Pd(II)-catalyzed and diethylzinc-mediated asymmetric umpolung allylation of aldehydes in the presence of chiral phosphine-Schiff base type ligands

Article abstract of DOI:10.1016/j.tetasy.2010.06.039

Chiral phosphine-Schiff base type ligand L3 prepared from (R)-(-)-2-(diphenylphosphino)-1,1′-binaphthyl-2′-amine was found to be a fairly effective chiral ligand for the Pd(II)-catalyzed and diethylzinc-mediated enantioselective umpolung allylation of ald

Full text of DOI:10.1016/j.tetasy.2010.06.039

Tetrahedron: Asymmetry 21 (2010) 2050–2054
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Tetrahedron: Asymmetry
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Pd(II)-catalyzed and diethylzinc-mediated asymmetric umpolung allylation
of aldehydes in the presence of chiral phosphine-Schiff base type ligands
Jia-Jun Jiang a, De Wang a, Wen-Feng Wang a, Zhi-Liang Yuan a, Mei-Xin Zhao a, Fei-Jun Wang a, Min Shi a,b,
*
a Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science and Technology,
130 Mei Long Lu, Shanghai 200 237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200 032, China
a r t i c l e i n f o
a b s t r a c t
Chiral phosphine-Schiff base type ligand L3 prepared from (R)-(ꢀ)-2-(diphenylphosphino)-1,10-binaph-
thyl-20-amine was found to be a fairly effective chiral ligand for the Pd(II)-catalyzed and diethylzinc-med-
iated enantioselective umpolung allylation of aldehydes to give homoallylic alcohols in good yields,
moderate enantioselectivities and high syn diastereoselectivities.
Article history:
Received 9 June 2010
Accepted 29 June 2010
Available online 24 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, we explored the phosphine-Schiff base-Pd(II)-cata-
lyzed asymmetric allylic alkylation. Herein, we demonstrate that
Catalytic asymmetric synthesis provides chemists with new and
powerful tools for the efficient synthesis of complex molecules.
Amongst the many suitable reactions, the asymmetric allylic alkyl-
ation (AAA) reaction is a very attractive and powerful synthetic
strategy, as it enables the direct and stereocontrolled formation
of stereogenic centers bearing a range of functionalities available
for further structural elaboration.1 Since an initial publication con-
cerning umpolung allylation by Brown et al. in 1987,2 Tamaru et al.
these catalysts can also be used to effect diethylzinc-mediated
enantioselective umpolung allylation of aldehydes.
2. Results and discussion
Chiral phosphine-Schiff base type ligands L1–L66 were synthe-
sized from the reaction of salicylaldehydes as well as its analogues
with (R)-(ꢀ)-2-(diphenylphosphino)-1,10-binaphthyl- 20-amine7 in
absolute ethanol at reflux for 12 h, respectively. After the usual
workup, these ligands were obtained in good yields (Scheme 1).
have effectively demonstrated that the latent reactivity of the p-al-
lyl palladium complex can be reversed from electrophilic to
nucleophilic in the presence of Et2Zn or Et3B.3 The umpolung of
the
method for aldehydes and ketones via nucleophilic metal-coordi-
nated allylic moieties. The first -allyl palladium complexes and
p-allyl palladium complexes has provided a versatile allylation
R3
NH2
reflux, 12 h
ethanol
p
L1-L6
OHC
R2
R1
+
diethylzinc-mediated enantioselective catalytic umpolung allyla-
tion were reported by Zanoni et al. in 2004.4 Following this pio-
neering work, Feringa et al.5a and Hou et al.5b provided further
examples of this reaction in the presence of diethylzinc by using
chiral monodentate phosphoramidite and planar chiral [2,2]para-
cyclophane monophosphine ligands, respectively. Recently, our
group reported the first example of axially chiral bis(NHC)-Pd(II)
complex-catalyzed and Et2Zn-mediated enantioselective umpo-
lung allylation of aldehydes with cyclohex-2-enyl acetate.5c On
the other hand, Zhou et al. developed an analogous Et3B-mediated
version of this umpolung allylation by using a chiral spiro-mono-
dentate phospholane ligand, which is complementary to the dieth-
ylzinc-mediated methodology.5d
PPh2
HO
R3
R2
R1
N
N
HO
HO
PPh2
PPh2
L1: R1 = H, R2 = H, R3 = H
L6
L2: R1 = Bu, R2 = H, R3 = tBu
t
: R1 = Cl, R2 = H, R3 = Cl
: R1 = H, R2 = H, R3 = Me
L3
L4
L5: R1 = H, R2 = OMe, R3 = H
* Corresponding author.
