Pd-catalyzed Suzuki coupling reaction of chloroalkylidene-β-lactones with LB-Phos as the ligand

Article abstract of DOI:10.1039/c2ob26365c

In this paper, LB-Phos·HBF₄ salt has been applied for the Pd-catalysed Suzuki coupling reactions of optically active (Z)-α- choroalkylidene-β-lactones. Aryl, vinyl, alkyl and heteroaromatic boronic acids may be coupled with optically active β-l

Full text of DOI:10.1039/c2ob26365c

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Pd-catalyzed Suzuki coupling reaction of
chloroalkylidene-β-lactones with LB-Phos as the
ligand†
Cite this: Org. Biomol. Chem., 2013, 11, 98
Pengbin Li, Bo Lü, Chunling Fu and Shengming Ma*
Received 16th July 2012,
In this paper, LB-Phos·HBF4 salt has been applied for the Pd-catalysed Suzuki coupling reactions of opti-
cally active (Z)-α-choroalkylidene-β-lactones. Aryl, vinyl, alkyl and heteroaromatic boronic acids may be
coupled with optically active β-lactones affording corresponding optically active products highly selec-
tively and efficiently.
Accepted 12th September 2012
DOI: 10.1039/c2ob26365c
www.rsc.org/obc
amount of 3a to 1.2 equiv. had a slight negative effect on the
yield of (Z)-4a (Table 1, entry 5). However, reducing the loading
Introduction
Much progress has been achieved with C–Cl bond activation of Pd(OAc)2, LB-Phos·HBF4, or K2CO3, respectively, would all
reactions in past years thanks to the development of new phos- decrease the yield of (Z)-4a (Table 1, entries 5–8). This problem
phine ligands.1 Recently, we have developed a new type of was circumvented by using 2.0 equiv of K3PO4·3H2O as the
monophosphine ligand, which could be used in palladium- base affording (Z)-4a in 95% yield (Table 1, entry 9).
catalyzed Suzuki coupling reactions2 and aminations3 of
Optically active coupling product (S,Z)-4a could also be pro-
organic chlorides. In the Suzuki coupling of optically active duced from (S,Z)-2a under our optimized reaction conditions
chlorinated 2-(5H)-furanones, LB-Phos showed advantages in 98% yield with no racemization (eqn (1)). Thus, it is con-
over some other known ligands by affording the coupling pro- cluded that even such strained allylic C–O bonds may also be
ducts, i.e. optically active β-substituted butenolides, within kept untouched.4
5–10 min without racemization.4 In this paper, we wish to
report our recent results on the Suzuki coupling reaction of
optically active α-chloroalkylidene-β-lactones derivatives of
high ee.
Table 1 Suzuki coupling reactions of (Z)-2a with PhB(OH)23a
Results and discussion
At the beginning, (Z)-α-(1-chloropentylidene)-β-ethyl-β-lactone
((Z)-2a),5 which was prepared by the PdCl2-catalyzed cyclo-
carbonylation of propargyl alcohols with CuCl2 developed in
this group, and phenyl boronic acid (3a) (1.5 equiv) were used
to test the catalytic activity of Pd/LB-Phos·HBF4. We found that
the Suzuki coupling product (Z)-4a would be formed in 100%
yield using 3.0 equiv of K2CO3 at 110 °C in toluene (Table 1,
entry 1). Other solvents such as dioxane, DMSO and DMF
would lead to lower yields (Table 1, entries 2–4). Reducing the
Yield of
Recovery of
Entry
3a (equiv)
Solvent
Time (h)
(Z)-4aa (%)
(Z)-2aa (%)
1
2
3
4
1.5
1.5
1.5
1.5
1.2
1.2
1.2
1.2
1.2
Toluene
Dioxane
DMF
1.0
1.0
1.5
3.2
2.6
1.2
1.0
1.7
0.7
100
58
—
—
39
—
—
—
23
14
—
—
DMSO
—
5
Toluene
Toluene
Toluene
Toluene
Toluene
94
77
86
88
95
6b
7c
8d
9d,e
Laboratory of Molecular Recognition and synthesis, Department of Chemistry,
Zhejiang University, Hangzhou 310027, People’s Republic of China.
a Determined by 1H NMR analysis using methylene bromide as the
internal standard. b K2CO3 (2.0 equiv) was used. c LB-Phos·HBF4 (5 mol
%) was used. d Pd(OAc)2 (3 mol%) and LB-Phos·HBF4 (6 mol%) were
used. e K3PO4·3H2O (2.0 equiv) was used.
E-mail: masm@sioc.ac.cn; Fax: +86-21-64167510
†Electronic supplementary information (ESI) available. CCDC 888344, 888345.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c2ob26365c
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Table 2 Suzuki coupling reactions of (S,Z)-2 with organoboronic acidsa
Table 3 Suzuki coupling reactions of (Z)-2d with cyclopropyl acid 3i
3i
Time
(h)
Yield of
Recovery of
Entry (equiv)
Base
(E)-4la (%) (Z)-2da (%)
(S,Z)-2
3
1
2
1.2
1.5
3.0
0.0
1.2
1.2
1.2
1.2
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
Cs2CO3
1.0
1.8
1.5
1.5
5.0
1.3
1.1
23
17
12
0
19
12
0
0
0
<4
21
0
27
83
97
Entry
R1
R2 R3
Time (h) Yieldb (%)
3
1
2
3
4
5
6
7
8
(S,Z)-2a n-Bu Et Ph (3a)
0.8
2.0
1.0
3.7
2.8
1.0
1.0
1.0
1.5
1.5
98 ((S,Z)-4a)
84 ((S,Z)-4b)
77 ((S,Z)-4c)
69 ((S,Z)-4d)
91 ((S,Z,E)-4e)
93 ((S,Z)-4f)
71 ((S,Z)-4g)
86 ((S,Z)-4h)
94 ((S,Z)-4i)
93 ((S,Z)-4j)
95 ((S,E,E)-4k)
4b
5c
6
(S,Z)-2a n-Bu Et 4-MeOC6H4 (3b)
(S,Z)-2a n-Bu Et 3-MeOC6H4 (3c)
(S,Z)-2a n-Bu Et 2-MeOC6H4 (3d)
(S,Z)-2a n-Bu Et (E)-Styryl (3e)
(S,Z)-2a n-Bu Et 4-MeC6H4 (3f)
(S,Z)-2b n-Bu Me 4-MeC6H4 (3f)
(S,Z)-2a n-Bu Et 2-Naphthyl (3g)
(S,Z)-2c n-Bu i-Pr Ph (3a)
7
8
CsF
K2HPO4·3H2O 6.0
0
a Determined by 1H NMR analysis. b Neither Pd(OAc)2 nor ligand was
added here. c Pd2(dba)3·CHCl3 was used to replace Pd(OAc)2.
9
10
11
(S,Z)-2d Ph
(S,Z)-2d Ph
Et 4-MeOC6H4 (3b)
Et (E)-1-Pentenyl (3h) 0.8
a Standard conditions A: a mixture of 1.0 equiv of (S,Z)-2 (0.2 mmol or
0.4 mmol), 1.2 equiv of 3, 2.0 equiv of K3PO4·3H2O, 0.03 equiv of Pd
(OAc)2 and 0.06 equiv of LB-Phos·HBF4 was stirred in toluene (0.1 M)
at 110 °C. b Isolated yield.
Table 4 Suzuki coupling reactions of (Z)-2d with cyclopropylboronic acid 3i
using toluene and water as the solvent
ð1Þ
Time
Entry Toluene : H2O (h)
Yield of (E)-4la Recovery of (Z)-2da
(%)
(%)
1
2
3
5 : 1
10 : 1
20 : 1
8.0
3.0
0.7
29
54
24
50
0
0
Encouraged by these results, a series of optically active
α-chloroalkylidene-β-lactones6 were tested under the optimized
conditions (Table 2). Aromatic (Table 2, entries 1–4 and 6–10)
and vinylic boronic acids (Table 2, entries 5 and 11) could all
be coupled with the starting β-lactones to afford the products
within 0.8–3.7 h. Increasing the steric hindrance in the ortho-
position of aryl boronic acid led to longer reaction times and
lower yields (Table 2, compare entries 1 and 4). 2-Naphthyl
boronic acid (3g) was also used to couple with (S,Z)-2a
affording (S,Z)-4h in 86% yield (Table 2, entry 8).
a Determined by 1H NMR analysis.
decompose quickly even in absence of Pd(OAc)2 and
LB-Phos·HBF4 (Table 3, entry 5). Using weaker base such as
CsF and K2HPO4·3H2O gave no expected product but recovery
of (Z)-2d (Table 3, entries 7 and 8).
Further screening led to the observation that when toluene–
water (v/v = 5 : 1) was used as the mixed solvent, (E)-4l was
obtained in 29% yield with 50% of (Z)-2d being recovered
(Table 4, entry 1). Decreasing the amount of water to 1 : 10
ratio (water/toluene (v/v)) would lead to 54% yield (Table 4,
entry 2). Further decreasing the amount of water did not
improve the yield of (E)-4l (Table 4, entry 3).
One 5.0 mmol-scale reaction was carried out affording (S,Z)-
4b with a relatively higher yield (eqn (2)vs. entry 2, Table 2)
within 2.0 h when 1 mol% Pd(OAc)2 together with 2 mol%
LB-Phos·HBF4 was used as the catalyst (eqn (2)).
Under the newly optimized conditions (Table 4, entry 2),
cyclopropylboronic acid could couple with optically active
(S,Z)-2d affording (S,E)-4l in 46% yield (eqn (3)). However, the
coupling of n-butylboronic acid with (S,Z)-2d did not afford the
ð2Þ
However, when cyclopropylboronic acid 3i and (Z)-2d were desired coupling product (S,E)-4m. Increasing the loading of
coupled under the optimized conditions, the yield of product K2CO3 to 4.5 equiv solved the problem (Table 5, entry 1).
(E)-4l was only 23% (Table 3, entry 1).6 A higher loading of Under the same conditions (standard conditions B), n-hexyl-
boronic acid 3i did not help to give a higher yield (Table 3, boronic acid could easily couple with (S,Z)-2d affording (S,E)-
entries 2–3). The base-sensitive β-lactone (Z)-2d would 4n in 72% yield (Table 5 entry 2).
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Table 5 Suzuki coupling reactions of (S,Z)-2 with alkyl boronic acida
4
(S,Z)-2
Entry R1
3
3 (equiv) R2
Time (h) Yieldb (%)
ee%
1
2
Ph (S,Z)-2d 2.0
Ph (S,Z)-2d 2.0
n-Bu (Z)-2a 2.0
n-Bu (S,Z)-2a 3.0
n-Bu (3j) 3.0
n-Hex (3k) 6.0
n-Bu (3j) 8.0
n-Bu (3j) 3.0
73 ((S,E)-4m) 99.3
72 ((S,E)-4n) >99
3
23 (4o)
—
99.4
4c
55 ((S)-4o)
a Standard conditions B: a mixture of 1.0 equiv of (S,Z)-2, 2.0 equiv of
3, 4.5 equiv of K2CO3, 0.05 equiv of Pd(OAc)2 and 0.10 equiv of
LB-Phos·HBF4 were stirred in toluene–H2O = 10 : 1 at 110 °C. b Isolated
yield. c PdCl2(LB-Phos)2 (5 mol%) was used as catalyst.
Scheme 1
Scheme 3 Synthesis and ORTEP representation of trans-PdCl2(LB-Phos)2.
Scheme 2
ð3Þ
Scheme 4
Furthermore, we found that 2-thienylboronic acid 3l failed
to couple with (Z)-2d under the standard conditions A or B
(Scheme 1). We reasoned that the formation of Pd–S complex 5
was too stable to prevent the formation of P–Pd species
7
(Scheme 2). Then we synthesized complex PdCl2(LB-Phos)2 by
stirring PdCl2(PhCN)2 with LB-Phos in benzene for 3 days at
room temperature. Indeed, this problem was also conquered
by using PdCl2(LB-Phos)2 (Scheme 3) as the catalyst. (S,Z)-4p8
and (S,Z)-4q could be prepared in 77% and 83% yields,
respectively, under these conditions (Scheme 4). The absolute
configuration of (S,Z)-4p was further confirmed by X-ray diffr-
action studies (Fig. 1). It is interesting to note that by using
5 mol% PdCl2(LB-Phos)2 and 3.0 equiv of n-butylboronic acid,
Fig. 1 ORTEP representation of (S,Z)-4p.8
the yield of S-4o was also improved to 55% (Table 5, entry 4) as
compared with the results presented in entry 3 of Table 5.
