Chiral N-(tert-butyl)-N-methylaniline type ligands: synthesis and application to palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tet.2015.01.027

Abstract We found that N-(tert-butyl)-N-methylanilines 1 have C(aryl)-N(amine) bond axial chirality and succeeded the optical resolution of C-N bond atropisomers of amines 1 by a chiral palladium resolving agent and/or a chiral HPLC method. Finally, we de

Full text of DOI:10.1016/j.tet.2015.01.027

Tetrahedron 71 (2015) 5985e5993
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chiral N-(tert-butyl)-N-methylaniline type ligands: synthesis and
application to palladium-catalyzed asymmetric allylic alkylation
*
Takashi Mino , Minato Asakawa, Yamato Shima, Haruka Yamada, Fumitoshi Yagishita,
Masami Sakamoto
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522,
Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
We found that N-(tert-butyl)-N-methylanilines 1 have C(aryl)eN(amine) bond axial chirality and suc-
ceeded the optical resolution of CeN bond atropisomers of amines 1 by a chiral palladium resolving
agent and/or a chiral HPLC method. Finally, we demonstrated the ability of chiral amines 1 as a ligand in
palladium-catalyzed asymmetric allylic alkylation of allylic esters with malonates (up to 95% ee).
Ó 2015 Elsevier Ltd. All rights reserved.
Received 1 December 2014
Received in revised form 13 January 2015
Accepted 13 January 2015
Available online 19 January 2015
Dedicated to Professor Barry M. Trost on the
occasion of his shared receipt of the 2014
Tetrahedron Prize
Keywords:
Palladium catalyst
Asymmetric allylic alkylation
Chiral ligand
Axial chirality
1. Introduction
Then, we were interested in the C(aryl)eN(amine) bond axial chi-
rality of aniline derivatives with a tert-butyl group, which has
C(aryl)eC(aryl) bond axially chiral biaryls1 including BINAP2 are
important molecules that affect asymmetric inductions as ligands
for transition metal catalysts. For nonbiaryl CeC bond axially chiral
ligands, Clayden et al. reported the synthesis and optical resolution
of C(aryl)eC(carbonyl) bond axially chiral N,N-diisopropyl-2-ethyl-
6-diphenylphosphinylbenzamide.3 The half-life times of racemi-
a smaller substituent than the 1-adamantyl group. Herein, we
report the synthesis and optical resolution of N-(tert-butyl)-N-
zation of this compound and its palladium complex from [Pd(h3
-
C3H5)Cl]2 at 25 ꢀC were 2 days and 5 min, respectively. So, this
compound was not used as chiral ligand for transition metal cata-
lysts. On the other hand, CeN bond axially chiral cyclic amine
compounds4 have been reported, including the indoline-type li-
gands L15 (Fig. 1) and the indole-type ligands L26 (Fig. 1) for
palladium-catalyzed asymmetric reactions. Recently, we prepared
C(aryl)eN(amine) bond atropisomers of acyclic 1-adamantylamine
derivatives L37 (Fig. 1) using an approach similar to the synthesis of
ligands L1 and L2. The 1-adamantyl group is one of the most bulky
and rigid substituents. Thus, CeN bond axial chirality of L3 was
stable for use of chiral ligand in transition metal catalytic reactions.
* Corresponding author. E-mail address: tmino@faculty.chiba-u.jp (T. Mino).
Fig. 1. CeN bond axially chiral ligands L1eL3 and 1.
http://dx.doi.org/10.1016/j.tet.2015.01.027
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
methylanilines 1 (Fig. 1) with C(aryl)eN(amine) bond axial chirality
by a chiral palladium resolving agent and/or a chiral HPLC method,
the investigation of a rotation barrier for CeN bond axial stability,
and an application in a palladium-catalyzed asymmetric allylic al-
kylation of allylic esters with malonates.
1c by optical resolution using a chiral resolving agent. The optical
resolution of (ꢁ)-1c was achieved using a semi-preparative chiral
HPLC (Daicel CHIRALCELÒ OJ) (Scheme 3). The optical purities of
(aS)-(þ)-1c and (aR)-(ꢂ)-1c were more than 99% ee from chiral
HPLC analyses.
We found that the palladium complex (ꢁ)-1a$(S)-5 was easily
epimerizated to (aS)-1a$(S)-5 (ca. 30% de) in CHCl3. We also tried
the optical resolution of (ꢁ)-1a using a chiral resolving agent with
epimerization at 50 ꢀC in CHCl3 (Scheme 4). In this case, (aS)-(þ)-1a
(>99% ee) was obtained 50% yield from (ꢁ)-1a after chiral HPLC
purification.
The determination of the absolute configurations of 1 was made
by single-crystal X-ray analysis of (aS)-(þ)-1a (CCDC 1036778),
(aS)-1b$(S)-5 (CCDC 1036779), and (aR)-(ꢂ)-1c (CCDC 1036780)
(Figs. 2e4).
2. Results and discussion
Racemic amines (ꢁ)-1 were easily prepared in three steps. A
nucleophilic aromatic substitution (SNAr) reaction of the corre-
sponding
phosphine
oxides
such
as
2,3-
dimethoxyphenyldiphenylphosphine oxide (2a)7 with lithium salt
of tert-butylamine gave the corresponding aminophosphine oxide
3a. N-methylation of 3a occurred using MeI in the presence of
K2CO3. This aminophosphine oxide 4a was converted into the de-
sired racemic amine (ꢁ)-1a using trichlorosilaneetriethylamine in
good yield (Scheme 1). Racemic amines (ꢁ)-1b and (ꢁ)-1c were
also easily prepared from 2b8 and 2c9 in the same manner. To in-
vestigate whether C(aryl)eN(amine) bond axial chirality exists in
amines (ꢁ)-1, we analytically separated these isomers using HPLC
with a chiral stationary phase column. As a result, we obtained
nearly resolved UV plots for amines (ꢁ)-1 in addition to a pair of
clear positive (þ) and negative (ꢂ) CD trace signals of HPLC run at
254 nm.
Barriers to the racemization of amines 1 in nonane for the
stability of the CeN bond axial chirality were also determined. A
small portion of the solution of optically active 1 in nonane was
removed at regular intervals and subsequently analyzed for en-
antiomeric excesses by chiral HPLC analysis. We repeated the ex-
periment at four temperatures and determined the rate constants
(krac) of 1 at each temperature. For example, the rotational barrier
(D
Gzrac) of 1a was found to be 27.7 kcal/mol in nonane at 25 ꢀC
based on the Arrhenius and Eyring equations.11 This result corre-
sponds to a half-life of approximately 4 months in nonane at 25 ꢀC
(Table 1).
To investigate the nature of the palladium complex’s structure,
amine (ꢁ)-1c was treated with PdCl2(MeCN)2 to produce palladium
complex (ꢁ)-6 and a suitable crystal was obtained from hex-
aneeCHCl3. X-ray analysis of (ꢁ)-6 (CCDC 1036781) was carried out
(Fig. 5). The solid-state structure shows that amine 1c is co-
ordinated to palladium with a five-membered chelate ring by
phosphorus and nitrogen atom. The trans influence of the P,N-
ligand is reflected in the lengthening of the PdeCl bond in trans
disposition to the phosphorus to the PdeCl distance the trans to the
ꢀ
nitrogen [2.4118(11) versus 2.2975(11) A].
Finally, we investigated the ability of chiral amines 1 as ligands
for the palladium-catalyzed asymmetric allylic alkylation.12 This
reaction was carried out in the presence of 2 mol % of [Pd(h
3-C3H5)
Cl]2, 4 mol % of 1, 3 equiv of N,O-bis(trimethylsilyl)acetamide
(BSA), and 10 mol % of base (Table 2). Although the reaction using
adamantylamine-type ligand L3 acquired 10 mol % of palladium
and ligand for a long reaction time such as 48 h,7 chiral ligands 1
can induce 71e88% yield and 77e83% ee in dichloromethane at
0
ꢀC using 1,3-diphenyl-2-propenyl acetate (7a) with dimethyl
malonate (8a) using 4 mol % of palladium and ligand for 24 h
(entries 1e3). When the reaction was carried out using (aS)-1a as
a ligand, the enantioselectivity of product (S)-9a obtained was
higher than the case of chiral amines (aS)-1b and (aS)-1c with
good yields (entry 1 vs entries 2 and 3). We examined the effect of
the reaction solvents and bases using chiral ligand (aS)-1a. When
the reaction was carried out in ether, (S)-9a was obtained in good
yield with good enantioselectivity (90.2% ee) (entry 5). With
NaOAc instead of LiOAc, the enantioselectivity was decreased
(entry 5 vs entry 10). When the reaction under ꢂ10 ꢀC was also
carried out, the enantioselectivity of (S)-9a was slightly decreased
to 89.9% ee (entry 11). We next investigated the asymmetric allylic
alkylation of similar malonates and allylic esters. The reaction with
diethyl malonate (8b) instead of 8a gave corresponding product in
good yield with 95% ee (entry 12). The reaction with dibenzyl or
di-t-butyl malonates (8c or 8d) gave corresponding products in
78% with 92% ee and 77% yield with 88% ee, respectively (entries
13 and 14). The reaction with diethyl methylmalonate (8e) also
gave the corresponding product in good yield with good enan-
tioselectivity (entry 15). When 1,3-diphenyl-2-propenyl pivalate
(7b) was used instead of 7a, the reaction with a diethyl malonate
Scheme 1. Preparation of racemic amines (ꢁ)-1.
