Enantioselective vinylation of aldehydes with the vinyl Grignard reagent catalyzed by magnesium complex of chiral BINOLs

Article abstract of DOI:10.1002/chir.23038

Enantioselective vinylation of aldehydes via direct catalytic asymmetric Grignard reaction of aldehdyes and the vinyl Grinard reagent is a long-standing challenge. This work demonstrated that the magnesium (S)-3,3′-dimethyl BINOLate enantioselectively catalyze the direct vinylation of aldehydes with the deactivated vinylmagnesium bromide by bis(2-[N,N′-dimethylamino]ethyl) ether (BDMAEE) in the addition of n-butylmagnesium chloride. The highest ee of 63% was achieved up to date.

Full text of DOI:10.1002/chir.23038

Received: 10 August 2018
DOI: 10.1002/chir.23038
Revised: 29 October 2018
Accepted: 1 November 2018
R E G U L A R A R T I C L E
Enantioselective vinylation of aldehydes with the vinyl
Grignard reagent catalyzed by magnesium complex of chiral
BINOLs
Pei Wang1
| Guo‐Rong Ma1 | Sheng‐Li Yu2 | Chao‐Shan Da2,3
1 School of Basic Medical Sciences,
Ningxia Medical University, Yinchuan,
China
2 Institute of Biochemistry and Molecular
Biology, School of Life Sciences, Lanzhou
University, Lanzhou, China
3 State Key Laboratory of Organic
Chemistry, Lanzhou University, Lanzhou,
China
Abstract
Enantioselective vinylation of aldehydes via direct catalytic asymmetric Gri-
gnard reaction of aldehdyes and the vinyl Grinard reagent is a long‐standing
challenge. This work demonstrated that the magnesium (S)‐3,3′‐dimethyl
BINOLate enantioselectively catalyze the direct vinylation of aldehydes with
the deactivated vinylmagnesium bromide by bis(2‐[N,N′‐dimethylamino]ethyl)
ether (BDMAEE) in the addition of n‐butylmagnesium chloride. The highest ee
of 63% was achieved up to date.
Correspondence
Pei Wang, School of Basic Medical
Sciences, Ningxia Medical University,
Yinchuan 750004, China.
KEYWORDS
asymmetric catalysis, BINOL, deactivation, Grignard reaction, vinylation
Email: wangp13@lzu.edu.cn
Funding information
The Higher Education Scientific Research
Project of Ningxia, Grant/Award Number:
NGY2018‐92; The Ningxia High School
first‐class Disciplines (West China first‐
class Disciplines Basic Medical Sciences
at Ningxia Medical University), Grant/
Award Number: NXYLXK2017B07; The
Project of Ningxia Medical University,
Grant/Award Number: XT2017016
1 | INTRODUCTION
(Oi‐Pr)3, and then R‐Ti (Oi‐Pr)3 highly enantioselectively
delivered R group to aldehydes catalyzed by chiral diol‐Ti
Grignard reagents are among the most useful and impor-
tant organic metal reagents. The addition of Grignard
reagents to aldehydes is commonly used cost‐effective
methodology to construct secondary alcohols via carbon–
carbon bond formation. Because of greatly reactive,
however, the catalytic asymmetric addition of Grignard
reagents to aldehydes is typically challenging.1-10 Only
recently successful strategies were developed in access to
highly enantiopure secondary alcohols via catalytic asym-
metric Grignard reactions.11-13 The groups of Harada,14-16
Xu,17,18 and Yus19,20 utilized superstoichiometric Ti (Oi‐
Pr)4 to transmetallate RMgX (Br, Cl) to less reactive R‐Ti
(Oi‐Pr)2 complexes. Our group demonstrated that the addi-
tive bis([2‐[N,N′‐dimethylamino)]thyl) ether (BDMAEE)
effectively deactivated the reactivity of Grignard reagents
and then similarly transmetallated R functional group
of RMgBr to R‐Ti (Oi‐Pr)3 by using stoichiometric Ti (Oi‐
Pr)4.21-27 The complex of chiral BINOL‐Ti (Oi‐OPr)2 or
H8‐BINOL‐Ti (Oi‐OPr)2 highly catalyzed the enantiose-
lective delivery of R group to aldehydes. Irrespective of
the impressive advancement of catalytic alkylation and
aromatization of aldehydes with Grignard reagents, the
catalytic enantioselective vinylation of aldehydes to pro-
duce enaniopure allyl alcohols are far from exploration.