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0.99 (d, J = 6.9 Hz, 3H, CH3), 0.93 (t, J = 7.2 Hz, 3H. CH3);
13C NMR (75 MHz, CDCl3) δ 161.5, 138.9, 131.9, 83.5, 36.2,
Conclusions
We have prepared a series of optically active α-alkylidene-β-lac- 30.9, 28.8, 22.0, 18.4, 15.6, 13.7; IR (neat) ν (cm−1) 2965, 2934,
tones of high ee via the Suzuki coupling reaction of arylic, 2876, 1814, 1702, 1467, 1429, 1389, 1370, 1344, 1287, 1216,
vinylic boronic acid with optically active α-chloroalkylidene- 1191, 1166, 1109, 1081, 1058; MS (70 ev, EI) m/z (%): 218
β-lactones using LB-Phos as ligand.9 When a mixture of (M+(37Cl), 0.33), 216 (M+(35Cl), 0.99), 173 (100); Anal. Calcd For
toluene and H2O in 10 : 1 in volume was used, alkyl boronic C11H17ClO2: C, 60.97; H, 7.91. Found: C, 61.09; H, 7.97.
acid could also be coupled to afford the products in a mode-
The following compounds were prepared according to this
rate yields. 2-Benzothienylboronic acid and 2-thienylboronic procedure.
acid could also be coupled easily in presence of the pre-
formed PdCl2(LB-Phos)2. Further studies in this area are being
conducted in our laboratory.
(2) (S,Z)-α-(1-Chlorobenzylidene)-β-ethyl-β-lactone
((S,Z)-
2d). The mixture of (S)-1-phenylpent-1-yn-3-ol (805.4 mg,
5.0 mmol, ee > 99%) and anhydrous CuCl2 (3.3611 g,
25.0 mmol) were stirred in 50 mL of dry THF at room tempera-
ture for about 10 min followed by the addition of PdCl2
(88.3 mg, 0.50 mmol). Then the mixture was stirred for 4.2 h
under 20 atm of CO atmosphere at 40 °C to afford (S,Z)-2d
(723.3 mg, 65%) (eluent: petroleum ether/ethyl acetate = 8/1,
then recrystallization in n-hexane and ethyl acetate): ee > 99%
as determined by HPLC (Chiralpak OD-H, n-hexane–i-PrOH =
Experimental section
General information
1H and 13C NMR spectra were recorded on the instruments
operated at 300 and 75 MHz, respectively, in CDCl3. Chemical
shifts (δ) are given in parts per million (ppm) with the residual
peak of CHCl3 at 7.260 ppm or TMS at 0.000 ppm as the
internal standard. Infrared spectra were recorded from thin
films of pure samples on sodium chloride plates for liquid or
in the form of KBr discs for the solid samples. Mass and
HRMS spectra were carried out in EI mode. Thin layer chroma-
tography was performed on pre-coated glass-back plates and
visualized with UV light at 254 nm. Anhydrous CuCl2 (96%)
was purchased from Energy Chemical and heated at 200 °C
under vacuum (<1 mmHg) to remove residual water before
use. Flash column chromatography was performed on silica
gel (10–40 μ). Dioxane and toluene used was refluxed in the
presence of sodium wire using diphenyl ketone as indicator
and distilled right before use. All the boronic acids were pur-
chased from Alfa Aesar, Aldrich, or J&K chemical LTD.
98 : 2, 0.8 mL min−1, λ = 230 nm, tR = 14.0 min (major)): [α]D20
=
−96.1 (c = 1.14, CHCl3); white solid, m.p. 83–84 °C (n-hexane/
1
ethyl acetate); H NMR (300 MHz, CDCl3) δ 7.58–7.51 (m, 2H,
Ar–H), 7.51–7.42 (m, 3H, Ar–H), 5.35 (dd, J1 = 7.5 Hz, J2 = 3.0
Hz, 1H, OCH) 1.95–1.78 (m, 1H, one proton in CH2), 1.72–1.52
(m, 1H, one proton in CH2), 0.92 (t, J = 7.4 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3) δ 161.6, 134.2, 133.5, 132.8, 131.4,
128.9, 128.0, 81.2, 24.4, 8.2; IR (KBr) ν (cm−1) 3063, 2976, 2922,
2871, 1806, 1675, 1588, 1579, 1495, 1461, 1445, 1309, 1267,
1236, 1184, 1151, 1129, 1077, 1060, 1024; MS (70 ev, EI), m/z
(%): 224 (M+(37Cl), 12.73), 222 (M+(35Cl), 38.89), 221 (100);
Anal. Calcd for C12H11ClO2: C, 64.73; H, 4.98. Found: C, 64.75;
H, 4.95.
(3) (Z)-α-(1-Chlorobenzylidene)-β-ethyl-β-lactone ((Z)-2d). The
mixture of 1-phenylpent-1-yn-3-ol (799.4 mg, 5.0 mmol) and
anhydrous CuCl2 (3.3629 g, 25.0 mmol) were stirred in 50 mL
of dry THF at room temperature for about 10 min followed by
the addition of PdCl2 (88.5 mg, 0.50 mmol). Then the mixture
was stirred for 4.0 h under 20 atm CO atmosphere at 40 °C
1. SYNTHESIS OF STARTING MATERIAL. (S,Z)-2a–2b and racemic
compounds (Z)-2a–2c are known compounds and prepared
according to our published procedure.5
(1) Synthesis of (S,Z)-α-(1-chloropentylidene)-β-isopropyl-
β-lactone ((S,Z)-2c). Typical procedure. In a flame-dried flask, a afforded (Z)-2d (658.5 mg, 59%) (eluent: petroleum ether/ethyl
solution of (S)-2-methylnon-4-yn-3-ol (282 mg, 1.8 mmol, ee = acetate = 100/1, then recrystallization in n-hexane and ethyl
99%) and anhydrous CuCl2 (1.2252 g, 9 mmol) in 20 mL of dry acetate): a white solid: m.p. 54–55 °C (n-hexane/ethyl acetate);
THF was stirred for about 5 min at room temperature followed 1H NMR (300 MHz, CDCl3) δ 7.58–7.51 (m, 2H, Ar–H),
by the addition of PdCl2 (32.7 mg, 0.18 mmol). Then the flask 7.51–7.42 (m, 3H, Ar–H), 5.35 (dd, J1 = 7.5 Hz, J2 = 3.0 Hz, 1H,
was transferred to a Parr pressure reactor and charged with 20 OCH), 1.95–1.80 (m, 1H, one proton in CH2), 1.72–1.54 (m, 1H,
atm of CO gas. After the mixture was stirred for 4.3 h at 40 °C, one proton in CH2), 0.92 (t, J = 7.4 Hz, 3H, CH3); 13C NMR
the gas was carefully ventilated, and the residue was diluted (75 MHz, CDCl3) δ 161.7, 134.2, 133.5, 132.7, 131.4, 128.9,
with Et2O. Filtration through a short column of silica gel 128.0, 81.2, 24.3, 8.3; IR (KBr) ν (cm−1) 2967, 2936, 2920, 2877,
(eluent: Et2O 2 × 70 mL), evaporation, and flash chromato- 1797, 1675, 1493, 1447, 1436, 1389, 1311, 1269, 1236, 1161,
graphy on silica gel (eluent: petroleum ether/ethyl acetate = 1134, 1065; MS (70 ev, EI), m/z (%): 224 (M+(37Cl), 12.73), 222
100/1) afforded 237.6 mg (60%) of (S,Z)-2c as a colorless liquid (M+(35Cl), 39.49), 221 (100); Anal. Calcd for C12H11ClO2: C,
in 99% ee, as determined by HPLC (Chiralpak AS-H, n-hexane– 64.73; H, 4.98. Found: C, 64.82; H, 4.97.
i-PrOH = 98 : 2, 0.8 mL min−1, λ = 230 nm, tR = 8.4 min
2. SYNTHESIS OF PdCl2(LB-PHOS)2. A solution of PdCl2(PhCN)2
(major), 10.2 min (minor)): [α]2D0 = −45.9 (c = 1.14, CHCl3), H (0.9650 g, 2.51 mmol) and LB-Phos2,4 (1.8299 g, 5.03 mmol) in
NMR (300 MHz, CDCl3) δ 4.89 (d, J = 3.6 Hz, 1H, OCH), 2.34 (t, 10 mL of dry benzene was stirred for 3 days. Then filtration
J = 7.7 Hz, 2H, CH2), 2.24–2.07 (m, 1H, CH), 1.79–1.49 (m, 2H, with petroleum ether (3 × 10 mL) afforded a yellow solid of
CH2), 1.44–1.26 (m, 2H, CH2), 1.09 (d, J = 6.9 Hz, 3H, CH3), PdCl2(LB-Phos)2 (1.4124 g, 62%): m.p. 218–219 °C (ether : ethyl
1
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acetate); H NMR (300 MHz, CDCl3) δ 6.12 (s, 4H, Ar–H), 3.89 CH2), 2.20–2.06 (m, 1H, one proton in CH2), 1.96–1.77 (m, 1H,
(s, 12H, 4 × OCH3), 3.83 (s, 6H, 2 × OCH3), 2.96–2.77 (m, 4H, 2 one proton in CH2), 1.44–1.27 (m, 4H, 2 × CH2), 1.11 (t, J =
× CH2), 2.24–2.00 (m, 4H, 2 × CH2), 1.90–1.08 (m, 36H, 16 × 7.4 Hz, 3H, CH3), 0.86 (t, J = 7.1 Hz, 3H, CH3); 13C NMR δ
CH2 and 4 × CH); 13C NMR (75 MHz, CDCl3) δ 164.4, 163.2, 163.3, 148.6, 134.9, 132.1, 129.6, 128.3, 128.0, 79.0, 33.0, 30.1,
94.5 (t, J = 19.4 Hz), 91.0, 55.8, 55.1, 33.4, 29.7, 28.6, 27.5 (t, 26.3, 22.6, 13.8, 8.6; IR (neat) ν (cm−1) 3063, 2959, 2931, 2873,
J = 5.0 Hz), 27.3 (t, J = 7.1 Hz), 26.5; 31P NMR (121 MHz, 1801, 1683, 1496, 1461, 1446, 1380, 1312, 1240, 1159, 1128,
CDCl3) δ 17.6; IR (KBr) ν (cm−1) 2925, 2848, 1598, 1580, 1465, 1104, 1049; MS (70 ev, EI) m/z (%): 245 (M+ + 1, 4.69), 244 (M+,
1454, 1405, 1331, 1287, 1266, 1225, 1206, 1180, 1160, 1121, 30.31), 145 (100); HRMS Calcd for C16H20O2 (M+): 244.1463.
1089, 1034, 1003. MS (ESI-TOF) 871 (C42H6637ClO6P2Pd+, 100), Found: 244.1460.
869 (C42H6635ClO6P2Pd+, 99.11); Anal. Calcd For C42H66Cl2-
(3) (S,Z)-α-(1-Butyl-(4′-methoxyl)benzylidene)-β-ethyl-β-lactone
O6P2Pd: C, 55.66; H, 7.34. Found: C, 55.75; H, 7.44.