We firstly attempted the optical resolution of (ꢁ)-1a into each
atropisomer using a chiral HPLC. Although we tried optical reso-
lution using a semi-preparative HPLC with a chiral stationary phase
column (Daicel CHIRALCELÒ OD), we obtained only moderate op-
tical purities of (aS)-(þ)-1a and (aR)-(ꢂ)-1a with low yields. So, we
attempted the optical resolution of (ꢁ)-1a using (S)-(þ)-di-
m-
chloro-bis[1-[(dimethylamino)ethyl]-2-naphthyl-C,N]dipalladiu-
m(II) ((S)-5)10 as a chiral resolving agent (Scheme 2). The resulting
diastereomeric palladium complex mixtures (aS)-1a$(S)-5 and
(aR)-1a$(S)-5 were separable by silica gel column chromatography.
The individual diastereomers were treated with ethylenediamine
(EDA) to release optically active (aS)-(þ)-1a and (aR)-(ꢂ)-1a. After
the optical purification using a semi-preparative chiral HPLC (Dai-
cel CHIRALCELÒ OD), the optical purity of (aS)-(þ)-1a was more
than 99% ee from chiral HPLC analyses. We also obtained the optical
purity of (aS)-(þ)-1b with more than 99% ee under a similar
method (Scheme 2). On the other hand, we could not obtain chiral

T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
5987
Scheme 2. Optical resolution and purification of (ꢁ)-1a and (ꢁ)-1b.
4. Experimental section
4.1. General experimental
1H NMR and 13C NMR spectra were measured with a Bruker
DPX-300 spectrometer (300 MHz for 1H NMR and 75 MHz for 13C
NMR). The chemical shifts are expressed in parts per million
Scheme 3. Optical resolution of (ꢁ)-1c by chiral HPLC.
Scheme 4. Optical resolution of (ꢁ)-1a with epimerization.
(8b) gave product (S)-9b in good yield with high enantioselectivity
(entry 16). When 1,3-di-(4-chlorophenyl)-2-propenyl acetate (7c)
was used instead of 7a, the reaction with a diethyl malonate (8b)
gave product (S)-9f in good yield with moderate enantioselectivity
(entry 17).
downfield from tetramethylsilane as an internal standard. The Mass
spectra (MS) of the compounds were recorded using a Shimadzu
GCMS-QP 5050 (EI-MS) spectrometer. The high-resolution Mass
spectra (HRMS) of the compounds were recorded using a Thermo
Fisher Sci. Exactive (ESI-MS) spectrometer. Optical rotations were
recorded on a Jasco P-2100 polarimeter. Chiral HPLC was performed
on Jasco HPLC systems consisting of the following: Pump, PU-980,
PU-1580, or PU-2089; detector, UV-970 or UV-2075 and CD-2095.
3. Conclusion
We found that N-(tert-butyl)-N-methylanilines (ꢁ)-1 were
easily prepared in three steps and have C(aryl)eN(amine) bond
axial chirality. We succeeded the optical resolution of CeN bond
atropisomers of amines 1 by a chiral palladium resolving agent and/
or a semi-preparative chiral HPLC method. We also found that
chiral amines 1 are effective ligands for palladium-catalyzed
asymmetric allylic alkylation of allylic esters with malonates (up
to 95% ee).
4.2. Preparation of aminophosphine oxide 3a
To the solution of tert-butylamine (1.60 mL, 15.1 mmol) in THF
(4.0 mL) at ꢂ80 ꢀC was added slowly n-BuLi in hexane (9.5 mL,
15.2 mmol, 1.60 M). The reaction mixture was stirred for 60 min at
ꢂ80 ꢀC and for 135 min at room temperature. After phosphine
oxide 2a (1.692 g, 5.0 mmol) in THF (3.0 mL) was added, and the

5988
T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
Fig. 4. ORTEP drawing of (aR)-(ꢂ)-1c.
Fig. 2. ORTEP drawing of (aS)-(þ)-1a.
Table 1
Racemization parameter of 1
Thermodynamic parameter at 25 ꢀC 1a
1b
1c
Half-life (year)
Krac
3.5ꢃ10ꢂ1
2.7ꢃ103
2.7ꢃ103
3.16ꢃ10ꢂ8 4.09ꢃ10ꢂ12 4.09ꢃ10ꢂ12
DH (kcal/mol)
DS (cal/mol K)
DG (kcal/mol)
27.9
0.844
27.7
39.5
22.0
33.0
46.8
46.5
33.0
Fig. 3. ORTEP drawing of (aS)-1b$(S)-5.
stirring was continued for 16 h at room temperature. The mixture
was diluted with ether and quenched with satd NH4Cl aq. The or-
ganic layer was washed with brine, dried over MgSO4, and con-
centrated under reduced pressure. The residue was purified by
silica gel chromatography (hexaneeEtOAc¼2:1): 1.772 g,
Fig. 5. X-ray structure of palladium complex (ꢁ)-6 (Solvent molecules (CHCl3) are
omitted for clarity).
4.67 mmol, 93%; mp 140e142 ꢀC; 1H NMR (300 MHz, CDCl3)
d 1.05
Jcp¼11.8 Hz), 128.3ꢃ4 (d, Jcp¼12.1 Hz), 131.7ꢃ2 (d, Jcp¼2.7 Hz),
132.0ꢃ4 (d, Jcp¼9.9 Hz), 133.0ꢃ2 (d, Jcp¼103.4 Hz), 143.7 (d,
Jcp¼5.5 Hz), 152.5 (d, Jcp¼11.8 Hz); 31P NMR (121 MHz, CDCl3)
(s, 9H), 3.81 (s, 3H), 6.30 (br s, 1H), 6.41 (ddd, J¼1.3, 7.7 and 14.2 Hz,
1H), 6.70 (td, J¼7.8 and 3.5 Hz, 1H), 6.95 (d, J¼7.9 Hz, 1H), 7.43e7.66
(m, 10H); 13C NMR (75 MHz, CDCl3)
Jcp¼2.1 Hz), 118.8 (d, Jcp¼15.6 Hz), 120.4 (d, Jcp¼103.8 Hz), 125.7 (d,
d
30.6ꢃ3, 53.5, 54.9, 115.2 (d,
d
35.8; EI-MS m/z (rel intensity) 379 (Mþ, 20); HRMS (ESI-orbitrap)
m/z calcd for C23H26O2NPþNa 402.1593, found 402.1582.

T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
5989
Table 2
Palladium-catalyzed asymmetric allylic alkylation using (aS)-1a
Entry
Ar
R1
R2
R3
Solvent
Base
Yield (%)b
Ee (%)c
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
t-Bu
Me
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OEt
OCH2Ph
Ot-Bu
OEt
OEt
OEt
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
DCM
DCM
DCM
THF
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
NaOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
88(9a)
71(9a)
82(9a)
85(9a)
96(9a)
90(9a)
89(9a)
90(9a)
71(9a)
73(9a)
76(9a)
89(9b)
78(9c)
77(9d)
88(9e)
80(9b)
64(9f)
83
80
77
87
90.2
89
87
87
89.7
88
89.9
95
92
88
93
2d
3e
4
5
6
7
8
Et2O
1,4-dioxane
PhMe
PhCF3
MeCN
Et2O
Et2O
Et2O
Et2O
Et2O
9
10
11f
12
13
14g
15
16
17
Et2O
Et2O
Et2O
94
84
p-ClC6H4
a
The reactions were carried out on 0.2 mmol scale of 7 in various solvent (0.4 mL) at various temperature with 3.0 equiv of 8 and BSA, in the presence of LiOAc (10 mol %),
(aS)-1 (4 mol %) and [Pd(
h
3-C3H5)Cl]2 (2 mol %; Pd¼4 mol %).
b
Isolated yields.
c
Determined by HPLC analysis using a chiral column.
This reaction was carried out using (aS)-1b instead of (aS)-1a.
This reaction was carried out using (aS)-1c instead of (aS)-1a.
This reaction was carried out at ꢂ10 ꢀC.
d
e
f
g
This reaction was carried out for 48 h.
