Synthesis of novel P-stereogenic phenylphosphonamides and their application to Lewis base-catalyzed asymmetric allylation of benzaldehyde

Article abstract of DOI:10.1016/j.tetasy.2007.08.006

The synthesis of novel P-stereogenic phenylphosphonamides 3 and 11 via an intramolecular nucleophilic substitution of P-stereogenic phosphoramide 8 is described. These compounds were used as chiral Lewis basic catalysts for the asymmetric allylation of be

Full text of DOI:10.1016/j.tetasy.2007.08.006

Tetrahedron: Asymmetry 18 (2007) 1844–1849
Synthesis of novel P-stereogenic phenylphosphonamides and their
application to Lewis base-catalyzed asymmetric
allylation of benzaldehyde
Tetsuhiro Nemoto,a Tsukasa Hitomi,a Hiroshi Nakamura,a Long Jin,a Keiichiro Hatanob
and Yasumasa Hamadaa,*
aGraduate School of Pharmaceutical Sciences, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
bGraduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Received 29 June 2007; accepted 6 August 2007
Abstract—The synthesis of novel P-stereogenic phenylphosphonamides 3 and 11 via an intramolecular nucleophilic substitution of
P-stereogenic phosphoramide 8 is described. These compounds were used as chiral Lewis basic catalysts for the asymmetric allylation
of benzaldehyde, providing the corresponding homoallylic alcohol derivatives in up to 54% ee.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
preligands in transition metal catalysis.12,13 These chiral
phosphonamides were synthesized from aspartic acid-
derived branched triamines through the following three-
step reaction sequence: diastereoselective formation of a
triaminophosphine intermediate 2; addition of water to
the phosphorus atom via an SN2-type process, and P(III)
to P(V) tautomerization (Scheme 1). This background
led us to hypothesize that diastereoselective formation of
P-stereogenic phosphoramides, followed by intramolecular
nucleophilic substitution on the phosphorus atom, would
be an efficient synthetic route for P-stereogenic phenyl-
phosphonamides such as 3 and 4. Herein, we describe
the synthesis of novel P-stereogenic phenylphosphon-
amides, which can be utilized as chiral Lewis base cata-
lysts for asymmetric allylation of benzaldehyde using
allyltrichlorosilanes.
The coordination of Lewis-basic oxygen to a central ele-
ment (or metal) provides characteristic reactivity to the
parent reagents. In 1993, Kobayashi first reported that
Lewis-basic molecules such as N,N-dimethylformamide
coordinate to the silicon atom of allyltrichlorosilanes to
form reactive hypervalent silicon intermediates for the
allylation of aldehydes.1 Since this pioneering finding, the
interaction between silicon atoms and Lewis-basic mole-
cules has been recognized as one of the most important
modes of activating organosilanes in organic synthesis.2
A recent focus in this field is the development of Lewis
base-catalyzed asymmetric reactions.3,4 Chiral Lewis
bases, such as chiral phosphoramides,5,6 formamides,7 N-
oxides,8 phosphine oxides,9 sulfoxides,10 and ureas,11 were
designed, synthesized, and applied to the catalytic asym-
metric allylation of aldehydes using allyltrichlorosilanes.
2. Results and discussion
Although various types of chiral Lewis bases have been
developed, there are few reports of asymmetric reactions
using chiral phosphonamides as Lewis base catalysts.5f,g
We previously reported that P-stereogenic diaminophos-
phine oxide 1 and related compounds are useful chiral
2.1. Synthesis of P-stereogenic phenylphosphonamides
3 and 11
Our synthesis started with (S)-aspartic acid dianilide 6,
which was prepared from commercially available chiral
acid anhydride 5 using a known method12a (Scheme 2).
First, compound 6 was reacted with 2-iodobenzoyl chloride
to give the corresponding triamide, which was transformed
*
Corresponding author. Tel./fax: +81 43 290 2987; e-mail: hamada@
p.chiba-u.ac.jp
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.08.006

T. Nemoto et al. / Tetrahedron: Asymmetry 18 (2007) 1844–1849
1845
Ph
H
N
N
H
N
H
H O, SiO
PCl , NEt
2
2
3
3
P
HN
*
N
H
O
Ar
N
H
*
N
S 2-type attack of
N
H O on the P atom
and tautomerization
diastereoselective
formation of
triaminophosphine
P
HN
N
2
H
Ph
2
1
diastereoselective
formation of P-chirogenic
phosphoramides
O=PCl
3
NEt
3
X
N
H
H
metal-halogen exchange
O
N
HN
and S 2-type attack
N
O
H
N
O
N
P
on the P atom
or
*
P
*
N
P
*
N
N
N
H
3
4
P-Chirogenic Phenylphosphonamides
Scheme 1. Plan for the synthesis of P-stereogenic phenylphosphonamides.
