An N-linked bidentate phosphoramidite ligand (N-Me-BIPAM) for rhodium-catalyzed asymmetric 1,4-Addition of arylboronic acids to α,β-unsaturated ketones

Article abstract of DOI:10.3390/molecules18010014

A new bidentate phosphoramidite (N-Me-BIPAM) based on Shibasaki's N-linked BINOL was synthesized. This ligand appears to be highly effective for rhodium-catalyzed asymmetric conjugated addition of arylboronic acids to α,β-unsaturated enones. The reaction

Full text of DOI:10.3390/molecules18010014

Molecules 2013, 18, 14-26; doi:10.3390/molecules18010014
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
An N-Linked Bidentate Phosphoramidite Ligand (N-Me-BIPAM)
for Rhodium-Catalyzed Asymmetric 1,4-Addition of
Arylboronic Acids to α,β-Unsaturated Ketones
Yasunori Yamamoto *, Kazunori Kurihara, Yoshinori Takahashi and Norio Miyaura
Frontier Chemistry Center, Faculty of Engineering, Hokkaido University, Sapporo 060-8628, Japan
* Author to whom correspondence should be addressed; E-Mail: yasuyama@eng.hokudai.ac.jp;
Tel./Fax: +81-11-706-6560.
Received: 30 November 2012; in revised form: 14 December 2012 / Accepted: 17 December 2012 /
Published: 20 December 2012
Abstract: A new bidentate phosphoramidite (N-Me-BIPAM) based on Shibasaki’s N-linked
BINOL was synthesized. This ligand appears to be highly effective for rhodium-catalyzed
asymmetric conjugated addition of arylboronic acids to α,β-unsaturated enones. The
reaction of ortho-substituted arylboronic acid with acyclic and cyclic enones provides the
corresponding products in good yields and enantioselectivities.
Keywords: asymmetric conjugate addition; rhodium catalyst; bidentate phosphoramidite ligand
1. Introduction
Metal-catalyzed conjugated addition reactions of carbon nucleophiles to α,β-unsaturated compounds
are the most widely used reactions for asymmetric carbon-carbon bond formation [1–3]. Much interest
has recently been shown in rhodium-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated
carbonyl compounds [1–8] using various ligands [9–21] such as biaryl bisphosphines [4–8],
phosphoramidites [22–28], diphosphonite [29], amidomonophosphines [30,31], N-heterocyclic
carbenes [32,33], P-chiral phosphine [34], and dienes [35–43]. Although many chiral ligands give
adducts with good selectivity for cyclic enones, there are few ligands that give good results for both
acyclic and cyclic enones. In addition, though conjugate addition of ortho-substituted arylboronic acids
to α,β-unsaturated cyclic enones has been achieved in high enantioselectivities [9–21,44–50], there
have been few reports on this reaction for acyclic enones [38,51,52]. On the other hand, we have
already reported that a new bidentate phosphoramidite ligand (Me-BIPAM) based on O-linked-BINOL

Molecules 2013, 18
15
was synthesized and that a rhodium/Me-BIPAM complex was a better catalyst than several monodentate
phosphoramidites for conjugate addition of arylboronic acids to α,β-unsaturated cyclic and acyclic
carbonyl compounds [53,54]. However, we were not satisfied with the enantioselectivities for acyclic
enones such as (E)-3-nonene-2-one using Me-BIPAM. Therefore, we reported that the bidentate
phosphoramidite N-Me-BIPAM, which was newly synthesized on the basis of N-linked-BINOL [55],
was highly efficient for rhodium-catalyzed asymmetric arylation of N-sulfonyl aldimine with arylboronic
acids [56].
Herein we report that rhodium/N-Me-BIPAM catalyzed 1,4-addition of arylboronic acids to
α,β-unsaturated enones. N-Me-BIPAM was found to be highly effective for rhodium-catalyzed conjugate
addition of arylboronic acids to α,β-unsaturated acyclic and cyclic enones. Furthermore, the use of
N-Me-BIPAM was necessary to achieve high enantioselectivity for the reaction of ortho-substituted
arylboronic acids to acyclic and cyclic enones.
2. Results and Discussion
N-linked bidentate phosphoramidite was easily synthesized from Shibasaki’s N-linked BINOL and
31
P(NMe2)3 in good yield (Scheme 1). P-NMR of the mixture of Rh(acac)(C2H4)2 and N-Me-BIPAM
exhibited a single signal at 160.0 ppm (d, JRh-P = 292.3 Hz), suggesting the intramolecular complexation
of two phosphorous atoms to a rhodium metal center. The formation of a 1:1 complex was also
confirmed by mass spectroscopy (ESI), which showed a molecular weight of 976.2152 (M+H).
Scheme 1. Synthesis of bisphosphoramidite (N-Me-BIPAM).
N
P(NMe2)3
N
OH HO
OH HO
toluene
O
P
NMe2
O
P
30°C, 2 days
O
O
73%
Me2N
N-Me-BIPAM (2)
N-Linked BINOL (1)
The efficiency of N-Me-BIPAM was investigated in rhodium-catalyzed conjugate addition of
arylboronic acids to enones. We first examined the addition of phenylboronic acid to (E)-3-nonene-2-one
in an aqueous solvent (Table 1). Preparation of the rhodium catalyst from [Rh(coe)2Cl]2, N-Me-BIPAM
and a base in 1,4-dioxane or in DME resulted in low selectivity (entries 1–5). Among the representative
inorganic bases employed, K2CO3 was found to be the best, giving 87% ee (entry 4). However, the use
of triethylamine for a combination of [Rh(nbd)2]BF4 and N-Me-BIPAM resulted in a quantitative yield
with 92% ee (entry 7).
Table 1. Optimization of the reaction conditions.
[Rh] (3 mol%)
O
N-Me-BIPAM (3.3 mol%)
O
+
B(OH)2
n-C5H11
Base (1 eq), solvenet/H2O (10/1)
25°C, 16h
n-C5H11
3
4
5
1.5 eq