E-mail address: Mshi@mail.sioc.ac.cn (M. Shi).
Scheme 1. Preparation of phosphine-Schiff base type ligands L1–L6.
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.06.039

J.-J. Jiang et al. / Tetrahedron: Asymmetry 21 (2010) 2050–2054
2051
Table 1
Optimization of the reaction conditions in the asymmetric umpolung allylation of cyclohex-2-enyl acetate 1 and benzaldehyde 2a
OH
H
1'
Ph
OAc
O
Pd metal (5 mol %)/L1 (10 mol %)
1
+
Et2Zn (3.5 equiv), 4Å MS, solvent, rt, 72 h
Ph
H
3a
1
2a
Entrya
Solvent
Pd metal
Pd(PhCN)2Cl2
[(
3-C3H5PdCl)2]
Pd(MeCN)2Cl2
Pd(OAc)2
Pd2dba3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Yieldb (%)
syn:antic
eed (%)
1
2
3
4
5
6e
7
8
THF
THF
THF
THF
THF
THF
Toluene
CH2Cl2
51
13
46
16
54
51
20
14
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
20 (1R, 10S)
20 (1R, 10S)
35 (1R, 10S)
53 (1R, 10S)
30 (1R, 10S)
24 (1R, 10S)
33 (1R, 10S)
23 (1R, 10S)
g
a
All reactions were performed using 1 (0.24 mmol), 2a (0.2 mmol), Pd metal (0.01 mmol), L1 (0.02 mmol), 4 Å MS (50 mg) and Et2Zn (0.7 mmol) in 1.0 mL of solvent at rt
for 72 h.
b
Isolated yield.
c
d
e
Determined by 1H NMR analysis.
Determined by chiral HPLC analysis.
5.0 equiv of Et2Zn was added.
Initial examination using cyclohex-2-enyl acetate 1 and benzalde-
hyde 2a as the substrates in the presence of a chiral phosphine-
Schiff base type ligand L1 (10 mol %) combined with various palla-
dium sources (5 mol %) was aimed at determining the optimal con-
ditions; the results of these experiments are summarized in
Table 1. We found that by using tetrahydrofuran (THF) as a solvent
and 4 Å MS (50 mg) as an additive, the corresponding product 3a
could be obtained in moderate yields with a variety of palladium
sources at room temperature. Up to 53% ee was achieved using
Pd(OAc)2 as the palladium source with high syn-selectivity (syn:an-
ti >30:1), albeit in only 13% yield (Table 1, entries 1–5). The abso-
lute configuration of the adduct was assigned by comparison of the
specific rotation with that from the literature.5a By screening vari-
ous solvents such as toluene and CH2Cl2, we found that THF was
the best solvent (Table 1, entries 4, 7 and 8). Furthermore, an at-
tempt to increase the amount of the Et2Zn reagent led to higher
yield but lower enantioselectivity (Table 1, entry 6).
With these optimized conditions in hand, we next attempted to
examine various chiral phosphine-Schiff base type ligands L1–L6 in
this asymmetric reaction. The results are summarized in Table 2.
