Low-temperature Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1021/jo4014707

Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds was achieved at temperatures below 0 C using a Rh/MeO-F₁₂-BIPHEP catalyst. The reaction of cyclohexenone or N-R-maleimide with arylboronic acids proceeded even at -80 C in the presence of the Rh catalyst. In the latter case, high enantioselectivity was observed because a low-temperature method was used, regardless of the type of substituent on maleimide.

Full text of DOI:10.1021/jo4014707

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Note
Low-Temperature Rh-Catalyzed Asymmetric 1,4-Addition of
Arylboronic Acids to alpha,beta-Unsaturated Carbonyl Compounds
Toshinobu Korenaga, Aram Ko, and Kazuaki Shimada
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo4014707 • Publication Date (Web): 29 Aug 2013
Downloaded from http://pubs.acs.org on September 2, 2013
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LowꢀTemperature RhꢀCatalyzed Asymmetric 1,4ꢀAddition of Arylboronic Acids to
α,βꢀUnsaturated Carbonyl Compounds
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Toshinobu Korenaga,* Aram Ko, Kazuaki Shimada
Department of Chemistry and Bioengineering, Faculty of Engineering, Iwate University,
4ꢀ3ꢀ5 Ueda, Morioka, Iwate 020ꢀ8551, Japan
*Eꢀmail: korenaga@iwateꢀu.ac.jp.
Table of Contents/Abstract Graphic
O
O
Rh/(R)-MeO-F12-BIPHEP
> 99% ee
(0.5 mol% Rh)
Ph
PhB(OH)
+
2
O
O
with or without base
Solvent / H2O
N R
N R > 90% ee
(R=H:
0 °C ~ –80 °C
Ph
87% ee)
O
O
Abstract
Rhodiumꢀcatalyzed asymmetric 1,4ꢀaddition of arylboronic acids to α,βꢀunsaturated
carbonyl compounds was achieved at temperatures below 0 °C using a
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Rh/MeOꢀF12ꢀBIPHEP catalyst. The reaction of cyclohexenone or NꢀR maleimide with
arylboronic acids proceeded even at −80 °C in the presence of the Rh catalyst. In the
latter case, high enantioselectivity was observed because a lowꢀtemperature method was
used, regardless of the type of substituent on maleimide.
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Rhodiumꢀcatalyzed asymmetric 1,4ꢀaddition of arylboronic acids to α,βꢀunsaturated
carbonyl compounds is one of the most attractive catalytic reactions. Over 150 papers
have been reported since 1998 on this reaction,1,2 and that has been used for the
asymmetric synthesis of several bioꢀactive compounds.3 Initially, the reaction was
performed using 3 mol% of a Rh/BINAP catalyst at 100 °C.1a In 2003, a chiral diene
ligand was reported as an excellent ligand4 that made room temperature reactions
possible. Since then, the reaction at room temperature has been reported using many
rhodium catalysts ligated with chiral dienes, chiral sulfoxides, and chiral
phosphoramidites.5 On the other hand, we explored uniquely “highly electronꢀpoor
chiral diphosphine ligands”,6 and first demonstrated that they significantly accelerate
reactions with Rh catalysts at room temperature and above. Although many types of
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chiral Rh catalysts have been reported, including our catalysts, to our knowledge,
Rhꢀcatalyzed asymmetric 1,4ꢀaddition of arylboronic acid below 0 °C has not yet been
attained.7 This is quite a contrast to a Cuꢀcatalyzed asymmetric 1,4ꢀaddition of dialkyl
zinc, which was usually preformed below 0 °C.8 In general, lowꢀtemperature conditions
often improve the stereoselectivity of catalytic reactions, but at the same time, decrease
the catalytic activity. To extend the range of applications of Rhꢀcatalyzed asymmetric
1,4ꢀadditions, we, therefore, developed a catalyst that is active at 0 °C and below.
