Enantioselective allylation of aldehydes catalyzed by new bifunctional bisoxazoline-metal complexes

Article abstract of DOI:10.1016/j.tet.2007.02.104

The asymmetric allylation reactions of aldehydes catalyzed by a 10 mol % bisoxazoline complex bearing a phosphine oxide moiety, which was newly designed and synthesized from l-serine, afforded the corresponding homoallylic alcohols in 48-74% yields with 3

Full text of DOI:10.1016/j.tet.2007.02.104

Tetrahedron 63 (2007) 5319–5322
Enantioselective allylation of aldehydes catalyzed by new
bifunctional bisoxazoline–metal complexes
*
Keiichi Takeuchi, Takuma Takeda, Tetsuya Fujimoto and Iwao Yamamoto
*
Department of Functional Polymer Science, Faculty of Textile Science and Technology, Shinshu University,
3-15-1, Tokida, Ueda 386-8567, Japan
Received 30 August 2006; revised 22 February 2007; accepted 23 February 2007
Available online 25 February 2007
Abstract—The asymmetric allylation reactions of aldehydes catalyzed by a 10 mol % bisoxazoline complex bearing a phosphine oxide
moiety, which was newly designed and synthesized from L-serine, afforded the corresponding homoallylic alcohols in 48–74% yields with
39–86% ee. The reaction proceeds with the dual activation of the aldehyde and allylsilane by the Lewis acid and base of the catalyst. The
evidence for the activation of the allylsilane was clarified by the 31P NMR spectra.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
O
X
O
X
1: X = P(O)Ph2
2: X = CHPh2
N
N
Mtl
The asymmetric allylation of aldehydes is an important pro-
cess to obtain chiral homoallylic alcohols, and numerous
methodologies have already been reported.1 Allyltributyl-
stannane is well known as an allylation reagent for the asym-
metric allylation of aldehydes.2 These allylations proceed
through activation of the carbonyl group catalyzed by
a Lewis acid. Furthermore, some examples of the asymmet-
ric allylation using allyltrimethylsilane3 or allyltrimethoxy-
silane4 have been developed to produce the corresponding
homoallylic alcohols with high enantioselectivities. On the
other hand, in 1999, Shibasaki et al. reported the cyanosilyl-
ation of aldehydes with trimethylsilylcyanide using a Lewis
acid–Lewis base bifunctional catalyst to give cyanohydrines
with high yields and excellent enantioselectivities.5 This re-
action proceeded via the dual activation system in which the
metal acted as a Lewis acid to activate the carbonyl group,
and the phosphine oxide acted as a Lewis base to activate
the silicon. On the basis of these concepts, we prepared a
novel bisoxazoline derivative catalyst bearing a Lewis acid
(metal) and a Lewis base (phosphine oxide). In this paper,
we describe the asymmetric allylations of allyltrichloro-
silane to aldehydes catalyzed by the Zn(II)–bisoxazoline
complex 1.
Lewis base
Lewis acid
The novel bisoxazoline derivative ligand 1-L was synthe-
sized using L-serine. Oxazolidine 3 prepared from L-serine
was treated with diphenylphosphine in the presence of
tert-BuOK in THF, followed by oxidation with hydrogen
peroxide to give the phosphinoylmethyloxazolidine 4 in
62% yield. The oxazolidine 4 was deprotected, and then
the resulting amino alcohol reacted with dimethylmalononi-
trile catalyzed by zinc chloride6 to afford phosphinoylme-
thylbisoxazoline 1-L (PM-BOX) in a 96% yield (Scheme 1).
O
OH
OTs
5 steps
N
H N
2
COOH
Boc
L-Serine
3
O
PPh
O
1) Ph PH, t-BuOK
HClaq.
2
2
N
Boc
2) H O
99.6%
2
2
62%
4
O
PPh
O
N
O
2
NC
ZnCl
CN
2
N
O
OH
H N
2
P
Ph
Ph
Ph
P
Ph
Keywords: Dual activation catalyst; Bisoxazoline–zinc complex; Asymmet-
ric allylation.