((S,Z)-4b). The reaction of (S,Z)-2a (39.1 mg, 0.19 mmol, ee >
3. Pd-CATALYSED SUZUKI COUPLING OF α-CHLOROALKYLIDENE-β-LAC- 99%), 4-methoxylphenylboronic acid 3b (37.4 mg, 0.25 mmol),
TONES WITH ARYL AND VINYL BORONIC ACID
Pd(OAc)2 (1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg,
0.012 mmol), and K3PO4·3H2O (108.6 mg, 0.41 mmol) in 2 mL
of toluene at 110 °C under nitrogen afforded (S,Z)-4b (44.7 mg,
84%) (eluent: 30–60 °C petroleum ether/ethyl acetate = 20/1) as
a liquid in ee = 99.7%, as determined by HPLC (Chiralpak
(1) Synthesis of (S,Z)-α-(1-butylbenzylidene)-β-ethyl-β-lactone
((S,Z)-4a). Typical procedure (condition A). A rubber-capped
Schlenk vessel was dried with flame under vacuum and back-
filled with nitrogen for three times. Then Pd(OAc)2 (1.3 mg,
0.006 mmol), LB-Phos·HBF4 (5.3 mg, 0.012 mmol),
K3PO4·3H2O (107.1 mg, 0.40 mmol), phenylboronic acid
(29.4 mg, 0.24 mmol), and 1 mL of toluene were added into
the Schlenk vessel sequentially. After being stirred for about
10 min at room temperature, (S,Z)-2a (40.7 mg, 0.20 mmol,
ee > 99%) and 1 mL of toluene were added sequentially to the
vessel. The resulting mixture was heated at 110 °C with a pre-
heated oil bath. After 45 min, the reaction was complete as
monitored by TLC. Then the reaction mixture was cooled to
room temperature and diluted by 10 mL of Et2O and filtered
through a short column of silica gel (eluent: 2 × 10 mL of
Et2O). Evaporation and purification by chromatography
(eluent: petroleum ether/ethyl acetate = 60/1) on silica gel
afforded (S,Z)-4a (48.4 mg, 98%) as a liquid in ee > 99%, as
determined by HPLC (Chiralpak OD-H, n-hexane–i-PrOH =
OD-H, n-hexane–i-PrOH = 97 : 3, 1.0 mL min−1, 230 nm, tR
=
14.9 min (major), 25.8 (minor)); [α]2D0 = +5.6 (c = 1.01, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.56 (d, J = 9.0 Hz, 2H, Ar–H),
6.93 (d, J = 9.0 Hz, 2H, Ar–H), 5.00 (dd, J1 = 7.7 Hz, J2 = 3.2 Hz,
1H, OCH), 3.83 (s, 3H, OCH3), 2.58–2.29 (m, 2H, CH2),
2.17–2.02 (m, 1H, one proton in CH2), 1.94–1.75 (m, 1H, one
proton in CH2), 1.45–1.20 (m, 4H, 2 × CH2), 1.09 (t, J = 7.4 Hz,
3H, CH3), 0.87 (t, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3) δ 163.6, 160.7, 148.1, 130.4, 129.7, 127.0, 113.7, 78.9,
55.2, 32.7, 30.4, 26.4, 22.6, 13.8, 8.6; IR (neat) ν (cm−1) 2958,
2933, 2870, 2838, 1789, 1674, 1605, 1574, 1514, 1463, 1443,
1380, 1301, 1255, 1182, 1157, 1127, 1097, 1040; MS (70 ev, EI)
m/z (%): 275 (M+ + 1, 12.52), 274 (M+, 62.30), 175 (100); HRMS
Calcd for C17H22O3 (M+): 274.1569. Found 274.1577.
(4) (Z)-α-(1-Butyl-(4′-methoxyl)benzylidene)-β-ethyl-β-lactone
((Z)-4b). The reaction of (Z)-2a (40.6 mg, 0.20 mmol), 4-meth-
oxylphenyl boronic acid 3b (36.8 mg, 0.24 mmol), Pd(OAc)2
(1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.3 mg, 0.012 mmol),
and K3PO4·3H2O (107.1 mg, 0.40 mmol) in 2 mL of toluene at
110 °C under nitrogen afforded (Z)-4b (50.2 mg, 91%) (eluent:
petroleum ether/ethyl acetate = 60/1) as a liquid: 1H NMR
(300 MHz, CDCl3) δ 7.56 (d, J = 8.7 Hz, 2H, Ar–H), 6.93 (d, J =
8.7 Hz, 2H, Ar–H), 5.00 (dd, J1 = 7.7 Hz, J2 = 3.2 Hz, 1H, OCH),
3.83 (s, 3H, OCH3), 2.57–2.30 (m, 2H, CH2), 2.17–2.03 (m, 1H,
one proton in CH2), 1.94–1.76 (m, 1H, one proton in CH2),
1.47–1.23 (m, 4H, 2 × CH2), 1.10 (t, J = 7.4 Hz, 3H, CH3), 0.87
(t, J = 7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.7,
160.7, 148.1, 130.4, 129.7, 127.1, 113.7, 78.9, 55.2, 32.7, 30.4,
26.4, 22.6, 13.8, 8.6; IR (neat) ν (cm−1) 2959, 2934, 2873, 2840,
1795, 1676, 1605, 1574, 1514, 1462, 1377, 1301, 1256, 1183,
98 : 2, 0.8 mL min−1, λ = 230 nm, tR = 9.9 min (major)): [α]D20
=
−26.1 (c = 1.56, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.57–7.47
(m, 2H, Ar–H), 7.46–7.34 (m, 3H, Ar–H), 5.03 (dd, J1 = 7.5 Hz,
J2 = 3.0 Hz, 1H, OCH), 2.60–2.36 (m, 2H, CH2), 2.20–2.04 (m,
1H, one proton in CH2), 1.96–1.78 (m, 1H, one proton in CH2),
1.44–1.24 (m, 4H, 2 × CH2), 1.11 (t, J = 7.4 Hz, 3H, CH3), 0.87
(t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.3,
148.5, 134.8, 132.1, 129.5, 128.3, 128.0, 79.0, 33.0, 30.0, 26.3,
22.5, 13.7, 8.6; IR (neat) ν (cm−1) 3056, 3028, 2955, 2936, 2873,
1799, 1683, 1577, 1496, 1459, 1446, 1380, 1367, 1312, 1291,
1240, 1159, 1106, 1049, 1014; MS (70 ev, EI) m/z (%): 245 (M+ +
1, 6.32), 244 (M+, 42.33), 145 (100); HRMS Calcd for C16H20O2
(M+): 244.1463. Found 244.1457.
The following compounds were prepared according to these
procedures.
(2) (Z)-α-(1-Butylbenzylidene)-β-ethyl-β-lactone ((Z)-4a). The 1157, 1127, 1097, 1040; MS (70 ev, EI) m/z (%): 275 (M+ + 1,
reaction of (Z)-2a (40.5 mg, 0.20 mmol), phenyl boronic acid 13.42), 274 (M+, 70.85), 175 (100); HRMS Calcd for C17H22O3
3a (29.5 mg, 0.24 mmol), Pd(OAc)2 (1.2 mg, 0.006 mmol), (M+): 274.1569. Found: 274.1574.
LB-Phos·HBF4 (5.4 mg, 0.012 mmol), and K3PO4·3H2O
(5) (S,Z)-α-(1-Butyl-(3′-methoxyl)benzylidene)-β-ethyl-β-lactone
(106.9 mg, 0.40 mmol) in 2 mL of toluene at 110 °C under ((S,Z)-4c). The reaction of (S,Z)-2a (80.8 mg, 0.40 mmol, ee >
nitrogen afforded (Z)-4a (43.6 mg, 89%) (eluent: petroleum 99%), 3-methoxylphenyl boronic acid 3c (73.4 mg, 0.48 mmol),
ether/ethyl acetate = 60/1) as a liquid. 1H NMR (300 MHz, Pd(OAc)2 (2.7 mg, 0.012 mmol), LB-Phos·HBF4 (10.8 mg,
CDCl3) δ 7.57–7.48 (m, 2H, Ar–H), 7.46–7.36 (m, 3H, Ar–H), 0.024 mmol), and K3PO4·3H2O (212.0 mg, 0.80 mmol) in 4 mL
5.03 (dd, J1 = 7.7 Hz, J2 = 3.2 Hz, 1H, OCH), 2.60–2.36 (m, 2H, of toluene at 110 °C under nitrogen afforded (S,Z)-4c (83.9 mg,
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77%) (eluent: petroleum ether/ethyl acetate = 50/1) as a liquid (cm−1) 2955, 2935, 2873, 1806, 1698, 1599, 1580, 1491, 1463,
in ee > 99%, as determined by HPLC (Chiralpak OD-H, n- 1435, 1380, 1294, 1243, 1161, 1124, 1093, 1050; MS (70 ev, EI)
hexane–i-PrOH = 97 : 3, 0.8 mL min−1, 230 nm, tR = 10.0 min m/z (%): 275 (M+ + 1, 19.03), 274 (M+, 100); HRMS Calcd for
(major)): [α]2D0 = −25.8 (c = 0.89, CHCl3); 1H NMR (300 MHz, C17H22O3 (M+): 274.1569. Found: 274.1577.
CDCl3) δ 7.31 (t, J = 8.1 Hz, 1H, Ar–H), 7.15 (s, 1H, Ar–H), 7.08
(8) (Z)-α-(1-Butyl-(2′-methoxyl)benzylidene)-β-ethyl-β-lactone
(d, J = 3.9 Hz 1H, Ar–H), 6.97–6.89 (m, 1H, Ar–H), 5.01 (dd, J1 = ((Z)-4d). The reaction of (Z)-2a (40.2 mg, 0.20 mmol), 2-meth-
7.8 Hz, J2 = 2.7 Hz, 1H, OCH), 3.84 (s, 3H, OCH3), 2.58–2.33 oxylphenyl boronic acid 3d (36.7 mg, 0.48 mmol), Pd(OAc)2
(m, 2H, CH2), 2.21–2.02 (m, 1H, one proton in CH2), 1.97–1.77 (1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.5 mg, 0.012 mmol),
(m, 1H, one proton in CH2), 1.50–1.23 (m, 4H, 2 × CH2), 1.10 and K3PO4·3H2O (107.0 mg, 0.40 mmol) in 2 mL of toluene at
(t, J = 7.4 Hz, 3H, CH3), 0.87 (t, J = 6.6 Hz, 3H, CH3); 13C NMR 110 °C under nitrogen afforded (Z)-4d (35.7 mg, 65%) (eluent:
(75 MHz, CDCl3) δ 163.2, 159.3, 148.3, 136.1, 132.1, 129.3, petroleum ether/ethyl acetate = 40/1) as a liquid: 1H NMR
120.1, 115.4, 113.7, 79.0, 55.3, 33.0, 30.1, 26.3, 22.6, 13.8, 8.6; (300 MHz, CDCl3) δ 7.38–7.28 (m, 1H, Ar–H), 7.15 (dd, J1
=
IR (neat) ν (cm−1) 2959, 2930, 2873, 2838, 1801, 1684, 1599, 7.5 Hz, J2 = 1.8 Hz, 1H, Ar–H), 7.02–6.86 (m, 2H, Ar–H), 5.07
1579, 1489, 1464, 1430, 1374, 1319, 1290, 1235, 1181, 1153, (dd, J1 = 7.4 Hz, J2 = 3.2 Hz, 1H, OCH), 3.80 (s, 3H, OCH3),
1106, 1050; MS (70 ev, EI) m/z (%): 275 (M+ + 1, 18.18), 274 2.58–2.35 (m, 2H, CH2), 2.20–2.04 (m, 1H, one proton in CH2),
(M+, 100); HRMS Calcd for C17H22O3 (M+): 274.1569. Found 1.97–1.80 (m, 1H, one proton in CH2), 1.36–1.20 (m, 4H, 2 ×
274.1565.
CH2), 1.11 (t, J = 7.5 Hz, 3H, CH3), 0.84 (t, J = 6.9 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3) δ 163.2, 156.3, 147.0, 133.1, 130.1,
(6) (Z)-α-(1-Butyl-(3′-methoxyl)benzylidene)-β-ethyl-β-lactone
((Z)-4c). The reaction of (Z)-2a (40.4 mg, 0.20 mmol), 3-meth- 130.0, 124.8, 120.3, 110.8, 79.4, 55.4, 33.2, 29.5, 26.2, 22.5,
oxylphenyl boronic acid 3c (36.5 mg, 0.24 mmol), Pd(OAc)2 13.8, 8.4; IR (neat) ν (cm−1) 2955, 2935, 2873, 1806, 1699, 1599,
(1.2 mg, 0.006 mmol), LB-Phos·HBF4 (5.3 mg, 0.012 mmol), 1580, 1491, 1463, 1435, 1380, 1294, 1267, 1243, 1181, 1161,
and K3PO4·3H2O (107.2 mg, 0.40 mmol) in 2 mL of toluene at 1124, 1093, 1050; MS (70 ev, EI) m/z (%): 275 (M+ + 1, 18.92),
110 °C under nitrogen afforded (Z)-4c (43.8 mg, 80%) (eluent: 274 (M+, 100); HRMS Calcd for C17H22O3 (M+): 274.1569.
petroleum ether/ethyl acetate = 50/1) as a liquid: 1H NMR Found: 274.1569.