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The asymmetric 1,4ꢀadditions of PhB(OH)2 (2a) to cyclohexenone (1) at 0 °C was first
evaluated to test the performance of different catalytic systems (Table 1). The reaction
using 1.5 mol% [RhCl(C2H4)2]2 (3.0 mol% Rh) as the catalyst precursor and (R)ꢀBINAP
as the ligand (ligand/Rh = 1.0) in the presence of an aqueous KOH solution in toluene
or 1,4ꢀdioxane for 3 h gave no or minor amounts of the desired product (R)ꢀ3 (entries 1,
2). The BINAP ligand was effective for this reaction in 1,4ꢀdioxane at 35 °C.9
Nonetheless, it is an ineffective ligand for lowꢀtemperature 1,4ꢀaddition. The use of
electronꢀpoor (R)ꢀdifluorphos10 gave similar results (entries 3, 4). Although the reaction
using Hayashi’s chiral diene ((1R,4R)ꢀ2,5ꢀdiphenylbicyclo[2,2,2]octaꢀ2,5ꢀdiene,
diene*)11 did not proceed in toluene (entry 5), the product was obtained in 1,4ꢀdioxane
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in good yield (80%) with high enantioselectivity (97% ee) for 1.5 h (entry 6). However,
the reaction using 0.5 mol% Rh/diene* provided only 19% yield of (R)ꢀ3 (entry 7). In
contrast, highly electronꢀpoor (R)ꢀMeOꢀF12ꢀBIPHEP ((R)ꢀ4), which we previously
developed,6a,6b significantly increased the activity of the rhodium catalyst in toluene at
0 °C. The reaction using the Rh catalyst (0.5 mol%) with (R)ꢀ4 was completed in 1.5 h
and afforded (R)ꢀ3 with >99% ee. (entry 8). Although the more electronꢀpoor
(R)ꢀMeOꢀBFPyꢀBIPHEP6c ((R)ꢀ5)ꢀligated Rh catalyst also showed high catalytic
activity (entry 9, 75% yield), 14% yield of the 1,2ꢀ,1,4ꢀ adduct was simultaneously
obtained as a side product.12 The ligand screening thus highlighted that the (R)ꢀ4 ligand
is appropriate for lowꢀtemperature 1,4ꢀaddition.
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Table 1 Asymmetric 1,4ꢀaddition of 2a to 1 at 0 °C a
[RhCl(C2H4)2]2 / Ligand
O
O
(Rh/Ligand = 1.0)
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+
PhB(OH)2
1.2 equiv.
0 °C
KOH
Solvent / H2O
Ph
1
2a
3
(R)-
Ligand:
O
F
F
PPh2
PPh2
PPh2
PPh2
O
O
Ph
F
F
Ph
diene*
O
(R)-BINAP
(R)-Difluorphos
F
F
(R)-MeO-F12-BIPHEP (4)
Ar =
Ar =
PAr2
PAr2
MeO
MeO
F
CF3
(R)-MeO-BFPy-BIPHEP (5)
N
CF3
Rh
(%)
Time Yield Ee
(h)
Entry (R)ꢀLigand
Solvent
(%) (%)b
1
2
3
4
5
6
7
8
9
BINAP
BINAP
Difluorphos 3.0 Toluene
Difluorphos 3.0 Dioxane
3.0 Toluene
3.0 Dioxane
3
3
3
3
0
5
0
6
0
ꢀ
99
ꢀ
97
ꢀ
diene*
diene*
diene*
4
3.0 Toluene
3.0 Dioxane 1.5 80 97
0.5 Dioxane 1.5 19 97
0.5 Toluene
0.5 Toluene
3
1.5 98 99.6
1.5 75 96
5
a
Reactions were carried out with 1 (0.52 mmol), 2a (0.62 mmol), KOH (0.10 mmol) in the presence of
Rh catalyst in solvent (0.35 mL) and H2O (0.3 mL) at 0 °C. b Determined by HPLC analysis.