4.3. Preparation of aminophosphine oxide 3b
diluted with ether and quenched with satd NH4Cl aq. The organic
layer was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by silica gel
chromatography (hexaneeEtOAc¼2:1): 5.149 g, 12.89 mmol, 86%;
To the solution of tert-butylamine (1.60 mL, 15.1 mmol) in THF
(2.0 mL) at ꢂ80 ꢀC was added slowly n-BuLi in hexane (9.4 mL,
15.1 mmol, 1.60 M). The reaction mixture was stirred for 30 min at
ꢂ80 ꢀC and for 2 h at room temperature. After phosphine oxide 2b
(1.612 g, 5.0 mmol) in THF (10.0 mL) was added, and the stirring
was continued for 18 h at room temperature. The mixture was di-
luted with ether and quenched with satd NH4Cl aq. The organic
layer was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by silica gel
chromatography (hexaneeEtOAc¼2:1): 0.919 g, 2.53 mmol, 51%;
mp 132e133 ꢀC; 1H NMR (300 MHz, CDCl3)
d 1.11 (s, 9H), 6.84 (br s,
1H), 6.94 (q, J¼4.4 and 8.5 Hz, 1H), 7.31 (dd, J¼2.3 and 8.5 Hz 1H),
7.41e7.56 (m, 8H), 7.64e7.72 (m, 5H), 8.53 (d, J¼8.4 Hz, 1H); 13C
NMR (75 MHz, CDCl3)
d
31.7ꢃ3, 56.4, 116.5 (d, Jcp¼103.9 Hz), 120.6
(d, Jcp¼13.2 Hz), 124.4, 127.2, 127.9, 128.1, 128.39 (d, Jcp¼12.6 Hz),
128.43ꢃ4 (d, Jcp¼11.9 Hz), 131.8ꢃ2 (d, Jcp¼2.7 Hz), 132.0ꢃ4 (d,
Jcp¼9.6 Hz), 132.5 (d, Jcp¼9.9 Hz), 133.8ꢃ2 (d, Jcp¼103.3 Hz), 136.1
(d, Jcp¼2.1 Hz), 154.8 (d, Jcp¼4.4 Hz); 31P NMR (121 MHz, CDCl3)
mp 129e130 ꢀC; 1H NMR (300 MHz, CDCl3)
d
1.03 (s, 9H), 2.40 (s,
d
36.4; EI-MS m/z (rel intensity) 399 (Mþ, 27); HRMS (ESI-orbitrap)
3H), 6.21 (br s, 1H), 6.69e6.81 (m, 2H), 7.29 (d, J¼6.8 Hz, 1H),
m/z calcd for C26H26ONPþH 400.1825, found 400.1814.
7.42e7.48 (m, 4H), 7.51e7.56 (m, 2H), 7.59e7.65 (m, 4H); 13C NMR
(75 MHz, CDCl3)
d
22.1 (d, Jcp¼1.5 Hz), 31.0ꢃ3, 54.6, 120.1 (d,
4.5. Preparation of aminophosphine oxide 4a
Jcp¼14.4 Hz), 122.8 (d, Jcp¼102.4 Hz), 128.4ꢃ4 (d, Jcp¼12.1 Hz),
131.7ꢃ2 (d, Jcp¼1.0 Hz), 131.8 (d, Jcp¼11.4 Hz), 132.0ꢃ4 (d,
Jcp¼9.6 Hz), 133.7ꢃ2 (d, Jcp¼102.8 Hz), 135.1 (d, Jcp¼8.4 Hz), 135.6
(d, Jcp¼2.3 Hz), 153.2 (d, Jcp¼4.4 Hz); 31P NMR (121 MHz, CDCl3)
To the solution of phosphine oxide 3a (1.518 g, 4.0 mmol) in
MeCN (15.0 mL) was added K2CO3 (1.106 g, 8.0 mmol) and MeI
(5.0 mL, 80.0 mmol) at room temperature. The reaction mixture
was stirred for 16 h at room temperature. The reaction mixture was
filtered and evaporated under reduced pressure. The residue was
purified by silica gel chromatography (hexaneeEtOAc¼2:1):
1.568 g, 3.99 mmol, 100%; mp 163e165 ꢀC; 1H NMR (300 MHz,
d
36.8; EI-MS m/z (rel intensity) 363 (Mþ, 12); HRMS (ESI-orbitrap)
m/z calcd for C23H26ONPþH 364.1825, found 364.1808.
4.4. Preparation of aminophosphine oxide 3c
CDCl3)
and 13.6 Hz, 1H), 7.01e7.12 (m, 2H), 7.38e7.50 (m, 6H), 7.63e7.70
(m, 2H), 7.82e7.88 (m, 2H); 13C NMR (125 MHz, CDCl3)
33.1, 54.8, 56.3, 115.3 (d, Jcp¼2.4 Hz), 125.8 (d, Jcp¼12.8 Hz), 126.0 (d,
Jcp¼15.5 Hz), 127.7ꢃ2 (d, Jcp¼12.8 Hz), 128.0ꢃ2 (d, Jcp¼11.9 Hz),
130.3 (d, Jcp¼2.4 Hz), 130.8 (d, Jcp¼2.7 Hz), 130.9ꢃ2 (d, Jcp¼9.5 Hz),
132.3ꢃ2 (d, Jcp¼8.4 Hz), 134.2 (d, Jcp¼17.9 Hz), 135.1 (d,
d
1.18 (s, 9H), 1.83 (s, 3H), 3.79 (s, 3H), 6.64 (ddd, J¼1.7, 7.3
To the solution of tert-butylamine (4.74 mL, 45.0 mmol) in THF
(10.0 mL) at ꢂ80 ꢀC was added slowly n-BuLi in hexane (27.0 mL,
45.1 mmol, 1.67 M). The reaction mixture was stirred for 15 min at
ꢂ80 ꢀC and for 4 h at room temperature. After phosphine oxide 2c
(5.376 g, 15.0 mmol) in THF (20.0 mL) was added, and the stirring
was continued for 16 h at room temperature. The mixture was
d
27.8ꢃ3,

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T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
Jcp¼25.0 Hz), 137.3 (d, Jcp¼107.3 Hz), 144.1 (d, Jcp¼3.9 Hz), 160.7 (d,
Jcp¼21.5 Hz), 144.7, 159.5 (d, Jcp¼3.6 Hz); 31P NMR (121 MHz, CDCl3)
Jcp¼10.7 Hz); 31P NMR (121 MHz, CDCl3)
d
23.9; EI-MS m/z (rel in-
d
ꢂ13.2; EI-MS m/z (rel intensity) 377 (Mþ, 23); HRMS (ESI-orbi-
tensity) 393 (Mþ, 3); HRMS (ESI-orbitrap) m/z calcd for
trap) m/z calcd for C24H28ONPþNa 400.1801, found 400.1796; HPLC
C
24H28O2NPþNa 416.1750, found 416.1740.
(Daicel CHIRALCELÒ OD-H, 0.46
hexane¼100, 0.5 mL/min: tR¼14.7 min (CD: lext
16.6 min (CD: lext
ε) 254 (ꢂ)).
f
ꢃ25 cm, UV 254 nm),
(D
ε) 254 (þ)) and
4.6. Preparation of aminophosphine oxide 4b
(D
To the solution of phosphine oxide 3b (0.759 g, 2.09 mmol) in
CHCl3 (2.0 mL) was added K2CO3 (0.553 g, 4.0 mmol), MeI (2.5 mL,
40.0 mmol) and MeCN (8.0 mL) at room temperature. The reaction
mixture was stirred at 50 ꢀC. After 24 h and 48 h, MeI (2.5 mL,
40.0 mmol) was added. After 72 h, the reaction mixture was filtered
and evaporated under reduced pressure. The residue was purified
by silica gel chromatography (hexaneeEtOAc¼4:1): 0.731 g,
4.9. Preparation of aminophosphine ( )-1b
To a mixture of phosphine oxide 4b (0.189 g, 0.5 mmol) and
triethylamine (1.5 mL, 10.8 mmol) in m-xylene (2.0 mL) was added
trichlorosilane (1.0 mL, 9.91 mmol) at 0 ꢀC under an Ar atmosphere.
The reaction mixture was stirred at 130 ꢀC for 24 h. After being
cooled to room temperature, the mixture was diluted with Et2O and
quenched with 2 M aqueous NaOH solution. The organic layer was
washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel chroma-
tography (hexaneeEtOAc¼80:1): 0.115 g, 0.318 mmol, 64%; mp
1.94 mmol, 93%; mp 172e173 ꢀC; 1H NMR (300 MHz, CDCl3)
d 1.23
(s, 9H), 1.86 (s, 3H), 2.33 (s, 3H), 6.89e7.04 (m, 2H), 7.31 (d, J¼7.3 Hz,
1H), 7.37e7.49 (m, 6H), 7.57e7.64 (m, 2H), 7.79e7.86 (m, 2H); 13C
NMR (75 MHz, CDCl3)
d
20.8 (d, Jcp¼1.4 Hz), 28.1ꢃ3, 33.9, 56.7, 124.7
(d, Jcp¼14.7 Hz), 127.7, 127.9, 128.0ꢃ2 (d, Jcp¼11.1 Hz), 130.4 (d,
Jcp¼2.6 Hz), 130.7 (d, Jcp¼2.6 Hz), 130.9ꢃ2 (d, Jcp¼9.5 Hz), 132.3ꢃ2
(d, Jcp¼8.1 Hz), 132.7 (d, Jcp¼13.7 Hz), 134.2 (d, Jcp¼9.9 Hz), 135.6 (d,
Jcp¼16.5 Hz), 136.2 (d, Jcp¼2.2 Hz), 137.3 (d, Jcp¼107.8 Hz), 140.7 (d,
108e110 ꢀC; 1H NMR (300 MHz, CDCl3)
d 1.29 (s, 9H), 2.18 (s, 3H),
2.30 (s, 3H), 6.68 (dt, J¼2.1 and 7.5 Hz, 1H), 6.97 (t, J¼7.4 Hz, 1H),
7.12 (d, J¼6.9 Hz, 1H), 7.19e7.31 (m, 10H); 13C NMR (75 MHz, CDCl3)
d
20.6 (d, Jcp¼2.1 Hz), 28.5ꢃ3 (d, Jcp¼6.6 Hz), 34.3 (d, Jcp¼1.5 Hz),
Jcp¼7.7 Hz), 153.7 (d, Jcp¼4.3 Hz); 31P NMR (121 MHz, CDCl3)
d
24.5;
55.8, 125.5, 127.8, 128.1ꢃ2 (d, Jcp¼7.7 Hz), 128.3ꢃ2 (d, Jcp¼5.6 Hz),
128.4, 131.8, 132.2, 133.7ꢃ2 (d, Jcp¼20.0 Hz), 134.5ꢃ2 (d,
Jcp¼21.1 Hz), 138.4 (d, Jcp¼13.0 Hz), 139.4 (d, Jcp¼1.4 Hz), 139.7 (d,
Jcp¼16.1 Hz), 144.0, 152.9 (d, Jcp¼22.5 Hz); 31P NMR (121 MHz,
EI-MS m/z (rel intensity) 377 (Mþ, 5); HRMS (ESI-orbitrap) m/z
calcd for C24H28ONPþH 378.1981, found 378.1968.
