Enantioselective addition of alkenylzinc reagents to aldehydes with organoboronates as the alkenyl source

Article abstract of DOI:10.1016/j.tetasy.2007.02.026

Alkenylboronates were used as a vinyl source in the asymmetric addition of an alkenylzinc reagent to aldehydes catalyzed by a dendritic ligand. The resulting allylic alcohol products were obtained in 66-96% ee and 35-64% yields.

Full text of DOI:10.1016/j.tetasy.2007.02.026

Tetrahedron: Asymmetry 18 (2007) 724–728
Enantioselective addition of alkenylzinc reagents to aldehydes
with organoboronates as the alkenyl source
Zhuo Chai, Xin-Yuan Liu, Jun-Kang Zhang and Gang Zhao*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received 2 January 2007; accepted 28 February 2007
Abstract—Alkenylboronates were used as a vinyl source in the asymmetric addition of an alkenylzinc reagent to aldehydes catalyzed by a
dendritic ligand. The resulting allylic alcohol products were obtained in 66–96% ee and 35–64% yields.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
reagent in situ generated from dialkylzinc and alkenyl-
boronic pinacol esters in DMF. However, disappointing
results were obtained when aldehydes and ketones were
subjected to similar reaction conditions and no asymmetric
attempts were reported. In view of the good stability and
easy availability of most alkenyboronic esters, we con-
ceived that the generation of alkenylzinc species with them
as the alkenyl source could provide a useful complement to
the present methodology for asymmetric synthesis. During
the preparation of this manuscript, Bolm et al.8a reported a
similar protocol using alkenylboronic acids as the alkenyl
source, however, the enantioselectivities were not ideal,
which would be disadvantageous for further application
in asymmetric synthesis. Keeping in mind that the struc-
tures of alkenylboronic esters, especially the different alco-
hol moieties, could have an influence on their reactivities9
and based on our own experience with the generation of
organozinc reagents via boron–zinc transmetallation,10
we hypothesized that examination of the effects of solvent,
temperature and more importantly the structures of the
alkenylboronic esters could provide better results. Herein
we report our improvement on the use of alkenylboronic
esters as the alkenyl source for the asymmetric alkenylation
of aldehydes.
Optically active secondary allylic alcohols represent a very
important class of compounds as both versatile synthetic
intermediates1 and key structures commonly found in
numerous natural compounds.2 Recently, great progress
has been made in the preparation of this class of compounds
by enantioselective addition reactions of in situ generated
alkenylzinc reagents to aldehydes in the presence of different
types of chiral ligands.3–5 In general, alkenylzinc reagents
are not temperature stable and thus should be used immedi-
ately after generation. Presently, two approaches have been
extensively applied to prepare the alkenylzinc reagents for
asymmetric use:3 (a) One procedure based on a boron–zinc
transmetallation mechanism involving the hydroboration of
terminal alkynes followed by an in situ exchange with di-
alkylzinc was developed by Oppozler et al.;4 (b) another pro-
tocol involving hydrozirconation of alkynes with Schwartz
reagent followed by transmetallation with dimethylzinc
was established by Wipf et al.5 In addition, Walsh et al.6
have also reported the use of tris(vinyl ether) borane as
the alkenyl source in the asymmetric alkenylation reactions
of aldehydes. Since a stereogenic center and a new carbon–
carbon bond are formed concomitantly, this methodology
for generating optically active secondary allylic alcohols is
attractive, and thus the development of other vinyl sources,
remains an intriguing subject in this field.
2. Results and discussion
More recently, Pandya et al.7 reported that the alkenyl-
ation of nitrones could be conducted with an alkenylzinc
In an initial study, (E)-styrylboronic acid 1a was tested for
the in situ generation of alkenylzinc reagents. Dendritic
ligand 2 (see Table 1), which has been previously success-
fully applied in the asymmetric arylation of aldehydes,10a
was used in the following reactions. To our delight, the
*
Corresponding author. E-mail: zhaog@mail.sioc.ac.cn
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.02.026

Z. Chai et al. / Tetrahedron: Asymmetry 18 (2007) 724–728
725
Table 1. Screening of alkenyl source and optimization of reaction
We then turned our attention to the use of the correspond-
ing alkenylboronic esters as the alkenyl source. Esters 1b–e
(see Table 1) were easily prepared by condensation with the
corresponding diols.13 Next, when 1b–d were treated with a
2-fold excess of Et2Zn in hexanes at 0 ꢁC, the times at
which the respective mixtures began to turn black were
found to be quite different: 5 min for 1b, 15 min for 1c
and 40 min for 1d, which may be explained by the decreas-
ing Lewis acidity of the boron atom in 1b and 1c resulting
from the different electron back-donating ability of the
oxygen atom to the spare p-orbital of the boron atom.