Next, the performance of the Rh/(R)ꢀ4 catalyst for reactions below 0 °C was evaluated
(Table 2). Not surprisingly, when the reaction was performed in the presence of 0.25
mol% of [RhCl(C2H4)2]2 and 0.5 mol% of (R)ꢀ4 with KOH at −40 °C, a longer reaction
time was required, with the desired product (R)ꢀ3 obtained in 90% yield for 12 h using
2.0 equiv. of PhB(OH)2 (entry 1). Notably, the reaction proceeded even at −80 °C to
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give 85% yield of (R)ꢀ3 for 24 h (entry 2). At −40 and −80 °C, the water layer turned
into ice powder, which was roiled in toluene. Nevertheless, H2O is crucial for this
catalytic reaction. When the reaction was performed without H2O using
[RhOH{(R)ꢀ4}]2 as an active catalytic species,9 only 17% of (R)ꢀ3 was obtained at
−40 °C (entry 3), suggesting that H2O acts not only to convert [RhCl{(R)ꢀ4}]2 to
[RhOH{(R)ꢀ4}]2 but also as a hydrolysis agent in the catalytic cycle.9
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In general, the advantage of lowꢀtemperature reactions is the improvement of
stereoselectivity. However, no improvement in enantioselectivity was observed when
the reaction temperature was decreased (Table 2 entries 1, 2), because the ee at 20 °C
(99.6% ee, Table 1 entry 4) had already reached the detection limits by HPLC analysis.
The advantage of the lowꢀtemperature reaction was demonstrated in the reaction using
[RhOH(cod)]2 as the catalyst precursor. Although the reaction of [RhOH(cod)]2 with
chiral phosphine ligands readily proceeds to form the active species
[RhOH(phosphine)]2 without the addition of a base such as KOH,9 use of this complex
as a catalyst precursor in situ has been avoided except in a few cases.7a,13 The liberated
COD ligand, generated during ligand exchange, cannot be removed by distillation, and
trace amounts of highly active [RhOH(cod)]214 regenerated by equilibrium form racemic
3 to decrease enantioselectivity.15 When the reaction of 1 with 2a in toluene using 0.25
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mol% [RhOH(cod)]2 with 0.5 mol% (R)ꢀ4 (0.5 mol% Rh, (R)ꢀ4/Rh = 1.0) at 20 °C was
performed, the enantioselectivity of (R)ꢀ3 was slightly decreased to 98.0% ee (entry 5).
Under the same conditions without (R)ꢀ4, 17% racemic 3 was obtained using
[RhOH(cod)]2 (entry 6), suggesting that [RhOH(cod)]2 reduced the enantioselectivity of
the reaction with [RhOH(cod)]2/(R)ꢀ4 as the catalytic system. However, the catalytic
activity of [RhOH(cod)]2 was largely reduced at 0 °C and below compared with that at
20 °C (entries 8, 10, 12). Therefore, a decrease in the enantioselectivity of (R)ꢀ3 using
[RhOH(cod)]2/(R)ꢀ4 was not observed from 0 to −80 °C (entries 7, 9, 11).
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Table 2 Asymmetric 1,4ꢀaddition at low temperature a
Temp Time Yield Ee
Entry
Rh catalyst
(°C)
(h)
12
24
12
1
(%)a (%)b
90 99.6
85 99.6
17 99.5
99 99.6
99 98.0
1e
[RhCl(C2H4)2]2/(R)ꢀ4 ꢀ40
[RhCl(C2H4)2]2/(R)ꢀ4 ꢀ80
2f
3c,d,e
4g
[RhOH{(R)ꢀ4}]2
ꢀ40
[RhCl(C2H4)2]2/(R)ꢀ4 20
5c,g [RhOH(cod)]2/(R)ꢀ4 20
1
6c,g
[RhOH(cod)]2
20
0
0
1
17
ꢀ
7c,h [RhOH(cod)]2/(R)ꢀ4
1.5
1.5
12
98 99.5
6
87 99.7
8c,h
[RhOH(cod)]2
ꢀ
9c,e
[RhOH(cod)]2/(R)ꢀ4 ꢀ40
[RhOH(cod)]2 ꢀ40
10c,e
12
24
24
4
ꢀ
11c,f [RhOH(cod)]2/(R)ꢀ4 ꢀ80
84 99.6
2
12c,f
[RhOH(cod)]2
ꢀ80
ꢀ
a
Unless otherwise noted, reactions were carried out with 1 (0.52 mmol), 2a, KOH (0.10 mmol) in the
b
presence of rhodium complex (1.3 ꢁmol) and (R)ꢀ4 (2.6 ꢁmol) in toluene (0.35 mL) and H2O (0.3 mL).
c
d
e
f
g
Determined by HPLC analysis. Without KOH. Without H2O. 2.0 equiv. of 2a. 3.0 equiv. of 2a.
