R. Shen et al. / Tetrahedron 67 (2011) 5610e5614
5613
Fig. 3. Partial 13C NMR spectrum (100 MHz, CDCl3) and its chemical shift data for all-E-lycopene 1.
3.1.1. Propenyl-C6-phosphonate 6. To a solution of sodium hydride
(4.4 g, 60% content, 0.11 mol) in toluene (20 mL), methylenebi-
sphosphonic acid tetraethyl ester 5(34.5 g, 0.12mol) in toluene (60mL)
was added dropwise at 10e15 ꢀC over 30 min under a nitrogen at-
mosphere, and the resulting mixture was then stirred for 30 min. Then
4,4-dimethoxy-3-methylbutanal 4 (14.4 g, 0.1 mol) in toluene (40 mL)
was added dropwise at 10e15 ꢀC over 30 min, and the mixture was
stirred for 30 min. Then water (40 mL) was added and stirred for an-
other 10 min. The organic layer was washed with brine (10%, 40 mL),
then dried over anhydrous MgSO4, and evaporated in vacuo to leave
26.2 g of crude propenyl-C6-phosphonate 6 as a colorless liquid (GC
content 92.2%, yield 86.9%. bp about 107e111ꢀC/1mmHg). IR nmax
(neat) 1631, 1246, 1053, 1025, 967, 829 cmꢁ1; GCeMS (m/z): 279, 265,
249, 220, 205,195,177,163,149,121,111, 95, 81, 75 (100%), 67, 47, 29; 1H
1.75 (s, 3H, ]CCH3); 2.04e2.18 (m, 4H, CH2CH2); 2.93e2.97 (m, 1H,
CHCH3); 3.378, 3.381 (s, s, 6H, CH(OCH3)2); 4.12e4.14 (m, 1H,
CH(OCH3)2); 5.10e5.13 (m, 1H, ]CH); 5.19e5.27 (q, J¼10.4 Hz, 1H,
]CH); 6.06 (d, J¼11.2 Hz, 1H, ]CH); 6.19e6.25 (m, 1H, ]CH); 13C
NMR (d, ppm, 100 MHz, CDCl3): 139.4 (]C); 131.6 (]C); 130.1 (]
CH); 124.9 (]CH); 124.1 (]CH); 119.8 (]CH); 108.2 (CH); 53.6
(CH3); 40.3 (CH2); 35.3 (CH); 26.6 (CH2); 25.7 (CH3); 17.7 (CH3); 16.5
(CH3); 16.2 (CH3); DEPT135: 139.4; 131.6; 130.1; 124.9; 124.1; 119.8;
108.2; 53.6; 40.3 (D); 35.3; 26.6 (D); 25.7; 17.7; 16.5; 16.2; HRMS
(EIþ) m/z calcd for C16H28O2, 252.2089, found: 252.2087.
3.1.3. C14-Aldehyde 9. Dimethoxy-3,5,9-triene 8 (12.6 g, 0.05 mol),
THF (100 mL), p-TSA (1.5 g), and water (22 g) were added into a 3-
neck reaction flask under a nitrogen atmosphere, then the resulting
mixture was stirred at 20e25 ꢀC for 24 h. When the hydrolysis
finished completely (GC), aqueous NaHCO3 (9%, 20 mL) was added,
and THF was removed under reduced pressure. Then cyclohexane
(100 mL) was added and the organic layer was washed with water
(30 mL), then dried, and evaporated in vacuo to leave the crude
C14-aldehyde 9 (10.5 g, GC content 85.1%, yield 86.8%), which were
composed of four isomers same as the stereochemistry of raw
material dimethoxy-3,5,9-triene 8, the spectra data of 3Z,5E-(major
product) are presented as follow: GCeMS (m/z): 206, 191, 163, 135,
NMR (
d
, ppm, 400 MHz, CDCl3):0.92(d, J¼6.8 Hz, 3H, eCHCH3); 1.33 (t,
J¼7.2 Hz, 6H, OCH2CH3); 1.91e1.97 (m, 1H, eCHCH3); 2.03e2.10,
2.43e2.49(m, m, 2H, eCH2); 3.34, 3.36 (s, s, 6H, CH(OCH3)2); 4.04e4.11
(m, 4H, OCH2CH3); 4.05 (d, J¼6.4 Hz, 1H, CH(OCH3)2); 5.67 (dd,
J¼16.8 Hz, 21.6 Hz, 1H, CH]CHCH2); 6.70e6.79 (m, 1H, CH]CHCH2);
13C NMR (
d, ppm,100 MHz, CDCl3): 152.1 (d, J¼4.6 Hz, ]CH); 118.5 (d,
J¼186 Hz, ]CHPO); 108.1 (s, CH); 61.6 (d, J¼5.4 Hz, OCH2); 54.3 (d,
J¼59 Hz, OCH3);36.7 (d,J¼22.2 Hz, CH2); 35.2 (s, CH); 16.4 (d, J¼6.5 Hz,
CH2CH3); 14.5 (s, CH3); HRMS (EIþ) m/z calcd for C12H25O5P, 280.1440,
found: 280.1437.