However, in the case of pinacol ester 1e, the mixture
remained almost unchanged, even at room temperature
for 3 h, which may be due to the large steric hinderance
around the boron atom. Additionally, the different reactiv-
ities of 1b–e were also reflected in their stabilities: the more
reactive 1b and 1c underwent facile decomposition upon
flash column chromatography, while the less reactive 1d
and 1e could be purified by flash column chromatography.
conditions for the asymmetric alkenylation of benzaldehydea
OH
OR
B
1. hexanes, time
+ Et2Zn
OR
2. 2, benzaldehyde
3b
ligand 2
O
Ph
1a: R = H
1b: R =
O
O
O
O
Ph
Ph
N
1c: R = CH2CH2
1d: R = CH2CH2CH2
1e: R = C(CH3)2C(CH3)2
HO
n
n=2
O
Ph
Entry Boronate/ Solvent
acid
Timeb % Yieldc % eed,e
(min)
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1b
1c
1d
1e
1d
1d
1d
1d
1d
1d
1d
1d
Various solvents 10
Hexane–toluene
Hexane–toluene 15
Hexane–toluene 40
Hexane–toluene 60
Hexane–CH2Cl2 40
32–71
77f
51
60
5g
15–62
0
70
96
91
93
92
n.d.
96
90
5
Subsequently, the asymmetric alkenylation of benzalde-
hyde were re-studied with boronates 1b–e in the presence
of ligand 2 using the following procedure: a mixture of
boronates (0.4 mmol in 0.4 mL of n-hexane) and Et2Zn
(0.8 mmol, 1.0 M in hexanes) was stirred for specified times
in hexane at 0 ꢁC before the addition of ligand and benzal-
dehyde (0.2 mmol) in other specified solvents. The results
obtained are shown in Table 1 (entries 2–11). The different
reactivities of 1b–e were well reflected in these results.
While the most reactive catechol-derived 1b provided the
highest yield (77%) in racemic form (Table 1, entry 2),
extremely low conversion and yield was observed for the
most unreactive 1e (Table 1, entry 5). As shown in entry
9, the best result in terms of both yield (61%) and ee
(96%) was obtained with 1d as the alkenyl source in the
presence of 5 mol % of 2; this result was highly reproduc-
ible over several runs. Dendritic ligand 2, which could be
easily recovered by the precipitation method,10a could be
reused at least twice without significant decreases in yield
and ee (Table 1, entries 11 and 12). In addition, we also
tested several small molecule ligands under the same reac-
tion conditions, and similarly good results in terms of
yields and ees were obtained.14
38
46
Hexane–Et2O
Hexane–THF
40
40
Trace
61h
51i
17j
57k
60l
Hexane–toluene 40
Hexane–toluene 40
Hexane–toluene 40
Hexane–toluene 40
Hexane–toluene 40
96
93
94
a Conditions: boronates/Et2Zn/PhCHO/ligand = 2.0:4.0:1.0:0.05, 0 ꢁC,
8 h.
b Time for the mixing of boronates and Et2Zn.
c Yields after silica gel column chromatography.
d Determined by HPLC using a chiral OD column (DAICEL).
e The absolute configuration was determined to be (S) by comparison of
the specific rotation value with that of the literature data.
f The reaction time was 2 h.
g 85% benzaldehyde recovered.
h 5 mol % of 2 was used.
i 2.5 mol % of 2 was used.
j The reaction was performed at ꢀ15 ꢁC and 60% benzaldehyde was
recovered.
k Second reuse of ligand 2.
l Third reuse of ligand 2.