From the ligands screened, L3, bearing an electron-withdrawing
group on the benzene ring, was the best chiral phosphine-Schiff
base type ligand for this asymmetric umpolung allylation, afford-
ing product 3a in 65% ee and 41% yield at room temperature for
72 h (Table 2, entries 1–6). In addition, an electron-donating group
on the benzene ring such as chiral phosphine-salen type ligands L2,
L4 and L5 gave the product 3a in moderate ees (10–40% ee) and
moderate yields (Table 2, entries 2, 4 and 5). These results sug-
gested that the substituent on the benzene ring in the chiral phos-
phine-Schiff base type ligands played a very important role in
chiral induction in this asymmetric umpolung allylation. Elevating
the reaction temperature resulted in a decrease in the yield as well
as the ee of the product 3a (Table 2, entry 7). In the absence of 4 Å
MS, the yield of the product 3a could be slightly improved upon
Table 2
Optimization of the reaction conditions in the asymmetric umpolung allylation of cyclohex-2-enyl acetate 1 and benzaldehyde 2a
OH
1'
Ph
H
OAc
O
Pd(OAc)2 (5 mol %)/Ligand (10 mol %)
Et2Zn (3.5 equiv), additive, THF, rt, 72 h
1
+
Ph
H
2a
1
3a
Entrya
Additive
Ligand
L1
Yieldb (%)
syn:antic
eed (%)
1
2
3
4
4 Å MS
4 Å MS
4 Å MS
4 Å MS
4 Å MS
4 Å MS
4 Å MS
—
16
32
41
43
32
32
20
46
27
62
>30:1
28:1
>30:1
26:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
53 (1R, 10S)
40 (1S, 10R)
65 (1R, 10S)
35 (1R, 10S)
10 (1R, 10S)
8 (1R, 10S)
53 (1R, 10S)
66 (1R, 10S)
65 (1R, 10S)
66 (1R, 10S)
L2
L3
L4
L5
L6
L3
L3
L3
L3
5
6
7e
8
9f
10g
—
—
a
All reactions were performed using 1 (0.24 mmol), 2a (0.2 mmol), Pd(OAc)2 (0.01 mmol), ligand (0.02 mmol), additive (50 mg) and Et2Zn (0.7 mmol) in 1.0 mL of THF at rt
for 72 h.
b
Isolated yield.
c
d
e
f
Determined by 1H NMR analysis.
Determined by chiral HPLC analysis.
The reaction was performed at 50 °C.
Compounds 1 (0.2 mmol) and 2a (0.24 mmol) were used.
Compounds 1 (0.4 mmol) and 2a (0.2 mmol) were used.
g

2052
J.-J. Jiang et al. / Tetrahedron: Asymmetry 21 (2010) 2050–2054
Table 3
Asymmetric umpolung allylation of cyclohex-2-enyl acetate 1 and aldehydes 2 under the optimal conditions
OH
1'
H
OAc
Pd(OAc)2 (5 mol %)/L3 (10 mol %)
R
1
+
RCHO
Et2Zn (3.5 equiv), THF, rt
2
1
3
Entrya
R
t (h)
Yieldb (%)
syn:antic
eed (%)
1
2
3
4
5
6
7
8
9
C6H5 (2a)
72
48
48
48
48
48
48
72
72
3a, 62
3b, 79
3c, 88
3d, 68
3e, 68
3f, 82
3g, 94
3h, 25
3i, 46
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
>30:1
66 (1R, 10S)
68 (1R, 10S)
66 (1R, 10S)
64 (1R, 10S)
46 (1R, 10S)
67 (1R, 10S)
62 (1R, 10S)
37 (1R, 10S)
47 (1R, 10S)
2-ClC6H4 (2b)
3-ClC6H4 (2c)
4-ClC6H4 (2d)
4-FC6H4 (2e)
4-CF3C6H4 (2f)
2,4-Cl2C6H3 (2g)
4-CH3C6H4 (2h)
1-Np (2i)
a
b
c
All reactions were performed using 1 (0.4 mmol), 2 (0.2 mmol), Pd(OAc)2 (0.01 mmol), L3 (0.02 mmol) and Et2Zn (0.7 mmol) in 1.0 mL of THF at rt.