Chirality. 2018;1–8.
wileyonlinelibrary.com/journal/chir
© 2018 Wiley Periodicals, Inc.
1

2
WANG ET AL.
Only two examples were dispersed in the literature. In
the first example, stoichiometric chiral BINOL‐modified
divinylmagnesium was used, and only 12% of enantio-
selectivity was afforded (Equation 1, Scheme 1).28 In
the second examples, we also investigated deactivated
vinylmagnesium bromide with BDMAEE, but low 33% of
enantioselectivity was achieved by using substoichiometric
chiral catalyst (Equation 2, Scheme 1).21 The desired and
challenging highly enantioselective vinylation of alde-
hydes hopes novel strategy.
Reactions were monitored by thin‐layer chromatography
(TLC); column and preparative TLC purification were car-
ried out using silica gel. Melting points were recorded on
an X‐4 melting point apparatus and are uncorrected. Opti-
1
cal rotations were recorded on a polarimeter. H nuclear
magnetic resonance (NMR) and 13C NMR spectra were
measured on 200 and 100 MHz spectrometers, respec-
tively, in CDCl3 with TMS as an internal standard; chem-
ical shifts are reported in parts per million. The
determination of ee values was carried out using chiral
high‐performance liquid chromatography (HPLC) with
an OD‐H, OJ‐H, or AS‐H column.
Chiral allylic secondary alcohols are key structural
motifs in a considerable number of natural products and
pharmaceutically active compounds29-33 and an impor-
tant class of indispensable precursors of a wide range of
organic transformations.34-40 These chiral building blocks
are typically achieved by enzymatic or nonenzymatic
kinetic resolution of the corresponding racemic com-
pounds,41-44 vinylation of aldehydes with less reactive
vinyl metal reagents vinyl zinc,45-49 silane,50-52 boron,53-
2.1 | General procedure for the catalytic
asymmetric vinylation of aldehydes
Ligand L6 (0.15 mmol, 47.1 mg) and 2.0 mL of dry methyl
t‐butyl ether (MTBE) were introduced into a dry 10‐mL
round bottom flask A equipped with a clean stir bar
under an argon atmosphere. n‐BuMgCl (0.18 mmol,
0.2 mL) was slowly added to the flask A at 0°C, and the
mixture was stirred for 1 hour. The vinyl Grignard
reagent (2.14 mL, 1.5 mmol) and 7.56 mL of dry MTBE
were introduced into another dry 25 mL round bottom
flask B equipped with a clean stir bar under an argon
atmosphere. Bis(2‐[N,N′‐dimethylamino]ethyl) ether
(BDMAEE) (282 μL, 1.5 mmol) was slowly added to flask
B at 0°C, and the mixture was stirred 1.5 hours. Benzalde-
hyde (54 μL, 0.5 mmol) was added to the flask A. After
0.5 hour, the supernatant (6.0 mL, ~1.0 mmol) of flask
B was slowly added to the flask A for 30 minutes at
−20°C. The mixture was warmed to 0°C and stirred for
5 hours. The reaction was quenched with 1 N HCl at
0°C and extracted with ethyl acetate (5 mL x 3). The
55
bismuthine,56 and aluminum57 and hydroxylation via
asymmetric allylic substitution.58-62 Only Oppolzer and
coworker observed the simplest asymmetric vinylation
of aldehydes with divinylzinc.34 And while these methods
successfully affording highly enantiopure allylic alcohols,
their practicality was significantly hampered by cost‐
effectiveness. Herein, we firstly reported direct catalytic
asymmetric vinylation of aldehydes catalyzed chiral mag-
nesium BINOlate (Equation 3, Scheme 1).