4.7. Preparation of aminophosphine oxide 4c
CDCl3)
d
ꢂ12.0; EI-MS m/z (rel intensity) 361 (Mþ, 33); HRMS (ESI-
orbitrap) m/z calcd for C24H28NPþH 362.2032, found 362.2021;
To the solution of phosphine oxide 3c (3.995 g, 10.0 mmol) in
MeCN (40.0 mL) was added K2CO3 (2.764 g, 20.0 mmol) and MeI
(12.5 mL, 200 mmol) at room temperature. The reaction mixture
was stirred at 50 ꢀC. After 24 h, MeI (12.5 mL, 200 mmol) was
added. After 48 h, the reaction mixture was filtered and evaporated
under reduced pressure. The residue was purified by silica gel
chromatography (hexaneeEtOAc¼2:1): 4.003 g, 9.68 mmol, 97%;
HPLC (Daicel CHIRALCELÒ OD-H, 0.46
hexane¼100, 0.3 mL/min: tR¼11.6 min (CD: lext
12.7 min (CD: lext
ε) 254 (ꢂ)).
fꢃ25 cm, UV 254 nm),
(
D
ε) 254 (þ)) and
(D
4.10. Preparation of aminophosphine ( )-1c
To a mixture of phosphine oxide 4c (0.414 g, 1.0 mmol) and
triethylamine (3.0 mL, 21.6 mmol) in m-xylene (10.0 mL) was added
trichlorosilane (2.0 mL, 19.8 mmol) at 0 ꢀC under an Ar atmosphere.
The reaction mixture was stirred at 100 ꢀC for 1 h and 120 ꢀC for 6 h.
After being cooled to room temperature, the mixture was diluted
with Et2O and quenched with 2 M aqueous NaOH solution. The
organic layer was washed with brine, dried over MgSO4, and con-
centrated under reduced pressure. The residue was purified by
silica gel chromatography (hexaneeEtOAc¼40:1): 0.244 g,
mp 194e195 ꢀC; 1H NMR (300 MHz, CDCl3)
d 1.29 (s, 9H), 2.15 (s,
3H), 7.15 (q, J¼4.2 and 8.5 Hz, 1H), 7.37e7.40 (m, 3H), 7.45e7.55 (m,
5H), 7.58e7.66 (m, 3H), 7.85e7.91 (m, 3H), 8.10 (d, J¼8.3 Hz,1H); 13
C
NMR (125 MHz, CDCl3)
d
27.7ꢃ3, 35.6, 57.1, 125.6, 125.7 (d,
Jcp¼13.1 Hz), 126.8, 127.3, 127.8ꢃ2 (d, Jcp¼11.9 Hz), 128.2ꢃ2 (d,
Jcp¼10.7 Hz), 128.7, 129.6 (d, Jcp¼14.3 Hz), 130.5 (d, Jcp¼3.3 Hz),
130.9 (d, Jcp¼2.4 Hz) 131.0ꢃ2 (d, Jcp¼9.5 Hz), 132.3ꢃ2 (d,
Jcp¼7.8 Hz), 133.6 (d, Jcp¼108.5 Hz), 134.6 (d, Jcp¼58.7 Hz), 135.2 (d,
Jcp¼3.6 Hz), 135.5 (d, Jcp¼54.9 Hz), 137.0, 154.9 (d, Jcp¼3.6 Hz); 31P
0.613 mmol, 61%; mp 111e112 ꢀC; 1H NMR (300 MHz, CDCl3)
d 1.35
NMR (121 MHz, CDCl3)
d
23.7; EI-MS m/z (rel intensity) 413 (Mþ, 2);
(s, 9H), 2.52 (s, 3H), 7.03 (dd, J¼8.5 and 2.6 Hz, 1H), 7.25e7.35 (m,
HRMS (ESI-orbitrap) m/z calcd for C27H28ONPþH 414.1981, found
10H), 7.43e7.47 (m, 2H), 7.57 (d, J¼8.5 Hz, 1H), 7.79e7.82 (m, 1H),
414.1968.
8.07e8.10 (m, 1H); 13C NMR (75 MHz, CDCl3)
d
28.8ꢃ3 (d,
Jcp¼6.3 Hz), 36.0 (d, Jcp¼3.3 Hz), 56.0, 125.4, 125.9, 125.98, 126.01,
126.1, 127.9, 128.2 (d, Jcp¼7.3 Hz), 128.37ꢃ2 (d, Jcp¼1.5 Hz),
128.42ꢃ2 (d, Jcp¼1.0 Hz), 130.2, 133.5ꢃ2 (d, Jcp¼19.8 Hz), 134.3ꢃ2
(d, Jcp¼21.3 Hz), 134.9 (d, Jcp¼2.5 Hz), 135.4, 138.6 (d, Jcp¼13.9 Hz),
139.4 (d, Jcp¼16.3 Hz), 139.7 (d, Jcp¼3.3 Hz), 152.4 (d, Jcp¼24.0 Hz);
4.8. Preparation of aminophosphine ( )-1a
To a mixture of phosphine oxide 4a (0.394 g, 1.04 mmol) and
triethylamine (3.0 mL, 21.5 mmol) in m-xylene (4.0 mL) was added
trichlorosilane (2.0 mL, 19.8 mmol) at 0 ꢀC under an Ar atmosphere.
The reaction mixture was stirred at 120 ꢀC for 8 h. After being
cooled to room temperature, the mixture was diluted with Et2O and
quenched with 2 M aqueous NaOH solution. The organic layer was
washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel chroma-
tography (hexaneeEtOAc¼40:1): 0.295 g, 0.781 mmol, 75%; mp
31P NMR (121 MHz, CDCl3)
d
ꢂ12.2; EI-MS m/z (rel intensity) 397
(Mþ, 35), 154 (100); HRMS (ESI-orbitrap) m/z calcd for C27H28NPþH
398.2032, found 398.2029; HPLC (Daicel CHIRALCELÒ OJ, 0.46
f
ꢃ25 cm, UV 254 nm), hexaneeEtOH¼80:20, 0.3 mL/min:
tR¼11.6 min (CD: lext
(þ)).
(
D
ε) 254 (ꢂ)) and 15.9 min (CD: lext
(Dε) 254
119e121 ꢀC; 1H NMR (300 MHz, CDCl3)
d
1.22 (s, 9H), 2.01 (s, 3H),
4.11. Optical resolution of ( )-1a (Scheme 2)
3.76 (s, 3H), 6.39 (ddd, J¼1.4 and 2.5 and 7.6 Hz, 1H), 6.82 (d,
J¼8.0 Hz,1H), 7.04 (ddd, J¼1.0 and 7.7 and 8.0 Hz,1H), 7.20e7.36 (m,
A mixture of (ꢁ)-1a (0.113 g, 0.30 mmol) and (S)-(þ)-di-
m-
10H); 13C NMR (125 MHz, CDCl3)
d
28.3ꢃ3 (d, Jcp¼4.8 Hz), 33.5, 54.7,
chloro-bis[1-[(dimethylamino)ethyl]-2-naphthyl-C,N]dipalladiu-
55.9, 111.7, 124.5, 126.4, 127.8, 128.1ꢃ2 (d, Jcp¼7.2 Hz), 128.2ꢃ2 (d,
Jcp¼6.0 Hz), 128.4, 133.8ꢃ2 (d, Jcp¼20.3 Hz), 134.7ꢃ2 (d,
Jcp¼22.1 Hz), 138.0 (d, Jcp¼11.6 Hz), 139.7 (d, Jcp¼16.7 Hz), 142.3 (d,
m(II) ((S)-5) (0.103 g, 0.15 mmol) in CHCl3 (2.0 mL) was stirred at
room temperature for 2 h. The mixture was concentrated under
reduced pressure, and the residue was purified by silica gel column

T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
5991
chromatography (CHCl3eEtOAc¼3:1) to separate the di-
astereomeric mixture. 0.1 solution of ethylenediamine
(0.5 mmol) in chloroform (5.0 mL) was added to an individual di-
astereomer at room temperature and stirred for 20 min. The mix-
ture was concentrated under reduced pressure, and the residue was
128.1ꢃ2 (d, Jcp¼8.1 Hz), 128.2ꢃ2 (d, Jcp¼6.2 Hz), 128.4, 133.8ꢃ2 (d,
Jcp¼19.8 Hz), 134.7ꢃ2 (d, Jcp¼21.6 Hz), 138.0 (d, Jcp¼11.7 Hz), 139.7
(d, Jcp¼16.1 Hz), 142.3 (d, Jcp¼21.2 Hz), 144.7, 159.5 (d, Jcp¼3.0 Hz);
M
31P NMR (121 MHz, CDCl3)
d
ꢂ13.2; EI-MS m/z (rel intensity) 377
(Mþ, 19); HRMS (ESI-orbitrap) m/z calcd for C24H28ONPþH
purified
by
silica
gel
column
chromatography
378.1981, found 378.1975; HPLC (Daicel CHIRALCELÒ OD-H, 0.46
(hexaneeEtOAc¼100:1) (and semi-preparative chiral HPLC (Daicel
CHIRALCELÒ OD) for (aS)-(þ)-1a) to afford optically active (aS)-
(þ)-1a or (aR)-(ꢂ)-1a.