96%
O
5
1-L
* Corresponding authors. Tel.: +81 268 21 5491; fax: +81 268 21 5494
(I.Y.); e-mail: ganchan@shinshu-u.ac.jp
Scheme 1. Synthesis of bisoxazoline derivative ligand.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.104

5320
K. Takeuchi et al. / Tetrahedron 63 (2007) 5319–5322
First, the metal complex catalyzed asymmetric allylations of
benzaldehyde with allyltrichlorosilane in the presence of
10 mol % PM-BOX 1-L in CH2Cl2 at room temperature
were investigated. When Ti(OiPr)4 and Et2AlCl as Lewis
acids were used, the reactions hardly proceeded (Table 1, en-
tries 1 and 2). Using Cu(OTf)2, the reaction gave the homo-
allylalcohol in 22% yield with an 63% ee along with about
40% recovered benzaldehyde containing a small amount
of benzoic acid (entry 3). The PM-BOX–ZnI2 system pro-
duced a good enantioselectivity, and the combination of
PM-BOX–ZnCl2 showed a lower yield with a good enantio-
selectivity (Table 1, entries 4 and 7). The reaction using
Zn(OTf)2 instead of ZnI2 at room temperature produced a
racemic product (Table 1, entry 5). The reaction at 0 ꢀC in
THF gave the product in 22% yield with 47% ee (Table 1,
entry 6). The reaction at ꢁ78 ꢀC did not occur at all. From
entries 4–9 in Table 1, it can be seen that the combination
of PM-BOX–ZnI2 in a coordinating solvent, such as THF,
is the most matched one to give the product in up to 74%
yield with an 86% ee. The catalytic loading amount of
5 mol % widely decreased the yield, but the ee only slightly
decreased (51% yield, 77% ee). When the other allylic re-
agents, such as the allyltrimethylsilane and allyltrimethoxy-
silane, were employed, the homoallylic alocohols were only
slightly obtained. The allylations of aldehydes with allyltri-
chlorosilane in the absence of ZnI2 in THF at room temper-
ature for 24 h afforded a trace amount of the product.
To clarify the interaction between the diphenylphosphinoyl
moiety and the allyltrichlorosilane, the 31P NMR was mea-
sured. 31P NMR spectrum of the PM-BOX–ZnI2 complex in-
dicated a peak at 29.9 ppm, and that of an equimolar mixture
of the complex and allylsilane appeared at 44.5 ppm (Fig. 1).
Finally, we investigated the catalytic enantioselective addi-
tion of allyltrichlorosilane to typical aromatic, aliphatic,
and a,b-unsaturated aldehydes in the presence of a
10 mol % PM-BOX–ZnI2 complex. These results are sum-
marized in Table 2. The allylation of the p-nitro and p-chloro-
benzaldehyde gave similar results as those of the
benzaldehyde in terms of enantioselectivity (Table 2, entries
2 and 3). On the other hand, the reaction with p-methoxy-
benzaldehyde gave a product with a low chemical yield and
enantioselectivity (Table 2, entry 4). The aliphatic aldehyde
provided a homoallylic alcohol with a moderate yield and
enantioselectivity compared with the aromatic aldehydes
(Table 2, entry 5). For the reaction with the a,b-unsaturated
aldehyde, the 1,2-addition reaction exclusively occurred
(Table 2, entry 6).
In conclusion, we described that the PM-BOX–ZnI2 com-
plex, easily prepared from the inexpensive L-serine, was
effective as a bifunctional catalyst for the asymmetric
allylation of aldehydes with allyltrichlorosilane. Although
the reaction mechanism was not completely revealed, we
assumed a dual activation pathway based on the 31P NMR
The reaction catalyzed by the benzhydrylmethylbisoxazo-
line–ZnI2 complex 2 instead of PM-BOX–ZnI2 gave the
product in only 4% yield along with a 13% ee (Scheme 2).