Isolated yield.
Determined by 1H NMR analysis.
Determined by chiral HPLC analysis.
d
without the loss of ee under identical conditions (Table 2, entry 8).
Furthermore, we found that increasing the amount of 1 provided
product 3a in higher yield (Table 2, entries 9 and 10).
MC polarimeter; [a .
]D-values are given in units of 10ꢀ1 deg cm2 gꢀ1
Infra-red spectra were measured on a spectrometer. The 1H NMR
spectra and 13C NMR spectra were recorded on a Bruker AM-300
spectrometer for solution in CDCl3 with tetramethylsilane (TMS)
as an internal standard. Mass spectra were recorded with a HP-
5989 instrument and HRMS was measured by a Finnigan MA+ mass
spectrometer. Organic solvents used were dried by standard meth-
ods when necessary. Commercially obtained reagents were used
without further purification. All reactions were monitored by TLC
with Huanghai GF254 silica gel coated plates. Flash column chroma-
tography was carried out using 300–400 mesh silica gel at increased
pressure. All reactions were performed under argon using standard
Schlenk techniques. Chiral HPLC was performed by using a SHIMA-
DZU SPD-10A vp series instrument with chiral columns (Chiralpak
AS-H, AD-H columns, / 4.6 ꢁ 250 mm, Daicel Chemical Co. Ltd)
and the absolute configuration of the major enantiomer was as-
signed according to the sign of the specific rotation.
Therefore, the best reaction conditions were to carry out the
reaction in THF using Pd(OAc)2 (5 mol %) as the palladium source
and being diethylzinc mediated in the presence of phosphine-
Schiff base type ligand L3 (10 mol %) at room temperature.
With these optimal reaction conditions in hand, a series of alde-
hydes 2b–2i with various substituents on the aromatic scaffold were
used to further explore the substrate scope (Table 3). For all of the
substrates, the reactions demonstrated excellent diastereoselectiv-
ities. It was found that for substrates 2b–2g bearing an electron-
withdrawing group on the benzene ring, the corresponding products
3b–3g were obtained in moderate enantioselectivities (46–68% ee)
and good yields (68–94%) (Table 3, entries 2–7). Substrate 2h with
an electron-donating group on the benzene ring also produced the
product 3h in 37% ee, albeit in 25% yield (Table 3, entry 8). Similarly,
1-naphthaldehyde 2i produced the product 3i in 47% ee and 46%
yield in this asymmetric umpolung allylation (Table 3, entry 8).
Chiral phosphine-Schiff base type ligands L1–L6 were prepared
according to our previously reported procedure.6f
4.2. General procedure for the catalytic asymmetric umpolung
allylation of aldehydes with cyclohex-2-enyl acetate
3. Conclusion
In conclusion, chiral phosphine-Schiff base type ligand L3,
which was prepared from (R)-2-(diphenylphosphino)-1,10-binaph-
thyl-20-amine was found to be a fairly effective chiral ligand for the
Pd(II)-catalyzed and Et2Zn-mediated asymmetric umpolung allyla-
tion of aldehydes with cyclohex-2-enyl acetate, giving the corre-
sponding products in good yields, moderate enantioselectivities
and high syn diastereoselectivities under mild conditions. These re-
sults will prompt us to design and synthesize more new effective
chiral phosphine-Schiff base type ligands for asymmetric reactions.
Efforts are currently underway to elucidate the mechanistic details
of this asymmetric umpolung allylation of aldehydes with cyclo-
hex-2-enyl acetate and to disclose the exact structure of the active
species in this catalytic system.