X
O
O
H
I
NHPh
NHPh
O
N
c
ref. 12a
a,b
N
O
O
P
ZHN
N
H
H N
2
N
O
NHPh
NHPh
5
6
7
8 (X = I)
9 (X = H)
Li
O
H
N
N
HN
O
P
O
P
e
d
N
Ph
N
P
N
O
N
N
N
H
H
Ph
10
3
11
Scheme 2. Synthesis of P-stereogenic phenylphosphonamides. Reagents and conditions: (a) 2-iodobenzoyl chloride, NEt3, THF–DMF, rt, 1 h, 92%; (b)
NaBH4, I2, THF, reflux, 8 h, 76%; (c) phosphoryl trichloride, NEt3, toluene, ꢀ78 ꢁC to rt, 18 h, 75%; (d) n-BuLi, THF, ꢀ78 ꢁC, 1.5 h, then
Na2SO4Æ10H2O, 78%; (e) n-BuLi, THF, ꢀ78 ꢁC, 10 min, then benzoyl chloride, ꢀ78 ꢁC (10 min) to rt (20 min), 95%.
into chiral branched triamine 7 by treatment with the
BH3ÆTHF complex generated from NaBH4 and I2 in
THF in situ. The reaction of triamine 7 with phosphoryl
2.20 Å
trichloride proceeded diastereoselectively to afford the cor-
HN
responding P-stereogenic phosphoramide 8 in 75% yield.
We then examined the transformation of 8 into P-stereo-
genic phenylphosphonamides through an intramolecular
nucleophilic substitution. Metal–halogen exchange was
performed using 1.1 equiv of n-BuLi at ꢀ78 ꢁC, and the
resulting yellow solution was stirred for 1.5 h at the same
temperature. After the reaction was quenched with
Na2SO4Æ10H2O at ꢀ78 ꢁC, the crude residue was purified
by silica gel column chromatography to give a tricyclic
phenylphosphonamide adduct in 78% yield, accompanied
by the formation of dehalogenated product 9 (11%). The
absolute structure of the tricyclic phenylphosphonamide
adduct was determined to be 3 by X-ray crystal structure
analysis (Fig. 1). The six-membered ring moiety in 3 adopts
a boat-like conformation, and the crystal structure indi-
cates that there is a hydrogen bond interaction between
O
P
N
N
H
Figure 1. X-ray structure of 3.
the phosphine oxide moiety and the amino group on the
˚
sidearm in 3 (P@Oꢁ ꢁ ꢁHN: 2.20 A). Another possible reac-
1
tion adduct 4 was not observed in H NMR analysis of
the crude residue, indicating that the intramolecular nucleo-
philic substitution proceeded selectively through one of two
possible reaction pathways (Scheme 2, intermediate 10). In
addition, the amine moiety of 3 was protected with a

1846
T. Nemoto et al. / Tetrahedron: Asymmetry 18 (2007) 1844–1849
benzoyl group to provide P-stereogenic phenylphosphon-
amide 11, bearing a tertiary amide group on the sidearm.
3 (20 mol %) or 11 (10 mol %)
O
OH
(E
)-crotyltrichlorosilane
= 95:5), (3 equiv)
(E:
Z
H
i-Pr NEt (5 equiv)
2
4
CH
3
2.2. Application of P-stereogenic phenylphosphonamides
3 and 11 to the Lewis base-catalyzed asymmetric allylation
of benzaldehyde
n
-Bu NI (20 mol %)
(1R,2R)-13
CH Cl , –40 °C
2
2
3: 48 h, 72% (syn
/
anti = 7/93), 44% ee
11: 24 h, 86% (syn
/
anti = 7/93), 48% ee
We then attempted to use the enantiomerically pure P-
stereogenic phenylphosphonamides as chiral Lewis base
catalysts. We first examined asymmetric allylation of
benzaldehyde with allyltrichlorosilane using 3 as the cata-
lyst (Table 1). When 20 mol % of 3, 3 equiv of allyltrichlo-
rosilane, and 5 equiv of i-Pr2NEt were used in CH2Cl2, the
reaction proceeded at ꢀ40 ꢁC to give homoallylic alcohol
(R)-12 in 58% yield and in 35% ee (entry 1). To improve
both the reactivity and enantioselectivity, we investigated
the effect of additives. Berrisford and co-workers reported
that Lewis base-catalyzed allylation of aldehydes using
allyltrichlorosilane was accelerated by tetra-n-butylammo-
nium salts.14 Thus, we performed the reaction in the pres-
ence of several tetra-n-butylammonium salts (entries 2–7).