1.05 equiv. of 2a. h 1.2 equiv. of 2a.
Next, we demonstrated an improvement in the enantioselectivity of asymmetric
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1,4ꢀaddition to NꢀR maleimides using the Rh/(R)ꢀ4 catalyst under lowꢀtemperature
conditions. Asymmetric 1,4ꢀaddition of arylboronic acids to NꢀR maleimides has been
reported by several researchers16 because resulting products, i.e., chiral substituted
succinimides, have potential as bioactive compounds.17 The enantioselectivity of the
reaction is significantly affected by the substituent (R group) on the nitrogen atom in the
maleimide. A comparison of previously reported enantioselectivities for asymmetric
1,4ꢀaddition reactions using NꢀMe and NꢀBn maleimides is presented in Figure S1 (see
Supporting Information). It can be seen in the figure that no catalysts yielded more than
90% ee succinimides using both NꢀMe and NꢀBn maleimides. Furthermore, the NꢀR
maleimides were relatively less reactive substrates for the Rhꢀcatalyzed 1,4ꢀaddition;
thus, a comparatively large amount of catalyst and a high reaction temperature were
required. In other words, performing lowꢀtemperature reactions using the known
catalyst systems are very difficult.
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The reaction of NꢀMe maleimide (6a) with 2a was performed in the presence of the
Rh/(R)ꢀ4 catalyst (0.5 mol% Rh) at 30 °C for 1 h (Table 3). The complex [RhOH(cod)]2
was used as the catalyst precursor because the complex without (R)ꢀ4 showed slightly
lower catalytic activity for the reaction of 6a with 2a, and the enantioselectivity using
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the [RhCl(C2H4)]2/(R)ꢀ4 catalytic system with KOH was identical to that of
[RhOH(cod)]2/(R)ꢀ4 (entries 2,3 vs. 1). In this reaction, it was found that the solvent
influenced the enantioselectivity. Using Et2O as the solvent afforded higher
enantioselectivity (87% ee) of (R)ꢀ7aa compared with that obtained in toluene,
1,4ꢀdioxane, CH2Cl2, and THF (entry 1 vs. 4–7). When the reaction temperature was
decreased to 0 or −10 °C in Et2O, the enantioselectivity of (R)ꢀ7aa was improved to
90% or 92% ee, respectively (entries 8 and 9). Improvement in the enantioselectivity at
decreased reaction temperature is due to the common “lowꢀtemperature effect”, because
the [RhOH(cod)]2 precursor complex has very little catalytic activity in this reaction, as
mentioned above (entry 2). Although lowering the reaction temperature even further
(−40 °C) did not improve the enantioselectivity (entry 10), over 90% ee could be
achieved using only 0.5 mol% Rh/(R)ꢀ4 catalyst.
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Table 3 Asymmetric 1,4ꢀaddition of 2a to NꢀMeꢀmaleimide(6a) a
0.25 mol% of [RhOH(cod)]2
O
O
4
0.5 mol% of (R)-
4
(0.5 mol% Rh, /Rh = 1.0)
N
Me
N Me
+
PhB(OH)2
Solvent / H2O
Ph
2a
O
O
6a
(R)-7aa
Temp Time Yield Ee
(°C) (h)
(%) (%)b
99 87
2a
(equiv.)