(300 MHz, CDCl3) δ 7.31 (t, J = 6.0 Hz, 1H, Ar–H), 7.15 (t, J =
(9) (S)-α-(1(Z)-(2′(E)-Phenylethenyl)pentylidene)-β-ethyl-β-lactone
2.0 Hz, 1H, Ar–H), 7.08 (d, J = 3.9 Hz, 1H, Ar–H), 6.97–6.87 (m, ((S,Z,E)-4e). The reaction of (S,Z)-2a (80.4 mg, 0.40 mmol, ee >
1H, Ar–H), 5.02 (dd, J1 = 7.8 Hz, J2 = 3.0 Hz, 1H, OCH), 3.84 (s, 99%), E-phenylethenyl boronic acid 3e (71.2 mg, 0.48 mmol),
3H, OCH3), 2.57–2.33 (m, 2H, CH2), 2.20–2.03 (m, 1H, one Pd(OAc)2 (2.7 mg, 0.012 mmol), LB-Phos·HBF4 (10.8 mg,
proton in CH2), 1.96–1.77 (m, 1H, one proton in CH2), 0.024 mmol) and K3PO4·3H2O (212.7 mg, 0.8 mmol) in 4 mL
1.46–1.23 (m, 4H, 2 × CH2), 1.11 (t, J = 7.4 Hz, 3H, CH3), 0.87 of toluene at 110 °C under nitrogen afforded (S,Z,E)-4e
(t, J = 7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.2, (97.3 mg, 91%) (eluent: petroleum ether/ethyl acetate = 60/1)
159.4, 148.3, 136.1, 132.2, 129.3, 120.1, 115.5, 113.7, 79.0, 55.3, as a liquid in ee > 99%, as determined by HPLC (Chiralpak
33.0, 30.2, 26.3, 22.6, 13.8, 8.6; IR (neat) ν (cm−1) 2959, 2935, AD-H, n-hexane–i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR
=
2873, 2837, 1801, 1685, 1599, 1579, 1489, 1464, 1430, 1380, 10.4 min (major)); [α]2D0 = −17.0 (c = 0.88, CHCl3); 1H NMR
1319, 1289, 1234, 1181, 1153, 1127, 1106, 1049; MS (70 ev, EI) (300 MHz, CDCl3) δ 7.61 (d, J = 16.5 Hz, 1H, CvCH), 7.57–7.47
m/z (%): 275 (M+ + 1, 17.84), 274 (M+, 100); HRMS Calcd for (m, 2H, Ar–H), 7.43–7.27 (m, 3H, Ar–H), 6.90 (d, J = 16.5 Hz,
C17H22O3 (M+): 274.1569. Found: 274.1569.
1H, CvCH), 5.01 (dd, J1 = 7.8 Hz, J2 = 3.3 Hz, 1H, OCH),
2.43–2.26 (m, 2H, CH2), 2.15–1.97 (m, 1H, one proton in CH2),
(7) (S,Z)-α-(1-Butyl-(2′-methoxyl)benzylidene)-β-ethyl-β-lactone
((S,Z)-4d). The reaction of (S,Z)-2a (81.1 mg, 0.40 mmol, ee > 1.92–1.73 (m, 1H, one proton in CH2), 1.69–1.32 (m, 4H, 2 ×
99%), 2-methoxylphenyl boronic acid 3d (73.3 mg, CH2), 1.08 (t, J = 7.4 Hz, 3H, CH3), 0.96 (t, J = 7.1 Hz, 3H, CH3);
0.48 mmol), Pd(OAc)2 (2.7 mg, 0.012 mmol), LB-Phos·HBF4 13C NMR (75 MHz, CDCl3) δ 164.1, 144.9, 135.9, 134.5, 133.1,
(10.9 mg, 0.024 mmol), and K3PO4·3H2O (212.9 mg, 129.0, 128.7, 127.3, 123.5, 79.6, 31.5, 28.6, 26.3, 23.0, 13.8, 8.7;
0.80 mmol) in 4 mL of toluene at 110 °C under nitrogen IR (neat) ν (cm−1) 3079, 3056, 3037, 3018, 2959, 2933, 2873,
afforded (S,Z)-4d (90.5 mg, 82%) (eluent: petroleum ether/ethyl 1793, 1670, 1627, 1573, 1492, 1464, 1449, 1378, 1366, 1321,
acetate = 40/1) as a liquid in ee = 99.6%, as determined by 1295, 1236, 1148, 1125, 1054; MS (70 ev, EI) m/z (%): 271 (M+ +
HPLC (Chiralpak OD-H, n-hexane–i-PrOH = 98 : 2, 0.8 mL 1, 4.69), 270 (M+, 16.98), 213 (100); HRMS Calcd for C18H22O2
min−1, 214 nm, tR = 12.4 min (major), tR = 15.6 min (major)); (M+): 270.1620. Found 270.1627.
[α]2D0 = −16.9 (c = 1.04, CHCl3); 1H NMR (300 MHz, CDCl3) δ
(10) α-(1(Z)-(2′(E)-Phenylethenyl)pentylidene)-β-ethyl-β-lactone
7.38–7.27 (m, 1H, Ar–H), 7.16 (dd, J1 = 7.5 Hz, J2 = 1.8 Hz, 1H, ((Z,E)-4e). The reaction of (Z)-2a (40.6 mg, 0.20 mmol), E-
Ar–H), 7.02–6.87 (m, 2H, Ar–H), 5.07 (dd, J1 = 7.5 Hz, J2
=
phenylethenyl boronic acid 3e (35.6 mg, 0.24 mmol), Pd(OAc)2
3.0 Hz, 1H, OCH), 3.80 (s, 3H, OCH3), 2.57–2.35 (m, 2H, CH2), (1.3 mg, 0.006 mmol), 1·HBF4 (5.4 mg, 0.012 mmol), and
2.20–2.04 (m, 1H, one proton in CH2), 1.97–1.80 (m, 1H, one K3PO4·3H2O (107.1 mg, 0.40 mmol) in 2 mL of toluene at
proton in CH2), 1.36–1.22 (m, 4H, 2 × CH2), 1.11 (t, J = 7.4 Hz, 110 °C under nitrogen afforded (Z,E)-4e9 (43.7 mg, 81%)
3H, CH3), 0.84 (t, J = 7.1 Hz, 3H, CH3); 13C NMR (75 MHz, (eluent: petroleum ether/ethyl acetate = 60/1) as a liquid: 1H
CDCl3) δ 163.2, 156.3, 147.0, 133.2, 130.1, 130.0, 124.8, 120.3, NMR (300 MHz, CDCl3) δ 7.61 (d, J = 16.5 Hz, 1H, CvCH),
110.9, 79.4, 55.4, 33.2, 29.5, 26.2, 22.5, 13.8, 8.4; IR (neat) ν 7.57–7.50 (m, 2H, Ar–H), 7.43–7.27 (m, 3H, Ar–H), 6.90 (d, J =
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16.5 Hz, 1H, CvCH), 5.01 (dd, J1 = 7.8 Hz, J2 = 3.3 Hz, 1H, 71%) (eluent: petroleum ether/ethyl acetate = 40/1) as a liquid
OCH), 2.44–2.25 (m, 2H, CH2), 2.16–1.97 (m, 1H, one proton in in ee > 99%, as determined by HPLC (Chiralpak OD-H,
CH2), 1.91–1.73 (m, 1H, one proton in CH2), 1.69–1.34 (m, 4H, n-hexane–i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR = 9.0 min
2 × CH2), 1.08 (t, J = 7.4 Hz, 3H, CH3), 0.97 (t, J = 7.2 Hz, 3H, (major)); [α]2D0 = +9.5 (c = 0.97, CHCl3); 1H NMR (300 MHz,
CH3); 13C NMR (75 MHz, CDCl3) δ 164.1, 144.9, 135.9, 134.4, CDCl3) δ 7.46 (d, J = 8.1 Hz, 2H, Ar–H), 7.22 (d, J = 8.1 Hz, 2H,
133.1, 129.0, 128.7, 127.3, 123.4, 79.6, 31.4, 28.6, 26.3, 22.9, Ar–H), 5.12 (q, J = 6.3 Hz, 1H, OCH), 2.60–2.31 (m, 5H, CH3
13.8, 8.7; IR (neat) ν (cm−1) 3082, 3060, 3044, 3028, 2959, 2933, and CH2), 1.67 (d, J = 6.0 Hz, 3H, CH3), 1.44–1.24 (m, 4H, 2 ×
2873, 1791, 1669, 1622, 1576, 1496, 1449, 1374, 1317, 1295, CH2), 0.87 (t, J = 7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ
1236, 1148, 1125, 1094, 1054; MS (70 ev, EI) m/z (%): 271 (M+ + 163.3, 148.4, 139.8, 133.0, 131.8, 129.0, 127.9, 74.2, 32.5, 30.2,
1, 5.52), 270 (M+, 27.71), 213 (100).
22.5, 21.3, 19.5, 13.7; IR (neat) ν (cm−1) 3021, 2957, 2930, 2869,
1798, 1680, 1610, 1513, 1454, 1378, 1339, 1258, 1157, 1107,
(11) (S,Z)-α-(1-Butyl-(4′-methyl)benzylidene)-β-ethyl-β-lactone
((S,Z)-4f). The reaction of (S,Z)-2a (40.4 mg, 0.20 mmol, ee > 1086, 1061, 1014; MS (70 ev, EI) m/z (%): 245 (M+ + 1, 4.22),
99%), 4-methylphenyl boronic acid 3f (32.6 mg, 0.24 mmol), 244 (M+, 23.54), 143 (100); HRMS Calcd for C16H20O2 (M+):
Pd(OAc)2 (1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg, 244.1463. Found 244.1459.
0.012 mmol), and K3PO4·3H2O (106.7 mg, 0.40 mmol) in 2 mL
(14) (Z)-α-(1-Butyl-(4′-methyl)benzylidene)-β-methyl-β-lactone
of toluene at 110 °C under nitrogen afforded (S,Z)-4f9 ((Z)-4g). The reaction of (Z)-2b (38.0 mg, 0.20 mmol), 4-methyl-
(48.1 mg, 93%) (eluent: petroleum ether/ethyl acetate = 50/1) phenyl boronic acid 3f (33.2 mg, 0.24 mmol), Pd(OAc)2
as a liquid in ee > 99%, as determined by HPLC (Chiralpak (1.4 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg, 0.012 mmol),
OD-H, n-hexane–i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR
9.3 min (major)); [α]D20 = −10.8 (c = 0.72, CHCl3, Lit. [α]2D0
=
=
and K3PO4·3H2O (107.2 mg, 0.40 mmol) in 2 mL of toluene at
110 °C under nitrogen afforded (Z)-4g (37.9 mg, 77%) (eluent:
−10.1 (c = 1.0, CHCl3, ee = 99.9%)9): 1H NMR (300 MHz, petroleum ether/ethyl acetate = 40/1) as a liquid: 1H NMR
CDCl3) δ 7.45 (d, J = 8.1 Hz, 2H, Ar–H), 7.22 (d, J = 8.1 Hz, 2H, (300 MHz, CDCl3) δ 7.51–7.42 (m, 2H, Ar–H), 7.22 (d, J =
Ar–H), 5.01 (dd, J1 = 7.7 Hz, J2 = 2.9 Hz, 1H, OCH), 2.61–2.31 7.8 Hz, 2H, Ar–H), 5.12 (q, J = 6.2 Hz, 1H, OCH), 2.60–2.33 (m,
(m, 5H, CH3 and CH2), 2.20–2.04 (m, 1H, one proton in CH2), 5H, CH3 and CH2), 1.67 (d, J = 6.3 Hz, 3H, CH3), 1.46–1.22 (m,
1.95–1.77 (m, 1H, one proton in CH2), 1.45–1.24 (m, 4H, 2 × 4H, 2 × CH2), 0.87 (t, J = 7.1 Hz, 3H, CH3); 13C NMR (75 MHz,
CH2), 1.11 (t, J = 7.4 Hz, 3H, CH3), 0.87 (t, J = 7.1 Hz, 3H, CH3); CDCl3) δ 163.2, 148.4, 139.8, 133.0, 131.8, 129.1, 127.9, 74.2,
13C NMR (75 MHz, CDCl3) δ 163.4, 148.6, 139.7, 131.9, 131.3, 32.5, 30.2, 22.5, 21.3, 19.5, 13.7; IR (neat) ν (cm−1) 3031, 2957,
129.0, 127.9, 79.0, 32.9, 30.2, 26.3, 22.6, 21.3, 13.7, 8.5; IR 2931, 2869, 1798, 1679, 1610, 1513, 1454, 1378, 1339, 1258,
(neat) ν (cm−1) 3028, 2959, 2926, 2873, 1798, 1681, 1610, 1564, 1157, 1107, 1090, 1061, 1014; MS (70 ev, EI) m/z (%): 245 (M+ +
1513, 1460, 1380, 1312, 1291, 1239, 1158, 1128, 1095, 1048, 1, 4.54), 244 (M+, 26.94), 143 (100); HRMS Calcd for C16H20O2
1020; MS (70 ev, EI) m/z (%): 259 (M+ + 1, 5.06), 258 (M+, (M+): 244.1463. Found: 244.1466.
28.77), 159 (100).
