ConVergent Approach to Coenzyme Q
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11671
3H), 1.32 (s, 3H); 13C NMR (100 MHz) δ 146.2, 144.4, 135.9, 135.7,
135.0, 131.2, 129.5, 128.5, 127.3, 124.1, 123.4, 110.5, 56.1, 39.7, 26.8,
26.6, 26.2, 25.7, 21.6, 17.7, 16.2, 16.0; LREIMS m/z 428(M+, 2%),
157(13), 69(10); HREIMS m/z calcd for C27H40O2S, M+ 428.2749,
found 428.2758.
Representative Desilylation of an Acetylenic Silane; (E,E,E,E)-
6,10,14,18,22-Pentamethyltricosa-5,9,13,17,21-pentaen-1-yne (32).
TBAF (18.75 mL of a 1 M solution in THF, 18.75 mmol) was added
dropwise to a solution of TMS-protected alkyne 31 (5.67 g, 12.5 mmol)
in THF (40 mL) at 0 °C. The mixture was stirred for 30 min and then
poured into ice-cold water and extracted with Et2O (3×). The combined
organic layer was washed with water and brine, dried (anhydrous
MgSO4), and evaporated in vacuo. Silica gel column chromatography
of the residue (3% EtOAc/petroleum ether) afforded the alkyne (4.58
g, 96%) as a pale yellow oil; Rf ) 0.23 (hexanes); IR 3312, 2965,
2922, 2849, 2114, 1446, 1383, 838; 1H NMR (500 MHz) δ 5.19-5.17
(m, 1H), 5.13-5.08 (m, 4H), 2.25-2.18 (m, 4H), 2.11-2.04 (m, 8H),
2.02-1.97 (m, 8H), 1.94 (t, J ) 2.5 Hz, 1H), 1.68 (d, J ) 1.5 Hz,
3H), 1.62 (s, 3H), 1.60 (s, 12H); 13C NMR (125 MHz) δ 136.7, 135.0,
134.8, 134.8, 131.2, 124.4, 124.2, 124.0, 122.4, 84.5, 68.1, 39.7, 39.6,
27.2, 26.7, 26.7, 26.6, 26.5, 25.7, 18.9, 17.6, 16.1, 16.0, 16.0, 16.0;
HREIMS m/z calcd for C28H44, M+ 380.3443, found 380.3442.
Representative Alkylation of an Allylic Sulfone; (E,E,E,E)-6,10,
14,18,22-Pentamethyl-8-(p-toluenesulfonyl)-1-trimethylsilyltricosa-
5,9,13,17,21-pentaen-1-yne (30). n-BuLi (4.20 mL of a 2.4 M solution
in hexanes, 10.0 mmol) was added dropwise to a solution of ger-
anylgeranyl sulfone 29 (4.28 g, 10.0 mmol) in dry THF (40 mL) at
-78 °C. The mixture was stirred at this temperature for 45 min. A
solution of allylic chloride 25 (2.11 g, 9.83 mmol) in dry THF (15
mL) was pre-cooled to -78 °C and added dropwise via dry ice-cooled
cannula over 5-10 min. The reaction mixture was stirred for 30 min
at this temperature, allowed to warm to room temperature, and then
stirred for a further 3 h, after which time TLC indicated complete
disappearance of the starting material. The mixture was quenched at 0
°C with saturated aqueous ammonium chloride and extracted with Et2O.
