Eunho Choi et al.
COMMUNICATIONS
1H), 9.38 (s, 1H) ppm; 13C NMR: d=9.2, 9.2, 16.2, 16.4,
26.7, 26.9, 27.1, 37.9, 38.0, 64.4, 118.0, 119.7, 128.8, 128.9,
133.5, 137.2, 137.9, 139.4, 139.6, 143.8, 152.8, 153.7, 194.8,
applied to the expeditious assembly of other carote-
noid natural products.
195.0; IR (KBr): n=2944, 1686, 1447, 1303, 1145, 1084 cmÀ1
;
HR-MS (FAB+): m/z=443.2248, calcd. for C26H35O4S:
Experimental Section
443.2256.
1
Data for 7: H NMR: d=1.16 (d, J=1.3 Hz, 3H), 1.59 (s,
General Experimental Methods
3H), 1.66 (s, 3H), 1.68 (s, 3H), 1.72 (s, 3H), 1.94 (br s, 4H),
2.15 (dd, J=7.7, 6.8 Hz, 2H), 2.32–2.48 (m, 3H), 2.83–2.96
(m, 1H), 3.73 (ddd, J=10.5, 10.3, 3.5 Hz, 1H), 4.93–5.14 (m,
3H), 6.42 (t, J=5.5 Hz, 1H), 7.46–7.70 (m, 3H), 7.76–7.92
(m, 2H), 9.35 (s, 1H).
1H (300 MHz or 400 MHz) and 13C NMR (75.5 MHz or
100 MHz) spectra were recorded in CDCl3 with Me4Si (d=
0 ppm) as an internal standard. Solvents for extraction and
chromatography were reagent grade and used as received.
Column chromatography was performed by the method of
Still using silica gel 60, 230–400 mesh ASTM supplied by
Merck. Solvents used as reaction media were dried over
pre-dried molecular sieve (5 ꢂ) in a microwave oven. All re-
actions were performed under dry argon in oven-dried glass-
ware, except for those reactions with H2O as a solvent,
which were run in air.
Coupling Reaction: 8,16,25-Tris(benzenesulfonyl)-
2,6,10,14,19,23,27,31-octamethyldotriaconta-
2,6,10,14,18,22,26,30-octaene-9,24-diol (2a)
To a stirred solution of geranyl sulfone 3 (2.41 g, 8.65 mmol,
2.2 equivs.) in THF (30 mL) at À788C was added 1.6m solu-
tion of n-BuLi in hexane (6.14 mL, 9.83 mmol, 2.5 equivs.).
The resulting orange solution was stirred at that tempera-
ture for 1 h, and a solution of the dialdehyde 6 (1.74 g,
3.93 mmol, 1 equiv.) in THF (10 mL) was added for 5 min.
The resulting mixture was stirred at À788C for 1 h, and
quenched with 1M HCl solution (10 mL). The mixture was
warmed to room temperature, extracted with EtOAc
(30 mLꢃ2), washed with 1M HCl solution (20 mLꢃ2),
dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure. The crude product was purified by
silica gel column chromatography to give 2a; yield: 3.65 g
Double Allylic Oxidation: 8-Benzenesulfonyl-
2,6,11,15-tetramethylhexadeca-2,6,10,14-tetraenedial
(6)
To
a stirred suspension of SeO2 (3.48 g, 31.34 mmol,
2 equivs.) and salicylic acid (2.20 g, 15.67 mmol, 1 equiv.) in
MeCN (50 mL) at 08C was added a 3.0M solution of TBHP
in toluene (31.3 mL, 94.02 mmol, 6 equivs.). The mixture
was stirred at that temperature for 1.5 h, and a solution of 5
(6.50 g, 15.67 mmol, 1 equiv.) in MeCN (10 mL) was slowly
added for 10 min. The reaction mixture was stirred at 08C
for 3 h, and diluted with EtOAc (50 mL). The EtOAc solu-
tion was washed with 10% NaOH solution (20 mLꢃ3) and
then saturated Na2S2O3 solution (20 mLꢃ3), dried over an-
hydrous Na2SO4, filtered, and concentrated under reduced
pressure to give the crude allylic oxidation product; yield:
7.50 g.