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Table 1. Cont.
Entry
[Rh]
Solvent
dioxane
DME
Base
Yield (%) a
ee (%) b
1
2
3
4
5
6
7
[Rh(coe)2Cl]2
[Rh(coe)2Cl]2
[Rh(coe)2Cl]2
[Rh(coe)2Cl]2
[Rh(coe)2Cl]2
[Rh(nbd)2]BF4
[Rh(nbd)2]BF4
KOH
KOH
K3PO4
K2CO3
NEt3
96
99
78
81
73
87
-
DME
59
DME
94
DME
trace
57
DME
K2CO3
87
92
DME
NEt3
99
a Isolated yield; b Determined by HPLC.
With these optimized conditions, 1,4-addition of arylboronic acids to representative α,β-unsaturated
acyclic and cyclic enones was carried out in the presence of a [Rh(nbd)2]BF4/N-Me-BIPAM catalyst
(Table 2). N-Me-BIPAM achieved high enantioselectivities in the range of 92–95% ee for
(E)-3-nonen-2-one (entries 1–3). The selectivities were in the range of 82–90% ee for (E)-5-methyl-3-
hexen-2-one (entries 4–6). However, this ligand was not effective for substrates having a phenyl group
at the carbonyl carbon or the β-carbon due to steric hindrance of the aryl ring (entries 7 and 8).
Table 2. Asymmetric conjugated addition of arylboronic acids to α,β-unsaturated enones.
[Rh(nbd)2]BF4 (3 mol%)
FG
FG
O
N-Me-BIPAM (3.3 mol%)
+
O
R1
R2
B(OH)2
NEt3 (1 eq), DME / H2O (10/1)
Temp., 16h
R1
13-22
R2
6: R1 = i-Pr, R2 = Me
7: R1 = Me, R2 = Ph
8: R1 = Ph, R2 = Me
9: R1 = cyclohexyl, R2 = Me
10: 2-cyclohexenone
11: FG = MeO
12: FG = F
Entry
Enones
FG Temp. (°C) Product Yield (%) a ee (%) b
1
2 c
3
(E)-C5H11CH=CHCOCH3
(E)-C5H11CH=CHCOCH3
(E)-C5H11CH=CHCOCH3
(E)-(CH3)2CHCH=CHCOCH3
H
MeO
F
25
25
50
50
25
50
50
50
50
50
13
14
15
16
17
18
19
20
21
22
99
96
83
83
60
42
87
99
94
99
92 (S)
94 (S)
95 (+)
87 (R)
90 (R)
82 (+)
77 (+)
77 (+)
88 (+)
99 (R)
4
H
5
(E)-(CH3)2CHCH=CHCOCH3 MeO
6
(E)-(CH3)2CHCH=CHCOCH3
(E)-CH3CH=CHCOPh
F
7
MeO
MeO
8
(E)-PhCH=CHCOCH3
9 c
(E)-cyclo-C6H11CH=CHCOCH3 MeO
10 c
2-Cyclohexenone
H
a Isolated yield; b Determined by HPLC; c Used [Rh(coe)2Cl]2, KOH and dioxane/H2O instead of optimized condition.
The steric hindrance of an ortho-substituent on the arylboronic acids slows down the reaction rate
significantly and decreases the enantioselectivity. It was interesting that N-Me-BIPAM exhibited good
performance for such boronic acids. The results of 1,4-addition of 2-tolylboronic acid to (E)-3-nonen-2-one

Molecules 2013, 18
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are shown in Scheme 2. The use of neutral [Rh(coe)2Cl]2 and K2CO3 for N-Me-BIPAM resulted in a
quantitative yield and the best selectivity (94% ee).
Scheme 2. Asymmetric 1,4-addition of 2-tolylboronic acids to 3-nonene-2-one.
Rh cat. (3 mol%)
O
N-Me-BIPAM (3.3 mol%)
Base (1 eq), DME/H2O (10/1)
25°C, 16h
+
O
n-C5H11
B(OH)2
n-C5H11
3
23
1.5 eq
24
[Rh(nbd)2]BF4, NEt3, 99%, 87%ee (S); [Rh(coe)2Cl]2, KOH, 88%, 89%ee (S); [Rh(coe)2Cl]2, K2CO3, 99%,
94%ee (S).
Table 3 shows the results of 1,4-addition of arylboronic acids possessing a methyl, fluoro or
methoxy group at the ortho-carbon or 1-naphthylboronic acid to the representative acyclic and cyclic
enones. The use of a series of arylboronic acids for (E)-3-nonen-2-one showed enantioselectivities
decreasing in the order of F > Me > 1-naphthyl > MeO (entries 1–5). On the other hand, the effect of
substituents was F > MeO > 1-naphthyl > Me for (E)-CH3CH=CHCOPh (entries 6–9). Thus, the
selectivities were greatly dependent on the bulkiness and electronic property of substituted arylboronic
acids and enone substrates. Among them, 1,4-addition of ortho-tolylboronic acid to (E)-3-nonen-2-one
resulted in 92% yield and 97% ee with 0.1 mol% catalyst loading (entry 2). When benzylideneacetone
which have the bulky substitution on the β-position was used as a substrate, the product was obtained
in good enantioselectivity, but reactivity was lower (entry 10). There was no difficulty in achieving
high enantioselectivities for 5- and 6- and 7-membered enones at room temperature (entries 11–16).
Most of the reactions resulted in more than 94% ee for these cyclic substrates.
The good performance of N-Me-BIPAM for ortho-substituted arylboronic acids was applied to the
synthesis of optically active 4-alkyl-4H-chromenes (Scheme 3). Under conditions optimized in Scheme 3
using K2CO3 as the base, 1,4-addition of 2-hydroxyphenylboronic acid resulted in very low yield due
to hydrolytic B-C bond cleavage with water. However, the use of 3 equivalents of boronic acid and
KHCO3 at 80 °C afforded an 1,4-adduct in quantitative yield. The 1,4-adduct thus obtained was a 1:1
mixture of ketone and hemiacetal. It was then treated with TsOH·H2O and MS 4A in toluene at 100 °C [57]
to give optically active 2-methyl-4-pentyl-4H-chromene in 78% yield with 98% ee [58].
Table 3. Asymmetric conjugated addition of o-substituted arylboronic acids to α,β-unsaturated enones.
[Rh(coe)2Cl]2 (3 mol%)
FG
O
N-Me-BIPAM (3.3 mol%)
+
FG
O
R1
R2
K2CO3 (1 eq), DME/H2O (10/1)
Temp., 16h
B(OH)2
1.5 eq
R1
24, 30-43
R2
25: 2-cyclopentenone
26: 2-cycloheptenone
27: FG = MeO
28: FG = F
29: FG = 1-naphthyl