The organic layer was washed with water and brine, dried (anhydrous
MgSO4), and evaporated in vacuo. Silica gel column chromatography
(10% EtOAc/petroleum ether) afforded the coupled sulfone (5.45 g,
90%); Rf ) 0.57 (10% EtOAc/petroleum ether); IR 2969, 2921, 2860,
(E,E,E,E)-3,7,11,15,19-Pentamethyl-1-(p-toluenesulfonyl)eicosa-
2,6,10,14,18-pentaene (54). Dimethyl sulfide (0.3 mL, 254 mg, 4.08
mmol) was added dropwise to a solution of N-chlorosuccinimide (187
mg, 1.40 mmol) in dry CH2Cl2 (7 mL) at 0 °C and the resulting white
suspension cooled to -20 °C. A solution of the allylic alcohol prepared
from reduction of 53 (200 mg, 0.56 mmol) in dry CH2Cl2 (3 mL)
previously cooled to 0 °C, was added via cannula. The mixture was
warmed to 0 °C and stirred 1.5 h after which TLC showed complete
disappearance of the starting material. The mixture was poured onto
ice-cold brine and extracted with CH2Cl2 (3×), and the collected organic
phases were washed (ice-cold brine), dried (anhydrous MgSO4), and
evaporated in vacuo. The residue was mixed with sodium p-toluene-
sulfinate (500 mg, 2.81 mmol) and DMF (10 mL) and stirred overnight.
The suspension was poured into water and extracted with EtOAc (3×).
The combined organic phases were washed (water, brine), dried
(anhydrous MgSO4), and evaporated in vacuo. Silica gel chromatog-
raphy of the residue (10% EtOAc/petroleum ether) afforded the sulfone
(225 mg, 81%); Rf ) 0.84 (20% EtOAc/petroleum ether); Rf ) 0.35
(10% EtOAc/petroleum ether); Rf ) 0.13 (5% EtOAc/petroleum ether);
IR 2965, 2921, 2854, 1664, 1598, 1447, 1382, 1317, 1236, 1150, 1087,
899, 816, 745, 666; 1H NMR (400 MHz) δ 7.73, 7.32 (AA′XX′, 4H),
5.18 (tq, J ) 8 Hz, J ) 1 Hz, 1H), 5.15-5.00 (m, 4H), 3.78 (d, J )
8 Hz, 2H), 2.44 (s, 3H), 2.10-1.95 (m, 16H), 1.67 (d, J ) 1 Hz, 3H),
1.59, 1.58 (2xbr, 12H), 1.32 (d, J ) 1 Hz, 3H); 13C NMR (100 MHz)
δ 146.1, 144.3, 135.8, 135.6, 134.9, 134.8, 131.1, 129.5, 128.5, 124.3,
124.2, 124.0, 123.3, 110.4, 56.1, 39.6, 26.7, 26.6, 26.1, 25.6, 21.6, 21.5,
17.6, 16.2, 15.9; LREIMS m/z 496(M+, 0.88), 427(3), 217(2), 203(7),
157(16), 135(30), 81(65), 69(100); HREIMS m/z calcd for C32H48O2S,
M+ 496.3375; found 496.3370.
1
2174, 1446, 1313, 1302, 1250, 1145, 1087, 912, 843, 734, 665; H
NMR (500 MHz) δ 7.71 (d, J ) 8 Hz, 2H), 7.29 (d, J ) 8 Hz, 2H),
5.19-5.15 (m, 1H), 5.11-5.08 (m, 2H), 5.05-5.04 (m, 1H), 4.89 (d,
J ) 10 Hz, 1H), 3.86 (dt, J ) 11.5 Hz, J ) 3.5 Hz, 1H), 2.87 (d, J )
11.5 Hz, 1H), 2.43 (s, 3 H), 2.26 (dd, J ) 13 Hz, J ) 11 Hz, 1H),
2.16-2.15 (m, 4H), 2.08-2.04 (m, 4H), 1.99-1.93 (m, 8H), 1.68 (d,
J ) 1 Hz, 3H), 1.60 (s, 6H), 1.59 (d, J ) 1 Hz, 3H), 1.54 (s, 3H), 1.21
(d, J ) 1.5 Hz, 3H), 0.13 (s, 9H); 13C NMR (100 MHz) δ 144.9, 144.1,
135.5, 135.0, 134.9, 131.5, 131.1, 129.2, 129.2, 126.4, 124.3, 124.0,
123.4, 117.2, 106.8, 84.4, 63.4, 39.7, 39.6, 37.4, 27.4, 26.7, 26.5, 26.3,
25.6, 21.5, 20.0, 16.4, 16.0, 15.9, 0.1; LREIMS m/z 606(M+, 5%),
451(M+ - SO2Ar, 100), 377(C28H41+, 29); HREIMS m/z calcd for
C38H58SO2Si, M+ 606.3927, found 606.3928.