Then, a selected spectrum of aldehydes was examined under
the optimum reaction conditions. The results are summa-
rized in Table 2 (entries 1–11). Generally, aromatic alde-
hydes gave better results than aliphatic ones. The
electronic nature of substituents on the benzene ring seemed
not to have a significant influence on the enantioselectivi-
ties. However, in the case of 2-bromobenzaldehyde (Table
2, entry 7), the ethyl adduct was isolated along with a lower
ee, which may be due to the large steric hinderance of the
ortho-Br atom. Moreover, for the electronic-deficient
para-CF3 substituted benzaldehyde, an ethyl adduct prod-
uct was also observed, which may result from its high reac-
tivity, although no significant reduction in ee was observed
(Table 2, entry 4). The enantioselectivity dropped as the ste-
ric hinderance decreased in the case of aliphatic aldehydes
(Table 2, entries 9–11). As for the structural diversity of
the alkenylboronates moiety, both the alkenylboronic ester
1g (Table 2, entry 12) with the phenyl group connected to
treatment of 1a with a 3-fold excess of Et2Zn at 0 ꢁC for
15 min in hexanes followed by the addition of
2
(10 mol %) and benzaldehyde provided the corresponding
allylic alcohol 3a in moderate yield, which indicated the
intermediacy of alkenylzinc species generated under the
reaction conditions. Unfortunately, the reproducibility of
both the yields and ee values remained poor in spite of
much effort, including variation of solvents, ligands, and
the amount of Et2Zn11 (Table 1, entry 1). In addition, using
the anhydride of 1a which has a better chemical homogene-
ity could provide results of good reproducibility; however,
the enantioselectivity was poor (58–60% yield, 31–34% ee).
Notably, when the mixture of 1a and Et2Zn in hexanes was
allowed to stir over 15 min, the white turbid mixture would
gradually turn black, which might be due to the coupling of
the alkenylzinc species.12

726
Z. Chai et al. / Tetrahedron: Asymmetry 18 (2007) 724–728
Table 2. Asymmetric alkenylation of various aldehydesa
gel. NMR spectra were recorded at 300 MHz for 1H
NMR using SiMe4 as an internal standard in CDCl3 and
282 MHz for 19F NMR using CFCl3 as an internal stan-
dard in CDCl3. Enantiomeric excesses were determined
by chiral HPLC analysis. Optical rotations were measured
on a JASCO 1030 polarimeter. All solvents were dried
before use according to standard procedures.
R2 OH
R'
O
R2
O
B
Et2Zn
R1
R'
H
R1
O
5 mol% 2
hexane-toluene
R3
R3
3a-m
1d: R1 = Ph, R2, R3 = H
1f: R3 = Ph, R1, R2 = H
4.2. General procedure for the asymmetric alkenylation of
aldehydes
1g: R1 = n-Butyl, R2, R3 = H
Entry Boronate R0
Product % Yieldb % eec,d
Under an atmosphere of dry argon, to a solution of
alkenylboronic ester (0.4 mmol) in 0.4 mL of n-hexane
was added ZnEt2 (0.8 mmol, 1.0 M in hexanes) 0 ꢁC. After
stirring for 40 min at this temperature, ligand 2 in 1 mL tol-
uene was added and solution was again stirred for 10 min
followed by the dropwise addition of aldehyde in 0.5 mL
toluene over 15 min. The mixture was allowed to stir for
8 h at 0 ꢁC and quenched by the addition of 10 mL of
methanol to precipitate the dendritic ligand after which
the mixture was filtered and concentrated. To the residue
was added 3 mL of 1% aqueous NaOH and the mixture
stirred for 2 h at room temperature (this step could facili-
tate the purification of products by destroying the excess
boronic ester), then extracted with ethyl acetate
(3 · 3 mL), and dried over Na2SO4. After removal of the
solvent under reduced pressure, the residue was purified
by column chromatography (PE/ether = 8:1) to give the
desired allylic alcohols. The ee was determined by HPLC
analysis using a chiral column.
