W. Gładkowski et al. / Tetrahedron: Asymmetry 27 (2016) 227–237
235
4.8.3. (+)-(3S,4E)-3-(20,50-Dimethylphenyl)hex-4-enoic acid (+)-
7b
4.9.2. Data of iodolactones obtained from acid (ꢀ)-7a (1.25 g, 5
mmol)
Obtained from ester (+)-6b (1.8 g, 7 mmol); yield 76% (1.21 g);
4.9.2.1.
(ꢀ)-cis-(4S,5S,6R)-5-(1-Iodoethyl)-4-(40-isopropyl-
brown, oily liquid; ee = 99%; tR = 189.3 min; [
a]
20 = +23.0 (c 1.5,
phenyl)dihydrofuran-2-one (ꢀ)-8a.
Yield 33% (0.63 g);
D
CH2Cl2); IR (film, cmꢀ1): 3100–2600 (s,b), 1708 (s), 1502 (s),
1440 (m), 967 (m), 810 (s); 1H NMR (600 MHz, CDCl3) d 1.65 (d,
J = 6.0 Hz, 3H, CH3-6), 2.31, 2.32 (two s, 6H, 2 ꢁ CH3-Ph), 2.71
(dd, J = 15.6, 7.2 Hz, 1H, one of CH2-2), 2.75 (dd, J = 15.6, 9.0 Hz,
1H, one of CH2-2), 4.02 (m, 1H, H-3), 5.46 (dq, J = 15.0, 6.0 Hz,
1H, H-5), 5.53 (dd, J = 15.0, 6.6 Hz, 1H, H-4), 6.93 (d, J = 7.2 Hz,
1H, H-40), 6.95 (s, 1H, H-60), 7.04 (d, J = 7.2 Hz, 1H, H-30); 13C
NMR (150 MHz, CDCl3) d 17.9 (C-6), 19.0 (2 ꢁ CH3-Ph), 39.8 (C-
3), 39.9 (C-2), 125.6 (C-5), 126.8 (C-60), 127.0 (C-40), 130.4 (C-30),
132.5 (C-4), 132.6 (C-20), 135.6 (C-50), 140.9 (C-10), 178.2 (C-1);
HRMS: calcd for C14H18O2 [MꢀH]ꢀ: 217.1228, found 217.1220.
colourless crystals; (crystallization from mixture hexane/acetone
20:1); mp 68ꢀ70 °C; ee >99%; tR = 163.4 min; [
a]
20 = ꢀ1.9 (c 1.0,
D
CH2Cl2); spectroscopic data consistent with those reported for
rac-8a.34 Crystal data for (ꢀ)-8a: C15H19IO2, M = 358.20,
orthorhombic, P212121, a = 8.093(2), b = 9.432(2), c = 19.072(3) Å,
V = 1455.8(5) Å3, Z = 4, Dc = 1.634 Mg mꢀ3, T = 100(2) K, R = 0.026,
wR = 0.047 (11086 reflections with I >2r(I)) for 163 variables.
CCDC 1408083.
4.9.2.2.
phenyl)dihydrofuran-2-one (+)-9a.
(+)-trans-(4S,5R,6S)-5-(1-Iodoethyl)-4-(40-isopropyl-
Yield 19% (0.41 g);
brown, dense liquid; ee >99%; tR = 70.3 min; [a]
20 = +8.6 (c 0.6,
D
4.8.4. (ꢀ)-(3S,4E)-3-(20,50-Dimethylphenyl)hex-4-enoic acid (ꢀ)-
CH2Cl2); spectroscopic data identical to those reported for rac-9a.34
7b
Obtained from ester (ꢀ)-6b (1.9 g, 8 mmol); yield 77% (1.3 g);
4.9.3. Data of iodolactones obtained from acid (+)-7b (1.1 g, 5
mmol)
brown, oily liquid, ee = 98%; tR = 188.7 min; [
a]
20 = ꢀ22.9 (c 1.5,
D
CH2Cl2); spectroscopic data identical to those reported herein for
(+)-7a.
