Synthesis of Six Natural Phenylpropanoids
(dt, J = 17.8, 7.2 Hz, 1 H), 3.13 (dt, J = 17.0, 7.2 Hz, 1 H), 2.88
(dd, J = 13.3, 9.6 Hz, 1 H), 2.21 (quint, J = 6.6 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 172.5, 167.7, 160.6, 153.4, 144.5,
135.2, 129.7, 129.4, 128.9, 127.4, 127.1, 115.2, 114.8, 66.7, 66.3,
system had become a two-phase clear mixture. The phases were
separated. The aqueous layer was extracted with CH2Cl2
(2ϫ50 mL). The combined organic layers were washed in turn with
water and brine, and dried with anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chromatography (PE/
EtOAc, 1:1) on silica gel gave (R)-2 [41 mg, 0.174 mmol, 73% from
55.1, 51.5, 37.9, 32.0, 23.7 ppm. FTIR (KBr): ν = 3067, 3029, 2949,
˜
2918, 2882, 1782, 1704, 1633, 1603, 1434, 1388, 1352, 1289, 1252,
1209, 1170, 985, 830, 762, 703 cm–1. ESI-MS: m/z = 446.4 [M +
Na]+. ESI-HRMS: calcd. for C24H25NO6Na [M + Na]+ 446.1574;
found 446.1586.
(R)-4] as a white powder. Data for (R)-2: M.p. 64–68 °C. [α]2D3
=
+3.47 (c = 0.4, MeOH); [α]2D3 = +4.14 (c = 0.21, MeOH) [ref.[1a]
data for natural 2: [α]2D4 = –5.1 (c = 0.21, MeOH)]. ee = 90.3% [tR
for (R)-2 = 63.777 min, tR for (S)-2 = 60.477 min], as measured by
Methylation of 16 To Give 17: The procedure described above for
the conversion of 11a into 12a was used, but with 16 instead of 11a.
Purification by chromatography (PE/EtOAc, 3:1) gave 17 (1.113 g,
2.546 mmol, 84% from 16) as a white powder. Data for 17: M.p.
HPLC with
a Phenomenex Lux 5 μm Amylose-2 column
(25ϫ0.46 cm), eluting with n-hexane/iPrOH, 9:1, at a flow rate of
0.7 mL/min, with the UV detector set to 214 nm. 1H NMR
(400 MHz, CDCl3): δ = 7.32 (d, J = 8.6 Hz, 2 H), 6.85 (d, J =
8.9 Hz, 2 H), 6.55 (d, J = 15.7 Hz, 1 H), 6.24 (dt, J = 15.9, 5.9 Hz,
1 H), 4.30 (dd, J = 6.1, 1.6 Hz, 2 H), 4.08 (dt, J = 9.7, 5.8 Hz, 1
H), 4.02 (ddd, J = 9.3, 6.9, 5.6 Hz, 1 H), 3.56 (d, J = 5.7 Hz, 2 H),
1.97–1.87 (m, 2 H), 1.74–1.63 (m, 1 H), 1.00 (d, J = 6.6 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 158.5, 130.8, 129.5, 127.6,
126.3, 114.6, 67.9, 66.1, 63.8, 33.2, 32.7, 16.8 ppm. FTIR (film of
1
100–101 °C. [α]2D4 = –72.3 (c = 1.00, CHCl3). H NMR (400 MHz,
CDCl3): δ = 7.63 (d, J = 15.9 Hz, 1 H), 7.45 (d, J = 8.9 Hz, 2 H),
7.36–7.27 (m, 3 H), 7.22–7.19 (m, 2 H), 6.86 (d, J = 8.8 Hz, 2 H),
6.30 (d, J = 15.8 Hz, 1 H), 4.65 (ddt, J = 9.3, 8.0, 3.2 Hz, 1 H),
4.16–4.12 (m, 1 H), 4.11–4.05 (m, 2 H), 4.04–3.96 (m, 2 H), 3.79
(s, 3 H), 3.25 (dd, J = 13.6, 3.2 Hz, 1 H), 2.78 (dd, J = 13.2, 9.6 Hz,
1 H), 2.29 (ddt, J = 14.0, 8.0, 6.0 Hz, 1 H), 1.95 (dq, J = 13.9,
6.0 Hz, 1 H), 1.32 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 176.5, 167.7, 160.5, 153.0, 144.4, 135.2, 129.7, 129.4,
128.9, 127.4, 127.2, 115.3, 114.7, 66.0, 65.9, 55.3, 51.6, 37.9, 34.8,
a conc. solution in CH Cl ): ν = 3383, 3030, 2925, 2876, 1714,
˜
2
2
1699, 1633, 1605, 1574, 1512, 1506, 1471, 1452, 1433, 1393, 1303,
1248, 1173, 1113, 1087, 1017, 969, 933, 837, 798 cm–1. ESI-MS:
m/z = 259.2 [M + Na]+. ESI-HRMS: calcd. for C14H20O3Na [M +
Na]+ 259.1305; found 259.1306.