f
ꢃ25 cmꢃ2, UV 254 nm), hexane¼100, 0.1 mL/min: tR¼100.8 min
(major) and 108.8 min (minor); X-ray diffraction analysis data:
Colorless Plate crystals from hexaneeCHCl3, orthorhombic space
(aS)-(þ)-1a: 33.3 mg, 0.088 mmol, 29%, >99% ee; mp 98e99 ꢀC;
group P212121, a¼10.5224(2) A, b¼11.5963(3) A, c¼17.9011(4) A,
ꢀ
ꢀ
ꢀ
20 þ90.4 (c 0.51, CHCl3); 1H NMR (300 MHz, CDCl3)
d
1.22 (s, 9H),
a
¼90ꢀ,
b
¼90ꢀ,
g
¼90 , V¼2184.31(9) A , Z¼4,
r
¼1.148 g/cm3,
m
3
ꢀ
ꢀ
[
a
]
D
2.01 (s, 3H), 3.76 (s, 3H), 6.39 (ddd, J¼1.4 and 2.4 and 7.7 Hz, 1H),
(CuK
a
)¼1.196 mmꢂ1. The structure was solved by the direct method
6.83 (d, J¼7.5 Hz, 1H), 7.04 (ddd, J¼0.9 and 7.1 and 8.5 Hz, 1H),
of full-matrix leastesquares, where the final R and Rw were 0.0413
and 0.1043 for 3558 reflections.
7.20e7.33 (m, 10H); 13C NMR (75 MHz, CDCl3)
d
28.3ꢃ3 (d,
Jcp¼4.8 Hz), 33.5, 54.7, 55.9, 111.7, 124.5, 126.3 (d, Jcp¼1.1 Hz), 127.8,
128.1ꢃ2 (d, Jcp¼8.1 Hz), 128.2ꢃ2 (d, Jcp¼6.2 Hz), 128.4, 133.8ꢃ2 (d,
Jcp¼20.0 Hz), 134.7ꢃ2 (d, Jcp¼21.4 Hz), 138.0 (d, Jcp¼11.7 Hz), 139.7
(d, Jcp¼16.1 Hz), 142.3 (d, Jcp¼21.2 Hz), 144.7, 159.5 (d, Jcp¼3.0 Hz);
4.13. Optical resolution of ( )-1b (Scheme 2)
A mixture of (ꢁ)-1b (0.181 g, 0.50 mmol) and (S)-(þ)-di-
chloro-bis[1-[(dimethylamino)ethyl]-2-naphthyl-C,N]dipalladiu-
m-
31P NMR (121 MHz, CDCl3)
d
ꢂ13.2; EI-MS m/z (rel intensity) 377
(Mþ, 22); HRMS (ESI-orbitrap) m/z calcd for C24H28ONPþH
m(II) ((S)-5) (0.170 g, 0.25 mmol) in CHCl3 (2.0 mL) was stirred at
room temperature for 2 h. The mixture was concentrated under
reduced pressure, and the residue was purified by silica gel column
chromatography (hexaneeEtOAc¼4:1) to separate the di-
astereomeric mixture. 0.1 M solution of ethylendiamine (0.5 mmol)
in chloroform (5.0 mL) was added to an individual diastereomer at
room temperature and stirred for 20 min. The mixture was con-
centrated under reduced pressure, and the residue was purified by
silica gel column chromatography (hexaneeEtOAc¼100:1) (and
semi-preparative chiral HPLC (Daicel CHIRALCELÒ OD) for (aS)-
(þ)-1b) to afford optically active (aS)-(þ)-1b or (aR)-(ꢂ)-1b.
378.1981, found 378.1974; HPLC (Daicel CHIRALCELÒ OD-H, 0.46
f
ꢃ25 cmꢃ2, UV 254 nm), hexane¼100, 0.1 mL/min: tR¼90.9 min
(major) and 97.1 min (minor).
(aR)-(ꢂ)-1a: 42.7 mg, 0.113 mmol, 38%, 22% ee; mp 104e105 ꢀC;
[
a
]
20 ꢂ20.6 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
d 1.22 (s, 9H),
D
2.01 (s, 3H), 3.76 (s, 3H), 6.39 (ddd, J¼1.4 and 2.4 and 7.6 Hz, 1H),
6.83 (d, J¼7.7 Hz, 1H), 7.04 (ddd, J¼0.7 and 7.5 and 8.2 Hz, 1H),
7.20e7.33 (m, 10H); 13C NMR (75 MHz, CDCl3)
d
28.3ꢃ3 (d,
Jcp¼4.8 Hz), 33.5, 54.7, 55.9, 111.7, 124.5, 126.3 (d, Jcp¼1.2 Hz), 127.8,
128.1ꢃ2 (d, Jcp¼8.1 Hz), 128.2ꢃ2 (d, Jcp¼6.2 Hz), 128.4, 133.8ꢃ2 (d,
Jcp¼20.0 Hz), 134.7ꢃ2 (d, Jcp¼21.4 Hz), 138.0 (d, Jcp¼11.7 Hz), 139.7
(d, Jcp¼16.1 Hz), 142.3 (d, Jcp¼21.2 Hz), 144.7, 159.5 (d, Jcp¼3.0 Hz);
(aS)-(þ)-1b: 19.5 mg, 0.054 mmol, 11%, >99% ee; [
a
]
20 þ110.3 (c
D
0.50, CHCl3); 1H NMR (300 MHz, CDCl3)
d
1.29 (s, 9H), 2.18 (s, 3H),
31P NMR (121 MHz, CDCl3)
d
ꢂ13.1; EI-MS m/z (rel intensity) 377
2.30 (s, 3H), 6.68 (dt, J¼1.9 and 7.6 Hz, 1H), 6.97 (t, J¼7.5 Hz, 1H),
(Mþ, 22); HRMS (ESI-orbitrap) m/z calcd for C24H28ONPþH
7.12 (d, J¼7.3 Hz, 1H), 7.19e7.31 (m, 10H); 13C NMR (75 MHz, CDCl3)
378.1981, found 378.1974; HPLC (Daicel CHIRALCELÒ OD-H, 0.46
d
20.6 (d, Jcp¼2.2 Hz), 28.5ꢃ3 (d, Jcp¼6.5 Hz), 34.3 (d, Jcp¼1.5 Hz),
f
ꢃ25 cmꢃ2, UV 254 nm), hexane¼100, 0.2 mL/min: tR¼47.0 min
55.8, 125.5, 127.8, 128.1ꢃ2 (d, Jcp¼7.7 Hz), 128.3ꢃ2 (d, Jcp¼5.6 Hz),
128.4, 131.8, 132.2, 133.7ꢃ2 (d, Jcp¼20.0 Hz), 134.5ꢃ2 (d,
Jcp¼21.1 Hz), 138.4 (d, Jcp¼13.0 Hz), 139.4 (d, Jcp¼1.4 Hz), 139.7 (d,
Jcp¼16.1 Hz), 144.0, 152.9 (d, Jcp¼22.5 Hz); 31P NMR (121 MHz,
(minor) and 51.2 min (major).
4.12. Optical resolution of ( )-1a with epimerization
(Scheme 4)
CDCl3)
d
ꢂ12.0; EI-MS m/z (rel intensity) 361 (Mþ, 35); HRMS (ESI-
orbitrap) m/z calcd for C24H28NPþH 362.2032, found 362.2025;
A mixture of (ꢁ)-1a (0.394 g, 1.0 mmol) and (S)-(þ)-di-
m-chloro-
HPLC (Daicel CHIRALCELÒ OD-H, 0.46
fꢃ25 cmꢃ2, UV 254 nm),
bis[1-[(dimethylamino)ethyl]-2-naphthyl-C,N]dipalladium(II) ((S)-
5) (0.340 g, 0.50 mmol) in CHCl3 (5.0 mL) was stirred at 50 ꢀC for
24 h. The mixture was concentrated under reduced pressure, and
the residue was purified by silica gel column chromatography
(CHCl3eEtOAc¼3:1) to separate the diastereomeric mixture. 0.1 M
solution of ethylendiamine (0.5 mmol) in chloroform (5.0 mL) was
added to (aS)-1a$(S)-5 (94e97% de: Determined by 1H NMR anal-
ysis) at room temperature and stirred for 20 min. The mixture was
concentrated under reduced pressure, and the residue was purified
by silica gel column chromatography (hexaneeEtOAc¼100:1). On
the other hand, low de of (aR)-1a$(S)-5 was dissolved in CHCl3
(4.0 mL) and stirred at 50 ꢀC for 24 h. The solution was concentrated
again under reduced pressure, and the residue was separate the
diastereomeric mixture by silica gel column chromatography
(hexaneeEtOAc¼4:1). After three times of epimerization and sep-
aration, (aS)-(þ)-1a (91e95% ee: Determined by HPLC analysis) was
purified by semi-preparative chiral HPLC (Daicel CHIRALCELÒ OD)
to afford optically pure (aS)-(þ)-1a.
hexane¼100, 0.1 mL/min at 0 ꢀC: tR¼103.0 min (major) and
109.4 min (minor).