Table 1. Effects of metals and solvents on chemical yield and enantioselec-
tivitya
1-L (10 mol%)
Metal (10 mol%)
OH
SiCl3
+
PhCHO
Solvent
Ph
Entry
Metal
Solvent
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6e
7
8
9
Ti(OiPr)4
Et2AlCl
Cu(OTf)2
ZnI2
Zn(OTf)2
Zn(OTf)2
ZnCl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
CH2Cl2
THF
THF
24
24
24
24
1
24
24
24
24
1
ndd
ndd
63
67
5
47
84
86
80
Trace
22
65
61
22
38
74
30
ZnI2
ZnCl2
a
The reaction was carried out using allyltrichlorosilane (2.0 equiv) and
benzaldehyde (1 equiv) with PM-BOX (10 mol %) and metal
(10 mol %) at room temperature.
Yield of isolated product.
Determined by HPLC analysis.
b
c
d
e
Not determined.
Reaction was performed in THF at 0 ꢀC.
Catalyst 2 (10 mol%)
OH
Mtl = ZnI2
SiCl3
(2.0 equiv.)
+
PhCHO
THF, rt, 24h
Ph
4%, 13% ee
Scheme 2. Effects of phosphine oxide (Lewis base) on chemical yield and
enantioselectivity.
Figure 1. 31P NMR spectra of (1) PM-BOX–ZnI2 complex and (2) PM-
BOX–ZnI2+allyltricholorosilane.

K. Takeuchi et al. / Tetrahedron 63 (2007) 5319–5322
5321
Table 2. Asymmetric allylation of aldehydes catalyzed by PM-BOX–ZnI2
d 1.24–1.60 (m, 15H), 2.31–2.60 (m, 1H), 3.09–3.15
(m, 1H), 3.93–3.97 (br, 1H), 4.11–4.16 (br, 1H), 4.34–4.42
(br, 1H), 7.38–7.54 (m, 6H), 7.67–7.82 (m, 3H), 7.97–
7.98 (br, 1H); 13C NMR (100 MHz, CDCl3) d 27.6,
28.5, 32.1 (JCP¼67.1 Hz), 53.5, 67.1, 80.2, 128.2–130.4,
152.8; 31P NMR (162 MHz, CDCl3) d 30.5; IR (KBr)
3200, 1715, 1410, 1200, 1102 cmꢁ1; [a]D25 –14.8 (c 1.0,
CHCl3).
complexa
Entry
Aldehyde
Yieldb (%)
eec (%)
R/S
1
2
3
4
5
6
C6H5CHO
p-NO2C6H4CHO
p-ClC6H4CHO
p-MeOC6H4CHO
C6H5CH2CH2CHO
(E)-C6H5CH]CHCHO
74
73
65
52
48
54
86
79
76
39
68
64
R
R
R
R
S
R
a
2.1.2. (S)-2-Amino-3-(diphenylphosphinoylmethyl)pro-
pan-1-ol (5). To a solution of the protected intermediate 4
(3.49 g, 8.4 mmol) in THF (35 mL) was added 2 N aq HCl
(35 mL). The reaction mixture was stirred under reflux for
5 h, cooled to room temperature, and neutralized by 2 N aq
NaOH. The aqueous layer was extracted with CH2Cl2, the
combined organic layers were dried over Na2SO4, and then
concentrated under reduced pressure. The residual crude
product was purified by column chromatography on silica
gel (EtOAc/MeOH¼1/1) to afford 5 (2.3 g, 99.6% yield) as
The reaction was carried out using allyltrichlorosilane (2.0 equiv) and
aldehyde (1 equiv) with PM-BOX (10 mol %) and zinc iodide
(10 mol %) at room temperature for 24 h in THF.
Yield of isolated product.
b
c
Determined by HPLC analysis.
spectrum, which showed the interaction of oxygen atom of
phosphine oxide and allyltrichlorosilane. A study of the
reaction mechanism and further application of the PM-
BOX–metal complex to the other asymmetric reactions are
currently underway in our laboratory.