(12) (Z)-α-(1-Butyl-(4′-methyl)benzylidene)-β-ethyl-β-lactone
(15) (S,Z)-α-(1-(2′-Naphthyl)butylidene)-β-ethyl-β-lactone ((S,
Z)-4h). The reaction of (S,Z)-2a (80.6 mg, 0.40 mmol, ee >
((Z)-4f). The reaction of (Z)-2a (40.6 mg, 0.20 mmol), 4-methyl- 99%), 2-naphthyl boronic acid 3g (82.7 mg, 0.48 mmol),
phenyl boronic acid 3f (33.2 mg, 0.24 mmol), Pd(OAc)2 Pd(OAc)2 (2.8 mg, 0.012 mmol), LB-Phos·HBF4 (10.9 mg,
(1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg, 0.012 mmol), 0.024 mmol), and K3PO4·3H2O (212.9 mg, 0.80 mmol) in 4 mL
and K3PO4·3H2O (106.4 mg, 0.40 mmol) in 2 mL of toluene at of toluene 110 °C under nitrogen afforded (S,Z)-4h (101.0 mg,
110 °C under nitrogen afforded (Z)-4f9 (50.1 mg, 97%) (eluent: 86%) (eluent: petroleum ether/methylene dichloride = 2/1) as a
petroleum ether/ethyl acetate = 50/1) as a liquid: 1H NMR solid in ee > 99%, as determined by HPLC (Chiralpak OD-H,
(300 MHz, CDCl3) δ 7.45 (d, J = 8.4 Hz, 2H, Ar–H), 7.22 (d, J = n-hexane–i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR = 12.8 min
7.8 Hz, 2H, Ar–H), 5.01 (dd, J1 = 7.7 Hz, J2 = 3.2 Hz, 1H, OCH), (major)); [α]2D0 = −5.1 (c = 2.26, CHCl3); m.p. 83–84 °C
2.60–2.26 (m, 5H, CH3 and CH2), 2.20–2.03 (m, 1H, one proton (n-hexane); 1H NMR (300 MHz, CDCl3) δ 8.03 (s, 1H, Ar–H),
in CH2), 1.95–1.77 (m, 1H, one proton in CH2), 1.45–1.24 (m, 7.97–7.78 (m, 3H, Ar–H), 7.73–7.61 (m, 1H, Ar–H), 7.59–7.43
4H, 2 × CH2), 1.11 (t, J = 7.4 Hz, 3H, CH3), 0.87 (t, J = 7.1 Hz, (m, 2H, Ar–H), 5.08 (dd, J1 = 7.7 Hz, J2 = 3.2 Hz, 1H, OCH),
3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.4, 148.6, 139.8, 2.74–2.43 (m, 2H, CH2), 2.27–2.05 (m, 1H, one proton in CH2),
131.9, 131.3, 129.0, 127.9, 79.0, 32.9, 30.2, 26.3, 22.6, 21.3, 2.04–1.80 (m, 1H, one proton in CH2), 1.53–1.23 (m, 4H, 2 ×
13.8, 8.5; IR (neat) ν (cm−1) 3025, 2959, 2930, 2873, 1798, 1681, CH2), 1.16, (t, J = 7.4 Hz, 3H, CH3), 0.87 (t, J = 6.9 Hz, 3H,
1610, 1564, 1513, 1460, 1380, 1312, 1291, 1239, 1158, 1128, CH3); 13C NMR (75 MHz, CDCl3) δ 163.3, 148.5, 133.7, 132.8,
1095, 1048, 1020; MS (70 ev, EI) m/z (%): 259 (M+ + 1, 5.05), 132.3, 128.5, 128.0, 127.8, 127.6, 126.8, 126.3, 125.4, 79.1, 33.0,
258 (M+, 27.60), 159 (100).
30.1, 26.3, 22.5, 13.7, 8.6; IR (KBr) ν (cm−1) 3057, 2959, 2933,
2872, 1797, 1681, 1597, 1504, 1461, 1380, 1311, 1239, 1155,
(13) (S,Z)-α-(1-Butyl-(4′-methyl)benzylidene)-β-methyl-β-lactone
((S,Z)-4g). The reaction of (S,Z)-2b (36.8 mg, 0.20 mmol, ee > 1123, 1097, 1048, 1017; MS (70 ev, EI) m/z (%): 295 (M+ + 1,
99%), 4-methylphenyl boronic acid 3f (33.0 mg, 0.24 mmol), 10.17), 294 (M+, 47.97), 237 (100); Anal. Calcd for C20H22O2: C,
Pd(OAc)2 (1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg, 81.60; H, 7.53. Found: C, 81.82; H, 7.58.
0.012 mmol), K3PO4·3H2O (106.6 mg, 0.40 mmol) in 2 mL of
toluene at 110 °C under nitrogen afforded (S,Z)-4g (34.1 mg, 4h). The reaction of (Z)-2a (40.7 mg, 0.20 mmol), 2-
(16) (Z)-α-(1-(2′-Naphthyl)butylidene)-β-ethyl-β-lactone ((Z)-
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naphthylboronic acid 3g (41.6 mg, 0.24 mmol), Pd(OAc)2 m/z (%): 259 (M+ + 1, 3.42), 258 (M+, 21.00), 145 (100); HRMS
(1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg, 0.012 mmol), Calcd for C17H22O2 (M+): 258.1620. Found: 258.1612.
K3PO4·3H2O (106.4 mg, 0.4 mmol) in 2 mL of toluene at
(19) (S,Z)-α-(1-(4′-Methoxylphenyl)benzylidene)-β-ethyl-β-lactone
110 °C under nitrogen afforded (Z)-4h (52.7 mg, 89%) (eluent: ((S,Z)-4j). The reaction of (S,Z)-2d (88.9 mg, 0.40 mmol, ee >
petroleum ether/ethyl acetate = 40/1) as a liquid: 1H NMR 99%), 4-methoxylphenyl boronic acid 3a (73.4 mg, 0.48 mmol),
(300 MHz, CDCl3) δ 8.03 (d, J = 1.2 Hz, 1H, Ar–H), 7.94–7.79 Pd(OAc)2 (2.7 mg, 0.012 mmol), LB-Phos·HBF4 (10.8 mg,
(m, 3H, Ar–H), 7.71–7.61 (m, 1H, Ar–H), 7.57–7.46 (m, 2H, Ar– 0.024 mmol), K3PO4·3H2O (212.8 mg, 0.80 mmol) in 4 mL of
H), 5.08 (dd, J1 = 7.8 Hz, J2 = 3.0 Hz, 1H, OCH), 2.72–2.45 (m, toluene at 110 °C under nitrogen afforded (S,Z)-4j (109.2 mg,
2H, CH2), 2.25–2.06 (m, 1H, one proton in CH2), 2.01–1.82 (m, 93%) (eluent: petroleum ether/ethyl acetate = 20/1) as a solid
1H, one proton in CH2), 1.50–1.24 (m, 4H, 2 × CH2), 1.15 (t, J = in ee > 99%, as determined by HPLC (Chiralpak OJ-H,
7.4 Hz, 3H, CH3), 0.87 (t, J = 7.1 Hz, 3H, CH3); 13C NMR n-hexane–i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR = 35.8 min
(75 MHz, CDCl3) δ 163.3, 148.5, 133.7, 132.9, 132.4, 132.3, (major)): [α]2D0 = +65.1 (c = 1.08, CHCl3); m.p. 68–69 °C
128.6, 128.0, 127.8, 127.6, 126.9, 126.3, 125.4, 79.1, 33.0, 30.2, (n-hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3)
δ
26.4, 22.6, 13.8, 8.6; IR (neat) ν (cm−1) 3057, 2959, 2933, 2873, 7.55–7.47 (m, 2H, Ar–H), 7.45–7.35 (m, 3H, Ar–H), 7.29–7.18
1798, 1681, 1600, 1501, 1461, 1374, 1308, 1239, 1155, 1123, (m, 2H, Ar–H), 6.94–6.85 (m, 2H, Ar–H), 5.17 (dd, J1 = 7.2 Hz,
1097, 1048, 1014; MS (70 ev, EI) m/z (%): 295 (M+ + 1, 10.23), J2 = 3.3 Hz, 1H, OCH), 3.84 (s, 3H, OCH3), 1.64–1.47 (m, 1H,
294 (M+, 47.88), 237 (100); HRMS Calcd for C20H22O2 (M+): one proton in CH2), 1.46–1.30 (m, 1H, one proton in CH2),
294.1620. Found: 294.1615.
0.85 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.8,
161.1, 146.7, 137.7, 131.8, 130.8, 129.3, 129.2, 128.6, 128.2,
113.6, 79.6, 55.3, 24.7, 8.1; IR (KBr) ν (cm−1) 3053, 2971, 2931,
2908, 2876, 2841, 1783, 1650, 1604, 1513, 1493, 1459, 1445,
1297, 1257, 1174, 1161, 1128, 1077, 1064, 1023; MS (70 ev, EI)
m/z (%): 295 (M+ + 1, 18.33), 294 (M+, 90.71), 265 (100); HRMS
Calcd for C19H18O3 (M+): 294.1256. Found: 294.1255.
(17) (S,Z)-α-(1-Butylbenzylidene)-β-isopropyl-β-lactone ((S,Z)-
4i). The reaction of (S,Z)-2c (86.6 mg, 0.40 mmol, ee = 99%),
phenyl boronic acid 3a (59.1 mg, 0.48 mmol), Pd(OAc)2
(2.8 mg, 0.012 mmol), LB-Phos·HBF4 (10.9 mg, 0.024 mmol),
K3PO4·3H2O (213.6 mg, 0.80 mmol) in 4 mL of toluene at
110 °C under nitrogen afforded (S,Z)-4i (97.1 mg, 94%)
(eluent: petroleum ether/ethyl acetate = 40/1) as a liquid in ee >
99%, as determined by HPLC (Chiralpak OD-H, n-hexane–
i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR = 8.1 min (major)):
[α]2D0 = −6.8 (c = 1.02, CHCl3); 1H NMR (300 MHz, CDCl3) δ
7.58–7.47 (m, 2H, Ar–H), 7.46–7.32 (m, 3H, Ar–H), 4.98 (d, J =
2.7 Hz, 1H, OCH), 2.63–2.49 (m, 1H, one proton in CH2),
2.49–2.36 (m, 1H, one proton in CH2), 2.36–2.18 (m, 1H, CH),
1.47–1.23 (m, 4H, 2 × CH2), 1.17 (d, J = 7.2 Hz, 3H, CH3), 1.05
(d, J = 6.9 Hz, 3H, CH3), 0.87 (t, J = 7.1 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3) δ 163.3, 148.6, 134.9, 131.3, 129.4, 128.2,
127.9, 82.3, 33.2, 30.6, 29.8, 22.5, 18.7, 14.9, 13.6; IR (neat) ν
(cm−1) 3059, 3022, 2963, 2932, 2873, 1801, 1682, 1573, 1494,
1466, 1445, 1387, 1375, 1341, 1296, 1244, 1187, 1148, 1105,
1072, 1038: MS (70 ev, EI) m/z (%): 259 (M+ + 1, 3.06), 258 (M+,
21.03), 145 (100); HRMS Calcd for C17H22O2 (M+): 258.1620.
Found: 258.1609.
(20) (Z)-α-(1-(4′-Methoxylphenyl)benzylidene)-β-ethyl-β-lactone
((Z)-4j). The reaction of (Z)-2d (44.7 mg, 0.20 mmol), 4-meth-
oxylphenyl boronic acid 3a (36.9 mg, 0.24 mmol), Pd(OAc)2
(1.3 mg, 0.006 mmol), LB-Phos·HBF4 (5.4 mg, 0.012 mmol),
K3PO4·3H2O (106.8 mg, 0.40 mmol) in 2 mL of toluene at
110 °C under nitrogen afforded (Z)-4j (57.7 mg, 97%) (eluent:
petroleum ether/ethyl acetate = 40/1) as a solid: m.p. 97–98 °C
(n-hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3)
δ
7.56–7.47 (m, 2H, Ar–H), 7.45–7.35 (m, 3H, Ar–H), 7.29–7.19
(m, 2H, Ar–H), 6.94–6.85 (m, 2H, Ar–H), 5.17 (dd, J1 = 7.2 Hz,
J2 = 3.6 Hz, 1H, OCH), 3.84 (s, 3H, OCH3), 1.64–1.48 (m, 1H,
one proton in CH2) 1.48–1.30 (m, 1H, one proton in CH2), 0.85
(t, J = 7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.8,
161.1, 146.7, 137.7, 131.8, 130.8, 129.3, 129.2, 128.6, 128.2,
113.6, 79.5, 55.3, 24.7, 8.1; IR (KBr) ν (cm−1) 2996, 2968, 2962,
2932, 2873, 2834, 1802, 1670, 1606, 1514, 1456, 1441, 1389,
1320, 1272, 1250, 1182, 1161, 1125, 1077, 1053, 1029; MS (70
(18) (Z)-α-(1-Butylbenzylidene)-β-isopropyl-β-lactone ((Z)-4i). The ev, EI) m/z (%): 295 (M+ + 1, 19.56), 294 (M+, 92.91), 265 (100);
reaction of (Z)-2c (43.5 mg, 0.20 mmol), phenylboronic acid 3a Anal. Calcd for C19H18O3 (M+): C: 77.53, H: 6.16. Found: C:
(30.1 mg, 0.25 mmol), Pd(OAc)2 (1.3 mg, 0.006 mmol), 77.44, H, 5.99.