There was a slight increase in the reactivity and enantio-
selectivity when tetra-n-butylammonium iodide was used as
the additive, and homoallylic alcohol (R)-12 was obtained
in up to 54% ee (entry 7).15 We next examined the same
reaction using 10 mol % of 11 as the Lewis base catalyst.
Although the reaction was sluggish in the absence of
tetra-n-butylammonium iodide (entry 8), there was an
increase in the reactivity when tetra-n-butylammonium
iodide was added, affording (R)-12 in 81% yield and in
46% ee (entry 9).16 Moreover, the catalytic asymmetric allyl-
ation of benzaldehyde using crotyltrichlorosilanes was
examined (Scheme 3). Using 20 mol % of 3 or 10 mol %
of 11, the reaction using (E)-crotyltrichlorosilane pro-
ceeded at ꢀ40 ꢁC in a highly diastereoselective manner to
give the anti-isomer (1R,2R)-13 in 72% yield and 44% ee,
and in 86% yield and 48% ee, respectively. Similarly, the
reaction using (Z)-crotyltrichlorosilane preformed under
the same reaction conditions, providing the syn-isomer
(1R,2S)-14 in 54% yield and 7% ee, and in 87% yield and
3 (20 mol %) or 11 (10 mol %)
O
OH
(Z)-crotyltrichlorosilane
(E:Z
= 1:99), (3 equiv)
H
i-Pr NEt (5 equiv)
2
4
CH
3
n
-Bu NI (20 mol %)
CH Cl , –40 °C
(1R,2S)-14
2
2
3: 48 h, 54% (syn
/
anti = 99/1), 7% ee
11: 24 h, 87% (syn
/
anti = 99/1), 26% ee
Scheme 3. Asymmetric allylation of benzaldehyde using crotyltrichloro-
silanes in the presence of P-stereogenic phenylphosphonamides 3 and 11.
26% ee, respectively. These results suggest that the present
catalytic asymmetric reactions proceed via a six-membered
chair-like transition state.
3. Conclusion
In conclusion, we succeeded in the synthesis of novel P-ste-
reogenic phenylphosphonamides 3 and 11. The synthesis
was achieved by the intramolecular nucleophilic substitu-
tion of P-stereogenic phosphoramide 8, where one of two
possible reaction pathways occurred selectively. These
compounds could be utilized as chiral Lewis base catalysts
for asymmetric allylation of benzaldehyde. Studies of other
catalytic asymmetric reactions using structurally optimized
P-stereogenic phenylphosphonamides are currently in
progress.
4. Experimental
4.1. General
Table 1. Asymmetric allylation of benzaldehyde using allyltrichlorosilane
in the presence of P-stereogenic phenylphosphonamides 3 and 11
3 or 11
O
OH
Infrared (IR) spectra were recorded on a JASCO FT/IR
230 Fourier transform infrared spectrophotometer. NMR
spectra were recorded on a JEOL ecp 400 spectrometer,
operating at 400 MHz for 1H NMR, 100 MHz for 13C
NMR, and 160 MHz for 31P NMR. Chemical shifts in
CDCl3, were reported downfield from TMS (=0 ppm) for
1H NMR. For 13C NMR, chemical shifts were reported
downfield from TMS (=0 ppm) or in the scale relative to
the solvent signal [CHCl3 (77.0 ppm)] as an internal refer-
ence. Optical rotations were measured on a JASCO P-
1020 polarimeter. EI mass spectra were measured on JEOL
GC mate. The enantiomeric excess (ee) was determined by
HPLC analysis. HPLC was performed on JASCO HPLC
systems consisting of the following: pump, PU-980; detec-
tor, UV-970, measured at 254 nm; column, DAICEL CHI-
RALCEL OD-H; mobile phase, 2-propanol/hexane.