2 | MATERIALS AND METHODS
All reactions were performed under an argon atmosphere,
and solvents were dried according to established proce-
dures prior to use. All of the reagents were commercial.
SCHEME 1 The asymmetric vinylation
of aldehydes with the vinyl Grignard
reagent

WANG ET AL.
3
2.1.4 | (S)‐1‐(4‐chlorophenyl)prop‐2‐en‐1‐
ol (3d)29
1
49% yield, 42% ee; [α]D20 = −5.0 (c 0.4, CHCl3); H NMR
(200 MHz, CDCl3): δ 7.31–7.26 (m, 4H), 6.09 to 5.92 (m,
1H), 5.38 to 5.18 (m, 3H); enantiometric excess was deter-
mined by HPLC with a Chiralpak OJ‐H column 1.0 mL/
min, (2‐propanol: hexane = 5:95), major enantiomer
tr = 14.6 minutes, minor enantiomer tr = 15.9 minutes.
SCHEME 2 The possible reaction process
2.1.5 | (S)‐1‐(4‐(trifluoromethyl)phenyl)
prop‐2‐en‐1‐ol (3e)29
combined organic layer was washed with saturated brine
and dried over Na2SO4, filtered, and concentrated. The
residue followed by flash column chromatography (Petro-
leum ether: ethyl acetate = 10:1) to give desired products.
41% yield, 48% ee; [α]D20 = −9.4 (c 0.32, CHCl3); 1H NMR
(200 MHz, CDCl3): δ 7.64 to 7.26 (m, 4H), 6.10 to 5.93 (m,
1H), 5.42 to 5.22 (m, 3H); enantiometric excess was deter-
mined by HPLC with a Chiralpak OJ‐H column 1.0 mL/
min, (2‐propanol: hexane = 5:95), major enantiomer
tr = 14.0 minutes, minor enantiomer tr = 15.3 minutes.
2.1.1 | (S)‐1‐phenylprop‐2‐en‐1‐ol (3a)28
20
Yield 49.8 mg; 47% yield, 61% ee; [α]D = −3.8 (c 0.8,
1
CHCl3); H NMR (200 MHz, CDCl3): δ 7.37 to 7.25 (m,
2.1.6 | (S)‐1‐(p‐tolyl)prop‐2‐en‐1‐ol (3f)28
5H), 6.13 to 5.97 (m, 1H), 5.38 to 5.17 (m, 3H);
enantiometric excess was determined by HPLC with a
Chiralpak OD‐H column 1.0 mL/min, (2‐propanol: hex-
ane = 5:95), minor enantiomer tr = 8.2 minutes, major
enantiomer tr = 9.9 minutes.
20
1
43% yield, 42% ee; [α]D = −11.8 (c 0.34, CHCl3); H
NMR (200 MHz, CDCl3): δ 7.28 to 7.14 (m, 4H), 6.12 to
5.96 (m, 1H), 5.38 to 5.15 (m, 3H), 2.34 (s, 3H), 2.03 (s,
1H); enantiometric excess was determined by HPLC with
a Chiralpak OJ‐H column 1.0 mL/min, (2‐propanol: hex-
ane = 5:95), major enantiomer tr = 16.3 minutes, minor
enantiomer tr = 20.7 minutes.
2.1.2 | (S)‐1‐(naphthalen‐1‐yl)prop‐2‐en‐1‐
ol (3b)14
20
1
68% yield, 57% ee; [α]D = −14 (c 1.1, CHCl3); H NMR
(200 MHz, CDCl3): δ 8.19–8.16 (m, 1H), 7.89 to 7.78 (m,
2H), 7.63 to 7.42 (m, 4H), 6.32 to 6.16 (m, 1H), 5.93 (m,
1H), 5.48 to 5.25 (m, 2H); enantiometric excess was deter-
mined by HPLC with a Chiralpak OD‐H column 1.0 mL/
min, (2‐propanol: hexane = 10:90), major enantiomer
tr = 9.4 minutes, minor enantiomer tr = 15.3 minutes.