LB-Phos·HBF4 (5.4 mg, 0.012 mmol), K3PO4·3H2O (107.1 mg,
(21) (S)-α-(1(E)-(Pent-1′(E)-enyl)benzylidene)-β-ethyl-β-lactone
0.40 mmol) in 2 mL of toluene at 110 °C under nitrogen ((S,E,E)-4k). The reaction of (S,Z)-2d (88.5 mg, 0.40 mmol, ee >
afforded (Z)-4i (45.0 mg, 87%) (eluent: petroleum ether/ethyl 99%), (1E)-pentenyl boronic acid 3h (55. 3 mg, 0.48 mmol),
acetate = 50/1) as a liquid: 1H NMR (300 MHz, CDCl3) δ Pd(OAc)2 (2.7 mg, 0.012 mmol), LB-Phos·HBF4 (10.7 mg,
7.55–7.46 (m, 2H, Ar–H), 7.46–7.35 (m, 3H, Ar–H), 4.97 (d, J = 0.024 mmol), K3PO4·3H2O (213.5 mg, 0.80 mmol) in 4 mL of
3.0 Hz, 1H, OCH), 2.63–2.34 (m, 2H, CH2), 2.34–2.16 (m, 1H, toluene at 110 °C under nitrogen afforded (S,E,E)-4k (96.6 mg,
CH), 1.44–1.23 (m, 4H, 2 × CH2), 1.16 (d, J = 6.9 Hz, 3H, CH3), 95%) (eluent: petroleum ether/ethyl acetate = 40/1) as a liquid
1.04 (d, J = 6.9 Hz, 3H, CH3), 0.86 (t, J = 7.1 Hz, 3H, CH3); in ee > 99%, as determined by HPLC (Chiralpak AD-H,
13C NMR (75 MHz, CDCl3) δ 163.4, 148.7, 135.0, 131.4, 129.5, n-hexane–i-PrOH = 98 : 2, 0.8 mL min−1, 230 nm, tR = 8.0 min
128.3, 128.0, 82.4, 33.4, 30.7, 29.9, 22.6, 18.8, 15.0, 13.7; IR (major), 8.5 min (minor)): [α]2D0 = −120.7 (c = 1.04, CHCl3);
(neat) ν (cm−1) 2963, 2932, 2873, 1801, 1682, 1489, 1465, 1445, 1H NMR (300 MHz, CDCl3) δ 7.45–7.32 (m, 3H, Ar–H),
1383, 1338, 1244, 1185, 1147, 1105, 1068, 1038: MS (70 ev, EI) 7.25–7.15 (m, 2H, Ar–H), 7.10 (d, J = 15.9 Hz, 1H, CvCH), 5.84
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(dt, J1 = 15.9 Hz, J2 = 7.4 Hz, 1H, CvCH), 4.97 (dd, J1 = 7.1 Hz, 3087, 3012, 2987, 2963, 2940, 2922, 2878, 1792, 1697, 1489,
J2 = 3.5 Hz, 1H, OCH), 2.18 (q, J = 7.3 Hz, 2H, CH2), 1.59–1.21 1463, 1441, 1420, 1306, 1235, 1194, 1168, 1119, 1055, 1011; MS
(m, 4H, 2 × CH2), 0.89 (t, J = 7.4 Hz, 3H, CH3), 0.78 (t, J = 7.5 (70 ev, EI) m/z (%): 229 (M+ + 1, 2.36), 228 (M+, 14.38), 153
Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 164.1, 145.0, 143.2, (100); Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C,
134.6, 131.3, 128.8, 128.5, 126.7, 79.9, 35.1, 25.3, 22.0, 13.7, 79.08; H, 7.36.
8.2; IR (neat) ν (cm−1), 2964, 2932, 2874, 1795, 1664, 1462,
The following compounds were prepared according to this
1444, 1322, 1310, 1301, 1236, 1163, 1106, 1054; MS (70 ev, EI) procedure.
m/z (%): 257 (M+ + 1, 2.24), 256 (M+, 11.22), 185 (100); HRMS
(2) (E)-α-(1-Cyclopropylbenzylidene)-β-ethyl-β-lactone ((E)-4l).
The reaction of (Z)-2d (90.1 mg, 0.41 mmol), n-butyl boronic
acid 3i (41.6 mg, 0.48 mmol), Pd(OAc)2 (2.6 mg, 0.012 mmol),
Calcd for C17H20O2 (M+): 256.1463. Found: 256.1458.
(22) α-(1(E)-(Pent-1′(E)-enyl)benzylidene)-β-ethyl-β-lactone ((E,
E)-4k). The reaction of (Z)-2d (45.1 mg, 0.40 mmol), (1E)-pen- LB-Phos·HBF4 (10.8 mg, 0.024 mmol), K3PO4·3H2O (213.2 mg,
tenylboronic acid 3h (27.9 mg, 0.24 mmol), Pd(OAc)2 (1.3 mg, 0.80 mmol) in the mixture solvent of 4 mL of toluene and
0.006 mmol), LB-Phos·HBF4 (5.4 mg, 0.012 mmol), 0.4 mL of H2O at 110 °C under nitrogen afforded (E)-4l
K3PO4·3H2O (107.6 mg, 0.40 mmol) in 2 mL of toluene at (22.6 mg, 24%) (eluent: petroleum ether/ethyl acetate = 30/1,
110 °C under nitrogen afforded (E,E)-4k (48.1 mg, 92%) then recrystallization in 8 mL n-hexane) as a solid: m.p.
(eluent: petroleum ether/ethyl acetate = 40/1) as a liquid: 1H 68–69 °C (n-hexane); 1H NMR (300 MHz, CDCl3) δ 7.42–7.28
NMR (300 MHz, CDCl3) δ 7.52–7.32 (m, 3H, Ar–H), 7.25–7.15 (m, 3H, Ar–H), 7.14–6.98 (m, 2H, Ar–H), 4.78 (dd, J1 = 7.2 Hz,
(m, 2H, Ar–H), 7.10 (d, J = 15.6 Hz, 1H, CvCH), 5.94–5.74 (m, J2 = 3.9 Hz, 1H, OCH), 2.66–2.49 (m, 1H, CH), 1.53–1.18 (m,
1H, CvCH), 4.97 (dd, J1 = 7.1 Hz, J2 = 3.8 Hz, 1H, OCH), 2.18 2H, CH2), 0.99–0.83 (m, 2H, CH2), 0.83–0.63 (m, 4H, CH3 and
(q, J = 7.1 Hz, 2H, CH2), 1.57–1.19 (m, 4H, 2 × CH2), 0.89 (t, J = one proton in CH2), 0.53–0.35 (m, 1H, one proton in CH2); 13
7.5 Hz, 3H, CH3), 0.78 (t, J = 7.4 Hz, 3H, CH3); 13C NMR NMR (75 MHz, CDCl3) δ 164.8, 151.7, 133.5, 131.9, 128.5,
(75 MHz, CDCl3) δ 164.1, 145.0, 143.2, 134.6, 131.3, 128.8, 128.3, 127.8, 79.9, 25.5, 14.9, 8.3, 6.9, 6.2; IR (KBr) ν (cm−1
128.5, 126.7, 79.9, 35.1, 25.3, 22.0, 13.7, 8.3; IR (neat) ν (cm−1
3009, 2965, 2940, 2917, 2873, 1790, 1695, 1603, 1496, 1461,
C
)
)
2964, 2931, 2869, 1794, 1665, 1629, 1462, 1444, 1382, 1322, 1435, 1312, 1261, 1235, 1194, 1169, 1119, 1094, 1056, 1042,
1304, 1293, 1236, 1163, 1106, 1073, 1054; MS (70 ev, EI) m/z 1012; MS (70 ev, EI) m/z (%): 229 (M+ + 1, 2.15), 228 (M+,
(%): 257 (M+ + 1, 1.52), 256 (M+, 8.33), 185 (100); HRMS Calcd 13.49), 153 (100); Anal. Calcd for C15H16O2: C, 78.92. H, 7.06.
for C17H20O2 (M+): 256.1463. Found: 256.1469.
4. Pd-CATALYSED SUZUKI COUPLING OF α-CHLOROALKYLIDENE-β-LACTONES
WITH CYCLOPROPYL BORONIC ACID
Found: C, 78.94; H, 7.14.
5. Pd-CATALYSED SUZUKI COUPLING OF α-CHLOROALKYLIDENE-β-LACTONES
WITH ALKYL BORONIC ACID
(1) Synthesis of (S,E)-α-(1-cyclopropylbenzylidene)-β-ethyl-
(1) Synthesis of (S,E)-α-(1-butylbenzylidene)-β-ethyl-β-lactone
β-lactone ((S,E)-4l). Typical procedure A rubber-capped Schlenk ((S,E)-4m). Typical procedure (condition B). A rubber-capped
vessel was dried with flame under vacuum and backfilled with Schlenk vessel was dried with flame under vacuum and back-
nitrogen for three times. Then Pd(OAc)2 (2.6 mg, 0.012 mmol), filled with nitrogen for three times. Then Pd(OAc)2 (2.2 mg,
LB-Phos·HBF4 (10.9 mg, 0.024 mmol), K3PO4·3H2O (212.8 mg, 0.01 mmol), LB-Phos·HBF4 (9.1 mg, 0.02 mmol), K2CO3
0.80 mmol), cyclopropylboronic acid 3i (41.4 mg, 0.48 mmol), (124.1 mg, 0.90 mmol), n-butylboronic acid 3j (40.8 mg,
2 mL of toluene and 0.4 mL of H2O were added into the 0.40 mmol), 1 mL of toluene and 0.2 mL of H2O were added
Schlenk vessel sequentially. Then (S,Z)-2d (89.1 mg, into the Schlenk vessel sequentially and stirred. Then (S,Z)-2d
0.40 mmol, ee > 99%) and 2 mL of toluene were added sequen- (44.3 mg, 0.20 mmol, ee > 99%) and 1 mL of toluene were
tially to the vessel. The resulting mixture was heated at 110 °C added sequentially to the vessel. The resulting mixture was
with a preheated oil bath. After 3.0 h, the reaction was com- heated at 110 °C with a preheated oil bath. After 3.0 h, the
plete as monitored by TLC. Then the reaction mixture was reaction was complete as monitored by TLC. Then the reaction
diluted by 10 mL of Et2O and filtered through a short column mixture was diluted by 10 mL of Et2O and filtered through a
of silica gel (eluent: 2 × 10 mL of Et2O). Evaporation and purifi- short column of silica gel (eluent: 2 × 10 mL of Et2O). Evapo-
cation by chromatography (eluent: petroleum ether/ethyl ration and purification by chromatography ((eluent: n-hexane–
acetate = 30/1) on silica gel and recrystallization (8 mL of n- CH2Cl2 = 2 : 1 (300 mL), then n-hexane/ethyl acetate = 100/1))
hexane) afforded (S,E)-4l (42.4 mg, 46%) as a solid in 99.5% ee, afforded (S,E)-4m (35.5 mg, 73%) as a liquid in ee 99.3%, as
as determined by HPLC (Chiralpak OJ-H, n-hexane–i-PrOH = determined by HPLC (Chiralpak AD-H, n-hexane–i-PrOH =
98 : 2, 0.8 mL min−1, λ = 230 nm, tR = 16.6 min (major), 98 : 2, 0.8 mL min−1, 230 nm, tR = 10.7 min (major)): [α]2D0
=
1
15.6 min (minor)); [α]2D0 = −29.0 (c = 1.02, CHCl3): m. +23.4 (c = 0.94, CHCl3); H NMR (300 MHz, CDCl3) δ 7.47–7.35
1
p. 87–88 °C (n-hexane); H NMR (300 MHz, CDCl3) δ 7.42–7.29 (m, 3H, Ar–H), 7.34–7.24 (m, 2H, Ar–H), 5.20 (dd, J1 = 7.2 Hz,
(m, 3H, Ar–H), 7.14–7.00 (m, 2H, Ar–H), 4.78 (dd, J1 = 7.2 Hz, J2 = 3.3 Hz, 1H, OCH), 3.28–3.07 (m, 1H, one proton in CH2),
J2 = 3.6 Hz, 1H, OCH), 2.66–2.48 (m, 1H, CH), 1.53–1.21 (m, 2.82–2.65 (m, 1H, one proton in CH2), 1.78–1.57 (m, 1H, one
2H, CH2), 0.99–0.84 (m, 2H, CH2), 0.84–0.63 (m, 4H, CH3 and proton in CH2), 1.56–1.24 (m, 5H, 2 × CH2 and one proton in
one proton in CH2), 0.53–0.37 (m, 1H, one proton in CH2); 13
C
CH2), 0.94–0.71 (m, 6H, 2 × CH3); 13C NMR (75 MHz, CDCl3) δ
NMR (75 MHz, CDCl3) δ 164.8, 151.7, 133.5, 131.9, 128.5, 164.7, 149.1, 136.3, 132.4, 129.3, 128.8, 127.2, 80.5, 31.5, 30.5,
128.3, 127.8, 79.9, 25.5, 14.9, 8.3, 6.9, 6.2; IR (KBr) ν (cm−1
)
24.7, 22.2, 13.7, 8.3; IR (neat) ν (cm−1) 2960, 2930, 2870, 2860,
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1797, 1687, 1459, 1442, 1378, 1309, 1239, 1161, 1131, 1088, determined by 1H NMR analysis, yield 80%) (eluent: petroleum
1054; MS (70 ev, EI) m/z (%): 245 (M+ + 1, 2.76), 244 (M+, ether/ethyl acetate = 80/1) as a liquid: 1H NMR (300 MHz,
20.81), 129 (100); HRMS Calcd for C16H20O2 (M+): 244.1463. CDCl3) δ 7.48–7.35 (m, 3H, Ar–H), 7.34–7.24 (m, 2H, Ar–H),
Found: 244.1458.