1
2
3
4
5
6
7
8
9
10
11
12
13
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1f
Ph
3a
3b
3c
61
64
96
92
93
93
84
94
82
91
82
76
66
94
94
4-Me–C6H4
4-Cl–C6H4
4-CF3–C6H4 3d
57
50e
58
4-Br–C6H4
3-Br–C6H4
2-Br–C6H4
2-Naph
c-C6H11
i-Propyl
n-C4H9
Ph
3e
3f
53
3g
3h
3i
40f
52
46
45
3j
3k
3l
58
35g
39g
1g
Ph
3m
a Conditions: boronates/Et2Zn/PhCHO/ligand = 2.0:4.0:1.0:0.05, 0 ꢁC,
8 h.
b Yields after silica gel column chromatography.
c Determined by HPLC using a chiral OD column (DAICEL).
d The absolute configurations of 3a, 3i, 3j, and 3k were determined by
comparison of the specific rotation value with that of the literature data.
Otherwise, the stereochemistry was assigned by assuming that a similar
reaction pathway was taken.
e 20% ethyl adduct was also isolated as a mixture inseparable from 3d and
the ratio was determined by 1H NMR analysis.
4.2.1. (S)-(E)-1,3-Diphenyl-prop-2-en-1-ol 3a.15 Colorless
24
oil; ½aꢁD ¼ ꢀ31:5 (c 0.75, CHCl3) for 96% ee {lit.12
f 16% ethyl adduct was also isolated as a mixture inseparable from 3g and
the ratio was determined by 1H NMR analysis.
24
1
½aꢁD ¼ ꢀ32:1 (c 0.5, CHCl3) for >99% ee (s)}; H NMR
(CDCl3): d 7.45–7.21 (m, 10H), 6.70 (d, J = 15.8 Hz, 1H),
6.39 (dd, J = 15.8, 6.7 Hz, 1H), 5.40 (m, 1H), 2.30 (d,
J = 3.9 Hz, 1H); HPLC: Daicel CHIRALCEL OD
column, hexane/IPA = 4:1, 0.60 mL/min, k = 254 nm,
tR(S) = 23.2 min, tR(R) = 28.7 min.
g 3 equiv of alkenylboronates were used.
the same carbon with the boron atom and 1f (Table 2, entry
13) derived from n-hexyne with an alkyl chain provided the
corresponding allylic alcohol products with benzaldehyde
in high enantioselectivity, albeit with lower yields.
4.2.2. (S)-(E)-3-Phenyl-1-(p-tolyl)-2-propenol 3b.8a Pale
22
yellow solid; mp 73–75 ꢁC; ½aꢁD ¼ ꢀ22:3 (c 0.50, CH2Cl2)
20
for 92% ee {lit.8a ½aꢁD ¼ þ8:0 (c 1.4, CH2Cl2) for 34% ee
(R)}; 1H NMR (CDCl3): d 7.39–7.16 (m, 9H), 6.68 (d,
J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 6.6 Hz, 1H), 5.33
(m, 1H), 2.34 (s, 3H), 2.02 (s, 1H); HPLC: Daicel CHI-
RALCEL OD column, hexane/IPA = 4:1, 0.60 mL/min,
k = 254 nm, tR(S) = 24.3 min, tR(R) = 36.1 min.
3. Conclusion
In conclusion, we have successfully developed a protocol
for the asymmetric alkenylation of aldehydes using
alkenylboronic esters as the vinyl source. This method
provides an alternative method for the synthesis of enantio-
merically enriched allylic alcohols. Efforts on further
optimization and extension of the scope of this method
are currently underway.
4.2.3.
3c.8a Pale yellow solid; mp 57–58 ꢁC; ½aꢁD ¼ ꢀ16:8 (c
(S)-(E)-1-(4-Chlorophenyl)-3-phenylprop-2-en-1-ol
22
20
0.65, CH2Cl2) for 93% ee {lit.8a ½aꢁD ¼ þ8:9 (c 1.4, CH2Cl2)
1
for 55% ee (R)}; H NMR (CDCl3): d 7.39–7.26 (m, 9H),
6.68 (d, J = 15.7 Hz, 1H), 6.32 (dd, J = 15.7, 6.7 Hz, 1H),
5.36 (d, J = 6.7 Hz, 1H), 2.84 (br s, 1H); HPLC: Daicel
CHIRALCEL OD column, hexane/IPA = 4:1, 0.60 mL/
min, k = 254 nm, tR(S) = 21.8 min, tR(R) = 31.1 min.