32.7, 18.0 ppm. FTIR (KBr): ν = 3031, 2950, 2890, 1787, 1765,
˜
1711, 1698, 1634, 1602, 1511, 1481, 1385, 1252, 1197, 1174, 1013,
985, 826, 762, 725, 698 cm–1. ESI-MS: m/z = 460.3 [M + Na]+. MnO2 Oxidation of (R)-2 To Give (R)-1: A mixture of (R)-2 (25 mg,
ESI-HRMS: calcd. for C25H27NO6Na [M + Na]+ 460.1731; found
460.1738.
0.1059 mmol) and activated MnO2 (88%, 78 mg, 0.794 mmol) in
dry CH2Cl2 (1 mL) was stirred at ambient temperature for 20 h,
after which time TLC showed that the reaction was complete. The
solids were removed by filtration [washing with CH2Cl2 (70 mL)].
The combined filtrate and washings were washed with water and
brine, and then dried with anhydrous Na2SO4. Removal of the sol-
vent by rotary evaporation gave rather pure (R)-1 [21 mg,
0.0897 mmol, 84% from (R)-2] as a white powder. Data for (R)-1:
M.p. Ͻ26 °C. [α]2D1 = +4.3 (c = 0.19, MeOH) [ref.[1a] data for natural
1: [α]2D4 = +5.7 (c = 0.15, MeOH)]. 1H NMR (400 MHz, CDCl3): δ
= 9.57 (d, J = 7.8 Hz, 1 H), 7.44 (d, J = 8.9 Hz, 2 H), 7.35 (d, J =
15.7 Hz, 1 H), 6.86 (d, J = 8.9 Hz, 2 H), 6.53 (dd, J = 15.9, 7.8 Hz,
1 H), 4.00 (dt, J = 9.6, 6.5 Hz, 1 H), 4.05 (dt, J = 9.4, 6.1 Hz, 1
H), 3.49 (d, J = 5.6 Hz, 2 H), 1.90 (dt, J = 12.6, 6.1 Hz, 1 H), 1.84
(dt, J = 12.3, 6.1 Hz, 1 H), 1.84–1.74 (br. s, 1 H), 1.61 (dq, J =
13.1, 6.5 Hz, 1 H), 0.94 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 193.8, 161.5, 152.8, 130.4, 126.7, 126.4,
Reductive Cleavage of the Chiral Auxiliary in 17 To Give (R)-4: The
procedure described above for the conversion of 12b into (S)-4 was
used, but with 17 as starting material. This gave (R)-4 (174 mg,
0.659 mmol, 96% from 17) as a white powder. Data for (R)-4: M.p.