5.20 (dd, J1 = 7.4 Hz, J2 = 3.5 Hz, 1H, OCH), 3.25–3.08 (m, 1H,
The following compounds were prepared according to these one proton in CH2), 2.82–2.65 (m, 1H, one proton in CH2),
procedure.
1.78–1.58 (m, 1H, one proton in CH2), 1.54–1.12 (m, 9H, 4 ×
(2) (E)-α-(1-Butylbenzylidene)-β-ethyl-β-lactone ((E)-4m). The CH2 and one proton in CH2), 0.96–0.72 (m, 6H, 2 × CH3); 13C
reaction of (Z)-2d (89.6 mg, 0.40 mmol), n-butylboronic acid 3j NMR (75 MHz, CDCl3), δ 164.7, 149.1, 136.3, 132.4, 129.3,
(81.7 mg, 0.80 mmol), Pd(OAc)2 (4.6 mg, 0.02 mmol), 128.8, 127.2, 80.5, 31.8, 31.4, 28.7, 28.4, 24.7, 22.4, 14.0, 8.3; IR
LB-Phos·HBF4 (18.0 mg, 0.04 mmol), K2CO3 (248.4 mg, (neat) ν (cm−1) 3059, 2957, 2929, 2858, 1798, 1688, 1492, 1460,
1.80 mmol) in the mixture solvent of 4 mL of toluene and 1445, 1382, 1309, 1239, 1160, 1131, 1090, 1055; MS (70 ev, EI)
0.4 mL of H2O at 110 °C under nitrogen afforded (E)-4m m/z (%): 273 (M+ + 1, 3.93), 272 (M+, 21.87), 143 (100); HRMS
(73.9 mg, containing 0.5% 1,3,5-trimethoxylbenzene as deter- Calcd for C18H24O2 (M+): 272.1776. Found: 272.1776.
1
mined by H NMR analysis, yield 75%) (eluent: 30–60 °C pet-
roleum ether/CH2Cl2 = 2/1) as a liquid: 1H NMR (300 MHz,
CDCl3) δ 7.47–7.35 (m, 3H, Ar–H), 7.34–7.22 (m, 2H, Ar–H),
5.20 (dd, J1 = 7.1 Hz, J2 = 3.2 Hz, 1H, OCH), 3.26–3.09 (m, 1H,
one proton in CH2), 2.81–2.65 (m, 1H, one proton in CH2),
1.78–1.58 (m, 1H, one proton in CH2), 1.56–1.24 (m, 5H, 2 ×
CH2 and one proton in CH2), 0.93–0.75 (m, 6H, 2 × CH3);
13C NMR (75 MHz, CDCl3) δ 164.7, 149.1, 136.3, 132.4, 129.4,
128.8, 127.2, 80.5, 31.6, 30.5, 24.7, 22.2, 13.7, 8.3; IR (neat) ν
(cm−1) 2960, 2930, 2870, 2860, 1797, 1688, 1460, 1442, 1309,
1239, 1161, 1131, 1088, 1054; MS (70 ev, EI) m/z (%): 245 (M+ +
1, 2.59), 244 (M+, 19.19), 129 (100); HRMS Calcd for C16H20O2
(M+): 244.1463. Found 244.1464.
(5) (S)-α-(5-Nonylidene)-β-ethyl-β-lactone ((S)-4o). The reac-
tion of (S,Z)-2a (80.1 mg, 0.40 mmol, ee > 99%), n-butylboronic
acid 3j (123.4 mg, 1.21 mmol), PdCl2(LB-Phos)2 (18.3 mg,
0.02 mmol), and K2CO3 (248.4 mg, 1.80 mmol) in the mixture
solvent of 4 mL of toluene and 0.4 mL of H2O at 110 °C under
nitrogen afforded (S)-4o (48.7 mg, 55%) (eluent: 30–60 °C pet-
roleum ether/CH2Cl2 = 2/1) as a liquid in ee = 99.4%, as deter-
mined by HPLC (Chiralpak AS-H, n-hexane–i-PrOH = 98 : 2,
0.8 mL min−1, 230 nm, tR = 6.3 min (major), 8.4 min (minor)):
[α]2D0 = −64.5 (c = 1.21, CHCl3); 1H NMR (300 MHz, CDCl3) δ
4.89 (dd, J1 = 7.5 Hz, J2 = 3.3 Hz, 1H, OCH), 2.60–2.39 (m, 2H,
CH2), 2.14–1.90 (m, 3H, CH2 and one proton in CH2),
1.84–1.64 (m, 1H, one proton in CH2), 1.56–1.18 (m, 8H, 4 ×
CH2), 1.03 (t, J = 7.4 Hz, 3H, CH3), 0.97–0.79 (m, 6H, 2 × CH3);
13C NMR (75 MHz, CDCl3) δ 164.6, 152.0, 131.4, 79.5, 31.7,
(3) (S,E)-α-(1-Hexylbenzylidene)-β-ethyl-β-lactone ((S,E)-4n). The
reaction of (S,Z)-2d (44.6 mg, 0.20 mmol, ee > 99%), n-hexyl-
boronic acid 3k (51.4 mg, 0.40 mmol), Pd(OAc)2 (2.3 mg,
0.01 mmol), LB-Phos·HBF4 (9.0 mg, 0.02 mmol), and K2CO3
(125.0 mg, 0.90 mmol) in the mixture solvent of 2 mL of
toluene and 0.2 mL of H2O at 110 °C under nitrogen afforded
(S,E)-4n (39.9 mg, containing 0.8% 1,3,5-trimethoxylbenzene
as determined by 1H NMR analysis, yield 72%) (eluent: pet-
roleum ether/ethyl acetate = 100/1) as a liquid in ee > 99%, as
determined by HPLC (Chiralpak AS-H, n-hexane–i-PrOH =
30.7, 30.1, 29.5, 26.3, 22.7, 22.4, 13.8, 8.6; IR (neat) ν (cm−1
)
2959, 2933, 2874, 2861, 1800, 1709, 1462, 1380, 1310, 1243,
1147, 1123, 1095, 1053, 1013; MS (70 ev, EI) m/z (%): 224 (M+,
2.75), 195 (100); HRMS Calcd for C14H24O2 (M+): 224.1776.
Found: 224.1780.
(6) α-(5-Nonylidene)-β-ethyl-β-lactone (4o). The reaction of
(Z)-2a (40.4 mg, 0.20 mmol), n-butylboronic acid 3j (61.0 mg,
0.60 mmol), PdCl2(LB-Phos)2 (9.2 mg, 0.01 mmol), and K2CO3
(125.5 mg, 0.91 mmol) in the mixture solvent of 2 mL of
toluene and 0.2 mL of H2O at 110 °C under nitrogen afforded
4o (25.3 mg, 56%) (eluent: 30–60 °C petroleum ether/CH2Cl2 =
98 : 2, 0.8 mL min−1, 230 nm, tR = 7.2 min (major)): [α]2D0
=
1
+20.6 (c = 1.18, CHCl3); H NMR (300 MHz, CDCl3) δ 7.48–7.36
(m, 3H, Ar–H), 7.35–7.24 (m, 2H, Ar–H), 5.20 (dd, J1 = 7.1 Hz,
J2 = 3.5 Hz, 1H, OCH), 3.25–3.09 (m, 1H, one proton in CH2),
2.83–2.66 (m, 1H, one proton in CH2), 1.77–1.58 (m, 1H, one
proton in CH2), 1.53–1.14 (m, 9H, 4 × CH2 and one proton in
CH2), 0.93–0.77 (m, 6H, 2 × CH3); 13C NMR (75 MHz, CDCl3) δ
164.7, 149.1, 136.3, 132.4, 129.3, 128.8, 127.2, 80.5, 31.8, 31.4,
28.7, 28.4, 24.7, 22.4, 14.0, 8.3; IR (neat) ν (cm−1) 3059, 2957,
2929, 2858, 1798, 1688, 1603, 1578, 1495, 1461, 1445, 1379,
1309, 1239, 1160, 1130, 1090, 1055; MS (70 ev, EI) m/z (%): 273
(M+ + 1, 1.33), 272 (M+, 8.97), 143 (100); HRMS Calcd for
C18H24O2 (M+): 272.1776. Found: 272.1777.
2/1) as a liquid: 1H NMR (300 MHz, CDCl3) δ 4.89 (dd, J1
=
7.5 Hz, J2 = 3.0 Hz, 1H, OCH), 2.60–2.39 (m, 2H, CH2),
2.14–1.90 (m, 3H, CH2 and one proton in CH2), 1.84–1.64 (m,
1H, one proton in CH2), 1.56–1.17 (m, 8H, 4 × CH2), 1.02 (t, J =
7.5 Hz, 3H, CH3), 0.97–0.79 (m, 6H, 2 × CH3); 13C NMR
(75 MHz, CDCl3) δ 164.6, 152.1, 131.4, 79.5, 31.7, 30.7, 30.1,
29.4, 26.3, 22.7, 22.4, 13.8, 8.6; IR (neat) ν (cm−1) 2959, 2932,
2874, 2860, 1799, 1709, 1463, 1380, 1310, 1257, 1243, 1147,
1123, 1095, 1053, 1013; MS (70 ev, EI) m/z (%): 224 (M+, 2.58),
195 (100); HRMS Calcd for C14H24O2 (M+) : 224.1776. Found:
224.1777.
(4) (E)-α-(1-Hexylbenzylidene)-β-ethyl-β-lactone ((E)-4n). The
reaction of (Z)-2d (88.3 mg, 0.40 mmol), n-hexylboronic acid 3k
(104.3 mg, 0.80 mmol), Pd(OAc)2 (2.7 mg, 0.012 mmol),
LB-Phos·HBF4 (10.8 mg, 0.024 mmol), and K2CO3 (244.4 mg,
6. Pd-CATALYSED SUZUKI COUPLING OF α-CHLOROALKYLIDENE-β-LACTONES
WITH HETEROAROMATIC BORONIC ACID
(1) Synthesis of (S,Z)-α-(1-(2′-thienyl)benzylidene)-β-ethyl-
1.77 mmol) in the mixture solvent of 4 mL of toluene and β-lactone ((S,Z)-4p). Typical procedure.
