 (m, 1H), 3.41 (m, 1H), 3.39 (dd, 1H, J )
9.8, 5.6 Hz), 3.36 (dd, 1H, J ) 9.5, 5.4 Hz), 3.30 (ddd, 1H, J )
11.2, 5.4, 1.7 Hz), 3.16 (ddd, 1H, J ) 11.2, 6.8, 1.5 Hz), 1.93-
1.83 (m, 3H), 1.73-1.19 (m, 43H), 0.92-0.85 (m, 21H), 0.88
(m, 21H), 0.11 (s, 3H), 0.07 (s, 3H), 0.055 (s, 3H), 0.047 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 138.5, 128.2, 127.5, 127.3,
82.7, 81.2, 80.8, 80.2, 75.3, 74.9, 74.2, 73.3, 71.6, 34.8, 33.0,
32.7, 32.0, 29.9, 29.8, 29.73, 29.70, 29.67, 29.63, 29.4, 28.2, 27.9,
27.3, 27.2, 26.1, 26.0, 25.6, 25.5, 25.3, 23.1, 22.7, 18.4, 18.3,
14.2, -3.9, -4.2, -4.6, -4.7; HRMS (FAB) calcd for C51H97O6
Si2 (MH+) 861.6827, found 861.6830. Alcoh ol 12 (+ in sep a -
mmol) in DMF (10 mL) at room temperature were added
imidazole (0.095 g, 1.40 mmol) and TBSCl (0.106 g, 0.70 mmol).
After 10 h of stirring, the mixture was extracted with Et2O,
washed with H2O, dried over MgSO4, and concentrated in
vacuo. The residue was purified by silica gel chromatography
(AcOEt/hexane 1:30) to afford TBS ether 13 (0.56 g, 98%) as a
colorless oil. [R]D +2.6 (c 1.44, CHCl3); IR (neat) νmax 2928,
1
1464, 1252, 1092 cm-1; H NMR (400 MHz, CDCl3) δ 7.36-
7.24 (m, 5H), 4.52 (s, 2H), 3.92-3.77 (m, 3H), 3.63 (m, 1H),
3.56 (m, 1H), 3.42-3.24 (m, 4H), 1.92-1.18 (m, 46H), 0.92-
0.85 (m, 30H), 0.09 (s, 3H), 0.06-0.01 (m, 15H); 13C NMR (100
MHz, CDCl3) δ 138.5, 128.2, 127.5, 127.3, 82.4, 81.1, 80.7, 80.2,
75.2, 74.9, 74.4, 73.3, 71.6, 34.8, 32.8, 32.0, 31.9, 30.0, 29.90,
29.88, 29.75, 29.71, 29.69, 29.4, 27.9, 27.7, 27.0, 26.1, 26.02,
25.99, 25.8, 25.3, 25.1, 23.4, 22.8, 18.4, 18.2, 14.2, -4.0, -4.15,
-4.24, -4.5, -4.6, -4.7; HRMS (FAB) calcd for C57H111O6 Si3
(MH+) 975.7692, found 975.7685.
1
r a ble m in or isom er s): H NMR (300 MHz, CDCl3) δ 7.35-
7.24 (m, 5H), 4.52 (s, 2H), 4.07-3.27 (m, 7H), 3.39 (dd, 1H, J
) 9.5, 5.5 Hz), 3.35 (dd, 1H, J ) 9.7, 5.5 Hz), 1.95-1.20 (m,
47H, including OH), 0.88 (s, 18H), 0.92-0.80 (m, 3H), 0.10-
0.02 (m, 12H).