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Table 3. Cont.
Entry
Enones
FG
Me
Me
MeO
F
Temp. (°C) Product Yield (%) a ee (%) b
1
2
(E)-n-C5H11CH=CHCOCH3
(E)-n-C5H11CH=CHCOCH3
(E)-n-C5H11CH=CHCOCH3
(E)-n-C5H11CH=CHCOCH3
25
50
50
50
80
50
50
50
50
50
25
25
25
25
25
25
24
24
30
31
32
33
34
35
36
37
38
39
40
41
42
43
99
92
86
90
77
80
88
86
87
49
90
67
32
77
94
92
94 (S)
97 c (S)
80 (+)
99 (+)
86 (+)
81 (−)
92 (+)
99 (−)
83 (−)
90 (R)
97 (R)
94 (R)
97 (R)
99 (R)
87 (R)
97 (R)
3
4
5
(E)-n-C5H11CH=CHCOCH3 1-naphtyl
6
(E)-CH3CH=CHCOPh
(E)-CH3CH=CHCOPh
(E)-CH3CH=CHCOPh
(E)-CH3CH=CHCOPh
(E)-PhCH=CHCOCH3
2-Cyclopentenone
Me
MeO
F
7
8
9
1-naphtyl
Me
10
11
12
13
14
15
16
Me
2-Cyclopentenone
MeO
F
2-Cyclopentenone
2-Cyclopentenone
1-naphtyl
Me
2-Cyclopentenone
2-Cycloheptenone
Me
a Isolated yield; b Determined by HPLC; c Used 0.1 mol% of rhodium catalyst.
Scheme 3. Synthesis of 2-methyl-4-pentyl-4H-chromene.
[Rh(coe)2Cl]2 (3 mol%)
O
HO
O
OH
O
N-Me-BIPAM (3.3 mol%)
OH
+
KHCO3 (1 eq)
DME/H2O (10/1)
80°C, 16h
B(OH)2
3
44
45
46
99% (1 : 1)
3 eq
TsOH H2O
O
MS 4A, toluene
100°C, 12h
47
83%, 93%ee
Finally, a stable conformation of the [Rh(Ph)(H2O)((R,R)-N-Me-BIPAM)] intermediate generated
by transmetalation of phenylboronic acid to [Rh(OH)(H2O)((R,R)-N-Me-BIPAM)] was calculated on
the basis of a theoretical method (B3LYP/6-31G++(d)/B3LYP/LANL2DZ level). There is a completely
planar coordination space in the upper and lower left areas consisting of a phenyl group on a rhodium
atom. A naphthoxy group in the upper right area occupies a pseudo-axial position and an NMe2 group
in the lower right area occupies a pseudo-equatorial position, thus suggesting that the space is
accessible to reactants in the upper right quadrant and two quadrants in the left area. On the basis of
this calculation, a mode of coordination of an enone to the phenyl rhodium(I) intermediate is proposed
in Figure 1. The re-coordination of a substrate can be preferred without significant steric interaction
for giving the experimentally observed R enantiomer by parallel coordination of the C-O double bond
to the Ph-Rh bond for the next insertion process. On the other hand, the coordination of an enone from
its opposite si face is blocked by the equatorial NMe2 group.

Molecules 2013, 18
Figure 1. Optimized structure of [Rh(Ph)(H2O)((R,R)-N-Me-BIPAM)].
19
O
Rh
O
Ph
H
R isomer
3. Experimental
3.1. General
1H-NMR spectra were recorded on a JEOL ECX-400 (400 MHz) in CDCl3 with tetramethylsilane
as an internal standard. Chemical shifts are reported in part per million (ppm), and signal are expressed
as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), and broad (br). 13C-NMR spectra were
recorded on a JEOL ECX-400 (100 MHz) in CDCl3 (δC = 77.0) with tetramethylsilane as an internal
standard. Chemical shifts are reported in part per million (ppm). HPLC analysis was directly performed
with chiral stationary phase column, Chiralpak AD-H, IB or Chiralcel OD-H, OB-H purchased from
DAICEL Co., Ltd. (Osaka, Japan). High resolution mass spectra (HRMS) were recorded on a JEOL
JMS 700TZ mass spectrometer at the Center for Instrumental Analysis, Hokkaido University, Japan.
Optical rotations were measured on a HORIBA SEPA-300 digital polarimeter. Kanto Chemical silica
gel 60N (particle size 0.063-0.210 mm) was used for flash column chromatography.
3.2. Synthesis of N-Me-BIPAM (2)
(R,R)-3,3'-[Methyliminobis(methylene)]bis(1,1'-binaphtylene-2,2'-diol) (1, 2.4 mmol) and P(NMe2)3
(6 mmol) in dry toluene were stirred for 2 days at 30 °C under nitrogen. The crude solid obtained by
evaporation of the solvent was purified by column chromatography to give N-Me-BIPAM (2) as a
white solid (73%). [α]2D2 = −578.3 (c 0.56, CHCl3),1H-NMR (400 MHz, CD2Cl2) δ = 8.32 (s, 2H), 7.93
(q, J = 9.1 Hz, 6H), 7.36–7.41 (m, 4H), 7.18–7.29 (m, 8H), 4.09 (d, J = 15.4 Hz, 2H), 3.76 (d,
J = 15.4 Hz, 2H), 2.58 (s, 3H), 2.32 (s, 6H), 2.30 (s, 6H), 13C-NMR (CD2Cl2) δ = 149.5, 149.4, 148.6,
132.9, 131.5, 130.9, 129.8, 129.3, 128.2, 127.6, 127.3, 126.9, 126.4, 125.5, 124.8, 124.0, 122.7, 122.6,
121.1, 57.3, 44.5, 36.1, 34.8 31P-NMR (100 MHz, CD2Cl2) 149.5 HRMS (FAB) calcd for C47H42N3O4P2
(M+H) 774.2651, Found 774.2667.
3.3. General Procedure for Asymmetric 1,4-Addition
A flask charged with rhodium catalyst (0.015 mmol) and N-Me-BIPAM (0.033 mmol) was flushed
with nitrogen. Solvent (3 mL) was then added. After being stirred for 1 h at room temperature, aryl
boronic acid (1.5 mmol), enone (1 mmol), base (1 mmol) and water (0.3 mL) were added. The resulting