1
a yellow syrup: H NMR (400 MHz, CDCl3) d 2.36–2.40
(m, 2H), 2.93 (br, 3H), 3.18–3.24 (m, 1H), 3.40–3.48 (m,
2H), 7.45–7.56 (m, 6H), 7.73–7.78 (m, 4H); 13C NMR
(100 MHz, CDCl3) d 34.6 (d, JCP¼70.1 Hz), 48.7, 67.7,
128.7–132.2; 31P NMR (162 MHz, CDCl3) d 33.1; IR
(neat) 3400, 2950, 1615, 1469, 1200 cmꢁ1; [a]D25 +9.23 (c
1.0, CHCl3).
2. Experimental section
2.1. General
NMR spectra were recorded on a BRUKER DRX-400 spec-
trometer, operating at 400 MHz for 1H NMR, 100 MHz for
13C NMR, and 162 MHz for 31P NMR. Chemical shifts
were reported in d from TMS as the internal standard for
2.1.3. 2,20-Bis[(S)-(4-diphenylphosphinoylmethyl)-2-oxa-
zolin-2-yl]propane (1-L). To a solution of dimethylmalono-
nitrile (0.15 g, 1.6 mmol) in PhCl (10 mL) was added a
solution of 5 (1.3 g, 4.7 mmol) in PhCl (10 mL) and ZnCl2
(0.64 g, 4.7 mmol). The reaction mixture was stirred under
reflux for 24 h, cooled to room temperature, and quenched
with a solution of ethylenediamine (4 mL) in water (20 mL).
The mixture was then stirred for 1 h. The layers were sepa-
rated, and the aqueous layer was extracted with CH2Cl2.
The combined organic layers were washed with brine and
dried over Na2SO4, and then concentrated under reduced
pressure. The residual crude product was purified by column
chromatography on silica gel (EtOAc/MeOH¼8/1) to afford
1-L (0.94 g, 96% yield) as a white solid: mp 168–170 ꢀC; IR
1650, 1430, 1180, 1160, 1118, 740, 710, 690 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 1.41 (s, 6H), 2.30–2.39 (m, 2H), 2.87–
2.93 (m, 2H), 4.26–4.37 (m, 6H), 7.43–7.54 (m, 12H), 7.70–
7.79 (m, 8H); 13C NMR (100 MHz, CDCl3) d 24.1, 36.1
(JCP¼68.6 Hz), 38.5, 61.1, 73.4, 128.6–134.0, 169.9; 31P
NMR (162 MHz, CDCl3) d 29.4; IR (KBr) 3440, 1660,
1450, 1190, 1130 cmꢁ1; [a]D25 +21.3 (c 1.0, CHCl3); HRMS
(EI): calcd for C35H37O4N2P2 (M++1) 611.2229, found
611.2229. Anal. Calcd for C35H36N2P2: C, 68.84; H, 5.94;
N, 4.59. Found: C, 68.35; H, 6.06; N, 4.53.
1
the H and 13C NMR spectra. 31P chemical shifts were re-
corded relative to the signal for 85% phosphoric acid, which
was used as the external reference. Flash column chromato-
graphy was carried out on silica gel 60 (Cica-MERCK). The
enantiomeric excess was determined by HPLC analysis. In
general, reactions were carried out in dry solvents under
N2 atmosphere, unless noted otherwise. Tetrahydrofuran
(THF) was distilled from sodium benzophenone ketyl.
Dichloromethane (CH2Cl2) and chlorobenzene (PhCl) were
distilled from calcium hydride. Other reagents were purified
by usual methods. (S)-N-tert-Butoxycarbonyl-4-[[(40-methyl-
benzenesulfonyl)oxy]methyl]-2,2-dimethyloxazolidine3was
synthesized via a literature procedure.7
2.1.1. (S)-N-tert-Butoxycarbonyl-4-(diphenylphosphi-
noylmethyl)-2,2-dimethyloxazolidine (4). To a solution
of diphenylphosphine (7.4 g, 40 mmol) in THF (100 mL)
was added tert-BuOK (4.5 g, 40 mmol) at 0 ꢀC. After
stirring for 1 h at room temperature, to this reaction mixture
was dropwise added 3 (7.0 g, 18.2 mmol) in THF (100 mL)
at 0 ꢀC. After completion of the reaction, water was added.