1
(3.66 mmol, 93%). H NMR: d=1.07 (s, 3H), 1.12 (s, 3H),
1.19 (d, J=1.5 Hz, 3H), 1.45 (s, 3H), 1.47 (s, 3H), 1.56 (s,
6H), 1.58 (s, 3H), 1.67 (s, 3H), 1.68 (s, 3H), 1.80–2.07 (m,
16H), 2.24–2.40 (m, 1H), 2.77–2.90 (m, 1H), 3.71 (br t, J=
9.5 Hz, 1H), 3.93 (dd, J=9.1, 7.0 Hz, 1H), 3.96 (dd, J=9.1,
6.6 Hz, 1H), 4.59 (d, J=9.2 Hz, 1H), 4.60 (d, J=8.9 Hz,
1H), 4.68 (d, J=10.1 Hz, 1H), 4.72 (d, J=9.0 Hz, 1H),
4.90–5.05 (m, 5H), 5.30–5.43 (m, 2H), 7.45–7.68 (m, 9H),
7.78–7.90 (m, 6H); 13C NMR: d=10.5, 10.5, 13.0, 15.8, 15.9,
16.2, 16.4, 16.5, 17.6, 25.7, 25.7, 25.8, 26.0, 26.2, 26.2, 26.5,
39.0, 39.5, 39.8, 64.7, 67.7, 68.4, 72.4, 76.4, 112.0, 114.2, 117.1,
119.0, 123.3, 123.6, 128.7, 128.7, 128.8, 129.0, 129.1, 129.2,
129.3, 129.5, 130.1, 131.9, 132.0, 132.0, 133.1, 133.4, 133.6,
133.7, 133.9, 137.4, 138.1, 144.4, 144.5, 144.7; IR (KBr): n=
3497, 2930, 1447, 1300, 1143, 1083 cmÀ1; HR-MS (FAB+):
m/z=697.4645, calcd. for C46H65O3S [C58H79O8S3À2
Swern Oxidation
To a stirred solution of DMSO (5.77 g, 73.87 mmol) in
CH2Cl2 (50 mL) at À788C was added oxalyl chloride
(3.28 mL, 36.93 mmol). The mixture was stirred for 5 min,
and a solution of the above allylic oxidation product (7.50 g)
in CH2Cl2 (10 mL) was added. The resulting mixture was
stirred at À788C for 15 min, and Et3N (23 mL, 167.9 mmol)
was added. Stirring for 5 min at that temperature, the mix-
ture was then warmed to room temperature. The reaction
mixture was diluted with CH2Cl2 (50 mL), washed with 1M
HCl solution (20 mLꢃ3) and then H2O (20 mLꢃ2), dried
over anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The crude product was purified by silica gel
column chromatography to give the dialdehyde 6 (yield:
4.10 g, 9.26 mmol; 60%), together with the mono-aldehyde 7
(yield: 1.20 g, 2.71 mmol, 17%).
A
Double Elimination Reactions to Lycopene (1)
From 2c: To a stirred solution of 2c (0.44 g, 0.38 mmol) in
cyclohexane (20 mL) and benzene (10 mL) was added
KOMe (0.79 g, 11.3 mmol). The mixture was heated to 70~
808C for 13 h, cooled to room temperature, and 1M HCl
(20 mL) was carefully added. The reaction mixture was ex-
tracted with a 2:1 (v:v) solution (30 mL) of hexane and ben-
zene, dried over anhydrous Na2SO4, filtered, and concentrat-
ed under reduced pressure. The resulting red solid was dilut-
ed with hexane (50 mL) and washed with CH3CN (10 mLꢃ
3). The hexane layer was concentrated under reduced pres-
sure to give lycopene 1; crude yield: 0.20 g (0.37 mmol,
97%), which presumably contained a small amount of 9-(Z)
1
Data for 6: H NMR: d=1.27 (d, J=1.3 Hz, 3H), 1.63 (s,
3H), 1.72 (d, J=1.1 Hz, 3H), 1.73 (d, J=0.9 Hz, 3H), 2.15
(t, J=7.4 Hz, 4H), 2.30–2.46 (m, 5H), 2.86 (ddd, J=14.4,
7.2, 3.7 Hz, 1H), 3.77 (ddd, J=10.3, 10.3, 3.7 Hz, 1H), 5.02
(dt, Jd =1.1, Jt =7.4 Hz, 1H), 5.06 (dd, J=10.3, 1.2 Hz, 1H),
6.39 (dt, Jd =1.3, Jt =7.0 Hz, 1H), 6.41 (dt, Jd =1.3, Jt =
7.2 Hz, 1H), 7.48–7.68 (m, 3H), 7.81–7.87 (m, 2H), 9.36 (s,
368
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 365 – 369