Molecules 2013, 18
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mixture was stirred for 16 h at 25 °C, 50 °C or 80 °C. The mixture was extracted with ethyl acetate,
washed with brine, and dried over MgSO4. After concentration, the residue was purified by column
chromatography on silica gel with hexane/ethyl acetate to give the product as a clear liquid.
The spectral data of compounds 13 [59], 14 [59], 15 [54], 16 [59], 17 [59], 18 [54], 20 [54], 21 [54],
22 [59], 24 [38], 38 [29], 39 [44], 40 [25], 41 [45], 42 [47], 43 [32] was previously reported. The
specific rotations of these compounds were (S)-13 ([α]2D3 = +15.2 (c 0.11, CHCl3)), (S)-14 [([α]D23 = +4.83
(c 0.30, CHCl3)], 15 ([α]2D3 = +12.6 (c 0.70, CHCl3)), (R)-16 [([α]2D3 = +27.4 (c 0.55, CHCl3)], (R)-17
([α]2D3 = +24.7 (c 0.33, CHCl3)), 18 ([α]2D3 = +20.1 (c 0.53, CHCl3)), 20 ([α]D23 = +1.04 (c 0.60, CHCl3)),
21 ([α]2D3 = +26.8 (c 0.41, CHCl3)), (R)-22 ([α]D23 = +17.9 (c 0.78, CHCl3)), (S)-24 ([α]2D2 = +12.2
(c 0.51, CHCl3)), (R)-38 ([α]2D3 = +39.4 (c 0.48, CHCl3)), (R)-39 ([α]2D3 = +13.8 (c 0.38, CHCl3)), (R)-40
([α]2D3 = +11.5 (c 0.31, CHCl3)), (R)-41 ([α]D23 = +8.70 (c 0.25, CHCl3)), (R)-42 ([α]2D3 = +19.4 (c 0.26,
CHCl3)), (R)-43 ([α]2D3 = +20.6 (c 0.30, CHCl3)).
3-(3-Methoxyphenyl)-1-phenylbutan-1-one (19). [α]2D4 = +0.41 (c 0.48, CHCl3), 77% ee [HPLC conditions:
Chiralcel OD-H column, hexane/ethanol = 9:1, flow = 0.5 mL/min, wavelength = 254 nm, tR = 29.4 min
and 32.8 min]; 1H-NMR (CDCl3) δ = 1.33 (d, J = 7.25 Hz, 3H), 3.18 (dd, J = 8.2, 16.8 Hz, 1H), 3.31
(dd, J = 5.4, 16.8 Hz, 1H), 3.45–3.54 (m, 1H), 3.79 (s, 3H), 6.74–6.76 (m, 1H), 6.84 (t, J = 1.81 Hz,
1H), 6.88 (d, J = 7.7 Hz, 1H), 7.23 (t, J = 7.7 Hz, 1H), 7.42–7.46 (m, 2H), 7.53–7.56 (m, 1H), 7.94
13
(dd, J = 1.36, 7.25 Hz, 2H); C-NMR (CDCl3) δ = 21.9, 35.7, 47.0, 55.3, 112.1, 112.2, 119.3, 127.4,
127.9, 129.0, 129.5, 130.4, 133.1, 137.2, 148.4, 159.8, 199.1; exact mass calcd for C17H18O2: 254.1307;
Found 254.1290.
4-(2-Methoxyphenyl)nonan-2-one (30). [α]2D4 = +3.13 (c 0.40, CHCl3), 80% ee [HPLC conditions: Chiralcel
OJ-H column, hexane/2-propanol = 100:1, flow = 0.3 mL/min, wavelength = 254 nm, tR = 20.5 min
and 23.0 min]; 1H-NMR (CDCl3) δ = 0.80–0.84 (m, 3H), 1.10–1.25 (m, 6H), 1.53–1.64 (m, 2H), 2.04
(s, 3H), 2.64–2.75 (m, 2H), 3.52–3.59 (m, 1H), 3.81 (s, 3H), 6.83–6.89 (m, 2H), 7.10–7.16 (m, 2H);
13C-NMR (CDCl3) δ = 13.9, 22.4, 27.0, 30.0, 31.7, 34.6, 34.8, 49.8, 55.2, 110.5, 120.5, 127.0, 127.7,
132.4, 157.1, 208.5; exact mass calcd for C15H24O2: 248.1776; Found 248.1786.
4-(2-Fluorophenyl)nonan-2-one (31). [α]2D2 = −3.32 (c 0.56, CHCl3), 99% ee [HPLC conditions:
Chiralpak IA column, hexane/2-propanol = 200:1, flow = 0.8 mL/min, wavelength = 254 nm, tR = 21.7 min
and 24.7 min]; 1H-NMR (CDCl3) δ =0.82 (d, J = 6.8 Hz, 3H), 1.08–1.32 (m, 6H), 1.57–1.62 (m, 2H),
2.05 (s, 3H), 2.76 (d, J = 7.3 Hz, 2H), 3.37–3.44 (m, 1H), 6.95–7.17 (m, 4H); 13C-NMR (CDCl3)
δ =14.1, 22.6, 27.2, 30.4, 31.7, 35.2, 49.5, 115.6, 124.2, 127.0, 128.6, 130.0, 131.2, 207.8, 161.5; exact
mass calcd for C15H21FO: 236.1576; Found 236.1576.
4-Naphthalen-1-yl-nonan-2-one (32). [α]2D2 = +18.6 (c 0.54, CHCl3), 81% ee [HPLC conditions: Chiralpak
IB column, hexane/2-propanol = 100:1, flow = 0.5 mL/min, wavelength = 254 nm, tR = 17.7 min and
18.9 min]; 1H-NMR (CDCl3) δ =0.80 (t, J = 6.7 Hz, 3H), 1.10–1.30 (m, 6H), 1.70–1.83 (m, 2H), 2.04
(s, 3H), 2.84 (d, J = 6.7 Hz, 2H), 4.02–4.17 (m, 1H), 7.35 (d, J = 7.0 Hz, 1H), 7.41–7.53 (m, 3H), 7.71
13
(d, J = 7.9 Hz, 1H), 7.85 (d, J = 7.9 Hz, 1H), 8.19 (d, J = 8.2 Hz, 1H); C-NMR (CDCl3) δ = 14.1,
22.6, 27.2, 30.7, 32.1, 36.2, 50.9, 123.3, 125.6, 126.1, 126.9, 129.1, 132.0, 134.2, 141.1, 208.1; exact
mass calcd for C19H24O: 268.1827; Found 268.1836.

