4138 J . Org. Chem., Vol. 63, No. 12, 1998
Notes
removed in vacuo and the resulting residue was diluted with
hexane and washed with 10% HCl. The aqueous layer was
extracted with hexane, and the combined organic layers were
washed with 10% HCl, 10% NaOH, and H2O, dried (MgSO4),
and concentrated. The residue was distilled under vacuum
(50 °C/0.1 mmHg) to obtain 0.56 g of 8b (72%) as a colorless
oil. 1H NMR (400.13 MHz, C6D6) δ 5.66 (t, J ) 4.1 Hz, 1H),
2.1-2.2 (m, 2H), 1.6-1.7 (m, 4H), 1.15 (s, 6H); 13C NMR
(100.61 MHz, CDCl3) δ 156.3, 118.8, 116.6, 39.5, 35.4, 26.7,
25.3, 18.9.
Eth yl 5-Dem eth ylr etin oa te (9b). In accordance with the
general procedure described above, a mixture of Pd2(dba)3 (5
mg, 0.005 mmol), AsPh3 (13.5 mg, 0.044 mmol), triflate 8b (57
mg, 0.22 mmol), and stannane 5 (120 mg, 0.24 mmol) in NMP
(3.3 mL) was stirred at 50 °C for 2 h. The residue was purified
by chromatography (SiO2, 98:2 hexane/ethyl acetate) to afford
57 mg (82%) of 9b25 as a yellow oil and 11 mg (22%) of 10.
Eth yl 1,1-Did em eth ylr etin oa te (9d ). In accordance with
the general procedure described above, a mixture of Pd2(dba)3
(6.9 mg, 0.0075 mmol), AsPh3 (18.4 mg, 0.06 mmol), triflate
8d (67 mg, 0.3 mmol), and stannane 5 (163 mg, 0.33 mmol) in
NMP (4.4 mL) was stirred at 50 °C for 3 h. The residue was
purified by chromatography (SiO2, 98:2 hexane/ethyl acetate)
to afford 68 mg (76%) of 9d 25 as a yellow oil and 12 mg (18%)
of 10.
Eth yl 1,5-Did em eth ylr etin oa te (9e). In accordance with
the general procedure described above, a mixture of Pd2(dba)3
(5.7 mg, 0.006 mmol), AsPh3 (15.3 mg, 0.05 mmol), triflate 8e
(61 mg, 0.25 mmol), and stannane 5 (136 mg, 0.275 mmol) in
NMP (3.3 mL) was stirred at room temperature for 1 h. The
residue was purified by chromatography (SiO2, 98:2 hexane/
ethyl acetate) to afford 52 mg (70%) of 9e25 as a yellow oil and
10 mg (17%) of 10.
Eth yl 1,1,5-Tr id em eth ylr etin oa te (9f). In accordance
with the general procedure described above, a mixture of Pd2-
(dba)3 (3.6 mg, 0.004 mmol), AsPh3 (9.6 mg, 0.031 mmol),
triflate 8f (36 mg, 0.156 mmol), and stannane 5 (85 mg, 0.172
mmol) in NMP (2.3 mL) was stirred at room temperature for
30 min. The residue was purified by chromatography (SiO2,
98:2 hexane/ethyl acetate) to afford 41 mg (92%) of 9f25 as a
yellow oil.
R et in oic Acid (1a ). Gen er a l P r oced u r e for E st er
Hyd r olysis. A solution of ethyl retinoate (9a ; 20 mg, 0.061
mmol) in 1.9 mL of a 1:4 mixture of 2 M aqueous KOH and
ethanol was refluxed for 10 min. The solution was cooled to
room temperature and diluted with Et2O (5 mL) and brine (5
mL). The organic layer was washed with H2O, and the
combined aqueous layers were acidified with 5% HCl to give
a solution which was extracted with Et2O. The combined
organic extracts were washed with H2O and brine and then
dried (MgSO4) and concentrated. The residue was purified on
silica gel (95:5 CH2Cl2/MeOH) to afford 13 mg of 1a (71%) as
a yellow solid (mp 178-180 °C, EtOH). Physical and spec-
troscopic data matched those of commercially available retinoic
acid.