The solvent was then removed, and any remaining material
was dissolved in CH2Cl2 (100 mL). To the resulting solution
was added a 30% aqueous solution of H2O2 (20 mL) at 0 ꢀC,
and stirred for 0.5 h at the same temperature. The reaction
mixture was then diluted with water and the aqueous layer
was extracted with EtOAc. The combined organic layers
were washed with brine, dried over Na2SO4, and then
concentrated under reduced pressure. The residual crude
product was purified by column chromatography on silica
gel (hexane/EtOAc¼1/1) to afford 4 (4.7 g, 62% yield) as
a white solid: mp 126–128 ꢀC; IR 2975, 1682, 1430, 1380,
2.2. General procedure for reactions of allyltrichloro-
silane with aldehydes
2.2.1. Synthesis of (R)-1-phenyl-3-buten-1-ol (entry 1 in
Table 2). A mixture of ZnI2 (24 mg, 0.074 mmol) and PM-
BOX (45 mg, 0.074 mmol) was dissolved in dry THF
(4 mL) under an argon atmosphere, and then stirred at
room temperature for 2 h. To the resulting solution was
dropwise added benzaldehyde (78.5 mg, 0.74 mmol) and
then allyltrichlorosilane (0.21 mL, 1.48 mmol) at room tem-
perature. The mixture was stirred for 24 h at this temperature
1
1180, 730, 710, 680 cmꢁ1; H NMR (400 MHz, CDCl3)

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K. Takeuchi et al. / Tetrahedron 63 (2007) 5319–5322
1
and then quenched with an aqueous saturated NaHCO3 solu-
tion. The aqueous layer was extracted with EtOAc. The com-
bined organic layers were washed with brine and dried over
Na2SO4, then concentrated under reduced pressure. The
residual crude product was purified by column chromato-
graphy on silica gel (hexane/EtOAc¼10/1) to afford the
homoallylic alcohol (80.2 mg, 74% yield) as a colorless
oil. The enantiomeric excess was determined by a chiral
HPLC analysis: IR (neat) 3400 (br), 3080, 3050, 2950,
2820, 1620, 1605, 1500, 1455, 1050, 1000, 920, 760,
690 cmꢁ1; H NMR (400 MHz, CDCl3) d 1.58 (br, 1H),
2.38–2.43 (m, 2H), 4.37 (dd, 1H, J¼13.0, 6.8 Hz), 5.10–
5.21 (m, 2H), 5.82–5.89 (m, 1H), 6.25 (dd, 1H, J¼15.9,
6.3 Hz), 6.59 (d, 1H, J¼15.7 Hz); [a]2D5 +5.98 (c 0.5,
CHCl3) [lit.2 [a]D –36.9 for (S) (c 1.06, CHCl3)]; HPLC
(Daicel Chiralcel OD-H, hexane/i-PrOH¼20/1, flow
rate¼1 mL/min): tR¼12.1 min, tS¼20.4 min.
Acknowledgements
1
700 cmꢁ1; H NMR (400 MHz, CDCl3) d 2.03 (br, 1H),
2.45–2.55 (m, 2H), 4.71–4.75 (m, 1H), 5.12–5.19 (m, 2H),
5.75–5.86 (m, 1H), 7.25–7.37 (m, 5H); [a]2D7 +46.5 (c 1.0,
CH2Cl2) [lit.8 [a]D +45.6 (c 0.92, CH2Cl2)]; HPLC (Daicel
Chiralcel OD-H, hexane/i-PrOH¼98/2, flow rate¼1.0 mL/
min): tR¼14.7 min, tS¼16.5 min.