2.1.7 | (S)‐1‐(m‐tolyl)prop‐2‐en‐1‐ol (3g)34
1
45% yield, 46% ee; H NMR (200 MHz, CDCl3): δ 7.28 to
7.08 (m, 4H), 6.13 to 5.96 (m, 1H), 5.39 to 5.16 (m, 3H),
2.35 (s, 3H), 2.00 (s, 1H); enantiometric excess was deter-
mined by HPLC with a Chiralpak OD‐H column 1.0 mL/
min, (2‐propanol: hexane = 3:97), minor enantiomer
tr = 11.1 minutes, major enantiomer tr = 15.1 minutes.
2.1.3 | (S)‐1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐
ol (3c)29
2.1.8 | (S)‐1‐(o‐tolyl)prop‐2‐en‐1‐ol (3h)28
1
66% yield, 35% ee; [α]D20 = + 2.0 (c 1.3, CHCl3); 1H NMR
(200 MHz, CDCl3): δ 7.84 to 7.81 (m, 4H), 7.49 to 7.45 (m,
3H), 6.20 to 6.03 (m, 1H), 5.44 to 5.20 (m, 3H);
enantiometric excess was determined by HPLC with a
Chiralpak AS‐H column 1.0 mL/min, (2‐propanol: hex-
ane = 3:97), minor enantiomer tr = 15.4 minutes, major
enantiomer tr = 17.7 minutes.
46% yield, 30% ee; H NMR (200 MHz, CDCl3): δ 7.46 to
7.43 (m, 1H), 7.23 to 7.17 (m, 3H), 6.12 to 5.95 (m, 1H),
5.42 to 5.18 (m, 3H), 2.36 (s, 1H), 1.92 (s, 1H);
enantiometric excess was determined by HPLC with a
Chiralpak OD‐H column 1.0 mL/min, (2‐propanol: hex-
ane = 3:97), minor enantiomer tr = 12.0 minutes, major
enantiomer tr = 13.6 minutes.

4
WANG ET AL.
2.1.9 | (S)‐1‐(2‐(trifluoromethyl)phenyl)
prop‐2‐en‐1‐ol (3i)34
2.1.14 | (S)‐5‐phenylpent‐1‐en‐3‐ol (3n)53
35% yield, 40% ee; [α]D = −5.0 (c 1.0, CHCl3);1H NMR
20
43% yield, 47% ee; [α]D20 = −11.8 (c 0.47, CHCl3); 1H NMR
(200 MHz, CDCl3): δ 7.75 to 7.26 (m, 4H), 6.12 to 5.95 (m,
1H), 5.66 (m, 1H), 5.43 to 5.19 (m, 2H); enantiometric excess
was determined by HPLC with a Chiralpak OD‐H column
1.0 mL/min, (2‐propanol: hexane = 3:97), minor enantio-
mer tr = 9.5 minutes, major enantiomer tr = 10.3 minutes.
(200 MHz, CDCl3): δ 7.32 to 7.18 (m, 5H), 5.99 to 5.82 (m,
1H), 5.28 to 5.11 (m, 2H), 4.14 to 4.11 (m, 1 H), 2.77 to
2.67 (m, 2H), 1.91 to 1.80 (m, 2H); enantiometric excess
was determined by HPLC with a Chiralpak OD‐H column
1.0 mL/min, (2‐propanol: hexane = 3:97), minor enantio-
mer tr = 18.2 minutes, major enantiomer tr = 27.1 minutes.