Eth yl (2E,4E,6E,8E)-3,7-Dim eth yl-9-(tr i-n -bu tylstan n yl)-
n on a -2,4,6,8-tetr a en oa te (5). A solution of diethyl 3-(ethoxy-
carbonyl)-2-methylprop-2-enylphosphonate 4 (1.07 g, 4.05
mmol) in THF (4 mL) was cooled to 0 °C and treated with
DMPU (1 mL, 8.32 mmol) and n-BuLi (1.66 M in hexanes, 2.3
mL, 3.82 mmol). The mixture was stirred at this temperature
for 20 min and then cooled to -78 °C. A solution of aldehyde
39 (0.87 g, 2.25 mmol) in THF (4 mL) was slowly added, and
the reaction mixture was stirred at -78 °C for 3 h. The
mixture was allowed to warm to 0 °C to complete the reaction.
Saturated aqueous NH4Cl was added, and the reaction mixture
was extracted with Et2O. The combined organic layers were
washed with H2O and brine, dried (MgSO4), and concentrated.
The residue was purified by chromatography on silica gel (93:
5:2 hexane/ethyl acetate/Et3N) to afford 0.82 g of 5 (73%) as a
yellow oil. IR (NaCl, cm-1) ν 1713 (m); 1H NMR (400.13 MHz,
C6D6) δ 6.93 (dd, J ) 19.2 Hz, 3J Sn-H ) 62.7 Hz, 1H), 6.89 (dd,
2
J ) 15.1, 11.4 Hz, 1H), 6.61 (dd, J ) 19.2 Hz, J Sn-H ) 97.7
Hz, 1H), 6.18 (d, J ) 15.1 Hz, 1H), 6.13 (d, J ) 11.4 Hz, 1H),
5.98 (s, 1H), 4.11 (q, J ) 7.1 Hz, 2H), 2.46 (s, 3H), 1.82 (s,
3H), 1.6-1.7 (m, 6H), 1.4-1.5 (m, 6H, 3 × CH2), 1.0-1.1 (m,
9H), 0.99 (t, J ) 7.3 Hz, 9H); 1H NMR (400.13 MHz, CDCl3) δ
3
6.98 (dd, J ) 15.0, 11.4 Hz, 1H), 6.63 (d, J ) 19.2 Hz, J Sn-H
2
) 61.4 Hz, 1H), 6.43 (d, J ) 19.2 Hz, J Sn-H ) 63.6 Hz, 1H),
6.32 (d, J ) 15.0 Hz, 1H), 6.17 (d, J ) 11.4 Hz, 1H), 5.78 (s,
1H), 4.17 (q, J ) 7.1 Hz, 2H), 2.36 (s, 3H), 1.95 (s, 3H), 1.5-
1.6 (m, 6H), 1.2-1.4 (m, 9H), 0.8-1.0 (m, 15H); 13C NMR
(100.61 MHz, CDCl3) δ 167.1, 152.5, 150.1 (5J Sn-C ) 10.4 Hz),
140.0, 136.0, 131.2 (1J Sn-C ) 213.9 Hz), 131.0, 130.4, 118.9,
59.7, 29.1 (3J Sn-C ) 20.4 Hz), 27.3 (2J Sn-C ) 54.0 Hz), 14.7,
13.8, 13.7, 12.4, 9.53 (1J Sn-C ) 336.5 Hz). HRMS m/z (M+)
calcd for C21H35O2118Sn 437.1653, found 437.1666.
E t h yl R et in oa t e (9a ). Gen er a l P r oced u r e for St ille
Rea ction s. A solution of Pd2(dba)3 (3.4 mg, 0.004 mmol) in
NMP (1.4 mL) was treated with AsPh3 (9 mg, 0.029 mmol)
and, after 5 min, with a solution of triflate 8a (40 mg, 0.147
mmol) in NMP (0.2 mL). After stirring for 10 min, a solution
of stannane 5 (80 mg, 0.161 mmol) in NMP (0.2 mL) was
added. The resulting solution was stirred at 70 °C for 2 h.