This work was partially supported by a Grant-in-Aid for Sci-
entific Research (C) No. 17550098 and The 21st Century
COE Program from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
References and notes
2.2.2. (R)-1-(p-Nitrophenyl)-3-buten-1-ol (entry 2 in
Table 2). IR (neat) 3400 (br), 3075, 2980, 2900, 2850,
1640, 1600, 1510, 1340, 1100, 1050, 915, 850, 710,
1. Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
2. For review, see: (a) Denmark, S. E.; Fu, J.-P. Chem. Rev. 2003,
103, 2763; For selected examples of the asymmetric allylation
of aldehydes using allyltributylstannane, see: (b) Costa, A. L.;
Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A.
J. Am. Chem. Soc. 1993, 115, 7001; (c) Yanagisawa, A.;
Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am. Chem. Soc.
1996, 118, 4723; (d) Cozzi, P. G.; Orioli, P.; Tagliavini, E.;
Umani-Ronchi, A. Tetrahedron Lett. 1997, 38, 145; (e)
Hanawa, H.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc.
2003, 125, 1708; (f) Lu, J.; Ji, S.-J.; Teo, Y.-C.; Loh, T.-P.
Org. Lett. 2005, 7, 159; (g) Lu, J.; Hong, M.-L.; Ji, S.-J.; Loh,
T.-P. Chem. Commun. 2005, 1010; (h) Teo, Y.-C.; Tan, K.-T.;
Loh, T.-P. Chem. Commun. 2005, 1318.
3. For selected examples of the catalytic asymmetric allylation of
aldehydes using allyltrimethylsilane, see: (a) Ishihara, K.;
Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.; Yamamoto, H.
J. Am. Chem. Soc. 1993, 115, 11490; (b) Gauthier, D. R., Jr.;
Carreira, E. M. Angew. Chem., Int. Ed. 1996, 35, 2363; (c)
Bode, J. W.; Gauthier, D. R., Jr.; Carreira, E. M. Chem.
Commun. 2001, 2560.
4. For selected examples of the catalytic asymmetric allylation of
aldehydes using allyltrimethoxysilane, see: (a) Yanagisawa,
A.; Kageyama, H.; Nakatsuka, Y.; Asakawa, K.; Matsumoto,
Y.; Yamamoto, H. Angew. Chem., Int. Ed. 1999, 38, 3701; (b)
Wadamoto, M.; Ozasa, N.; Yanagisawa, A.; Yamamoto, H.
J. Org. Chem. 2003, 68, 5593.
5. For a review of the asymmetric cyanosilylation catalyzed by
LA-LB catalysts, see: (a) Shibasaki, M.; Kanai, M.; Funabashi,
K. Chem. Commun. 2002, 1989; For some examples see: (b)
Hamashima, Y.; Sawada, D.; Kanai, M.; Shibasaki, M. J. Am.
Chem. Soc. 1999, 121, 2641; (c) Kanai, M.; Hamashima, Y.;
Shibasaki, M. Tetrahedron Lett. 2000, 41, 2405; (d) Hamashima,
Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 7412.
6. For selected example of the synthesis of bisoxazoline using zinc
chloride, see: (a) Wite, H.; Seeliger, W. Liebigs. Ann. Chem.
1974, 996; (b) Bolm, C.; Weickhardt, K.; Zehnder, M.; Ranff,
T. Chem. Ber. 1991, 124, 1173.
690 cmꢁ1 1H NMR (400 MHz, CDCl3) d 2.27 (s, 1H),
;
2.42–2.49 (m, 1H), 2.53–2.60 (m, 1H), 4.86 (dt, 1H, J¼7.8,
3.3 Hz), 5.15–5.21 (m, 2H), 5.73–5.84 (m, 1H), 7.56 (d,
2H, J¼8.9 Hz), 8.19 (d, 2H, J¼8.9 Hz); [a]2D5 +51.5
(c 1.0, CHCl3) [lit.9 [a]D –33.2 for (S) (c 0.5, CHCl3)];
HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH¼20/1,
flow rate¼0.4 mL/min): tR¼45.8 min, tS¼48.1 min.