Molecules 2013, 18
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1-Phenyl-3-o-tolylbutan-1-one (33). [α]2D4 = −20.1 (c 0.42, CHCl3), 81% ee [HPLC conditions: Chiralpak
IB column, hexane/2-propanol = 99.8:0.2, flow = 0.5 mL/min, wavelength = 254 nm, tR = 22.4 min
and 24.2 min]; 1H-NMR (CDCl3) δ = 1.31 (d, J = 6.8 Hz, 3H), 2.41 (s, 3H), 3.21 (dd, J = 8.2, 16.7 Hz,
1H), 3.30 (dd, J = 5.4, 16.7 Hz, 1H), 3.74–3.82 (m, 1H), 7.10–7.29 (m, 3H), 7.28 (d, J = 6.8 Hz, 1H),
13
7.46 (t, J = 7.7 Hz, 2H), 7.53–7.58 (m, 1H), 7.96 (d, J = 7.2 Hz, 2H); C-NMR (CDCl3) δ = 19.7,
21.5, 30.5, 46.4, 125.3, 125.4, 127.1, 127.9, 128.2, 129.5, 130.6, 132.3, 133.9, 135.4, 137.3, 144.9,
199.3; exact mass calcd for C17H18O: 238.1358; Found 238.1358.
3-(2-Methoxyphenyl)-1-phenylbutan-1-one (34). [α]2D2 = +6.73 (c 0.54, CHCl3), 92% ee [HPLC conditions:
Chiralpak IB column, hexane/2-propanol = 99.8:0.2, flow = 0.5 mL/min, wavelength = 254 nm,
tR = 30.4 min and 58.1 min]; 1H-NMR (CDCl3) δ = 1.32 (d, J = 6.8 Hz, 3H), 3.03–3.09 (m, 1H), 3.37
(dd, J = 4.5, 15.9 Hz, 1H), 3.80–3.90 (m, 1H), 3.82 (s, 3H), 6.86 (d, J = 8.2 Hz, 1H), 6.94 (t, J = 7.3 Hz,
1H), 7.26–7.18 (m, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.99 (d, J = 7.7 Hz, 2H);
13C-NMR (CDCl3) δ = 19.9, 29.7, 46.1, 55.4, 110.6, 120.7, 127.3, 127.5, 127.8, 128.1, 129.1, 129.4,
132.2, 133.8, 134.5, 137.3, 156.9, 199.8; exact mass calcd for C17H18O2: 254.1307 ; Found 254.1317.
3-(2-Fluorophenyl)-1-phenylbutan-1-one (35). [α]2D3 = −2.91 (c 0.53, CHCl3), 95% ee [HPLC conditions:
Chiralpak IB column, hexane/2-propanol = 99.8:2, flow = 0.5 mL/min, wavelength = 254 nm,
1
tR = 22.2 min and 24.2 min]; H-NMR (CDCl3) δ = 1.35 (d, J = 6.8 Hz, 3H), 3.21 (dd, J = 8.2, 16.8
Hz, 1H), 3.38 (dd, J = 5.9, 16.8 Hz, 1H), 3.71–3.80 (m, 1H), 6.98–7.09 (m, 2H), 7.14–7.20 (m, 1H),
7.27 (ddt, J = 1.36, 1.81, 7.7 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.54 (dd, J = 7.3, 7.7 Hz, 1H), 7.95 (dd,
J = 1.4, 7.3 Hz, 2H); 13C-NMR (CDCl3) δ = 20.7, 29.9, 45.4, 115.7, 123.5, 125.5, 127.0, 127.4, 127.9,
129.0, 129.5, 132.3, 134.0, 137.1, 160.9, 198.9; exact mass calcd for C16H15FO: 242.1107; Found
242.1119.
3-Naphthalen-1-yl-1-phenylbutan-1-one (36). [α]2D2 = −56.3 (c 0.51, CHCl3), 83% ee [HPLC conditions:
Chiralpak IB column, hexane/2-propanol = 99.8:0.2, flow = 0.5 mL/min, wavelength = 254 nm,
1
tR = 47.3 min and 63.0 min]; H-NMR (CDCl3) δ = 1.50 (d, J = 6.8 Hz, 3H), 3.32–3.45 (m, 2H),
4.39–4.48 (m, 1H), 7.44–7.59 (m, 7H), 7.75 (dd, J = 4.5, 5.0 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.98
13
(d, J = 7.7 Hz, 2H), 8.22 (d, J = 8.6 Hz, 1H); C-NMR (CDCl3) δ = 21.2, 29.7, 46.8, 122.6, 123.3,
125.2, 125.7, 126.2, 127.1, 127.4, 128.2, 128.7, 129.0, 129.9, 131.2, 132.4, 134.0, 137.3, 142.7, 199.5;
exact mass calcd for C20H18O: 274.1358; Found 274.1358.
(R)-4-Phenyl-4-o-tolylbutan-2-one (37). [α]2D4 = −66.6 (c 0.52, CHCl3), 90% ee [HPLC conditions:
Chiralcel OD-H column, hexane/ethanol = 9:1, flow = 0.5 mL/min, wavelength = 254 nm, tR = 14.8 min
and 16.8 min]; 1H-NMR (CDCl3) δ = 2.07 (s, 3H), 2.30 (s, 3H), 3.15 (d, J = 7.2 Hz, 2H), 4.78 (t, J = 7.2 Hz,
13
1H), 7.09–7.13 (m, 2H), 7.13–7.20 (m, 4H), 7.20–7.24 (m, 3H); C-NMR (CDCl3) δ = 19.8, 30.7,
41.9, 50.0, 126.0, 126.3, 126.3, 126.4, 127.9, 128.5, 130.8, 136.4, 141.5, 143.5, 206.9; exact mass
calcd for C17H18O: 238.1358; Found 238.1373.
2-Methyl-4-pentyl-4H-chromene (47). [α]2D2 = +282.1 (c 0.70, THF), 98% ee [HPLC conditions: Chiralcel
OD-H column, hexane/ethanol = 100:1, flow = 0.5 mL/min, wavelength = 254 nm, tR = 7.5 min and
8.6 min]; 1H-NMR (CD2Cl2) δ = 0.84 (t, J = 6.8 Hz, 3H), 1.17–1.33 (m, 6H), 1.51–1.59 (m, 2H), 1.87