Reactions were carried out in dry solvent under argon
allyltrichlorosilane (3 equiv)
i-Pr NEt (5 equiv)
2
H
CH Cl , –40 °C, 24 h
2
2
Additive
(R)-12
Entry Catalyst (mol %) Additive (mol %) Yielda (%) eeb (%)
1
2
3
4
5
6
7
8
9
3 (20)
3 (20)
3 (20)
3 (20)
3 (20)
3 (20)
3 (20)
11 (10)
11 (10)
—
58
65
68
60
48
69
62
53
84
35
44
42
23
45
52
54
47
46
n-Bu4NOTf (20)
n-Bu4NBF4 (20)
n-Bu4NCl (20)
n-Bu4NBr (20)
n-Bu4NI (20)
n-Bu4NI (50)
—
n-Bu4NI (20)
a Isolated yield.
b Determined by HPLC analysis.

T. Nemoto et al. / Tetrahedron: Asymmetry 18 (2007) 1844–1849
1847
atmosphere. Other reagents were purified by the usual
methods.
phosphoryl trichloride (0.27 mL, 2.89 mmol) slowly. The
reaction temperature was gradually warmed up to room
temperature, and then the mixture was kept stirring for
12 h. The reaction mixture was filtered, concentrated, and
then purified by flash column chromatography (SiO2, hex-
ane/AcOEt/CHCl3 600/100/7–100/100/2) to give 8 as a
white solid (850 mg, 75%). IR (KBr) m 2939, 2881, 1601,
4.2. Synthesis of P-stereogenic phenylphosphonamides
3 and 11
Compound 6 was prepared from commercially available N-
benzyloxycarbonyl-(S)-aspartic anhydride using a known
method, see: Ref. 12a.
1494, 1317, 1295, 1265, 1145, 763, 752 cmꢀ1 1H NMR
;
(CDCl3): d 1.44–1.55 (m, 1H), 2.48–2.55 (m, 1H), 3.39–
3.43 (m, 1H), 3.53–3.80 (m, 3H), 4.02–4.08 (m, 1H), 4.26
(dd, J = 5.6 (PNCH), 15.6 Hz, 1H), 4.42 (dd, J = 8.0
(PNCH), 15.6 Hz, 1H), 6.88–7.11 (m, 5H), 7.18–7.39 (m,
7H), 7.60–7.62 (m, 1H), 7.84–7.86 (m, 1H); 13C NMR
4.2.1.
N2-(2-Iodobenzyl)-N1,N4-diphenylbutane-1,2,4-tri-
amine 7. To a stirred mixture of 6 (1.13 g, 4 mmol) and
triethylamine (0.84 mL, 6 mmol) in THF/DMF (40 mL/
3 mL) at 0 ꢁC was added 2-iodobenzoyl chloride (1.28 g,
4.8 mmol), and the reaction mixture was stirred for 1 h at
room temperature. The reaction was quenched with aque-
ous saturated NaHCO3, and the mixture was extracted
with AcOEt. The organic layer was washed with H2O
(·2), and evaporated under reduced pressure. The residue
obtained was washed by ether to give the corresponding
triamide as a white solid (1.88 g, 92%). IR (KBr) m 3293,
1647, 1642, 1599, 1529, 1499, 1443, 1331, 1164, 754,
(CDCl3):
d
25.5, 47.5 (d, J = 1.5 Hz), 49.4 (d,
J = 9.9 Hz), 50.5 (d, J = 3.1 Hz), 53.3 (d, J = 4.6 Hz)
99.3, 115.0 (d, J = 5.3 Hz) (·2), 120.7, 122.5, 122.5,
123.5, 128.5, 128.8 (·2), 129.2 (·2), 129.2 (·2), 129.7,
139.4, 139.6, 141.6 (d, J = 6.5 Hz), 145.1; 31P NMR
(CDCl3): d 15.9; EI-LRMS m/z 515 (M+); EI-HRMS.
Calcd for C23H23IN3OP (M+): 515.0623. Found:
23
515.0611; ½aꢂD ¼ þ21:0 (c 0.62, CHCl3).