2.1.10 | (S)‐1‐(2‐chlorophenyl)prop‐2‐en‐1‐
3 | RESULTS AND DISCUSSION
ol (3j)45
Based upon previous results, BDMAEE was similarly
57% yield, 63% ee; [α]D = −6.0 (c 0.38, CHCl3);1H NMR
20
used
to
deactivate
vinylmagnesium
bromide
(200 MHz, CDCl3): δ 7.55 to 7.18 (m, 4H), 6.12 to 5.95 (m,
1H), 5.64 (m, 1H), 5.43 to 5.20 (m, 2H); enantiometric excess
was determined by HPLC with a Chiralpak OD‐H column
1.0 mL/min, (2‐propanol: hexane = 3:97), minor enantio-
mer tr = 11.3 minutes, major enantiomer tr = 13.8 minutes.
(CH2 = CHMgBr) in this work. A class of chiral Ligands
L2‐L9 were synthesized except the commercially avail-
able (S)‐BINOL (L1). L1 was initially examined, and
BDMAEE was added to deactivate the reactivity of
CH2 = CHMgBr in dichloromethane, and it obtained very
low ee of 8% with modest yield (Table 1, entry 1). The
smaller dihedral angle H8‐BINOL (L2) obtained similar
result (entry 2). While TADDOL was used, yield
increased accompanying with the slightly reduced ee
(entry 3). Unfortunately, chiral amine L4 and L5 only
obtained racemic allylic alcohol. The 3,3′‐bissubstituted
BINOLs L6 and L7 and (S)‐3,3′‐dimethyl H8‐BINOL L9
as ligands were observed but the results were still unsat-
isfactory (entries 6‐9), and the highest ee of 13% was
afforded with L6 (entry 6). Another additive was then
intended to increase the enantioselectitivty, and a series
of metal reagents was examined with L6 (entries 10‐14).
Regretfully, only n‐BuMgCl afforded slightly improved
ee of 18% (entry 10). Then, solvents were observed, and
THF and methyl tert‐butyl ether (MTBE) obtained the
highest enantioselectivity (28%) and MTBE obtained
higher yield than THF (entries 10 and 16–18). Then, the
amount of L6 and n‐BuMgCl was optimized, and the
highest 60% of enantioselectivity was obtained (entries
16‐25), indicating a possible chloride Grignard reagent
2.1.11 | (S)‐1‐(2‐bromophenyl)prop‐2‐en‐1‐
ol (3k)29
51% yield, 47% ee; [α]D = −25.0 (c 0.42, CHCl3);1H NMR
20
(200 MHz, CDCl3): δ 7.55 to 7.11 (m, 4 H), 6.11 to 5.95 (m,
1 H), 5.61 (m, 1 H), 5.44 to 5.21 (m, 2 H); enantiometric excess
was determined by HPLC with a Chiralpak OD‐H column
1.0 mL/min, (2‐propanol: hexane = 3:97), minor enantiomer
tr = 12.0 minutes, major enantiomer tr = 15.8 minutes.
2.1.12 | (S)‐1‐(thiophen‐3‐yl)prop‐2‐en‐1‐ol
(3l)41
27% yield, 34% ee; [α]D = −19.0 (c 0.26, CHCl3);1H
20
NMR (200 MHz, CDCl3): δ 7.33 to 7.06 (m, 3H), 6.17 to
6.00 (m, 1H), 5.61 (m, 1H), 5.40 to 5.19 (m, 3H);
enantiometric excess was determined by HPLC with a
Chiralpak OD‐H column 1.0 mL/min, (2‐propanol: hex-
ane = 3:97), major enantiomer tr = 26.3 minutes, minor
enantiomer tr = 34.4 minutes.
complex
A (Scheme 2) effectively catalyzing the
asymmetric vinylation of aldehydes with the vinyl
Grignard reagent.
In order to test the role of the magnesium additive,
other magnesium salts were evaluated. When MgBr2
and MgCl2 was respectively added the reaction as addi-
tive, the adduct ee dramatically decrease (entries 26‐27).