Molecules 2013, 18
22
(s, 3H), 3.38 (d, J = 5.4 Hz, 1H), 4.70 (d, J = 4.1 Hz, 1H), 6.81–6.83 (m, 1H), 6.94–6.99 (m, 1H),
7.07–7.11 (m, 1H); 13C-NMR (CD2Cl2) δ = 13.9, 19.1, 23.9, 31.4, 33.9, 39.5, 99.9, 115.8, 122.8, 124.6,
126.9, 128.4, 147.5, 151.9; exact mass calcd for C15H20O: 216.1514; found 216.1517.
4. Conclusions
We have synthesized a new bidentate phosphoramidite, N-Me-BIPAM, based on Shibasaki’s N-linked
BINOL. This ligand was found to be an excellent ligand for both cyclic and acyclic enones. Due to its
low electron-donating property, the reactions were completed in a shorter time at room temperature
than that of traditional BINAP complexes. Furthermore, N-Me-BIPAM allowed the 1,4-addition of
ortho-substituted arylboronic acid to acyclic and cyclic enones with high enantioselectivities.
References
1. Krause, N.; Hoffmann-Röder, A. Recent advances in catalytic enantioselective Michael additions.
Synthesis 2001, 2001, 171–196.
2. Tomioka, K.; Nagaoka, Y. Conjugate Addition of Organometallic Reagents. In Comprehensive
Asymmetric Catalysis; Jacobsen, E.N., Pfalts, A., Yamamoto, H., Eds.; Springer Verlag: Berlin,
Germany, 1999; Chapter 31.1, pp. 1105–1120.
3. Chan, A.S.C.; Kwong, F.Y.; Lu, G. C-C Bond Formation through Conjugate Addition of C-M to
C=C-C=O and C=C-NO2. In Comprehensive Organometallic Chemistry III; Crabtree, R.H.,
Mingos, S.M.P., Eds.; Elsevier: Oxford, UK, 2007; Volume 10, Chapter 10.08, pp. 369–491.
4. Hayashi, T. Rhodium-catalyzed asymmetric 1,4-addition of organoboronic acids and their
derivatives to electron deficient olefins. Synlett 2001, 2001, 879–887.
5. Fagnou, K.; Lautens, M. Rhodium-catalyzed carbon-carbon bond forming reactions of
organometallic compounds. Chem. Rev. 2003, 103, 169–196.
6. Hayashi, T.; Yamazaki, K. Rhodium-catalyzed asymmetric 1,4-addition and its related
asymmetric reactions. Chem. Rev. 2003, 103, 2829–2844.
7. Tian, P.; Dong, H.-Q.; Lin, G.-Q. Rhodium-catalyzed asymmetric arylation. ACS Catal. 2012, 2,
95–119.
8. Berthon-Gelloz, G.; Hayashi, T. Rhodium-catalyzed asymmetric conjugate addition of
organoboronic acids. In Boronic Acids Preparation and Applications in Organic Synthesis,
Medicine and Materials, 2nd ed.; Hall, D.G., Ed.; Wiley-VHC: Weinheim, Germany, 2011;
Chapter 5, pp. 263–313.
9. Narui, R.; Hayashi, S.; Oromo, H.; Shintani, R.; Hayashi, T. (S)-Phenylalanine-derived chiral
phosphorus-olefin ligands in rhodium-catalyzed asymmetric 1,4-addition reactions. Tetrahedron
Asymmetry 2012, 23, 284–293.
10. Grugel, H.; Albrecht, F.; Minuth, T.; Boysen, M.M. Efficient pseudo-enantiomeric carbohydrate
olefin ligands. Org. Lett. 2012, 14, 3780–3783.
11. Jin, S.-S.; Wang, H.; Zhu, T.-S.; Xu, M.-H. Design of N-cinnamyl sulfinamides as new
sulfur-containing olefin ligands for asymmetric catalysis: Achieving structural simplicity with a
categorical linear framework. Org. Biomol. Chem. 2012, 10, 1764–1768.