(2R,10S)-10-[(2S,6R)-Tetr ah ydr o-6-[(2R,5R)-tetr ah ydr o-
5-[(R)-1-(ter t-bu tyld im eth ylsilyloxy)tr id ecyl]fu r a n -2-yl]-
2H-pyr an -2-yl]-2,10-bis(ter t-bu tyldim eth ylsilyloxy)decan -
1-ol (14). To a solution of 13 (0.186 g, 0.190 mmol) in AcOEt
(9 mL) was added Pd(OH)2-C (20 wt %, 19 mg) at room
temperature. After 100 min of stirring under hydrogen atmo-
sphere, the mixture was filtered through a Celite pad and then
concentrated in vacuo to give sufficiently pure alcohol 14 (0.17
g, quant.) as a colorless oil. [R]D -4.9 (c 1.07, CHCl3); IR (neat)
νmax 3479, 2928, 1462, 1254 cm-1; 1H NMR (300 MHz, CDCl3,
D2O exchange) δ 3.93-3.82 (m, 2H), 3.72 (m, 1H), 3.62 (m,
1H), 3.58-3.50 (m, 2H), 3.42 (dd, 1H, J ) 10.8, 5.3 Hz), 3.33-
3.23 (m, 2H), 1.93-1.17 (m, 46H), 0.92-0.82 (m, 30H), 0.10-
0.02 (m, 18H); 13C NMR (75 MHz, CDCl3) δ 82.4, 81.1, 80.6,
80.2, 75.2, 74.3, 73.0, 66.3, 34.0, 32.7, 31.9, 31.8, 29.9, 29.83,
29.78, 29.68, 29.64, 29.62, 29.60, 29.3, 27.8, 27.6, 27.0, 26.1,
25.9, 25.8, 25.7, 25.3, 25.0, 23.3, 22.7, 18.3, 18.2, 18.1, 14.1,
-4.1, -4.3, -4.4, -4.58, -4.63, -4.8; HRMS (FAB) calcd for
Isom er iza tion of 12 to 11. To a solution of alcohol 12 along
with minor diastereomeric alcohols (0.395 g, 0.459 mmol) in
MeCN-CH2Cl2 (2:1 v/v, 15 mL) at room temperature were
added 4AMS (0.23 g), NMO (0.081 g, 0.689 mmol), and TPAP
(8.1 mg, 0.023 mmol). After 2 h of stirring, the mixture was
concentrated in vacuo to give the residue whose purification
by silica gel chromatography (AcOEt/hexane 1:6) afforded
ketone 12a (0.349 g, quant.) as a colorless oil. Ketone 12a ,
dissolved in MeOH-THF (5:2 v/v, 14 mL), was treated with
K2CO3 (0.19 g, 1.38 mmol) at room temperature. After 5 h of
stirring, the mixture was concentrated in vacuo, extracted with
Et2O, and washed with sat. NH4Cl. The extracts were dried
over MgSO4 and concentrated in vacuo. The residue was
purified by silica gel flash chromatography (AcOEt/hexane
1:20) to afford ketone 12b (0.29 g, 73%) as a colorless oil. To
ketone 12b (0.28 g, 0.326 mmol) in CH2Cl2 (10 mL) at -78 °C
was added Zn(BH4)2 (0.14 M in hexane, 2.76 mL, 0.386 mmol).
The mixture was stirred for 15 min, then at 0 °C for 45 min,
extracted with Et2O, and washed with sat. NH4Cl and the
extracts were dried over MgSO4. Following solvent evapora-
tion, purification of the residue by silica gel flash chromatog-
raphy (AcOEt/hexane 1:10) provided alcohols 11 (0.26 g, 93%)
and 12-epi-11 (0.011 g, 4%) as a colorless oil. Keton e 12b: [R]D
-7.4 (c 1.86, CHCl3); IR (neat) νmax 2928, 1717 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.36-7.24 (m, 5H), 4.52 (s, 2H), 3.98-
3.90 (m, 2H), 3.85-3.74 (m, 2H), 3.59 (m, 1H), 3.43-3.28 (m,
3H), 2.60 (dd, 2H, J ) 7.6, 7.1 Hz), 2.00-1.20 (m, 44H), 0.93-
0.84 (m, 21H), 0.09 (s, 3H), 0.07 (s, 3H), 0.053 (s, 3H), 0.046
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 211.7, 138.4, 128.2,
127.5, 127.3, 83.1, 82.7, 81.1, 80.3, 75.1, 74.9, 73.3, 71.5, 37.8,
34.8, 32.8, 32.0, 29.9, 29.71, 29.68, 29.67, 29.57, 29.4, 28.11,
28.06, 27.7, 26.8, 26.1, 26.0, 25.7, 25.3, 23.2, 23.0, 22.7, 18.3,
18.2, 14.2, -4.0, -4.3, -4.63, -4.65; HRMS (FAB) calcd for
C
50H105O6 Si3 (MH+) 885.7223, found 885.7224.