4. Experimental
4.1. General
All reactions were carried out under a dry argon atmo-
sphere unless noted otherwise. Analytical TLC was
performed on precoated silica gel plates. Column
chromatography was conducted with 300–400 mesh silica
4.2.4. (S)-(E)-3-Phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-
1
en-1-ol 3d.16 Colorless oil; H NMR (CDCl3): d 7.56 (d,
J = 8.3 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.35–7.20 (m,
5H), 6.60 (d, J = 15.8 Hz, 1H), 6.26 (dd, J = 15.8, 6.6 Hz,

Z. Chai et al. / Tetrahedron: Asymmetry 18 (2007) 724–728
727
1H), 5.34 (d, J = 6.6 Hz, 1H), 2.81 (br s, 1H); 19F NMR
(282 MHz, CDCl3): d ꢀ62.2; HPLC: Daicel CHIRALCEL
OD column, hexane/IPA = 4:1, 0.60 mL/min, k = 254 nm,
tR(S) = 20.3 min, tR(R) = 33.0 min.
column, hexane/IPA = 4:1, 0.60 mL/min, k = 254 nm,
tR(R) = 14.1 min, tR(S) = 19.4 min.
4.2.12. (R)-1,2-Diphenylprop-2-en-1-ol 3l.22 Colorless oil;
22
½aꢁD ¼ ꢀ47:6 (c 0.27, CHCl3) for 94% ee 1H NMR
4.2.5.
3e.17 White solid; mp 65–66 ꢁC; ½aꢁD ¼ ꢀ14:9 (c 0.47,
(S)-(E)-1-(4-Bromophenyl)-3-phenylprop-2-en-1-ol
22
(CDCl3): d 7.41–7.23 (m, 10H), 5.72 (s, 1H), 5.50 (d,
J = 7.6 Hz, 2H), 2.10 (br s, 1H); HPLC: Daicel CHIRAL-
CEL OD column, hexane/IPA = 4:1, 0.60 mL/min,
k = 254 nm, tR(S) = 13.4 min, tR(R) = 20.9 min.
1
CHCl3) for 84% ee; H NMR (CDCl3): d 7.51–7.26 (m,
9H), 6.68 (d, J = 15.8 Hz, 1H), 6.32 (dd, J = 15.8, 6.5 Hz,
1H), 5.36 (m, 1H), 2.03 (d, J = 3.2 Hz, 1H); HPLC: Daicel
CHIRALCEL OD column, hexane/IPA = 4:1, 0.60 mL/
min, k = 254 nm, tR(S) = 21.6 min, tR(R) = 30.9 min.
4.2.13.
(S)-(E)-4-Methyl-1-phenylpent-1-en-3-ol
3m.3k
22
Colorless oil; ½aꢁD ¼ þ34:2 (c 0.58, CHCl3) for 94% ee
20
1
{lit.3k ½aꢁD ¼ ꢀ37:1 (c 1.34, CHCl3) for 97% ee (R)}; H
NMR (CDCl3): d 7.38–7.24 (m, 5H), 5.81–5.62 (m, 1H),
5.16 (d, J = 6.1 Hz, 1H), 2.05 (m, 2H), 1.88 (s, 1H), 1.43–
1.26 (m, 4H); 0.89 (t, J = 7.0 Hz, 3H); HPLC: Daicel CHI-
RALCEL OD column, hexane/IPA = 4:1, 0.60 mL/min,
k = 254 nm, tR(R) = 10.5 min, tR(S) = 12.2 min.
4.2.6.
(S)-(E)-1-(3-Bromophenyl)-3-phenylprop-2-en-1-ol
1
3f.18 Colorless oil; H NMR (CDCl3): d 7.70–7.09 (m,
9H), 6.68 (d, J = 15.9 Hz, 1H), 6.32 (dd, J = 15.9, 6.0 Hz,
1H), 5.30 (m, 1H), 2.20 (br s, 1H); HPLC: Daicel CHI-
RALCEL OD column, hexane/IPA = 4:1, 0.60 mL/min,
k = 254 nm, tR(S) = 20.8 min, tR(R) = 30.3 min.