2.0
2.0
2.0
2.0
Entry
Solvent
1
2c
3d
4
5
6
7
8
9
Et2O
Et2O
Et2O
30
30
30
30
1
1
1
1
1
1
1
1
3
10
6
ꢀ
98 87
96 72
98 78
86 69
98 71
96 90
94 92
95 92
Toluene
2.0 1,4ꢀdioxane 30
2.0
2.0
3.0
5.0
5.0
CH2Cl2
THF
Et2O
Et2O
30
30
0
ꢀ10
ꢀ40
10
Et2O
a
Unless otherwise noted, reactions were carried out with 6a (1.04 mmol), 2a in the presence of
b
[RhOH(cod)]2 (2.6 ꢁmol) and (R)ꢀ4 (5.3 ꢁmol) in solvent (2 mL) and H2O (0.3 mL). Determined by
HPLC analysis. c Without (R)ꢀ4. d Using 0.25 mol% of [RhCl(C2H4)2]2 and 0.5 mol% of (R)ꢀ4 with KOH.
To further explore the scope of the reaction, the asymmetric 1,4ꢀaddition of other
arylboronic acids bearing electronꢀdonating or ꢀwithdrawing substituents (2) to NꢀMe
maleimide (6a) was performed at 0 °C or −10 °C (Table 4). Although the reaction of
arylboronic acids required longer reaction times as compared with that of 2a, the yields
and enantioselectivities of product 7 were over 90%, even when only 0.5 mol%
Rh/(R)ꢀ4 was used (entries 1–8). Thus, it can be concluded that the lowꢀtemperature
reaction using the Rh/(R)ꢀ4 catalyst is effective for the 1,4ꢀaddition of arylboronic acids
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to NꢀR maleimides. When the asymmetric 1,4ꢀaddition of 2a to NꢀR maleimide (R = Bn
(6b), Cy (6c), or Ph (6d)) was performed at −10 °C, the products 7ba–7da were
obtained in over 90% ee (entries 9–11). Notably, substrates 6c and 6d gave almost
enantiomerically pure products.
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Table 4 Asymmetric 1,4ꢀaddition of arylboronic acids (2) to NꢀR maleimide(6) a
0.25 mol% of [RhOH(cod)]2
O
O
0.5 mol% of (R)-4
(0.5 mol% Rh, 4/Rh = 1.0)
N
R
+
N R
ArB(OH)2
Et2O / H2O
Ar
2
O
O
6
(R)-7
Temp Time Yield
(°C) (h) (%)
Ee
Entry 6 of R
2 of Ar
(%)b
1c Me (a)
2c Me (a)
3c Me (a)
4d Me (a)
5d Me (a)
6c Me (a)
2ꢀFꢀC6H4 (b)
2ꢀMeOꢀC6H4 (c)
3ꢀFꢀC6H4 (d)
3ꢀClꢀC6H4 (e)
3ꢀMeOꢀC6H4 (f)
3ꢀMeꢀC6H4 (g)
0
0
0
24 99 (7ab) 91 (ꢀ)
36 97 (7ac) 95 (ꢀ)
36 99 (7ad) 91 (R)
48 98 (7ae) 92 (R)
24 96 (7af) 94 (R)
0
ꢀ10
ꢀ10
0
5
92 (7ag) 94 (R)
7d Me (a) 3,5ꢀ(CH3)2ꢀC6H3 (h)
48 98 (7ah) 94 (-)
48 98 (7ai) 95 (R)
8d Me (a)
9e Bn (b)
10f Cy (c)
11c Ph (d)
12c H (e)
13c H (e)
14c H (e)
15c H (e)
4ꢀFꢀC6H4 (i)
Ph (a)
0
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ50
ꢀ80
3
5
4
3
3
95 (7ba) 95 (R)
96 (7ca) 99 (R)
95 (7da) 99 (R)
10 (7ea)
96 (7ea) 84 (R)
Ph (a)
Ph (a)
Ph (a)
Ph (a)
Ph (a)
Ph (a)
ꢀ
24 94 (7ea) 87 (R)
24 70 (7ea) 87 (R)
a
Unless otherwise noted, reactions were carried out with 6 (1.04 mmol), 2 in the presence of
b
[RhOH(cod)]2 (2.6 ꢁmol) and (R)ꢀ4 (5.3 ꢁmol) in diethyl ether (2 mL) and H2O (0.3 mL). Determined
by HPLC analysis. c 5.0 equiv. of 2. d 8.0 equiv. of 2. e 3.0 equiv. of 2. f 4.0 equiv. of 2.