(2R,10S)-10-[(2S,6R)-Tetr ah ydr o-6-[(2R,5R)-tetr ah ydr o-
5-[(R)-1-(ter t-bu tyld im eth ylsilyloxy)tr id ecyl]fu r a n -2-yl]-
2H -p yr a n -2-yl]-2,10-b is(ter t-b u t yld im et h ylsilyloxy)d e-
cyl Tr iflu or om eth a n esu lfon a te (15). To a solution of alcohol
14 (0.17 g, 0.19 mmol) in CH2Cl2 (8 mL) at -78 °C were added
2,6-lutidine (0.068 mL, 0.583 mmol) and Tf2O (0.039 mL, 0.232
mmol). The mixture was stirred for 5 min, then at room
temperature for 5 min, extracted with Et2O, and washed with
sat. NaHCO3. The extracts were dried over MgSO4 and
concentrated in vacuo. The residue was purified by silica gel
chromatography (AcOEt/hexane 1:30) to afford triflate 15
(0.191 g, 99%) as a colorless oil. [R]D -4.2 (c 1.09, CHCl3); IR
(neat) νmax 2930, 1418, 1211, 1148, 953 cm-1 1H NMR (300
;
MHz, CDCl3) δ 4.38 (dd, 1H, J ) 9.9, 3.9 Hz), 4.31 (dd, 1H, J
) 9.9, 6.4 Hz), 3.98-3.80 (m, 3H), 3.63 (m, 1H), 3.55 (m, 1H),
3.35-3.22 (m, 2H), 1.92-1.17 (m, 46H), 0.92-0.80 (m, 30H),
0.10-0.02 (m, 18H); 13C NMR (75 MHz, CDCl3) δ 120.8, 116.5,
82.4, 81.1, 80.6, 80.3, 79.4, 75.2, 74.3, 69.9, 33.8, 32.7, 31.9,
31.8, 29.83, 29.82, 29.69, 29.64, 29.63, 29.59, 29.5, 29.4, 27.9,
27.6, 27.0, 26.1, 25.9, 25.71, 25.67, 25.0, 24.8, 23.3, 22.7, 18.3,
18.2, 18.0, 14.1, -4.1, -4.3, -4.6, -4.73, -4.76, -4.82; HRMS
(FAB) calcd for C51H103O8F3Si3SNa (M + Na)+ 1039.6535,
found 1039.6545.
C
51H94O6 Si2 (MH+) 859.6671, found 859.6653.
(1R,9R)-10-(Ben zyloxy)-9-(ter t-bu tyld im eth ylsilyloxy)-
1-[(2S,6R)-tetr ah ydr o-6-[(2R,5R)-tetr ah ydr o-5-[(R)-1-(ter t-
bu tyl d im eth ylsilyloxy)tr id ecyl]fu r a n -2-yl]-2H-p yr a n -2-
yl]d eca n -1-ol (12-epi-11): [R]D +13.4 (c 0.69, CHCl3); IR (neat)
ν
max 3450, 2928, 1462 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.38-
7.24 (m, 5H), 4.52 (s, 2H), 3.93-3.77 (m, 3H), 3.68 (m, 1H),
3.57 (m, 1H), 3.42-3.28 (m, 4H), 1.95-1.20 (m, 46H), 0.93-
0.80 (m, 21H), 0.10 (s, 3H), 0.07 (s, 3H), 0.06 (s, 3H), 0.05 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 138.5, 128.2, 127.5, 127.3,
82.5, 81.4, 80.5, 79.9, 75.1, 74.9, 73.35, 73.28, 71.6, 34.8, 32.8,
32.0, 31.7, 29.9, 29.81, 29.76, 29.73, 29.70, 29.67, 29.62, 29.4,
28.3, 27.7, 27.4, 26.09, 26.06, 26.04, 25.97, 25.7, 25.3, 24.0, 23.0,
22.7, 18.4, 18.3, 14.2, -4.0, -4.2, -4.6, -4.7; HRMS (FAB)
calcd for C51H97O6 Si2 (MH+) 861.6827, found 861.6808.
(1S,9R)-10-(Ben zyloxy)-1-[(2S,6R)-tetr ah ydr o-6-[(2R,5R)-
tetr a h yd r o-5-[(R)-1-(ter t-bu tyld im eth ylsilyloxy)tr id ecyl]-
fu r a n -2-yl]-2H -p yr a n -2-yl]-1,9-b is(ter t-b u t yld im et h ylsi-
lyloxy)d eca n e (13). To a solution of alcohol 11 (0.50 g, 0.582
(S )-D ih y d r o -3-[(2R ,10S )-10-[(2S ,6R )-t e t r a h y d r o -6-
[(2R,5R)-tetr ah ydr o-5-[(R)-1-(ter t-bu tyldim eth ylsilyloxy)-
tr id ecyl]fu r a n -2-yl]-2H-p yr a n -2-yl]-2,10-bis(ter t-bu tyld i-
m eth ylsilyloxy)decyl]-5-m eth yl-3-(ph en ylth io)fu r an -2(3H)-
on e (17). To a solution of LiHMDS (1.0 M in THF, 0.364 mL,
0.364 mmol) in THF at -78 °C was added lactone 16 (0.076 g,
0.364 mmol) in THF (2 mL). The mixture was stirred for 10
min, then at 0 °C for 7 min, and again cooled to -78 °C. After
11 min of stirring, HMPA (1.2 mL) was added and then after
6 min, triflate 15 (0.191 g, 0.188 mmol) in THF (2.8 mL) was
added. After 10 min, the mixture was allowed to warm to 0
°C over a period of 15 min, then stirred at room temperature
for 10 min, extracted with Et2O, and washed with sat. NH4-
J . Org. Chem, Vol. 69, No. 6, 2004 1997