121, 109, 95 (100%), 69, 55, 41; 1H NMR (
d, ppm, 400 MHz, CDCl3):
1.19e1.21 (m, 3H, CHCH3); 1.43 (s, 3H, ]CCH3); 1.61 (s, 3H, ]CCH3);
1.69 (s, 3H, ]CCH3); 1.75e1.87 (m, 2H, ]CHCH2); 2.09e2.13 (m, 2H,
]CCH2), 3.46e3.56 (m, 1H, CHCH3), 5.09e5.10 (m, 1H, ]CH),
5.10e5.16 (m, 1H, ]CH), 6.06 (d, J¼9.6 Hz, 1H, ]CH), 6.45 (t,
3.1.2. Dimethoxy-3,5,9-triene 8. To a solution of KOt-Bu (9.3 g,
0.083 mol) in 8:1 (v/v) mixture of dry THF and DMSO (50 mL),
propenyl-C6-phosphonate 6 (21.0 g, 0.075 mol) was added drop-
wise in 30 min at ꢁ30 to ꢁ25 ꢀC under a nitrogen atmosphere, and
the resulting mixture was stirred for further 1 h. Then, a few of the
reaction mixture was taken out followed by hydrolyzation, and GC
indicated propenyl-C6-phosphonate 6 had been converted to al-
lylic-C6-phosphonate 10 completely, which is a mixture of Z- and
E-isomers of same spectroscopic data according to GCeMS. A
sample of the above rearrangement product was identified as fol-
low: GCeMS (m/z): 279, 265, 249, 233, 220, 205, 189, 177, 161, 152,
138, 125, 111, 97, 81, 75 (100%), 67, 47, 29.
Then, 6-methyl-5-hepten-2-one 7 (9.5 g, 0.075 mol) was added
to the above mixture dropwise at ꢁ30 to ꢁ25 ꢀC over 1 h. The
mixture was warmed to room temperature and the stirring was
continued for another 30 min. Then, water (50 mL) and ether
(100 mL) were added, and the ether phase was separated, washed
with brine (10%, 3ꢂ15 mL), dried over anhydrous MgSO4, and
evaporated in vacuo to collect the distillate at 99e103 ꢀC/1mmHg
as a colorless liquid (14.1 g). GC and NMR showed the liquid con-
sisted of the mixture of 3E,5Z-; 3Z,5Z-; 3E,5E-; 3Z,5E-(major prod-
uct) four isomers of dimethoxy-3,5,9-triene 8 with the ratio of
about 1:2:2:4 (total GC content of the four isomers 87.5%, yield
65.3%).
J¼9.6 Hz, 1H, ]CH), 9.54 (s, 1H, eCHO); 13C NMR (
d, ppm, 100 MHz,
CDCl3): 201.0 (CHO); 142.1 (]C); 128.6 (]CH); 124.0 (]CH); 123.8
(]CH); 123.6 (]C); 119.3 (]CH); 45.9 (CH); 40.3 (CH2); 26.9 (CH2);
25.7 (CH3); 17.7 (CH3); 16.7 (CH3); 14.0 (CH3); DEPT135: 201.0;
128.6; 124.0; 123.8; 119.3; 45.9; 40.3 (D); 26.9 (D); 25.7; 17.7; 16.7;
14.0.
3.1.4. C15-Phosphonate 2. To a solution of sodium hydride (2.2 g,
60% content, 0.055 mol) in toluene (20 mL), a solution of methyl-
enebisphosphonic acid tetraethyl ester (17.3 g, 0.06 mol) in toluene
(40 mL) was added dropwise at 10e15 ꢀC over 30 min under a ni-
trogen atmosphere, and the resulting mixture was then stirred for
additional 30 min. Then C14-aldehyde 9 (10.3 g, 0.05 mol) in tol-
uene (20 mL) was added dropwise at 10e15 ꢀC over 30 min, and the
mixture was stirred for further 30 min. Then water (50 mL) was
added and stirred for further 10 min. The organic layer was washed
with aqueous NaCl (10%, 50 mL), dried over anhydrous MgSO4, and
evaporated in vacuo to leave crude product 3,7,11-trimethyl-
1,4,6,10-dodecatetraenylphosphonic acid diethyl ester 2 (15.1 g, GC
content 93.2%, yield 88.8%) as a pale brown liquid. The spectra data
of 1E,3Z,5E-(major product) are presented as follow: GCeMS (m/z):
340, 325, 297, 284, 271, 257, 243, 232, 217, 205, 192, 178, 164, 146,
The spectral data of only 3Z,5E-(major product) are presented as
follow: GCeMS (m/z): 252, 220, 192 (100%), 178, 165, 152, 115, 102,
133 (100%), 119, 105, 91, 79, 69, 55, 41; 1H NMR (
d, ppm, 400 MHz,
91, 77, 65, 51, 39; 1H NMR (
d, ppm, 400 MHz, CDCl3): 1.00 (d,
CDCl3): 6.74 (t, J¼19.6 Hz, 1H, ]CH); 6.24 (t, J¼11.2 Hz, 1H, ]CH);
J¼6.8 Hz, 3H, CHCH3); 1.61 (s, 3H, ]CCH3); 1.68 (s, 3H, ]CCH3);
6.00 (d, J¼11.6 Hz, 1H, ]CH); 5.63 (t, J¼19.2 Hz, 1H, ]CHPO),