After cooling, saturated aqueous KF solution (2 mL) was
added, and the mixture was stirred for 30 min and extracted
with Et2O. The combined organic extracts were washed with
H2O and saturated aqueous KF solution, dried over MgSO4,
and concentrated to dryness. The residue was purified by
chromatography (SiO2, 98:2 hexane/ethyl acetate) to afford 30
mg (62%) of 9a 15 as a yellow oil and 10 mg (30%) of diethyl
(2E,4E,6E,8E,10E,12E,14E,16E)-3,7,12,16-tetramethyloctadeca-
2,4,6,8,10,12,14,16-octaene-1,18-dioate (10) as a red solid
(mp: 150-158 °C). Data for 9a : 1H NMR (400.13 MHz,
CDCl3) δ 7.00 (dd, J ) 15.0, 11.2 Hz, 1H), 6.29 (d, J ) 15.0
Hz, 1H), 6.28 (d, J ) 16.1 Hz, 1H), 6.15 (d, J ) 11.2 Hz, 1H),
6.14 (d, J ) 16.1 Hz, 1H), 5.78 (s, 1H), 4.17 (q, J ) 7.1 Hz,
2H), 2.36 (d, J ) 1.0 Hz, 3H), 2.0-2.1 (m, 2H), 2.00 (s, 3H),
1.72 (s, 3H), 1.4-1.6 (m, 4H), 1.29 (t, J ) 7.1 Hz, 3H), 1.03 (s,
6H); 13C NMR (100.61 MHz, CDCl3) δ 167.2, 152.8, 139.5,
137.6, 137.2, 135.1, 130.9, 130.0, 129.4, 128.5, 118.5, 59.7, 39.4,
34.2, 33.0, 28.9, 21.8, 19.1, 14.3, 13.7, 12.9. Data for 10: IR
5-Dem eth ylr etin oic Acid (1b). Application of the general
procedure for ester hydrolysis to ethyl 5-demethylretinoate
(9b) afforded, after chromatography on silica gel (95:5 CH2-
Cl2/MeOH), an 83% yield of 5-demethylretinoic acid (1b) as a
yellow solid (mp 83-85 °C, EtOH).25
1,1-Did em eth ylr etin oic Acid (1d ). Application of the
general procedure for ester hydrolysis to ethyl 1,1-didemeth-
ylretinoate (9d ) afforded, after chromatography on silica gel
(95:5 CH2Cl2/MeOH), a 92% yield of 1,1-didemethylretinoic
acid (1d ) as a yellow solid (mp 211-213 °C, EtOH).25
1,5-Did em eth ylr etin oic Acid (1e). Application of the
general procedure for ester hydrolysis to ethyl 1,5-didemeth-
ylretinoate (9e) afforded, after chromatography on silica gel
(95:5 CH2Cl2/MeOH), a 66% yield of 1,5-didemethylretinoic
acid (1e) as a yellow solid (mp 170-172 °C, EtOH).25
1,1,5-Tr id em eth ylr etin oic Acid (1f). Application of the
general procedure for ester hydrolysis to ethyl 1,1,5-tride-
methylretinoate (9f) afforded, after chromatography on silica
gel (95:5 CH2Cl2/MeOH), a 75% yield of 1,1,5-tridemethylre-
tinoic acid (1f) (mp 173-175 °C, EtOH).25
(2E,4E,6E,8E)-3,7-Dim eth yl-9-(tr i-n -bu tylsta n n yl)n on a -
2,4,6,8-tetr a en -1-ol (6). A cooled (-78 °C) solution of tet-
raenylstannane 5 (0.25 g, 0.5 mmol) in THF (1.7 mL) was
treated with DIBALH (1 M, 1 mL, 1 mmol) and stirred at -78
°C for 1 h. The reaction was quenched with a 2:3 MeOH/Et2O
mixture (2 mL) and allowed to reach room temperature. H2O
was added, and the mixture was extracted with Et2O. The
1
(NaCl, cm-1) ν 1698 (s), 1574 (m), 1150 (s); H NMR (400.13
MHz, CDCl3) δ 6.98 (dd, J ) 15.0, 11.5 Hz, 2H), 6.4-6.5 (m,
4H), 6.33 (d, J ) 15.1 Hz, 2H), 6.24 (d, J ) 11.5 Hz, 2H), 5.80
(s, 2H), 4.18 (q, J ) 7.1 Hz, 4H), 2.36 (s, 6H), 2.00 (s, 6H),
1.30 (t, J ) 7.1 Hz, 6H); 13C NMR (100.61 MHz, CDCl3) δ 167.6,
152.9, 139.6, 138.2, 136.6, 132.2, 131.1, 130.9, 119.6, 60.2, 14.8,
14.2, 13.4; HRMS m/z (M+) calcd for C26H34O4 410.2457, found
410.2463.
(25) Spectroscopic data are provided in the Supporting Information.