Representative Palladium-Catalyzed Desulfonylation; (E,E,E,E)-
6,10,14,18,22-Pentamethyl-1-trimethylsilyltricosa-5,9,13,17,21-pen-
taen-1-yne (31). A mixture of sulfone 30 (2.62 g, 4.32 mmol) and
Pd(dppp)Cl2 (0.127 g, 0.216 mmol) in dry THF (30 mL) was cooled
to 0 °C. LiEt3BH (8.46 mL, 1 M solution in THF, 8.36 mmol) was
added dropwise over 10 min, whereupon the solution became clear
and brown. The mixture was allowed to warm to room temperature
over 3 h and then stirred for a further 6 h, after which time a brown
precipitate had formed. TLC indicated complete disappearance of the
starting material. NaOH (40 mL of a 3 M aqueous solution) was added
and the mixture was stirred for 45 min before being poured into
saturated aqueous KCN. The mixture was extracted with Et2O (3×)
and the organic layers combined and washed with water and brine,
dried over anhydrous Na2SO4, and evaporated in vacuo. Silica gel
chromatography (5% EtOAc/petroleum ether) afforded the alkyne (1.89
g, 97%); Rf ) 0.24 (petroleum ether); IR 2963, 2920, 2855, 2175, 1447,
1383, 1249, 842, 760; 1H NMR (500 MHz) δ 5.17-5.14 (m, 1H), 5.30-
5.08 (m, 4H), 2.23-2.22 (m, 4H), 2.09-2.04 (m, 8H), 2.01-1.97 (m,
8H), 1.68 (s, 3H), 1.62 (s, J ) 1.5 Hz, 3H), 1.60 (s, 12H), 0.14 (s,
9H); 13C NMR (125 MHz) δ 136.6, 135.0, 134.9, 134.8, 131.2, 124.4,
124.3, 124.2, 124.1, 122.5, 107.4, 84.2, 39.7, 39.7, 39.7, 27.4, 26.8,
26.7, 26.7, 26.6, 25.7, 20.3, 17.7, 16.2, 16.0, 16.0, 0.1; LREIMS m/z
452(M+, 1%), 73(70), 69(100); HREIMS m/z calcd for C31H52Si, M+
452.3838, found 452.3840.
E- and Z-2-Methyl-7-trimethylsilyl-2-buten-6-yn-1-ol (14, R )
TMS). n-BuLi (14.7 mL, 2.45 M in hexanes, 36 mmol) was added
dropwise to dry THF (30 mL) at -78 °C. After a few minutes, this
mixture was added via a dry ice-cooled cannula to a solution of
1-trimethylsilylpropyne 9 (5.9 mL, 40 mmol) in dry THF (30 mL) at
-78 °C. The mixture was stirred for 1 h at this temperature and then
for 30 min at -20 °C before being re-cooled to -78 °C. Zinc chloride
(36 mL, 0.5 M in THF, 18 mmol) was added dropwise, and the mixture
was warmed to 0 °C and allowed to stir for 30 min before being cooled
to -78 °C. A solution of CuCN (1.62 g, 18 mmol) and LiCl (1.53 g,
36 mmol) in dry THF (30 mL) was then added dropwise via cannula
over 10 min. The cooling bath was removed, and the mixture was
allowed to warm to 0 °C and stir further for 20 min at that temperature.
A solution of 2-methyl-2-vinyloxirane (1.77 mL, 18 mmol) in THF
(10 mL), cooled to 0 °C, was added via cannula over 10 min and the
mixture stirred for a further 3 h. The reaction was quenched with
saturated aqueous ammonium chloride and then extracted with Et2O