(aR)-(ꢂ)-1b: 15.1 mg, 0.042 mmol, 8%, 69% ee; mp 81e83 ꢀC;
[a
]
20 ꢂ78.5 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
d 1.29 (s, 9H),
D
2.18 (s, 3H), 2.30 (s, 3H), 6.68 (dt, J¼1.9 and 7.6 Hz, 1H), 6.97 (t,
J¼7.5 Hz, 1H), 7.12 (d, J¼6.8 Hz, 1H), 7.19e7.31 (m, 10H); 13C NMR
(75 MHz, CDCl3)
d
20.6 (d, Jcp¼2.1 Hz), 28.5ꢃ3 (d, Jcp¼6.6 Hz), 34.3
(d, Jcp¼1.5 Hz), 55.8, 125.5, 127.8, 128.1ꢃ2 (d, Jcp¼7.7 Hz), 128.3ꢃ2
(d, Jcp¼5.6 Hz),128.4,131.8, 132.2,133.7ꢃ2 (d, Jcp¼20.0 Hz),134.5ꢃ2
(d, Jcp¼21.1 Hz),138.4 (d, Jcp¼13.0 Hz),139.4 (d, Jcp¼1.4 Hz),139.7 (d,
Jcp¼16.1 Hz), 144.0, 152.9 (d, Jcp¼22.5 Hz); 31P NMR (121 MHz,
CDCl3)
d
ꢂ12.0; EI-MS m/z (rel intensity) 361 (Mþ, 43); HRMS (ESI-
orbitrap) m/z calcd for C24H28NPþH 362.2032, found 362.2024;
HPLC (Daicel CHIRALCELÒ OD-H, 0.46
fꢃ25 cmꢃ2, UV 254 nm),
hexane¼100, 0.2 mL/min: tR¼50.6 min (minor) and 54.5 min
(major).
4.14. Preparation of palladium complex (aS)-1b$(S)-5
(aS)-(þ)-1a: 188 mg, 0.50 mmol, 50%, >99% ee; mp 97e98 ꢀC;
[
a]
20 þ98.8 (c 0.50, CHCl3); 1H NMR (300 MHz, CDCl3)
d
1.22 (s, 9H),
A mixture of (ꢁ)-1b (0.072 g, 0.20 mmol) and (S)-(þ)-di-
chloro-bis[1-[(dimethylamino)ethyl]-2-naphthyl-C,N]dipalladiu-
m(II) ((S)-5) (0.068 g, 0.10 mmol) in CHCl3 (4.0 mL) was stirred at
room temperature for 2 h. The mixture was concentrated under
reduced pressure, and the residue was purified by silica gel column
m-
D
2.01 (s, 3H), 3.76 (s, 3H), 6.39 (ddd, J¼1.4 and 2.4 and 7.6 Hz, 1H),
6.83 (d, J¼7.6 Hz, 1H), 7.04 (ddd, J¼0.8 and 7.6 and 8.1 Hz, 1H),
7.20e7.34 (m, 10H); 13C NMR (75 MHz, CDCl3)
Jcp¼4.9 Hz), 33.5, 54.7, 55.9, 111.7, 124.5, 126.3 (d, Jcp¼1.1 Hz), 127.8,
d
28.3ꢃ3 (d,

5992
T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
chromatography (hexaneeEtOAc¼4:1) to separate the di-
astereomeric mixture and recrystallization from hexaneeCHCl3 to
afford (aS)-1b$(S)-5: 23.0 mg, 0.033 mmol, 16%, 94% de; mp
1.170 mmꢂ1. The structure was solved by the direct method of full-
matrix leastesquares, where the final R and Rw were 0.0419 and
0.0900 for 3101 reflections.
114e116 ꢀC; [
a]
20 ꢂ68.6 (c 0.51, CHCl3); 1H NMR (300 MHz, CDCl3)
D
d
1.45 (s, 3H),1.54 (s, 9H), 2.00 (d, J¼6.5 Hz, 3H), 2.28 (s, 3H), 2.78 (d,
4.16. Elucidation of the thermal racemization of optically
active 1
J¼1.3 Hz, 3H), 2.97 (d, J¼3.5 Hz, 3H), 4.33 (quin, J¼6.4 Hz, 1H), 6.58
(dd, J¼6.2 and 8.6 Hz, 1H), 6.87 (d, J¼8.6 Hz, 1H), 7.01 (dt, J¼1.8 and
7.7 Hz, 1H), 7.16e7.46 (m, 11H), 7.59e7.72 (m, 4H), 8.58 (br-s, 1H);
A small amount of optically active (aS)-1 or (aR)-1 was dissolved
in nonane at room temperature. The solution was kept at a constant
temperature in a thermostat oil bath, a small portion removed
every passage of times, and the transitions of enantiomeric excess
were measured by chiral HPLC analysis.
13C NMR (125 MHz, CDCl3)
d
21.4, 22.0, 30.8ꢃ3, 33.4, 48.0, 51.3 (d,
Jcp¼2.4 Hz), 57.7, 73.5 (d, Jcp¼3.3 Hz), 123.3ꢃ2, 123.5 (d, Jcp¼6.0 Hz),
123.9ꢃ2, 124.4 (d, Jcp¼10.7 Hz), 125.5, 127.2ꢃ2 (d, Jcp¼10.4 Hz),
128.3 (d, Jcp¼9.5 Hz), 128.6ꢃ2, 128.8, 129.0, 129.9 (d, Jcp¼2.4 Hz),
130.1 (d, Jcp¼2.1 Hz), 131.1, 132.0 (d, Jcp¼40.6 Hz), 133.6 (d,
Jcp¼41.7 Hz), 134.3ꢃ2 (d, Jcp¼2.1 Hz), 134.4 (d, Jcp¼8.4 Hz), 137.3 (d,
Jcp¼10.7 Hz), 138.5 (d, Jcp¼56.3 Hz), 140.7 (d, Jcp¼6.0 Hz), 147.9,
149.9 (d, Jcp¼2.1 Hz), 151.9 (d, Jcp¼7.2 Hz); 31P NMR (121 MHz,
4.17. Preparation of palladium complex ( )-6
To a solution of PdCl2(MeCN)2 (18.1 mg, 0.05 mmol) in a CHCl3
(4.0 mL) was added (ꢁ)-1c (19.7 mg, 0.05 mmol) at room temper-
ature and stirred for 24 h. The reaction mixture was filtered and
evaporated under reduced pressure. The residue was purified by
recrystallization from hexaneeCHCl3 to afford palladium complex
(ꢁ)-6: 25.4 mg, 0.044 mmol, 88%; mp 174e176 ꢀC; 1H NMR
CDCl3) d 39.2; HRMS (ESI-orbitrap) m/z calcd for C38H44N2ClPPdeCl
665.2271, found 665.2272; X-ray diffraction analysis data: Yellow
Prismatic crystals from hexaneeCHCl3, hexagonal space group P65,
ꢀ
ꢀ
ꢀ
a¼13.1253(4) A, b¼13.1253(4) A, c¼33.8217(11) A,
a
¼90ꢀ,
b
¼90ꢀ,
3
ꢀ
g
¼120ꢀ, V¼5046.0(3) A , Z¼6,
r
¼1.385 g/cm3,
m
(MoK
a
)¼
0.708 mmꢂ1. The structure was solved by the direct method of full-
matrix leastesquares, where the final R and Rw were 0.0225 and
0.0540 for 6828 reflections.