Acknowledgments
4.2.7.
(S)-(E)-1-(2-Bromophenyl)-3-phenylprop-2-en-1-ol
3g.8a 1H NMR (CDCl3): d 7.62–7.53 (m, 2H), 7.39–
7.12 (m, 7H), 6.74 (d, J = 15.7 Hz, 1H), 6.32 (dd, J =
15.7, 6.0 Hz, 1H), 5.76 (m, 1H), 2.26 (d, J = 4.2 Hz, 1H);
HPLC: Daicel CHIRALCEL OD column, hexane/
IPA = 4:1, 0.60 mL/min, k = 254 nm, tR(S) = 18.7 min,
tR(R) = 20.2 min.
We are grateful to National Natural Science Foundation of
China for financial support (Nos. 20525208, 203900502,
20532040), QT program, and Shanghai Natural Science
Council.
References
4.2.8.
3h.19 White solid; mp 77–78 ꢁC; ½aꢁD ¼ ꢀ25:2 (c 0.33,
(S)-(E)-1-(Naphthalen-2-yl)-3-phenylprop-2-en-1-ol
22
1. For recent examples, see: (a) Castoldi, D.; Caggiano, L.;
Panigada, L.; Sharon, O.; Costa, A. M.; Gennari, C. Angew.
Chem., Int. Ed. 2005, 44, 588–591; (b) Kim, H.-Y.; Lurain, A.
E.; Garcia-Garcia, P.; Carroll, P. J.; Walsh, P. J. J. Am.
Chem. Soc. 2005, 127, 13138–13139; (c) Smith, T. E.; Djiang,
M.; Velander, A. J.; Downey, C. W.; Carroll, K. A.; van
Alphen, S. Org. Lett. 2004, 6, 2317–2320.
2. For recent examples, see: (a) Nicolaou, K. C.; Nold, A. L.;
Milburn, R. R.; Schindler, C. S. Angew. Chem., Int. Ed. 2006,
45, 6527–6532; (b) Nickel, A.; Maruyama, T.; Tang, H. F.;
Murphy, P. D.; Greene, B.; Yusuff, N.; Wood, J. L. J. Am.
Chem. Soc. 2004, 126, 16300–16301; (c) Wu, Y.; Shen, X.;
Yang, Y.-Q.; Hu, Q.; Huang, J.-H. J. Org. Chem. 2004, 69,
3857–3865.
3. (a) Chen, Y. K.; Lurain, A. E.; Walsh, P. J. J. Am. Chem. Soc.
2002, 124, 12225–12231; (b) Lurain, A. E.; Walsh, P. J. J. Am.
Chem. Soc. 2003, 125, 10677–10683; (c) Lurain, A. E.;
Carroll, P. J.; Walsh, P. J. J. Org. Chem. 2005, 70, 1262–1268;
(d) Kelly, A. R.; Lurain, A. E.; Walsh, P. J. J. Am. Chem.
Soc. 2005, 125, 14668–14674; (e) Dahmen, S.; Bra¨se, S. Org.
Lett 2001, 25, 4119–4122; (f) Lauterwasser, F.; Gall, J.;
Ho¨fener, S.; Bra¨se, S. Adv. Synth. Catal. 2006, 348, 2068–
2074; (g) Sprout, C. M.; Richmond, M. L.; Seto, C. T. J. Org.
Chem. 2004, 69, 6666–6673; (h) Sprout, C. M.; Richmond, M.
L.; Seto, C. T. J. Org. Chem. 2005, 70, 7408–7417; (i)
Richmond, M. L.; Sprout, C. M.; Seto, C. T. J. Org. Chem.
2005, 70, 8835–8840; (j) Tseng, S.-L.; Yang, T.-K. Tetra-
hedron: Asymmetry 2005, 16, 773–782; (k) Ji, J.-X.; Qiu, L.
Q.; Yip, C. W.; Chan, A. S. C. J. Org. Chem. 2003, 68, 1589–
1590.