691 cmꢀ1
;
1H NMR (CDCl3): d 2.82 (dd, J = 7.6,
15.2 Hz, 1H), 2.96 (dd, J = 7.2, 15.2 Hz, 1H), 5.00 (ddd,
J = 7.2, 7.6, 7.6 Hz, 1H), 7.01–7.04 (m, 2H), 7.15–7.20
(m, 1H), 7.27–7.47 (m, 6H), 7.58–7.66 (m, 4H), 7.87–7.89
(m, 1H), 8.84 (d, J = 7.6 Hz, 1H), 10.01 (s, 1H), 10.09 (s,
1H); 13C NMR (CDCl3): d 36.9, 49.9, 92.3, 118.0 (·2),
118.3 (·2), 122.0, 122.3, 126.8, 127.3, 127.6 (·2), 127.6
(·2), 129.9, 137.8, 138.0, 138.0, 140.9, 166.9, 167.7, 168.1;
EI-LRMS m/z 513 (M+), 420; EI-HRMS. Calcd for
4.2.3. P-Stereogenic phenylphosphonamide 3. To a stirred
mixture of 8 (103 mg, 0.2 mmol) in THF (3 mL) at
ꢀ78 ꢁC was added n-BuLi (0.146 mL, 0.22 mmol, 1.5 M
solution in n-hexane), and the resulting mixture was stirred
for 1.5 h at a temperature below ꢀ60 ꢁC. The reaction
(yellow solution) was quenched by the addition of Na2SO4Æ
10H2O, and the resulting mixture was stirred for 10 min
(the reaction turned to clear solution). After diluting with
AcOEt, the reaction mixture was washed with water, brine,
and dried over Na2SO4. After concentration in vacuo, the
crude residue was purified by flash column chromatogra-
phy (SiO2, hexane/AcOEt 2/1–1/2) to give 3 as a pale yel-
low solid (60.6 mg, 78%). Mp 78–80 ꢁC; IR (KBr) m 3584,
3354, 3018, 2859, 2400, 1731, 1602, 1496, 1298, 1215,
C23H20IN3O3 (M+): 513.0549. Found: 513.0547;
24
½aꢂD ¼ ꢀ16:8 (c 0.94, DMF). To a stirred mixture of tri-
amide (5.13 g, 10 mmol), NaBH4 (2.84 g, 75 mmol) in
THF (100 mL) at 0 ꢁC was added a THF solution of I2
(7.61 g, 30 mmol, 60 mL of THF) over 1 h, and the result-
ing mixture was refluxed for 8 h. After cooling down to
room temperature, the reaction was quenched by the addi-
tion of 2 M HCl. The mixture was refluxed again for 3 h,
then cooled down to 0 ꢁC. After the solution was basified
by the addition of 1 M NaOH, the mixture was extracted
with AcOEt (·2), and the combined organic layers were
washed with brine and dried over Na2SO4. After concen-
tration in vacuo, the crude residue was purified by flash col-
umn chromatography (SiO2, hexane/AcOEt 7/1–2/1) to
give 7 as a yellow oil (3.56 g, 76%). IR (neat) m 3401,
3049, 2922, 2850, 1602, 1504, 1470, 1433, 1319, 1256,
1
1174, 1099, 756 cmꢀ1; H NMR (CDCl3): d 2.28–2.36 (m,
1H), 2.49–2.52 (m, 1H), 3.41–3.60 (m, 4H), 3.73–3.80 (m,
1H), 4.20 (dd, J = 6.4 (PNCH), 14.0 Hz, 1H), 4.63 (broad
peak (NH), 1H), 4.71 (dd, J = 6.4 (PNCH), 14.0 Hz, 1H),
6.69–6.72 (m, 4H), 7.04–7.07 (m, 1H), 7.17–7.21 (m, 2H),
7.25–7.46 (m, 6H), 7.56–7.60 (m, 1H); 13C NMR (CDCl3):
d 30.3 (d, J = 6.9 Hz), 47.2, 48.3, 55.3 (d, J = 17.2 Hz),
56.7, 113.0 (·2), 117.3, 120.4 (d, J = 4.2 Hz) (·2), 122.8,
123.6 (d, J = 10.7 Hz), 127.6 (d, J = 11.9 Hz), 127.9 (d,
J = 13.0 Hz), 129.2 (·2), 129.3 (·2), 131.4 (d, J = 2.6 Hz),
141.3 (d, J = 22.1 Hz), 145.0, 148.1; 31P NMR (CDCl3): d
1
748, 692 cmꢀ1; H NMR (CDCl3): d 1.91–1.96 (m, 2H),