(300 MHz, CDCl3)
(d, J¼8.3 Hz, 1H), 7.93e7.97 (m, 1H), 8.18 (dd, J¼4.9 and 12.0 Hz,
2H), 8.49e8.52 (m, 1H); 13C NMR (75 MHz, CDCl3)
d 1.65 (s, 9H), 4.64 (s, 3H), 7.21e7.67 (m,11H), 7.83
d
31.8, 51.2ꢃ3,
71.3, 125.9 (d, Jcp¼58.6 Hz), 127.0, 127.7, 128.2, 128.4 (d, Jcp¼3.0 Hz),
128.7, 128.8, 129.3ꢃ2 (d, Jcp¼11.5 Hz), 130.0, 130.1, 130.4 (d,
Jcp¼20.6 Hz), 131.0, 131.3 (d, Jcp¼7.3 Hz), 131.8 (d, Jcp¼3.0 Hz), 132.4
(d, Jcp¼3.0 Hz), 133.7ꢃ2 (d, Jcp¼8.9 Hz), 133.8, 133.9, 137.7, 155.1 (d,
4.15. Optical resolution of ( )-1c (Scheme 3)
HPLC resolution of (ꢁ)-1c (20.0 mg, 0.050 mmol) dissolved in
hexane (4 mL) was carried out by successive injections of 1 mL on
Jcp¼14.3 Hz); 31P NMR (121 MHz, CDCl3)
d 37.6; HRMS (ESI-orbi-
trap) m/z calcd for C27H28NCl2PPdeCl 538.0677, found 538.0679; X-
a CHIRALCELÒ OJ (1.0
working at a flow rate of 0.5 mL/min and with UV monitoring at
254 nm. Enantiomerically pure (S)-(þ)-1c and (R)-(ꢂ)-1c were,
respectively, obtained by evaporation of fractions.
f
ꢃ25 cm). A hexane was used as the eluent
ray diffraction analysis data: Yellow Prismatic crystals from hex-
ꢀ
aneeCHCl3, Triclinic space group P-1, a¼9.1121(4) A,
ꢀ
ꢀ
b¼11.5775(5) A, c¼17.0169(7) A,
a
¼81.1510(10)ꢀ,
b
¼89.4900(10)ꢀ,
3
¼70.9870(10)ꢀ, V¼1675.43(12) A , Z¼2,
r
¼1.613 Mg/m3,
m
ꢀ
(aS)-(þ)-1c: 10.0 mg, 0.025 mmol, 50%, >99% ee; mp
g
133e135 ꢀC; [
a
]
20 þ245.2 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
(MoK
a
)¼10.958 mmꢂ1. The structure was solved by the direct
D
d
1.35 (s, 9H), 2.52 (s, 3H), 7.03 (dd, J¼8.5 and 2.5 Hz, 1H), 7.25e7.33
method of full-matrix leastesquares, where the final R and Rw were
0.0604 and 0.1670 for 25,498 reflections.
(m, 10H), 7.42e7.49 (m, 2H), 7.57 (d, J¼8.5 Hz, 1H), 7.79e7.83 (m,
1H), 8.07e8.10 (m, 1H); 13C NMR (75 MHz, CDCl3)
d
28.8ꢃ3 (d,
Jcp¼6.3 Hz), 36.0 (d, Jcp¼3.3 Hz), 56.0, 125.4, 125.9, 125.98, 126.01,
126.1, 127.9, 128.2 (d, Jcp¼7.3 Hz), 128.37ꢃ2 (d, Jcp¼1.5 Hz),
128.42ꢃ2 (d, Jcp¼1.0 Hz), 130.2, 133.5ꢃ2 (d, Jcp¼19.8 Hz), 134.3ꢃ2
(d, Jcp¼21.3 Hz), 134.9 (d, Jcp¼2.5 Hz), 135.4, 138.6 (d, Jcp¼13.9 Hz),
139.4 (d, Jcp¼16.3 Hz), 139.7 (d, Jcp¼3.3 Hz), 152.4 (d, Jcp¼24.0 Hz);
4.18. General procedure for the palladium-catalyzed allylic
alkylation
To a mixture of [Pd(
aminophosphine ligand 1 (8.0
h
3-C3H5)Cl]2 (1.47 mg, 4.0
mol), and LiOAc (1.3 mg, 20
m
mol), chiral
mol)
m
m
31P NMR (121 MHz, CDCl3)
d
ꢂ12.2; EI-MS m/z (rel intensity) 397
in a solvent (0.4 mL) was added BSA (0.15 mL, 0.60 mmol) and ra-
cemic allylic ester 7 (0.20 mmol) at room temperature under an Ar
atmosphere. After 10 min, malonate 8 (0.6 mmol) was added at 0 or
ꢂ10 ꢀC. After 24 or 48 h, the reaction mixture was diluted with
ether and water. The organic layer was washed with brine and dried
over MgSO4. The filtrate was concentrated with a rotary evaporator
and the residue was purified by column chromatography.
(Mþ, 43); HRMS (ESI-orbitrap) m/z calcd for C27H28NPþH 398.2032,
found 398.2026; HPLC (Daicel CHIRALCELÒ OJ 0.46
fꢃ25ꢃ2, UV
254 nm), hexaneeEtOH¼95:5, 0.5 mL/min: tR¼17.1 min (minor)
and 24.8 min (major).
(aR)-(ꢂ)-1c: 9.7 mg, 0.025 mmol, 49%, >99% ee; mp 109e110 ꢀC;
[
a]
20 ꢂ242.2 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
d 1.35 (s, 9H),
D
2.51 (s, 3H), 7.03 (dd, J¼8.4 and 2.6 Hz, 1H), 7.24e7.33 (m, 10H),
7.42e7.48 (m, 2H), 7.57 (d, J¼8.5 Hz, 1H), 7.79e7.83 (m, 1H),
4.18.1. (S)-9a (Table 1, entry 5).13 62.0 mg, 0.191 mmol, 96%, 90.2%
20
8.07e8.10 (m, 1H); 13C NMR (75 MHz, CDCl3)
d
28.8ꢃ3 (d,
ee; [
a]
ꢂ19.3 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
d 3.52 (s,
D
Jcp¼6.3 Hz), 36.0 (d, Jcp¼3.3 Hz), 56.0, 125.4, 125.9, 125.98, 126.01,
126.1, 127.9, 128.2 (d, Jcp¼7.3 Hz), 128.37ꢃ2 (d, Jcp¼1.5 Hz),
128.42ꢃ2 (d, Jcp¼1.0 Hz), 130.2, 133.5ꢃ2 (d, Jcp¼19.8 Hz), 134.3ꢃ2
(d, Jcp¼21.3 Hz), 134.9 (d, Jcp¼2.5 Hz), 135.4, 138.6 (d, Jcp¼13.9 Hz),
139.4 (d, Jcp¼16.3 Hz), 139.7 (d, Jcp¼3.3 Hz), 152.4 (d, Jcp¼24.0 Hz);
3H), 3.71 (s, 3H), 3.96 (d, J¼10.9 Hz,1H), 4.27 (dd, J¼8.5 and 10.9 Hz,
1H), 6.33 (dd, J¼8.5 and 15.7 Hz, 1H), 6.48 (d, J¼15.8 Hz, 1H),
7.20e7.33 (m,10H); 13C NMR (75 MHz, CDCl3)
d 49.1, 52.4, 52.6, 57.6,
126.4, 127.1, 127.5, 127.8, 128.4, 128.7, 129.0, 131.8, 136.8, 140.1, 167.8,
168.2; EI-MS m/z (rel intensity) 324 (Mþ, 18); HPLC (Daicel
31P NMR (121 MHz, CDCl3)
d
ꢂ12.2; EI-MS m/z (rel intensity) 397
CHIRALPAKÒ AD-H, 0.46
f
ꢃ25 cm, UV 254 nm), hexanee2-
(Mþ, 30); HRMS (ESI-orbitrap) m/z calcd for C27H28NPþH 398.2032,
propanol¼90:10, 0.5 mL/min: tR¼31.2 min (minor) and 35.3 min
found 398.2025; HPLC (Daicel CHIRALCELÒ OJ 0.46
fꢃ25ꢃ2, UV
(major).
254 nm), hexaneeEtOH¼95:5, 0.5 mL/min: tR¼12.4 min (major)
and 17.8 min (minor); X-ray diffraction analysis data: Colorless
Plate crystals from hexaneeCHCl3, orthorhombic space group
4.18.2. (S)-9b (Table 1, entry 12).13 62.8 mg, 0.178 mmol, 89%, 95%
ee; [
a
]
20 ꢂ19.2 (c 0.51, CHCl3); 1H NMR (300 MHz, CDCl3)
d 1.01 (t,
D
ꢀ
ꢀ
ꢀ
P212121, a¼10.5342(6) A, b¼11.9064(7) A, c¼17.7165(9) A,
a
¼90ꢀ,
J¼7.1 Hz, 3H), 1.21 (t, J¼7.1 Hz, 3H), 3.90e4.02 (m, 3H), 4.17 (q,
3
ꢀ
¼1.188 Mg/m3,
m
(CuK
a
)¼
J¼7.2 Hz, 2H), 4.26 (dd, J¼8.4 and 11.0 Hz, 1H), 6.33 (dd, J¼8.4 and
ꢀ
b
¼90ꢀ,
g
¼90 , V¼2222.1(2) A , Z¼4,
r

T. Mino et al. / Tetrahedron 71 (2015) 5985e5993
5993
15.7 Hz, 1H), 6.48 (d, J¼15.8 Hz, 1H), 7.17e7.32 (m, 10H); 13C NMR
129.3, 129.4, 130.9, 133.0, 133.3, 135.0, 138.6, 167.1, 167.5; EI-MS m/z
(75 MHz, CDCl3)
d
13.8, 14.2, 49.2, 57.7, 61.3, 61.6, 126.3, 127.1, 127.5,
(rel intensity) 422 (Mþ, 29); HPLC (Daicel CHIRALPAKÒ IA, 0.46
128.0, 128.4, 128.6, 129.3, 131.6, 136.8, 140.3, 167.4, 167.8; EI-MS m/z
f
ꢃ25 cm, UV 254 nm), hexanee2-propanol¼85:15, 1.0 mL/min:
(rel intensity) 352 (Mþ, 20); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46
tR¼6.2 min (minor) and 7.5 min (major).
fꢃ25 cm, UV 254 nm), hexanee2-propanol¼85:15, 1.0 mL/min:
tR¼8.0 min (minor) and 10.1 min (major).