1
CH2Cl2) for 91% ee; H NMR (CDCl3): d 7.85 (m, 4H),
7.56–7.26 (m, 8H), 6.74 (d, J = 15.8 Hz, 1H), 6.32 (dd,
J = 15.8, 6.4 Hz, 1H), 5.56 (d, J = 5.0 Hz, 1H), 2.13 (br
s, 1H); HPLC: Daicel CHIRALCEL OD column,
hexane/IPA = 4:1, 0.60 mL/min, k = 254 nm, tR(S) = 28.5
min, tR(R) = 43.1 min.
4.2.9. (R)-(E)-1-Cyclohexyl-3-phenylprop-2-en-1-ol 3i.8a
24
Colorless oil; ½aꢁD ¼ ꢀ5:7 (c 0.47, CH2Cl2) for 82% ee
20
{lit.8a ½aꢁD ¼ þ2:5 (c 1.6, CH2Cl2) for 33% ee (S)}; 1H
NMR (CDCl3): d 7.40–7.23 (m, 5H), 6.54 (d, J =
15.8 Hz, 1H), 6.32 (dd, J = 15.8, 6.7 Hz, 1H), 4.02 (m,
1H), 1.01–1.93 (m, 12H); HPLC: Daicel CHIRALCEL
OD column, hexane/IPA = 4:1, 0.60 mL/min, k =
254 nm, tR(R) = 13.4 min, tR(S) = 17.5 min.
4.2.10. (R)-(E)-4-Methyl-1-phenylpent-1-en-3-ol 3j.1b Col-
22
orless oil; ½aꢁD ¼ ꢀ8:2 (c 0.75, EtOH) for 76% ee {lit.20
20
½aꢁD ¼ ꢀ8:0 (c 1.02, EtOH) for 69% ee (S)}; 1H NMR
(CDCl3): d 7.41–7.26 (m, 5H), 6.58 (d, J = 15.8 Hz, 1H),
6.24 (dd, J = 15.8, 6.8 Hz, 1H), 4.03 (m, 1H), 1.84 (m,
1H), 0.99 (d, J = 5.4 Hz, 3H), 0.95 (d, J = 6.7 Hz, 3H);
HPLC: Daicel CHIRALCEL OD column, hexane/
IPA = 4:1, 0.60 mL/min, k = 254 nm, tR(R) = 13.4 min,
tR(S) = 17.5 min.
4.2.11. (R)-(E)-1-Phenylhept-1-en-3-ol 3k.21 Colorless oil;
4. (a) Oppolzer, W.; Radinov, R. N.; El-Sayed, E. J. Org. Chem.
2001, 66, 4766–4770; (b) Oppolzer, W.; Radinov, R. N. J.
Am. Chem. Soc. 1993, 115, 1593–1594; (c) Oppolzer, W.;
Radinov, R. N. Helv. Chim. Acta 1992, 75, 170–173; (d)
Oppolzer, W.; Radinov, R. N. Tetrahedron Lett. 1988, 29,
5645–5648.
25
25
½aꢁD ¼ ꢀ2:7 (c 0.47, benzene) for 66% ee; {lit.21 ½aꢁD
¼
þ3:52 (c 3.95, benzene) for 76% ee (S)}; 1H NMR (CDCl3):
d 7.41–7.22 (m, 5H), 6.58 (d, J = 15.8 Hz, 1H), 6.24 (dd,
J = 15.8, 6.8 Hz, 1H), 4.28 (m, 1H), 1.60 (m, 3H), 1.38
(m, 4H), 0.92 (m, 3H); HPLC: Daicel CHIRALCEL OD

728
Z. Chai et al. / Tetrahedron: Asymmetry 18 (2007) 724–728
5. (a) Wipf, P.; Nunes, R. L. Tetrahedron 2004, 60, 1269–1279;
organoboronates: (a) Molander, G. A.; Zinke, P. W.
Organometallics 1986, 5, 2161–2162; For related other stud-
ies, see also: (b) Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2004,
(b) Wipf, P.; Jayasuriya, N.; Ribe, S. Chirality 2003, 15, 208–
212; (c) Wipf, P.; Kendall, C. Chem. Eur. J. 2002, 8, 1779–
1784; (d) Wipf, P.; Ribe, S. J. Org. Chem. 1998, 63, 6454–6455.