2.2.3. (R)-1-(p-Chlorophenyl)-3-buten-1-ol (entry 3 in
Table 2). IR (neat) 3380 (br), 3075, 2970, 2900, 1640,
1590, 1490, 1410, 1090, 1040, 1010, 910, 860, 810,
780 cmꢁ1 1H NMR (400 MHz, CDCl3) d 2.04 (s, 1H),
;
2.41–2.53 (m, 2H), 4.72 (m, 1H), 5.13–5.18 (m, 2H),
5.73–5.83 (m, 1H), 7.27–7.33 (m, 4H); [a]2D5 +47.3 (c 1.0,
CHCl3) [lit.9 [a]D –60.6 for (S) (c 1.5, CHCl3)]; HPLC
(Daicel Chiralcel OJ-H, hexane/i-PrOH¼98/2, flow rate¼
0.7 mL/min): tS¼23.2 min, tR¼25.1 min.
2.2.4. (R)-1-(p-Methoxyphenyl)-3-buten-1-ol (entry 4 in
Table 2). IR (neat) 3450 (br), 3080, 3020, 2950, 2920,
2850, 1640, 1615, 1590, 1520, 1470, 1440, 1300, 1250, 1180,
1040, 920, 830, 810, 770 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 2.03 (br, 1H), 2.50 (t, 2H, J¼12.6 Hz), 3.79 (s, 3H), 4.67 (t,
1H, J¼6.4 Hz), 5.10–5.17 (m, 2H), 5.74–5.82 (m, 1H), 6.86–
6.88 (m, 2H), 7.25–7.28 (m, 2H); [a]2D5 +21.9 (c 1.0, CHCl3)
[lit.2 [a]D –48.0 for (S) (c 1.0, CHCl3)]; HPLC (Daicel Chiral-
cel OD-H, hexane/i-PrOH¼20/1, flow rate¼0.5 mL/min):
tR¼21.1 min, tS¼23.7 min.
2.2.5. (S)-1-Phenyl-5-hexen-3-ol (entry 5 in Table 2). IR
(neat) 3350 (br), 3050, 3010, 2920, 2850, 1630, 1590,
1485, 1440, 1060, 1030, 980, 900, 850, 730, 680 cmꢁ1; 1H
NMR (400 MHz, CDCl3) d 1.66 (s, 1H), 1.73–1.81 (m,
2H), 2.14–2.21 (m, 1H), 2.28–2.35 (m, 1H), 2.64–2.68 (m,
1H), 2.70–2.84 (m, 1H), 3.64–3.70 (m, 1H), 5.14 (d, 2H,
J¼12.9 Hz), 5.76–5.86 (m, 1H), 7.16–7.29 (m, 5H); [a]D25
–6.63 (c 1.0, CHCl3) [lit.2 [a]D +1.8 for (R) (c 0.9, CHCl3)];
HPLC (Daicel Chiralcel OD-H, hexane/i-PrOH¼20/1, flow
rate¼0.5 mL/min): tS¼17.6 min, tR¼25.5 min.
7. Porte, A. M.; van der Donk, W. A.; Burgess, K. J. Org. Chem.
1998, 63, 5262.
8. See Ref. 2f.
2.2.6. (1E,3R)-1-Phenyl-1,5-hexadien-3-ol (entry 6 in
Table 2). IR (neat) 3400 (br), 3100, 3050, 3000, 2850,
1645, 1605, 1580, 1500, 1450, 1140, 970, 920, 875, 750,
9. Malkov, A. V.; Bell, M.; Orsini, M.; Pernazza, D.; Massa, A.;
ꢀ
Herrmann, P.; Meghani, P.; Kocovsky, P. J. Org. Chem. 2003,
ꢁ
68, 9659.