Molecules 2013, 18
23
12. Xue, F.; Li, X.; Wan, B. A class of benzene backbone-base olefin-sulfoxide ligands for
Rh-catalyzed enantioselective addition of arylboronic acids to enones. J. Org. Chm. 2011, 76,
7256–7262.
13. Qi, W.-Y.; Zhu, T.-S.; Xu, M.-H. Design of chiral sulfoxide-olefins as a new class of sulfur-based
olefin ligands for asymmetric catalysis. Org. Lett. 2011, 13, 3410–3413.
14. Jin, S.-S.; Wang, H.; Xu, M.-H. Design of N-sulfinyl homoallylic amines as novel sulfinamide-
olefin hybrid ligands for asymmetric catalysis: Application in Rh-catalyzed enantioselective
1,4-additions. Chem. Commun. 2011, 47, 7230–7232.
15. Thaler, T.; Guo, L.-N.; Steibo, A.K.; Raducan, M.; Karaghiosoff, K.; Mayer, P.; Knochel, P.
Sulfoxide-alkene hybrids: A new class of chiral ligands for the Hayashi-Miyaura reaction.
Org. Lett. 2011, 13, 3182–3185.
16. Feng, X.; Wei, B.; Yang, J.; Du, H. Chiral N-tert-butanesulfinyl a,b-unsaturated ketimine:
A simple and highly effective olefin/sulfinimide hybrid ligand for asymmetric 1,4-additions.
Org. Biomol. Chem. 2011, 9, 5927–5929.
17. Chen, G.; Gui, J.; Li, L.; Liao, J. Chiral sulfoxide-olefin ligands: Completely switchable
stereoselective in rhodium-catalyzed asymmetric conjugate additions. Angew. Chem. Int. Ed. Engl.
2011, 50, 7681–7685.
18. Hahn, B.T.; Tewes, F.; Fröhlich, R.; Glorius, F. Olefin-oxazolines (OlefOx): Highly modular,
easoly tunable ligands for asymmetric catalysis. Angew. Chem. Int. Ed. Engl. 2010, 49,
1143–1146.
19. Lang, F.; Li, D.; Chen, J.; Chen, J.; Li, L.; Cun, L.; Zhu, J.; Deng, J.; Liao, J.
tert-Butanesulfinylphosphines: Simple chiral ligands in rhodium-catalyzed asymmetric addition of
arylboronic acids to electron-deficient olefins. Adv. Synth. Catal. 2010, 352, 843–846.
20. Bürgi, J.J.; Mariz, R.; Gatti, M.; Drinkel, E.; Luan, X.; Blumentritt, S.; Linden, A.; Dorta, R.
Unprecedented selectivity via electronic substrate recognition in the 1,4-addition to cyclic olefins
using a chiral disulfoxide rhodium catalyst. Angew. Chem. Int. Ed. Engl. 2009, 48, 2768–2771.
21. Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R. A chiral bis-sulfoxide ligand in
late-transition metal catalysis; rhodium-catalyzed asymmetric addition of arylboronic acids to
electron-deficient olefins. J. Am. Chem. Soc. 2008, 130, 2172–2173.
22. Iguchi, Y.; Itooka, R.; Miyaura, N. Asymmetric conjugate addition of arylboronic acids to enones
catalyzed by rhodium-monodentate phosphoramidite Complexes in the presence of vases. Synlett
2003, 2003, 1040–1042.
23. Boiteau, J.-G.; Imbos, R.; Minnerd, A.J.; Feringa, B.L. Rhodium-catalyzed asymmetric conjugate
additions of boronic acids using monodentate phosphoramidite ligands. Org. Lett. 2003, 5,
681–684.
24. Duursma, A.; Hen, J.; Schuppan, J.; Minnerd, J.; Feringa, B.L. First examples of improved
catalytic asymmetric C-C bond formation using the monodentate ligand combination approach.
Org. Lett. 2003, 5, 3111–3113.
25. Boiteau, J.-G.; Minnerd, A.J.; Feringa, B.L. High efficiency and enantioselectivity in the
Rh-catalyzed conjugate addition of arylboronic acids using monodentate phosphoramidites.
J. Org. Chem. 2003, 68, 9481–9484.

Molecules 2013, 18
24
26. Duursma, A.; Boiteau, J.-G.; Lefort, L.; Boorgers, J.A.F.; de Vries, A.H.M.; de Vries, J.G.;
Minnerd, A.J.; Feringa, B.L. Highly enantioselective conjugate additions of potassium
organotrifluoroborates to enones by use of monodentate phosphoramidite ligands. J. Org. Chem.
2004, 69, 8045–8052.
27. Martina, S.L.X.; Minnerd, A.J.; Hesssen, B.; Feringa, B.L. Highly enantioselective
rhodium-catalyzed conjugate addition of arylboronic acids to enones at room temperature.
Tetrahedron Lett. 2005, 46, 7159–7163.
28. Drinkel, E.; Brieño, A.; Dorta, R.; Dorta, R. Hemilabile P-alkene ligands in chiral rhodium and
copper complexes: Catalytic asymmetric 1,4-additions to enones 2. Organometallics 2010, 29,
2503–2514.
29. Reetz, M.T.; Moulin, D.; Gosberg, A. BINOL-based diphosphonites as ligands in the asymmetric
Rh-catalyzed conjugate addition of arylboronic acids. Org. Lett. 2001, 3, 4083–4085.
30. Kuriyama, M.; Tomioka, K. Chiral amidomonophosphine-rhodium(I) catalyst for asymmetric
1,4-addition of arylboronic acids to cycloalkenones. Tetrahedron Lett. 2001, 42, 921–923.
31. Kuriyama, M.; Nagai, K.; Yamada, K.; Miwa, Y.; Tomioka, K. Hemilabile amidomonophosphine
ligand-rhodium(I) complex-catalyzed asymmetric 1,4-addition of arylboronic acids to
cycloalkenones. J. Am. Chem. Soc. 2002, 124, 8932–8939.
32. Ma, Y.; Song, C.; Ma, C.; Sun, Z.; Chai, Q.; Andrus, M.B. asymmetric addition of aryl boron
reagents to enones with Rhodium dicyclophane imidazolium carbene catalysis. Angew. Chem. Int.
Ed. Engl. 2003, 42, 5871–5874.
33. Becht, J.-M.; Bappert, E.; Helmchen, G. Application of rhodium complexes of chiral
diphenylphosphino-functionalized N-heterocyclic carbenes as catalysts in enantioselective
conjugate additions of arylboronic acids. Adv. Synth. Catal. 2005, 347, 1495–1498.
34. Imamoto, T.; Sugita, K.; Yoshida, K. An Air-Stable P-Chiral Phosphine Ligand for Highly
enantioselective transition-metal-catalyzed reactions. J. Am. Chem. Soc. 2005, 127, 11934–11935.
35. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. A chiral chelating diene as a new type of
chiral ligand for transition metal catalysts: Its preparation and use for the rhodium-catalyzed
asymmetric 1,4-addition. J. Am. Chem. Soc. 2003, 125, 11508–11509.
36. Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. C2-symmetric
bicyclo[2.2.2]octadienes as chiral ligands: Their high performance in rhodium-catalyzed
asymmetric arylation of N-tosylarylimines. J. Am. Chem. Soc. 2004, 126, 13584–13585.
37. Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E.M. Chiral [2.2.2] dienes as ligands for Rh(I) in
conjugate additions of boronic acids to a wide range of acceptors. Org. Lett. 2004, 6, 3873–3876.
38. Otomura, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. Preparation of C2-symmetric bicyclo
[2.2.2]octa-2,5-diene ligands and their use for rhodium-catalyzed asymmetric 1,4-addition of
arylboronic acids. J. Org. Chem. 2005, 70, 2503–2508.
39. Chen, F.-X.; Kina, A.; Hayashi, T. High performance of a chiral diene-rhodium catalyst for the
asymmetric 1,4-addition of arylboroxines to α,β-unsaturated ketones. Org. Lett. 2006, 8, 341–344.
40. Feng, C.-G.; Wang, Z.-Q.; Shao, C.; Xu, M.-H.; Lin, G.-Q. Highly practical catalytic asymmetric
1,4-addition of arylboronic acids in water using new hydrophilic chiral bicyclo[3.3.0]diene
ligands. Org. Lett. 2008, 10, 4101–4104.