6. Jeon, S.-J.; Chen, Y. K.; Walsh, P. J. Org. Lett. 2005, 7,
1729–1732.
´
126, 6538–6539; (c) Garcıa, C.; Libra, E. R.; Walsh, P. J. J.
Am. Chem. Soc. 2003, 125, 3210–3211; (d) Srebnik, M.
Tetrahedron Lett. 1991, 32, 2449–2452, and Ref. 3f.
13. Takahashi, G.; Shirakawa, E.; Tsuchimoto, T.; Kawakami,
Y. Chem. Commun. 2005, 1459–1461.
´
7. Pandya, S. U.; Pinet, S.; Chavant, P. Y.; Vallee, Y. Eur. J.
Org. Chem. 2003, 3621–3627.
8. (a) Schmit, F.; Rudolph, J.; Bolm, C. Synthesis 2006, 3625–
3630; The same group has successfully developed a protocol
for the catalytic asymmetric aryl transfer to aromatic
aldehydes with the arylzinc species generated in situ from
arylboronic acids and Et2Zn: (b) Rudolph, J.; Schmit, F.;
Bolm, C. Synthesis 2005, 840–842; (c) Bolm, C.; Rudolph, J.
J. Am. Chem. Soc. 2002, 124, 14850–14851; (d) Schmit, F.;
Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev.
2006, 35, 454–470.
9. For an excellent related study on the reactivities of allylbor-
onates with different alcohol moieties to aldehydes, see: (a)
Brown, H. C.; Racherla, U. S.; Pellechia, P. J. J. Org. Chem.
1990, 55, 1868–1874; For recent examples, see: (b) Lou, S.;
Moquist, P. N.; Schaus, S. E. J. Am. Chem. Soc. 2006, 128,
12660–12661; (c) Southwood, T. J.; Curry, M. C.; Hutton, C.
A. Tetrahedron 2006, 62, 236–242.
14. Several other small molecule ligands were also tested under
the same conditions:
Ph
N
Ph
OH
O
Ph
Ph
N
N
OH
HO
)-DPMPM
60% yield, 96% ee
(
S
(-)-MIB
51% yield,95% ee
61% yield, 96% ee
15. Roos, G. H. P.; Donovan, A. R. Tetrahedron: Asymmetry
1999, 10, 2299–2305.
16. Spogliarich, R.; Farnetti, E.; Graziani, M. Tetrahedron 1991,
47, 1965–1976.
10. (a) Liu, X.-Y.; Wu, X.-Y.; Chai, Z.; Zhao, G.; Zhu, S.-Z. J.
Org. Chem. 2005, 70, 7432–7435; (b) Wu, X.-Y.; Liu, X.-Y.;
Zhao, G. Tetrahedron: Asymmetry 2005, 16, 2299–2305.
11. A similar phenomenon was also reported by Bolm et al. (see
Ref. 8a) when commercial alkenylboronic acids were used. In
our case, the alkenylboronic acid used was prepared from the
reaction of the corresponding organomagnesium bromide
with B(OMe)3 and purified by column chromatography.
12. A small amount of (1E,3E)-1,4-diphenylbuta-1,3-diene was
isolated from the mixture. Molander et al. have found
coupling of alkenylzinc species in the presence of sodium
17. Keinan, E.; Peretz, M. J. Org. Chem. 1983, 48, 5302–5309.
18. Eisen, N.; Vo¨gtle, F. Angew. Chem. 1986, 98, 1029–1030.
19. Braude, E. A.; Gore, P. H. J. Chem. Soc. 1959, 41–49.
20. Yang, W. K.; Cho, B. T. Tetrahedron: Asymmetry 2000, 11,
2947–2953.
21. Rozema, M. J.; Rajagopal, D.; Tucker, C. E.; Knochel, P. J.
Organomet. Chem. 1992, 438, 11–27.
22. Krasovskiy, A.; Straub, B. F.; Knochel, P. Angew. Chem., Int.
Ed. 2006, 45, 159–162.