Considering Grignard reagent acitivity, n‐BuMgCl was
replaced with n‐BuMgBr, resulted in noticeable decreases
in enantioselectivity (entry 28). Having a small amount
chloride anion in reaction system might facilitate halide
metathesis in the vinyl Grignard leading to a less reactive
vinylmagnesium chloride. To verify this possibility, we
2.1.13 | (S,E)‐1‐phenylpenta‐1,4‐dien‐3‐ol
(3m)50
33% yield, 27% ee; [α]D = − 5.6 (c 0.9, CHCl3);1H NMR
20
(200 MHz, CDCl3): δ 7.41 to 7.24 (m, 5H), 6.66 to 6.58 (m,
1H), 6.29 to 6.18 (m, 1H), 6.07 to 5.90 (m, 1H), 5.38 to 5.17
(m, 1H), 4.82 to 4.80 (m, 1H); enantiometric excess was
determined by HPLC with a Chiralpak AS‐H column
1.0 mL/min, (2‐propanol: hexane = 3:97), minor enantio-
mer tr = 12.6 minutes, major enantiomer tr = 14.5 minutes.

WANG ET AL.
5
TABLE 1 Optimization of reaction conditionsa, e
Entry
1
Ligand (Mol%)
L1 (15)
L2 (15)
L3 (15)
L4 (15)
L5 (15)
L6 (15)
L7 (15)
L8 (15)
L9 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (15)
L6 (20)
L6 (30)
L6 (40)
L6 (30)
L6 (30)
L6 (30)
L6 (30)
L6 (30)
L6 (30)
L6 (30)
Additive (Mol%)
‐
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
THF
Yield%b
47
ee%c
8
2
‐
48
6
3
‐
64
4
4
‐
43
<1
<1
13
9
5
‐
45
6
‐
49
7
‐
47
8
‐
48
6
9
‐
45
10
18
<1
<1
<1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
n‐BuMgCl (30)
Et2AlCl (30)
Al (me)3 (30)
ZnEt2 (30)
Ti (Oi‐Pr)4 (30)
Al (Oi‐Pr)3 (30)
n‐BuMgCl (30)
n‐BuMgCl (30)
n‐BuMgCl (30)
n‐BuMgCl (40)
n‐BuMgCl (60)
n‐BuMgCl (80)
n‐BuMgCl (48)
n‐BuMgCl (42)
n‐BuMgCl (36)
n‐BuMgCl (30)
MgBr2 (36)
MgCl2 (36)
n‐BuMgBr (36)
48
39
53
47
d
d
‐
‐
49
43
45
47
<1
22
28
28
45
50
48
55
58
60
58
14
16
15
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
d
‐
d
‐
d
‐
d
‐
d
‐
d
‐
d
‐
45
46
61
aCondition: benzaldehyde (0.5 mmol), vinylmagnesium bromide (1.0 mmol), solvent (5 mL), BDMAEE (1.0 mmol), −20 to 0°C.
bIsolated yield.
cDetermined by chiral HPLC.
dNot determined.
eThe complexing agent was optimized, and see supporting information for the result.

6
WANG ET AL.
low eantioselectivity of 34% as well as low 27% of yield
(entry 12). The unsaturated aldehyde, ie, cinnamaldehyde,
obtained relatively yield and enantioselectivitie (entry 13).
Finally, the aliphatic aldehyde afforded yield of 35% and
enantioselectivity of 40% (entry 14).
SCHEME 3 The asymmetric vinylation of benzaldehyde with
vinylmagnesium chloride
4 | CONCLUSION
used vinylmagnesium chloride as starting material, but
enantioselectivity was not elevated, which was dropped
to 44% (Scheme 3). Therefore, halide metathesis is not
the main reason for enantioselectivity.
In summary, a new catalytic direct enantioselective
vinylation of aldehydes with vinyl Grignard reagent for
preparing chiral allylic alcohols was demonstrated.