3.08–3.31 (m, 5H), 3.88 (s, 2H), 6.57–6.73 (m, 6H), 6.96–
6.99 (m, 1H), 7.15–7.20 (m, 4H), 7.30–7.31 (m, 2H),
7.81–7.83 (m, 1H), amine protons could not be detected
26.0; EI-LRMS m/z 389 (M+); EI-HRMS. Calcd for
23
D
C23H24N3OP (M+): 389.1657. Found: 398.1663; ½aꢂ
¼
þ335:3 (c 0.25, CHCl3). X-ray data of compound 3: Col-
lected at 21 ꢁC, C23H24N3OP = 389.44, yellow rhombic
1
in H NMR; 13C NMR (CDCl3): d 31.8, 41.3, 46.2, 54.9,
˚ ˚ ˚
crystal, a = 11.493(1) A, b = 7.061(1) A, c = 13.034(1) A,
55.3, 77.2, 99.8, 112.9 (·2), 113.0 (·2), 117.5, 117.6,
3
3
˚
128.5, 129.2 (·2), 129.2 (·2), 130.2, 139.6, 141.3, 148.0,
V = 1020.7(4) A , P21, Z = 2, D = 1.27 g/cm , R(F) =
0.039, RW(F) = 0.041, GOF = 0.422. Crystallographic data
(excluding structure factors) for this compound have been
deposited with the Cambridge Crystallographic Data Cen-
tre as supplementary publication numbers CCDC-652149.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: +44(0)-1223-336033 or e-mail: deposit@
ccdc.cam.ac.uk].
148.2; EI-LRMS m/z 471 (M+); EI-HRMS. Calcd for
23
C23H26IN3 (M+): 471.1171. Found: 471.1153; ½aꢂ ¼ ꢀ2:4
D
(c 0.64, CHCl3).
4.2.2.
habicyclo[3.2.1]octane 1-oxide 8. To a stirred solution of
(1.24 g, 2.63 mmol) and triethylamine (1.40 mL,
10.3 mmol) in toluene (13.2 mL) at ꢀ78 ꢁC was added
8-(2-Iodobenzyl)-2,7-diphenyl-2,7,8-triaza-1-phosp-
7

1848
T. Nemoto et al. / Tetrahedron: Asymmetry 18 (2007) 1844–1849
4.2.4. P-Stereogenic phenylphosphonamide 11. To a stirred
mixture of 3 (78.0 mg, 0.2 mmol) in THF (3 mL) at ꢀ78 ꢁC
was added n-BuLi (0.146 mL, 0.22 mmol, 1.5 M solution in
n-hexane), and the resulting mixture was stirred at the same
temperature. After 10 min, benzoyl chloride (51 lL,
0.44 mmol) was added to the reaction, and the resulting
mixture was stirred for 10 min at ꢀ78 ꢁC, and then stirred
for 20 min at room temperature. The reaction was
quenched with aqueous saturated NaHCO3, and the mix-
ture was extracted with AcOEt. The organic layer was
washed with brine, dried over Na2SO4, and then concen-
trated under reduced pressure. The obtained residue was
purified by flash column chromatography (SiO2, hexane/
AcOEt 1/3) to give 11 as a white solid (94.0 mg, 94%).
IR (KBr) m 3449, 2925, 2850, 1648, 1596, 1494, 1298,
quenched with aqueous saturated NaHCO3, and the mix-
ture was extracted with AcOEt (·2). The combined organic
layers were washed with brine, dried over Na2SO4, and
then concentrated in vacuo. The obtained residue was puri-
fied by flash column chromatography (SiO2, hexane/
AcOEt 15/1) to give a mixture of syn- and anti-2-methyl-
1-phenyl-3-butene-1-ol as a colorless oil (55.7 mg, 86%,
syn/anti = 7/93, 48% ee). The enantiomeric excess of the
anti-isomer was determined by HPLC analysis (DAICEL
CHIRALCEL OD-H, 2-propanol/hexane 1/100, flow rate
0.5 mL/min, tR 34.9 min [(1S,2S)-isomer] and 40.2 min
[(1R,2R)-isomer], detection at 254 nm).