To a Schlenk tube of ligand L3 (12.5 mg, 0.02 mmol) in THF
(1.0 mL) was added Pd(OAc)2 (2.3 mg, 0.01 mmol), and the result-
ing solution was stirred at room temperature for 30 min. The reac-
tion tube was then allowed to cool down to 0 °C for another
15 min. Finally, aldehydes 2 (0.2 mmol) and Et2Zn (1.0 M in hex-
anes, 0.7 mmol, 0.7 mL) were added to the solution, followed by
the addition of the cyclohex-2-enyl acetate 1 (0.4 mmol) and the
resulting mixture was stirred for 48–72 h at room temperature.
After completion of the reaction, saturated aqueous NH4Cl solution
was added to quench the reaction. The aqueous layer was ex-
tracted with CH2Cl2. The combined organic layers were washed
with brine. After drying over anhydrous Na2SO4, the solvent was
removed under reduced pressure. Further purification of the resi-
due was performed by flash column chromatography on SiO2
(PE/EtOAc = 20:1) to give the pure product 3. The ee of the product
3 was determined by chiral HPLC analysis.
4. Experimental
4.1. General methods
4.2.1. (1R,10S)-(Cyclohex-2-enyl)(phenyl)methanol 3a
Melting points were obtained with a Yanagimoto micro melting
point apparatus and are uncorrected. Optical rotations were deter-
mined in a solution of CHCl3 at 20 °C by using a Perkin-Elmer-241
A colourless oil. Yield: 62%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) d 1.46–1.55 (m, 2H), 1.68–1.77 (m,

J.-J. Jiang et al. / Tetrahedron: Asymmetry 21 (2010) 2050–2054
2053
2H), 1.98 (br, 3H), 2.50 (br, 1H), 4.57 (d, J = 6.6 Hz, 1H), 5.36–5.39
(m, 1H), 5.79–5.83 (m, 1H), 7.25–7.34 (m, 5H); 13C NMR
(75 MHz, CDCl3, TMS) d 21.1, 23.8, 25.2, 42.9, 77.3, 126.5, 127.4,
128.0, 128.2, 130.3, 142.8. Enantiomeric excess was determined
by HPLC with a Chiralcel AS-H column (hexane/iPrOH = 99:1,
4.2.7. (1R, 10S)-(Cyclohex-2-enyl)(2,4-dichlorophenyl)methanol
3g
A colourless oil. Yield: 94%. 1H NMR (CDCl3, TMS, 300 MHz) d
1.39–1.52 (m, 3H), 1.68–1.77 (m, 1H), 1.99–2.04 (m, 2H) 2.07–
2.11 (m, 1H), 2.63 (br, 1H), 5.05–5.06 (m, 1H), 5.50 (m, 1H) 5.90–
5.94 (m, 1H) 7.24–7.27 (m, 1H), 7.34 (s, 1H), 7.48–7.51 (m, 1H).
13C NMR (75 MHz, CDCl3, TMS) d 21.2, 22.6, 25.1, 40.7, 72.7,
126.9, 127.6, 129.0, 129.2, 131.5, 132.5, 133.2, 138.5; IR (CH2Cl2)
0.7 mL/min, 214 nm, tminor = 18.64 min, tmajor = 22.92 min; ½a D20
¼
ꢂ
þ11 (c 1.0, C6H6), 66% ee.
4.2.2. (1R,10S)-(2-Chlorophenyl)(cyclohex-2-enyl)methanol 3b
m 3408, 2931, 1770, 1590, 1561, 1470, 1383, 1250, 1103,
A colourless oil. Yield: 79%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) d 1.43–1.57 (m, 3H), 1.74–1.80 (m,
1H), 2.00 (br, 3H), 2.65–2.68 (m, 1H), 5.10 (d, J = 6.6 Hz, 1H), 5.49
(m, 1H), 5.87–5.92 (m, 1H), 7.17–7.34 (m, 3H), 7.55 (d, J = 6.9 Hz,
1H); 13C NMR (75 MHz, CDCl3, TMS) d 21.3, 22.8, 25.1, 40.7, 73.2,
126.6, 128.0, 128.17, 128.24, 129.3, 131.0, 132.0, 139.9. Enantio-
meric excess was determined by HPLC with a Chiralcel AS-H col-
1077 cmꢀ1. MS (ESI) m/z 255 (M+ꢀH). HRMS (ESI) calcd for
C13H13Cl2O: 255.0343, found: 255.0341. Enantiomeric excess was
determined by HPLC with a Chiralcel AD-H column (hexane/
iPrOH = 100:1, 0.7 mL/min, 214 nm, tminor = 29.37 min, tma-
jor = 35.04 min; ½a D20
¼ ꢀ22 (c 2.2, CHCl3), 62% ee.