A
rubber-capped
0.4 mL of H2O at 110 °C under nitrogen afforded (E)-4n Schlenk vessel was dried with flame under vacuum and back-
(87.0 mg, containing 1.0% 1,3,5-trimethoxylbenzene as filled with nitrogen for three times. Then PdCl2(LB-Phos)2
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(18.2 mg, 0.02 mmol), K3PO4·3H2O (319.1 mg, 1.20 mmol), 2- 1H, Ar–H), 7.84–7.74 (m, 2H, Ar–H), 7.54–7.43 (m, 3H, Ar–H),
thienylboronic acid 3l (153.6 mg, 1.20 mmol), and 2 mL of 7.43–7.33 (m, 4H, Ar–H), 5.05 (dd, J1 = 7.2 Hz, J2 = 3.3 Hz,
toluene were added into the Schlenk vessel sequentially and 1H, OCH), 1.58–1.18 (m, 2H, CH2), 0.86 (t, J = 7.4 Hz, 3H,
stirred. Then (S,Z)-2d (88.7 mg, 0.40 mmol, ee > 99%) and CH3); 13C NMR (75 MHz, CDCl3) δ 162.8, 141.7, 139.5, 139.2,
2 mL of toluene were added sequentially to the vessel. The 138.8, 136.5, 132.3, 129.6, 129.3, 128.7, 126.0, 124.8, 124.7,
resulting mixture was heated to reflux with a preheated oil 122.1, 79.4, 24.9, 8.2; IR (KBr) ν (cm−1) 3058, 3027, 2970,
bath. After 4.8 h, the reaction was complete as monitored by 2937, 2877, 1790, 1651, 1594, 1504, 1457, 1443, 1431, 1343,
TLC. Then the reaction mixture was cooled and diluted by 1299, 1264, 1239, 1192, 1145, 1120, 1099, 1057, 1030; MS
10 mL of Et2O and filtered through a short column of silica gel (70 ev, EI) m/z (%): 321 (M+ + 1, 20.28), 320 (M+, 100);
(eluent: 2 × 10 mL of Et2O). Evaporation and purification by Anal. Calcd for C20H16O2S: C, 74.97; H, 5.03. Found: C, 74.77;
chromatography (petroleum ether/ethyl acetate
=
30/1) H, 5.01.
afforded (S,Z)-4p (83.3 mg, 77%) as a yellow solid in ee > 99%,
as determined by HPLC (Chiralpak OD-H, n-hexane–i-PrOH =
(4) (Z)-α-(1-(2′-Benzothienyl)benzylidene)-β-ethyl-β-lactone
98 : 2, 1.0 mL min−1, 230 nm, tR = 10.0 min (major), 14.7 min ((Z)-4q). The reaction of (Z)-2d (44.8 mg, 0.20 mmol), 2-benz-
(minor)); [α]2D0 = −104.6 (c = 1.02, CHCl3); m.p. 72–73 °C othienylboronic acid 3m (106.8 mg, 0.60 mmol), PdCl2-
(n-hexane and ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.89 (LB-Phos)2 (9.2 mg, 0.01 mmol), and K3PO4·3H2O (159.5 mg,
(dd, J1 = 3.8 Hz, J2 = 0.8 Hz, 1H, Ar–H), 7.53–7.39 (m, 4H, Ar– 0.60 mmol) in 2 mL of toluene under nitrogen afforded (Z)-4q
H), 7.39–7.30 (m, 2H, Ar–H), 7.16–7.08 (m, 1H, Ar–H), 5.00 (dd, (59.3 mg, 92%) (eluent: petroleum ether/ethyl acetate = 30/1)
J1 = 7.2 Hz, J2 = 3.6 Hz, 1H, OCH), 1.54–1.20 (m, 2H, CH2), 0.83 as a yellow solid: m.p. 145–146 °C (n-hexane and ethyl acetate);
(t, J = 7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.2, 1H NMR (300 MHz, CDCl3) δ 7.94 (s, 1H, Ar–H), 7.85–7.71 (m,
139.5, 139.1, 136.9, 132.2, 130.4, 129.8, 129.4, 128.65, 128.62, 2H, Ar–H), 7.55–7.42 (m, 3H, Ar–H), 7.42–7.33 (m, 4H, Ar–H),
128.1, 79.2, 25.0, 8.1; IR (KBr) ν (cm−1) 2969, 2936, 2871, 1787, 5.04 (dd, J1 = 7.1 Hz, J2 = 3.5 Hz, 1H, OCH), 1.60–1.20 (m, 2H,
1650, 1462, 1441, 1415, 1374, 1293, 1226, 1154, 1125, 1101, CH2), 0.86 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ
1052; MS (70 ev, EI) m/z (%): 271 (M+ + 1, 12.60), 270 (M+, 162.8, 141.7, 139.5, 139.2, 138.8, 136.6, 132.3, 129.6, 129.3,
65.41), 240 (100); Anal. Calcd for C16H14O2S: C, 71.08; H, 5.22. 128.7, 126.0, 124.8, 124.7, 122.2, 79.4, 24.9, 8.1; IR (KBr) ν
Found: C, 70.62; H, 5.16.
(cm−1) 2964, 2928, 1793, 1651, 1590, 1501, 1455, 1443, 1378,
The following compounds were prepared according to this 1365, 1300, 1253, 1237, 1190, 1160, 1146, 1118, 1075, 1058,
procedure.
1029; MS (70 ev, EI) m/z (%): 321 (M+ + 1, 31.86), 320 (M+, 100).
Anal. Calcd for C20H16O2S: C, 74.97; H, 5.03. Found: C, 74.73;
H, 5.04.
(2) (Z)-α-(1-(2′-Thienyl)benzylidene)-β-ethyl-β-lactone ((Z)-4p).
The reaction of (Z)-2d (44.4 mg, 0.20 mmol), 2-thienylboronic
acid 3k (76.7 mg, 0.60 mmol), PdCl2(LB-Phos)2 (9.1 mg,
0.01 mmol), K3PO4·3H2O (159.2 mg, 0.60 mmol) in 2 mL of
toluene afford (Z)-4p (41.1 mg, 76%) (eluent: petroleum ether/
ethyl acetate = 30/1) as a yellow solid: m.p. 75–76 °C (n-hexane
7. (S,Z)-α-(1-BUTYL-(4′-METHOXYL)BENZYLIDENE)-β-ETHYL-β-LACTONE
((S,Z)-4b) on
a 5 mmol scale. The Pd(OAc)2 (11.2 mg,
0.05 mmol), LB-Phos·HBF4 (45.5 mg, 0.10 mmol), K3PO4·3H2O
(2.6608 g, 10.0 mmol), 4-methoxylphenylboronic acid
(913.7 mg, 6.0 mmol), and 20 mL of toluene were added into a
rubber-capped Schlenk vessel under nitrogen sequentially.
After being stirred for about 5 min at room temperature, (S,Z)-
2a (1.0129 g, 5.0 mmol, ee > 99%)and 30 mL of toluene were
added sequentially to the vessel. The resulting mixture was
heated at 110 °C with a preheated oil bath. After 2.0 h, the
reaction was complete as monitored by TLC. Then the reaction
mixture was filtered through a short column of silica gel
(eluent: 3 × 20 mL of Et2O). Evaporation and purification by
1
and ethyl acetate); H NMR (300 MHz, CDCl3) δ 7.90 (dd, J1 =
3.8 Hz, J2 = 1.1 Hz, 1H, Ar–H), 7.52–7.39 (m, 4H, Ar–H),
7.39–7.31 (m, 2H, Ar–H), 7.14–7.07 (m, 1H, Ar–H), 4.99 (dd,
J1 = 7.1 Hz, J2 = 3.5 Hz, 1H, OCH), 1.53–1.18 (m, 2H, CH2), 0.82
(t, J = 7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 163.2,
139.4, 139.1, 136.9, 132.2, 130.4, 129.7, 129.4, 128.61, 128.59,
128.1, 79.2, 24.9, 8.1; IR (KBr) ν (cm−1) 3097, 2969, 2936, 2878,
1789, 1650, 1489, 1460, 1444, 1415, 1368, 1299, 1244, 1227,
1154, 1125, 1100, 1052; MS (70 ev, EI) m/z (%): 271 (M+ + 1,
13.24), 270 (M+, 13.24), 241 (100). Anal. Calcd for C16H14O2S:
C, 71.08; H, 5.22. Found: C, 71.03; H, 5.19.
chromatography (petroleum ether/ethyl acetate
=
40/1
(400 mL), then petroleum ether/ethyl acetate = 20/1) on silica
gel afforded (S,Z)-4b (1.2754 g, 93%) as a liquid in ee > 99%, as
(3) (S,Z)-α-(1-(2′-Benzothienyl)benzylidene)-β-ethyl-β-lactone
((S,Z)-4q). The reaction of (S,Z)-2d (89.2 mg, 0.40 mmol, ee > determined by HPLC (Chiralpak OD-H, n-hexane–i-PrOH =
99%), 2-benzothienylboronic acid 3m (214.4 mg, 1.20 mmol), 95 : 5, 1.0 mL min−1, λ = 230 nm, tR = 9.7 min (major)): [α]2D0
=
1
PdCl2(LB-Phos)2 (18.2 mg, 0.02 mmol), and K3PO4·3H2O +6.5 (c = 0.99, CHCl3); H NMR (300 MHz, CDCl3) δ 7.62–7.46
(319.6 mg, 1.20 mmol) in 4 mL of toluene under nitrogen (m, 2H, Ar–H), 6.97–6.83 (m, 2H, Ar–H), 5.00 (dd, J1 = 7.7 Hz,
afforded (S,Z)-4q (106.3 mg, 83%) (eluent: petroleum ether/ J2 = 2.9 Hz, 1H, OCH), 3.83 (s, 3H, OCH3), 2.58–2.29 (m, 2H,
ethyl acetate = 50/1) as a yellow solid in 99.1% ee, as deter- CH2), 2.17–2.02 (m, 1H, one proton in CH2), 1.94–1.75 (m, 1H,
mined by HPLC (Chiralpak OD-H, n-hexane–i-PrOH = 90 : 10, one proton in CH2), 1.45–1.20 (m, 4H, 2 × CH2), 1.09 (t, J =
1.0 mL min−1, 230 nm, tR = 9.16 min (major), 17.9 min 7.4 Hz, 3H, CH3), 0.87 (t, J = 6.8 Hz, 3H, CH3); 13C NMR
(minor)): [α]2D0 = −13.7 (c = 1.12, CHCl3); m.p. 102–103 °C (n- (75 MHz, CDCl3) δ 163.7, 160.7, 148.1, 130.4, 129.7, 127.0,
hexane and ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.94 (s, 113.7, 78.9, 55.2, 32.7, 30.4, 26.4, 22.6, 13.8, 8.6.
108 | Org. Biomol. Chem., 2013, 11, 98–109
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U. Dingerdissen and M. Beller, Chem.–Eur. J., 2004, 10, 2983;
(q) F. Y. Kwong and A. S. C. Chan, Synlett, 2008, 1440.
Acknowledgements
Financial support from the National Basic Research Program 2 B. Lü, C. Fu and S. Ma, Tetrahedron Lett., 2010, 51, 1284.
of China (2009CB825300) and National Natural Science Foun- 3 B. Lü, P. Li, C. Fu, L. Xue, Z. Lin and S. Ma, Adv. Synth.
dation of China (21172192) are greatly appreciated. Shengming
Catal., 2011, 353, 100.
Ma is a Qiu Shi Adjunct Professor at Zhejiang University. We 4 B. Lü, C. Fu and S. Ma, Chem.–Eur. J., 2010, 16, 6434.
thank Jingqiang Kuang in our group for reproducing the 5 (a) S. Ma, B. Wu and S. Zhao, Org. Lett., 2003, 5, 4429;
results presented in Table 2, entries 4, 11 and Table 5, entry 2.
(b) S. Ma, B. Wu, X. Jiang and S. Zhao, J. Org. Chem., 2005,
70, 2568.
6 (a) For review of Suzuki coupling within alkyl boronic acid
see: H. Douncet, Eur. J. Org. Chem., 2008, 2013; (b) K. Matos
and J. A. Soderquist, J. Org. Chem., 1998, 63, 461.
References
7 Crystal
data for compound trans-PdCl2(LB-Phos)2:
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A. Zapf, R. Jackstell, S. Harkal, T. Riermeier, A. Monsees,
ˉ
C46H76Cl2O7P2Pd, MW = 980.31, triclinic, space group P1,
final R indices [I > 2σ(I)], R1 = 0.0290, wR2 = 0.0839;
R indices (all data), R1 = 0.0323, wR2 = 0.0881; a =
12.8490(5) Å, b = 13.1603(5) Å, c = 17.5483(6) Å, α =
73.847(1)°, β = 68.570(1)°, γ = 65.921(1)°, V = 2492.57(16) Å3.
T = 296 K, wavelength: 0.71073 Å, Z = 2, reflections collected/
unique: 29003/8738. (Rint = 0.0178); number of observations
[>2σ(I)] 8018, parameters: 526. Supplementary crystallo-
graphic data have been deposited at the Cambridge Crystal-
lographic Data Centre, CCDC: 888344.
8 Crystal data for compound (S,Z)-4p: C16H14O2S, MW
270.33, monoclinic, space group P 21, final R indices [I >
2σ(I)], R1 = 0.0685, wR2 = 0.1807; R indices (all data), R1
0.0880, wR2 = 0.2043; a = 9.3629(6) Å, b = 16.6080(8) Å, c =
9.8929(5) Å, α = 90°, β = 115.250 (7)°, γ = 90°, V = 1391.37(17)
Å3. T = 293 K, wavelength: 1.54184 Å, Z = 4, reflections col-
lected/unique: 13412/4948 (Rint = 0.0516); number of obser-
vations [>2σ(I)] 3803, parameters: 346. Supplementary
crystallographic data have been deposited at the Cambridge
Crystallographic Data Centre, CCDC: 888345.
=
=
9 S. Ma, X. Jiang, X. Cheng and H. Hou, Adv. Synth. Catal.,
2006, 348, 2114.
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