4.3.3. (1R,2S)-syn-2-Methyl-1-phenyl-3-butene-1-ol 14.9c
This compound was prepared according to the experimen-
tal procedure for the Lewis base-catalyzed asymmetric ally-
lation. The enantiomeric excess of the syn-isomer was
determined by HPLC analysis (DAICEL CHIRALCEL
OD-H, 2-propanol/hexane 1/100, flow rate 0.5 mL/min,
1
1222, 1175, 699 cmꢀ1; H NMR (CDCl3): d 2.21–2.34 (m,
1H), 2.38–2.48 (m, 1H), 3.44–3.58 (m, 2H), 4.19–4.29 (m,
3H), 4.31 (dd, J = 6.4 (PNCH), 14.4 Hz, 1H), 4.87 (dd,
J = 6.0 (PNCH), 14.4 Hz, 1H), 7.02–7.56 (m, 19H); 13C
NMR (CDCl3): d 31.6 (d, J = 7.6 Hz), 47.1 (d, J =
3.1 Hz), 55.9, 56.1 (d, J = 7.2 Hz), 58.5, 120.2 (d, J =
3.8 Hz) (·2), 122.6, 123.4 (d, J = 10.7 Hz), 126.4, 127.1
(·2), 127.5 (d, J = 11.4 Hz), 127.7 (d, J = 13.4 Hz), 127.8
(·2), 128.5, 128.9 (·2), 129.1 (·2), 129.2 (·2), 130.0,
130.1, 131.2 (d, J = 2.1 Hz), 141.1 (d, J = 22.2 Hz), 144.7,
145.1 (d, J = 5.4 Hz), 170.9; 31P NMR (CDCl3): d 24.3;
tR 37.7 min [(1S,2R)-isomer] and 42.0 min [(1R,2S)-iso-
23
mer], detection at 254 nm). ½aꢂD ¼ þ6:2 (c 1.09, CHCl3,
26% ee, (1R,2S)-isomer).
Acknowledgment
EI-LRMS m/z 493 (M+); EI-HRMS. Calcd for
This work was supported in part by Grant-in Aid for
Encouragement of Young Scientists (A) from the Ministry
of Education, Culture, Sports, Science, and Technology,
Japan.
23
D
C30H28N3O2P (M+): 493.1919. Found: 493.1898; ½aꢂ
¼
þ68:8 (c 0.83, CHCl3).
4.3. Experimental procedure
References
4.3.1. Lewis base-catalyzed asymmetric allylation of benz-
aldehyde using allyltrichlorosilane. (R)-1-Phenyl-3-butene-1-
ol 12.9c To a stirred mixture of 3 (15.5 mg, 0.04 mmol), n-
Bu4NI (14.9 mg, 0.04 mmol), i-Pr2NEt (172 lL, 1 mmol) in
CH2Cl2 (0.4 mL) at ꢀ40 ꢁC was added allyltrichlorosilane
(87 lL, 0.6 mmol). After stirring for 30 min, benzaldehyde
(20 lL, 0.2 mmol) was added to the reaction and kept stir-
ring for 24 h at the same temperature. The reaction was
quenched with aqueous saturated NaHCO3, and the mix-
ture was extracted with AcOEt (·2). The combined organic
layers were washed with brine, dried over Na2SO4, and
then concentrated in vacuo. The obtained residue was puri-
fied by flash column chromatography (SiO2, hexane/
AcOEt 15/1) to give 1-phenyl-3-butene-1-ol 12 as a color-
less oil (20.3 mg, 69%, 52% ee). The enantiomeric excess
was determined by HPLC analysis (DAICEL CHIRAL-
CEL OD-H, 2-propanol/hexane 5/95, flow rate 0.5 mL/
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min, tR 18.0 min [(S)-isomer] and 20.0 min [(R)-isomer],
22
detection at 254 nm). ½aꢂD ¼ þ28:7 [c 0.18, CHCl3, 52%
ee (R)].
4.3.2. Lewis base-catalyzed asymmetric allylation of benz-
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methyl-1-phenyl-3-butene-1-ol 13.9c To a stirred mixture
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i-Pr2NEt (346 lL, 1.2 mmol) in CH2Cl2 (0.8 mL) at ꢀ40 ꢁC
was added (E)-crotyltrichlorosilane (E/Z = 95/5) (188 lL,
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¨
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´
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16. Enantioselectivity was not increased when the reaction was
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