Besides using BDMAEE as effective deactivating reagent,
n‐BuMgCl was found to be an indispensable additive in
improving the enantioselectivity of the reaction. MTBE
was the ideal solvent and (S)‐3,3′‐dimethyl‐BINOL was
the optimal ligand. The highest enantioselectivity is up
to 63%, and to the best our knowledge, this is the highest
enantioselectivity in the catalytic direct asymmetric addi-
tion of vinyl Grignard reagents to aldehydes. And this
work is the first case to systematically observe the cata-
lytic direct enantioselective vinylation of aldehydes with
a vinyl Grignard reagent. This protocol does not need to
transform the vinyl Grignard reagent into other less reac-
tive organometal reagent. Therefore, this work demon-
strates a cost‐effective and operationally convenient
method for the synthesis of chiral allylic alcohols.
With the optimized reaction conditions, the scope of
aldehydes for the Grignard reaction was examined. The
results were collected into Table 2. The results show that
various aldehydes are well suitable to this process. The
electron‐withdrawing and electron‐donating groups in
the benzene ring do not have remarkable effect on
enantioselectivity of the reaction. Naphthaldehydes
obtained good higher than 60% yield and modest
enantioselectivity (Table 2, entries 2‐3). 2‐Chloroben-
zaldehyde obtained the highest 63% enantioselectivity
(entry 10). To the best of our knowledge, this is the highest
enantioselectivity to date in the catalytic direct enantiose-
lective addition of vinyl Grignard reagent. Heterocyclic
aromatic aldehyde was also investigated, and it achieved
TABLE 2 Catalytic vinylation of aldehydesa
ACKNOWLEDGMENTS
The authors gratefully acknowledge the financial support of
The Higher Education Scientific Research Project of
Ningxia (NGY2018‐92), The Project of Ningxia Medical Uni-
versity (XT2017016), and The Ningxia High School first‐class
Disciplines (West China first‐class Disciplines Basic Medical
Sciences at Ningxia Medical University) (NXYLXK2017B07).
Entry
1
R
Allylic alcohol
Yield%b
47
ee%c
61
57
35
42
48
42
46
30
47
63
47
34
27
40
Ph
3a
3b
3c
3d
3e
3f
2
1‐naphthyl
2‐naphthyl
4‐cl‐C6H4
4‐CF3‐C6H4
4‐me‐C6H4
3‐me‐C6H4
2‐me‐C6H4
2‐CF3‐C6H4
2‐cl‐C6H4
2‐Br‐C6H4
3‐thiophene
(E)‐PhCH=CH
PhCH2CH2
68
3
66
4
49
5
41
ORCID
6
43
Pei Wang https://orcid.org/0000-0002-4177-9167
Chao‐Shan Da https://orcid.org/0000-0003-1306-4348
7
3g
3h
3i
45
8
46
9
43
REFERENCE
10
11
12
13
14
3j
57
1. Wakefield BJ (Ed). Organomagnesium Methods in Organic Syn-
thesis. Academic Press: San Diego. CA; 1995.
3k
3l
51
27
2. Franzén RG. Utilization of Grignard reagents in solid‐phase synthe-
sis: a review of the literature. Tetrahedron. 2000;56(5):685‐691.
3m
3n
33
35
3. Richey HG (Ed). New Developments: Grignard Reagents. Chich-
aCondition: aldehyde (0.5 mmol), vinylmagnesium bromide (1.0 mmol), L6
(0.15 mmol), MTBE (5 mL), n‐BuMgCl (0.18 mmol), BDMAEE (1.0 mmol),
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bIsolated yield.
cDetermined by chiral HPLC.
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SUPPORTING INFORMATION
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How to cite this article: Wang P, Ma G‐R, Yu S‐L,
Da C‐S. Enantioselective vinylation of aldehydes
with the vinyl Grignard reagent catalyzed by
magnesium complex of chiral BINOLs. Chirality.
2018;1–8. https://doi.org/10.1002/chir.23038
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vinylsilane additions: a new approach to the synthesis of
enantiopure β,γ‐unsaturated α‐Hydroxy acid derivatives. J Am
Chem Soc. 2006;128(34):11034‐11035.