Molecules 2013, 18
25
41. Hu, X.; Zhuang, Z.; Cao, Z.; Du, H. Simple chiral chain dienes as ligands for Rh(I)-catalyzed
conjugated additions. Org. Lett. 2009, 11, 4744–4747.
42. Li, Q.; Dong, Z.; Yu, Z.-X. α,β-Divinyl terahydropyrroles as chiral chain diene ligands in
rhodium(I)-catalyzed enantioselective conjugated additions. Org. Lett. 2011, 13, 1122–1125.
43. Liu, C.-C.; Janmanchi, D.; Chen, C.-C.; Wu, H.L. Expanding the C1-symmetric bicylo[2.2.1]
heptadiene ligand family: Highly enantioselective synthesis of cyclic β-aryl-substituted carbonyl
compounds. Eur. J. Org. Chem. 2012, 2012, 2503–2507.
44. Shi, Q.; Xu, L.; Li, X.; Jia, X.; Wang, R.; Au-Yeung, T.T.-L.; Chan, A.S.C.; Hayashi, T.;
Cao, R.C.; Hong, M. Bipyridyl-based diphosphine as an efficient ligand in the rhodium-catalyzed
asymmetric conjugate addition of arylboronic acids to α,β-unsaturated ketones. Tetrahedron Lett.
2003, 55, 6505–6508.
45. Madec, J.; Michaud, G.; Genêt, J.-P.; Marinetti, A. New developments in the synthesis of
heterotopic atropisomeric diphosphines via diastereoselective aryl coupling reactions.
Tetrahedron: Asymmetry 2004, 15, 2253–2261.
46. Stemmler, R.T.; Bolm, C. Planar-chiral cyrhetrenes for the Rhodium-catalyzed asymmetric
1,4-addition and the hydrogenation of enamides. J. Org. Chem. 2005, 70, 9925–9931.
47. Vandyck, K.; Matthys, B.; Willen, M.; Robeyns, K.; Meervelt, L.C.; der Eychen, J.V.
Rhodium-catalyzed asymmetric conjugate additions of boronic acids to enones using
DIPHONANE: A novel chiral bisphosphine ligand. Org. Lett. 2006, 8, 363–366.
48. Duan, W.-L.; Iwamura, H.; Shintani, R.; Hayashi, T. Chiral Phosphine-Olefin Ligands in the
Rhodium-Catalyzed Asymmetric 1,4-Addition Reactions. J. Am. Chem. Soc. 2007, 129, 2130–2138.
49. Monti, C.; Gennari, C.; Piarulli, U. Rh-catalyzed enantioselective conjugate addition of
arylboronic acids with a dynamic library of chiral tropos phosphorus ligands. Chem. Eur. J. 2007,
13, 1547–1558.
50. Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R. A chiral bis-sulfoxide ligand in
late-transition metal catalysis; rhodium-catalyzed asymmetric addition of arylboronic acids to
electron-deficient olefins. J. Am. Chem. Soc. 2008, 130, 2172–2173.
51. Liao, Y.-X.; Xing, C.-H.; Israel, M.; Hu, Q.-S. Sequential aldol condensation-transition
metal-catalyzed addition reactions of aldehydes, methyl ketones, and arylboronic acids. Org. Lett.
2011, 13, 2058–2061.
52. Wei, W.-T.; Yeh, J.-Y.; Kuo, T.-S.; Wu, H.-L. Highly enantioselective rhodium-catalyzed
asymmetric 1,4-addition reactions of arylboronic acids to acyclic α,β-unsaturated compounds: The
formal synthesis of (−)-Indatraline. Chem. Eur. J. 2011, 17, 11405–11409.
53. Yamamoto, Y.; Kurihara, K.; Sugishita, N.; Oshita, K.; Piao, D.; Miyaura, N. Chiral
bis-phosphoramidites based on linked-BINOL for rhodium-catalyzed 1,4-addition of arylboronic
acids to α,β-unsaturated carbonyl compounds. Chem. Lett. 2005, 34, 1224–1225.
54. Kurihara, K.; Sugishita, N.; Oshita, K.; Piao, D.; Yamamoto, Y.; Miyaura, N. Enantioselective
1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds catalyzed by
rhodium(I)-chiral phosphoramidite complexes. J. Organomet. Chem. 2007, 692, 428–435.
55. Majima, K.; Takita, R.; Okada, A.; Oshima, T.; Shibasaki, M. Catalytic asymmetric michael
reaction of β-keto esters: Effects of the linker heteroatom in linked-BINOL. J. Am. Chem. Soc.
2003, 125, 15837–15845.

Molecules 2013, 18
26
56. Kurihra, K.; Yamamoto, Y.; Miyaura, N. An N-linked bidentate phosphoramidite ligand
(N-Me-BIPAM) for Rhodium-catalyzed asymmetric addition of arylboronic acids to
N-sulfonylarylaldimines. Adv. Synth. Catal. 2009, 351, 260–270.
57. Zacheis, D.; Dhar, A.; Lu, S.; Madler, M.M.; Klucik, J.; Brown, C.W.; Liu, S.; Clement, F.;
Subramanian, S.; Weerasekare, G.M.; et al. Heteroarotinoids inhibit head and neck cancer cell
lines in vitro and in vivo through both RAR and RXR retinoic acid receptors J. Med. Chem. 1999,
42, 4434–4445.
58. Nishikata, T.; Yamamoto, Y.; Miyaura, N. Palladium(II)-catalyzed 1,4-addition of arylboronic
acids to β-arylenones for enantioselective synthesis of 4-aryl-4H-chromenes. Adv. Synth. Catal.
2007, 349, 1759–1764.
59. Itooka, R.; Iguchi, Y.; Miyaura, N. Rhodium-catalyzed 1,4-addition of arylboronic acids to
α,β-unsaturated carbonyl compounds: Large accelerating effects of bases and ligands. J. Org.
Chem. 2003, 68, 6000–6004.
Sample Availability: Samples of the bidentate phosphoramidite are available from the authors.
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