4.9.3.1. (ꢀ)-cis-(4R,5R,6S)-5-(1-Iodoethyl)-4-(20,50-dimethylphe-
nyl)dihydrofuran-2-one (ꢀ)-8b.
Yield 39% (0.67 g); colour-
less crystals (crystallization from mixture hexane/acetone 5:1);
4.8.5. (ꢀ)-(3S,4E)-3-(Benzo[d][10,30]-dioxol-50-yl)hex-4-enoic
acid (ꢀ)-7c
mp = 104ꢀ108 °C, ee >99%; tR = 205.1 min; [
a
]
D
20 = ꢀ31.1 (c 0.8,
CH2Cl2); IR (film, cmꢀ1): 1783 (s), 1506 (m), 1169 (s), 1028 (m),
982 (m), 835 (s); 1H NMR (600 MHz, CDCl3) d 2.05 (d, J = 6.6 Hz,
3H, CH3-7), 2.29 (s, 3H, CH3-50), 2.40 (s, 3H, CH3-20), 2.59 (d,
J = 17.4 Hz, 1H, one of CH2-3), 3.10 (dd, J = 17.4, 9.0 Hz, 1H, one of
CH2-3), 3.91 (dq, J = 10.8, 6.6 Hz, 1H, H-6), 4.11 (m, 1H, H-4), 4.87
(dd, J = 10.8, 6.6 Hz, 1H, H-5), 6.88 (s, 1H, H-60), 7.00 (d,
J = 7.8 Hz, 1H, H-40), 7.06 (d, J = 7.8 Hz, 1H, H-30); 13C NMR
(150 MHz, CDCl3) d 20.2 (CH3-20), 21.2 (CH3-50), 22.9 (C-6), 25.7
(C-7), 38.9 (C-3), 39.6 (C-4), 88.2 (C-5), 126.3 (C-60), 128.5 (C-40),
131.0 (C-30), 133.1 (C-20), 136.1, 136.2 (C-10, C-50), 176.5 (C-2);
HRMS: calcd for C14H17IO2 [M+Na]+: 367.0171, found 367.0179.
Obtained from ester (ꢀ)-6c (2 g, 7 mmol); yield 90% (1.6 g);
dense, brown liquid; ee = 99%; tR = 234.1; [
a
]
20 = ꢀ7.4 (c 0.1,
D
CH2Cl2); spectroscopic data consistent with those reported previ-
ously for rac-7a.15
4.8.6. (+)-(3S,4E)-3-(Benzo[d][10,30]-dioxol-50-yl)hex-4-enoic
acid (+)-7c
Obtained from ester (+)-6c (1.6 g, 6 mmol); yield 92% (1.31 g);
brown, oily liquid; ee = 93%, tR = 234.9 min; [a]
20 = +7.0 (c 0.1,
D
CH2Cl2); spectroscopic data identical to those reported for rac-7a.15
Crystal data for (ꢀ)-8b:
a = 8.437(3), b = 9.510(3), c = 9.517(3) Å,
= 114.76(3)°, V = 681.1(4) Å3, Z = 2, Dc = 1.678 Mg mꢀ3, T = 100
C
14H17IO2, M = 344.17, triclinic, P1,
4.9. General procedure for the synthesis of iodolactones 8a–c
and 9a–c
a
= 97.86(2), b = 93.39(3),
c
(2) K, R = 0.070, wR = 0.157 (3297 reflections with I >2r(I)) for
A solution of acid 7 (6 mmol) in 20 mL of diethyl ether was stir-
308 variables. CCDC 1446200.
red with 20 mL of saturated solution of NaHCO3 for 1 h at room
temperature. Afterwards
a
solution of I2 (12 mmol) and KI
4.9.3.2. (+)-trans-(4R,5S,6R)-5-(1-Iodoethyl)-4-(20,50-dimethyl-
phenyl)dihydrofuran-2-one (+)-9b. Yield 20% (0.35 g);
dense, brown liquid; ee = 99%; tR = 220.1 min; [
20 = +14.6 (c
(59 mmol) in water (5 mL) was added dropwise and the mixture
was stirred until the substrate reacted completely (24 h, TLC,
GC). The mixture was washed with saturated Na2S2O3 and the
organic fraction was separated and dried over anhydrous MgSO4.