Acknowledgements
4.18.3. (S)-9c (Table 1, entry 13).13 74.6 mg, 0.157 mmol, 78%, 92%
This work was supported by a Grant-in-Aid for Scientific Re-
search (C) (No. 26410109) from Japan Society for the Promotion of
Science (JSPS) and the COE Program in Chiba University.
20
ee; mp 53e55 ꢀC; [
a]
ꢂ6.7 (c 0.5, CHCl3); 1H NMR (300 MHz,
D
CDCl3)
d
4.04 (d, J¼10.9 Hz, 1H), 4.30 (dd, J¼8.2 and 10.9 Hz, 1H),
4.93 (dd, J¼12.3 and 14.2 Hz, 2H), 5.10 (dd, J¼12.2 and 14.0 Hz, 2H),
6.30 (dd, J¼8.2 and 15.8 Hz, 1H), 6.42 (d, J¼15.8 Hz, 1H), 7.03e7.06
Supplementary data
(m, 2H), 7.17e7.34 (m, 18H); 13C NMR (75 MHz, CDCl3)
d 49.2, 57.8,
67.1ꢃ2, 67.3ꢃ2,126.4ꢃ2,127.1, 127.5,127.9ꢃ2,128.1ꢃ2,128.2,128.3,
128.36, 128.40ꢃ3, 128.5, 128.7ꢃ2, 129.0, 131.9ꢃ2, 135.07, 135.10,
136.7, 140.1, 167.1, 167.5; HRMS (ESI-orbitrap) m/z calcd for
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.01.027.
C
32H28O4þNa 499.1880, found 499.1873; HPLC (Daicel CHIRALPAKÒ
References and notes
AD-H, 0.46
f
ꢃ25 cm, UV 254 nm), hexanee2-propanol¼85:15,
1.0 mL/min: tR¼18.9 min (minor) and 23.0 min (major).
1. Reviews: (a) Rosini, C.; Eranzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992,
503e517; (b) Hayashi, T. Catal. Today 2000, 62, 3e15; (c) Kumobayashi, H.;
Miura, T.; Sayo, N.; Saito, N.; Zhang, X. Synlett 2001, 1055e1064 SI; (d) Berthod,
M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem. Rev. 2005, 105, 1801e1836;
(e) Canac, Y.; Chauvin, R. Eur. J. Org. Chem. 2010, 2325e2335.
2. Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.;
Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629e635.
3. Clayden, J.; Johnson, P.; Pink, J. H.; Helliwell, M. J. Org. Chem. 2000, 65,
7033e7040.
4. (a) Kamikawa, K.; Kinoshita, S.; Matsuzaka, H.; Uemura, M. Org. Lett. 2006, 8,
1097e1100; (b) Kamikawa, K.; Kinoshita, S.; Furusyo, M.; Takemoto, S.; Mat-
suzaka, H.; Uemura, M. J. Org. Chem. 2007, 72, 3394e3402; (c) Ototake, N.;
Morimoto, Y.; Mokuya, A.; Fukaya, H.; Shida, Y.; Kitagawa, O. Chem.dEur. J.
2010, 16, 6752e6755.
5. (a) Mino, T.; Tanaka, Y.; Hattori, Y.; Yabusaki, T.; Saotome, H.; Sakamoto, M.;
Fujita, T. J. Org. Chem. 2006, 71, 7346e7353; (b) Mino, T.; Wakui, K.; Oishi, S.;
Hattori, Y.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2008, 19,
2711e2716.
6. (a) Mino, T.; Komatsu, S.; Wakui, K.; Yamada, H.; Saotome, H.; Sakamoto, M.;
Fujita, T. Tetrahedron: Asymmetry 2010, 21, 711e718; (b) Mino, T.; Ishikawa, M.;
Nishikawa, K.; Wakui, K.; Sakamoto, M. Tetrahedron: Asymmetry 2013, 24,
499e504.
4.18.4. (S)-9d (Table 1, entry 14).13 62.9 mg, 0.154 mmol, 77%, 88%
20
ee; mp 63e65 ꢀC; [
a
]
ꢂ8.7 (c 0.5, CHCl3); 1H NMR (300 MHz,
D
CDCl3)
d
1.22 (s, 9H), 1.42 (s, 9H), 3.73 (d, J¼10.9 Hz, 1H), 4.16 (dd,
J¼8.1 and 11.0 Hz, 1H), 6.33 (dd, J¼8.1 and 15.8 Hz, 1H), 6.45 (d,
J¼15.8 Hz, 1H), 7.18e7.32 (m, 10H); 13C NMR (75 MHz, CDCl3)
d 27.6,
27.9, 49.0, 59.3, 81.5, 81.8, 126.3, 126.8, 127.3, 128.2, 128.4, 128.5,
130.1, 131.2, 137.0, 140.8, 166.7, 167.2; HRMS (ESI-orbitrap) m/z calcd
for
C
26H32O4þNa 431.2193, found 431.2182; HPLC (Daicel
CHIRALPAKÒ AD-H, 0.46
f
ꢃ25 cm, UV 254 nm), hexanee2-
propanol¼97:3, 0.3 mL/min: tR¼35.5 min (minor) and 51.4 min
(major).
4.18.5. (S)-9e (Table 1, entry 15).13 64.2 mg, 0.175 mmol, 88%, 93%
20
ee; [
a]
þ32.7 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
d 1.16 (t,
D
J¼7.1 Hz, 3H), 1.23 (t, J¼7.1 Hz, 3H), 1.47 (s, 3H), 4.08 (q, J¼7.1 Hz,
2H), 4.17 (dq, J¼1.3 and 7.1 Hz, 2H), 4.29 (d, J¼8.9 Hz, 1H), 6.44 (d,
J¼15.7 Hz, 1H), 6.70 (dd, J¼8.9 and 15.7 Hz, 1H), 7.17e7.35 (m, 10H);
7. Mino, T.; Yamada, H.; Komatsu, S.; Kasai, M.; Sakamoto, M.; Fujita, T. Eur. J. Org.
Chem. 2011, 4540e4542.
8. Mino, T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2001, 12,
2435e2440.
9. Mino, T.; Tanaka, Y.; Akita, K.; Anada, K.; Sakamoto, M.; Fujita, T. Tetrahedron:
Asymmetry 2001, 12, 1677e1682.
10. Kim, D. H.; Im, J. K.; Kim, D. W.; Lee, H.; Kim, H.; Kim, H. S.; Cheong, M.; Mu-
kherjee, D. K. Transit. Met. Chem. 2010, 35, 949e957.
13C NMR (75 MHz, CDCl3)
d 13.9, 14.0, 18.8, 53.7, 58.8, 61.3, 126.3,
127.1, 127.3, 128.2, 128.4, 128.8, 129.6, 132.6, 137.3, 139.4, 170.9,
171.2; EI-MS m/z (rel intensity) 366 (Mþ, 5); HPLC (Daicel
CHIRALPAKÒ AD-H, 0.46
f
ꢃ25 cm, UV 254 nm), hexanee2-
propanol¼199:1, 0.3 mL/min: tR¼44.2 min (minor) and 52.6 min
11. (a) Eyring, H. Chem. Rev. 1935, 17, 65e77; (b) Cagle, F. W., Jr.; Eyring, H. J. Am.
Chem. Soc. 1951, 73, 5628e5630; (c) Cooke, A. S.; Harris, M. M. J. Chem. Soc. C
1967, 988e992.
(major).
4.18.6. (S)-9f (Table 1, entry 17).14 67.6 mg, 0.160 mmol, 64%, 84%
12. (a) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1e14; (b) Trost, B. M.; Crawley, M. L.
Chem. Rev. 2003, 103, 2921e2943 Graening, T.; Schmalz, H.-G. Angew. Chem., Int.
Ed. 2003, 42, 2580e2584; (c) Trost, B. M. J. Org. Chem. 2004, 69, 5813e5837; (d)
Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258e297; (e) Guerrero Rios, I.;
Rosas-Hernandez, A.; Martin, E. Molecules 2011, 16, 970e1010.
13. Tanaka, Y.; Mino, T.; Akita, K.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2004, 69,
6679e6687.
20
ee; mp 78e80 ꢀC; [
a
]
ꢂ3.0 (c 0.5, CHCl3); 1H NMR (300 MHz,
D
CDCl3)
d
1.05 (t, J¼7.1 Hz, 3H), 1.20 (t, J¼7.1 Hz, 3H), 3.86 (d,
J¼10.9 Hz, 1H), 4.00 (dq, J¼1.3 and 7.1 Hz, 2H), 4.2 (m, 3H), 6.27 (dd,
J¼9.0 and 15.0 Hz, 1H), 6.41 (d, J¼15.0 Hz, 1H), 7.3 (m, 8H); 13C NMR
(75 MHz, CDCl3)
d
13.8, 14.1,48.4, 57.5,61.6, 61.7, 127.5, 128.7, 128.9,
14. Jin, Y.; Du, D.-M. Tetrahedron 2012, 68, 3633e3640.