60–61 °C. [α]2D3 = +4.5 (c = 0.26, MeOH); [α]2D3 = +4.2 (c = 0.55,
MeOH); the [α]20 (c = 0.40, MeOH) for (R)-4 was also measured
on another polarimeter (Rudolph Autopol VI, with changeable
wavelength): +3.4 (633 nm), +4.6 (589 nm), +5.8 (546 nm), +8.7
(436 nm), +9.5 (405 nm); data were also measured at a lower con-
centration (c = 0.23, MeOH): +3.1 (633 nm), +5.3 (589 nm), +6.4
(546 nm), +9.6 (436 nm), +9.3 (405 nm); [ref.[2] data for natural 4:
[α]500 = +4.34 (c = 0.23, MeOH)]. ee = 90.2% [tR for (R)-4 =
15.417 min, tR for (S)-4 = 16.727 min], as measured by HPLC with
a Phenomenex Lux 5 μm Cellulose-3 column (25ϫ0.46 cm), elut-
ing with n-hexane/iPrOH, 8:2, at a flow rate of 0.7 mL/min, with
115.0, 67.8, 66.4, 33.0, 32.6, 16.7 ppm. FTIR (film): ν = 3439, 3037,
˜
1
the UV detector set to 214 nm. H NMR (400 MHz, CDCl3): δ =
2957, 2926, 2874, 1673, 1621, 1600, 1570, 1511, 1473, 1426, 1392,
1308, 1259, 1175, 1129, 1014, 973, 819 cm–1. ESI-MS: m/z = 235.1
[M + H]+. ESI-HRMS: calcd. for C14H19O3 [M + H]+ 235.13287;
found 235.1331.
7.65 (d, J = 15.9 Hz, 1 H), 7.46 (d, J = 8.6 Hz, 2 H), 6.89 (d, J =
8.8 Hz, 2 H), 6.31 (d, J = 16.0 Hz, 1 H), 4.06 (ddd, J = 12.5, 9.2,
7.3 Hz, 1 H), 4.09 (dt, J = 9.2, 6.6 Hz, 1 H), 3.79 (s, 3 H), 3.55 (d,
J = 5.6 Hz, 2 H), 1.99–1.87 (m, 2 H), 1.83 (br. s, 1 H), 1.72–1.62
(m, 1 H), 1.00 (d, J = 6.7 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.8, 160.7, 144.5, 129.7, 127.1, 115.2, 114.8, 67.9,
Hydrogenation of (R)-2 To Give (R)-5: The procedure described
above for the conversion of (S)-2 into (S)-5 was used [with (R)-2
66.2, 51.6, 33.1, 32.6, 16.7 ppm. FTIR (film): ν = 3322, 2927, 2873, instead of (S)-2 as the starting material]. This gave (R)-5 (6 mg,
˜
1714, 1636, 1604, 1574, 1513, 1456, 1434, 1288, 1259, 1171, 1111,
1014, 983, 831, 818 cm–1. ESI-MS: m/z = 265.2 [M + H]+. ESI-
HRMS: calcd. for C15H20O4Na [M + Na]+ 287.1254; found
287.1257.
0.025 mmol, 100%) as a white solid. Data for (R)-5: M.p. 56–57 °C.
[α]2D4 = +5.7 (c = 0.25, MeOH). ee = 88.0% [tR for (R)-5 =
6.451 min, tR for (S)-5 = 7.379 min], as measured by HPLC with a
Phenomenex Lux 5 μm Cellulose-4 column (25ϫ0.46 cm), eluting
with MeCN/H2O, 9:1, at a flow rate of 0.7 mL/min, with the UV
detector set to 254 nm. Other data were the same as those reported
DIDBAL-H Reduction of (R)-4 To Give (R)-2: DIBAL-H (1.0 m
solution in cyclohexane; 0.48 mL, 0.48 mmol) was added to a
stirred solution of (R)-4 (63 mg, 0.242 mmol) in dry CH2Cl2 (3 mL)
at –78 °C (EtOH/dry ice bath) under argon (balloon). The mixture
was stirred at the same temperature for 1 h, then satd. aq. NH4Cl
(2 mL) was added carefully, followed by CH2Cl2 (4 mL). Stirring
was continued at ambient temperature for 4 h, after which time the
for (S)-5. ESI-HRMS: calcd. for C14H22O3Na [M
261.14612; found 261.1467.
+
Na]+
Conversion of 17 into 18: H2O2 (30%; 0.18 mL) was added to a
stirred solution of 17 (400 mg, 0.915 mmol) and LiOH (monohy-
drate; 46 mg, 1.098 mmol) in THF (5 mL) and H2O (0.5 mL) in an
Eur. J. Org. Chem. 2014, 3451–3459
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3457