After evaporation of diethyl ether in vacuo the products were sep-
arated by column chromatography (hexane/acetone, 20:1).
a]
D
0.3, CH2Cl2); IR (film, cmꢀ1): 1785 (s), 1505 (m), 1188 (s), 1150
(s), 998 (m), 812 (m); 1H NMR (600 MHz, CDCl3) d 1.83 (d,
J = 6.6 Hz, 3H, CH3-7), 2.32 (s, 3H, CH3-50), 2.37 (s, 3H, CH3-20),
2.52 (dd, J = 18.6, 7.2 Hz, 1H, one of CH2-3), 3.12 (dd, J = 18.6,
10.2 Hz, 1H, one of CH2-3), 3.82 (ddd, J = 10.2, 7.2, 4.8 Hz, 1H,
H-4), 4.35–4.40 (two m, 2H, H-5, H-6), 6.99 (d, J = 7.8 Hz, 1H,
H-40), 7.02 (s, 1H, H-60), 7.07 (d, J = 7.8 Hz, 1H, H-30); 13C NMR
(151 MHz, CDCl3) d 19.6 (CH3-20), 21.1 (CH3-50), 23.6 (C-7), 28.8
(C-6), 38.0 (C-3), 41.1 (C-4), 89.3 (C-5), 126.5 (C-60), 128.2 (C-
40), 130.9 (C-30), 132.0 (C-20), 136.8 (C-50), 139.5 (C-10), 174.9
4.9.1. Data of iodolactones obtained from acid (+)-7a (1.4 g, 6
mmol)
4.9.1.1. (+)-cis-(4R,5R,6S)-5-(1-Iodoethyl)-4-(40-isopropylphenyl)-
dihydrofuran-2-one (+)-8a.
Yield 28% (0.60 g); colourless
crystals (crystallization from mixture hexane/acetone 20:1); mp
63ꢀ65 °C; ee = 99%; tR = 166.0 min; [
a
]
20 = +1.9 (c 0.8, CH2Cl2);
(C-2); HRMS: calcd for
367.0172.
C
14H17IO2 [M+Na]+: 367.0171, found
D
spectroscopic data in accordance with those reported for rac-8a.34
Crystal data for (+)-8a: C15H19IO2, M = 358.20, orthorhombic,
P212121, a = 8.090(2), b = 9.405(2), c = 19.074(3) Å, V = 1451.3
(5) Å3, Z = 4, Dc = 1.639 Mg mꢀ3, T = 100(2) K, R = 0.044, wR = 0.097
4.9.4. Data of iodolactones obtained from acid (ꢀ)-7b (1.2 g, 5
mmol)
4.9.4.1. (+)-cis-(4S,5S,6R)-5-(1-Iodoethyl)-4-(20,50-dimethylphe-
(5163 reflections with I >2r(I)) for 163 variables. CCDC 1408082.
nyl)dihydrofuran-2-one (+)-8b.
less crystals (crystallization from mixture hexane/acetone 5:1);
20 = +31.1 (c 0.6,
CH2Cl2); spectroscopic data identical to those reported herein for
(ꢀ)-8b.
Yield 40% (0.75 g); colour-
4.9.1.2.
(ꢀ)-trans-(4R,5S,6R)-5-(1-Iodoethyl)-4-(40-isopropyl-
phenyl)dihydrofuran-2-one (ꢀ)-9a.
Yield 20% (0.43 g);
mp 108ꢀ112 °C; ee >99%; tR = 202.2 min; [
a]
D
brown, dense liquid; ee = 99%; tR = 70.1 min; [
a]
D
20 = ꢀ8.5 (c 1.7,
CH2Cl2); spectroscopic data identical to those reported for rac-9a.34