ꢂ
4.2.8. (1R, 10S)-(Cyclohex-2-enyl)(p-tolyl)methanol 3h
umn
(hexane/iPrOH = 99:1, 0.7 mL/min, 214 nm,
tminor
=
A colourless oil. Yield: 25%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) 1H NMR (300 MHz, CDCl3, TMS) d
1.43–1.54 (m, 2H), 1.65–1.76 (m, 2H), 1.88 (br, 1H), 1.97 (br, 2H),
2.34 (s, 3H), 2.47–2.48 (m, 1H), 4.52 (d, J = 6.6 Hz, 1H), 5.34–5.38
(m, 1H), 5.76–5.81 (m, 1H), 7.13–7.16 (m, 2H), 7.21–7.25 (m,
2H). Enantiomeric excess was determined by HPLC with a Chiralcel
AS-H column (hexane/iPrOH = 99:1, 0.7 mL/min, 214 nm, tmi-
11.96 min, tmajor = 14.71 min; ½a D20
ꢂ
¼ ꢀ24 (c 1.6, CHCl3), 68% ee.
4.2.3. (1R,10S)-(3-Chlorophenyl)(cyclohex-2-enyl)methanol 3c
A colourless oil. Yield: 88%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) d 1.45–1.55 (m, 2H), 1.58–1.79 (m,
2H), 1.98 (br, 2H), 2.07 (s, 1H), 2.45–2.47 (m, 1H), 4.57 (d,
J = 6.3 Hz, 1H), 5.36–5.40 (m, 1H), 5.82–5.88 (m, 1H), 7.18–7.29
(m, 3H), 7.34 (s, 1H); 13C NMR (75 MHz, CDCl3, TMS) d 21.0, 23.4,
25.1, 42.9, 76.5, 124.6, 126.6, 127.4, 127.5, 129.4, 131.0, 134.1,
144.9. Enantiomeric excess was determined by HPLC with a Chiral-
nor = 12.54 min, tmajor = 16.87 min; ½a D20
¼ þ5 (c 0.5, CHCl3), 37% ee.
ꢂ
4.2.9. (1R, 10S)-(Cyclohex-2-enyl)(naphthalen-1-yl)methanol 3i
A colourless oil. Yield: 46%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) d 1.42–1.63 (m, 3H), 1.73–1.78 (m,
1H), 1.99–2.07 (m, 3H), 2.74–2.78 (m, 1H), 5.42 (d, J = 5.1 Hz,
1H), 5.47–5.50 (m, 1H), 5.82–5.87 (m, 1H), 7.45–7.51 (m, 3H),
7.67 (d, J = 7.2 Hz, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.84–7.88 (m, 1H),
8.02–8.05 (m, 1H). Enantiomeric excess was determined by HPLC
with a Chiralcel AD-H column (hexane/iPrOH = 95:5, 0.7 mL/min,
cel AS-H column (hexane/iPrOH = 99:1, 0.7 mL/min, 214 nm, tminor
=
15.12 min, tmajor = 16.71 min; ½a D20
¼ þ7 (c 1.7, CHCl3), 66% ee.
ꢂ
4.2.4. (1R,10S)-(4-Chlorophenyl)(cyclohex-2-enyl)methanol 3d
A colourless oil. Yield: 68%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) d 1.45–1.56 (m, 2H), 1.63–1.77 (m,
2H), 1.97 (br, 3H), 2.45–2.47 (m, 1H), 4.58 (d, J = 6.0 Hz, 1H),
5.36–5.40 (m, 1H), 5.81–5.87 (m, 1H), 7.25–7.33 (m, 4H). Enantio-
meric excess was determined by HPLC with a Chiralcel AD-H
230 nm, tmajor = 27.17 min, tminor = 34.97 min; ½a D20
¼ ꢀ27 (c 0.8,
ꢂ
CHCl3), 47% ee.
column (hexane/iPrOH = 99:1, 0.7 mL/min, 214 nm, tminor
=
Acknowledgements
25.71 min, tmajor = 27.79 min; ½a D20
¼ þ5 (c 1.4, CHCl3), 64% ee.
ꢂ
Financial support from the Shanghai Municipal Committee of
Science and Technology (08dj1400100-2), National Basic Research
Program of China (973)-2010CB833302, and the National Natural
Science Foundation of China (20902019, 20872162, 20672127,
20821002, 20732008, 20772030 and 20702059) is greatly
acknowledged.
4.2.5. (1R,10S)-(Cyclohex-2-enyl)(4-fluorophenyl)methanol 3e
A colourless oil. Yield: 68%. 1H NMR (CDCl3, TMS, 300 MHz) d
1.43–1.57 (m, 2H), 1.64–1.81 (m, 2H), 1.93–1.99 (m, 3H), 2.42–
2.50 (m, 1H), 4.57–4.59 (m, 1H), 5.35–5.39 (m, 1H), 5.80–5.86
(m, 1H), 7.00–7.06 (m, 2H), 7.26–7.33 (m, 2H). 13C NMR (CDCl3,
TMS, 75 MHz) d 21.0, 23.7, 25.2, 43.0 (d, J = 1.1 Hz), 76.7, 115.0
(d, J = 21.2 Hz), 127.6, 128.0 (d, J = 7.7 Hz), 130.7, 138.5 (d,
J = 3.4 Hz), 162.0 (d, J = 243.6 Hz). 19F NMR (282 MHz, CDCl3,
References
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CF3CO2H) d ꢀ115.4. IR (CH2Cl2)
m 3391, 3023, 2927, 2861, 1604,
1510, 1223, 1156, 839 cmꢀ1. MS (ESI) m/z 205 (M+ꢀH). HRMS
(ESI) calcd for C13H14FO: 205.1029, found: 205.1024. Enantiomeric
excess was determined by HPLC with a Chiralcel AD-H column
(hexane/iPrOH = 95:5, 0.7 mL/min, 214 nm, tminor = 12.54 min, tma-
jor = 13.74 min; ½a D20
¼ þ4 (c 1.2, CHCl3), 46% ee.
ꢂ
4.2.6. (1R,10S)-(Cyclohex-2-enyl)(4-(trifluoromethyl)phenyl)-
methanol 3f
A colourless oil. Yield: 82%. This is a known compound.5c 1H
NMR (CDCl3, TMS, 300 MHz) d 1.44–1.62 (m, 3H), 1.68–1.78 (m,
1H), 1.99–2.05 (m, 3H), 2.46–2.52 (m, 1H), 4.68 (d, J = 5.7 Hz,
1H), 5.38–5.42 (m, 1H), 5.84–5.90 (m, 1H), 7.44 (d, J = 8.1 Hz,
2H), 7.59 (d, J = 8.1 Hz, 2H); 19F NMR (282 MHz, CDCl3, CF3CO2H)
d ꢀ68.0. Enantiomeric excess was determined by HPLC with a Chi-
ralcel AD-H column (hexane/iPrOH = 99:1, 0.7 mL/min, 214 nm,
tminor = 19.54 min, tmajor = 21.96 min;
67% ee.
½
a 2D0
ꢂ
¼ þ1 (c 1.8, CHCl3),

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