Finally, the asymmetric 1,4ꢀadditon of 2a to NꢀH maleimide (6e) was performed. This
substrate 6e has been reported as being inactive for Rhꢀcatalyzed asymmetric
1,4ꢀadditions.16i Although the reaction using the Rh/(R)ꢀ4 catalyst (0.5 mol%) at −10 °C
for 3 h gave only 10% yield of the desired product 7ea (entry 12), the use of 3.0 mol%
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catalyst afforded 7ea in 96% yield with 84% ee (entry 13). When the reaction
temperature was decreased to −50 °C, the enantioselectivity of 7ea increased to 87% ee
(entry 14); further improvement in the ee was not observed at −80 °C (entry 15).
Although the enantioselectivity did not reach 90% ee, this result is the first successful
example of Rhꢀcatalyzed asymmetric 1,4ꢀadditon of arylboronic acid to NꢀH
maleimide.18
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In conclusion, we demonstrated the first example of Rhꢀcatalyzed asymmetric
1,4ꢀaddition below 0 °C. The electronꢀpoor (R)ꢀ4 ligand highly activates Rh catalysts
for asymmetric 1,4ꢀadditions, and the catalysts retain their activity at reaction
temperatures as low as −80 °C for improving enantioselectivities. Thus, the Rh/(R)ꢀ4
catalyst will be useful for the asymmetric synthesis of several bioactive compounds by
asymmetric 1,4ꢀaddition reactions under lowꢀtemperature conditions.
Experimental Section
General information. All reactions were carried out under an argon atmosphere with
dry solvents under anhydrous conditions, unless otherwise noted. All solvents were
purchased as dehydrated grade and then were stored in Schlenk tubes under an argon
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atmosphere. Chiral ligands, BINAP, difluorphos, and diene* were purchased and used
without further purification. Reagents were purchased at the highest commercial quality
and used without further purification, unless otherwise noted. Preparative column
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chromatography was carried out by using silica gel (BWꢀ127 ZH, 100－270 mesh). H
NMR and 13C NMR spectra were measured at 400 MHz and 101 MHz, respectively, and
chemical shifts are given relative to tetramethylsilane (TMS). 19F NMR spectra were
measured at 376 MHz, and chemical shifts are given relative to CCl3F using C6F6 as
secondary reference (–162.9 ppm).
General procedure for the 1,4ꢀaddition of phenylboronic acid (2a) to
2ꢀcyclohexenꢀ1ꢀone (1).
A 20 mL Schlenk flask was flushed with argon and charged with (R)ꢀ4 (2.05 mg, 2.6
ꢁmol), [RhCl(C2H4)2]2 (0.50 mg, 1.3 ꢁmol), potassium hydroxide (5.6 mg, 0.10 mmol),
deoxygenated 1,4ꢀdioxane (0.3 mL) and deoxygenated water (0.1 mL). The mixture was
stirred at room temperature for 15 minutes, and then the solvent was removed under
reduced pressure. After addition of phenylboronic acid (2a) (76.0 mg, 0.62 mmol),
2ꢀcyclohexenꢀ1ꢀone (1) (50 ꢁL, 0.52 mmol), deoxygenated toluene (0.35 mL), and
deoxygenated water (0.3 mL), the resulting mixture was stirred at 0 °C for 1.5 hours and
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then sat. NaHCO3 aq. was added. After extraction with ethyl acetate, the organic layer
was dried over MgSO4, filtrated with suction, and then concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc
= 5/1) to give (R)ꢀ3ꢀphenylcyclohexanone (3)9 as a colorless oil (88.7 mg, 98% yield,
99.6% ee). 1H NMR (400 MHz, CDCl3): δ = 1.74 – 1.93 (m, 2H), 2.05 – 2.20 (m, 2H),
2.33 – 2.64 (m, 4H), 2.96 – 3.07 (m, 1H), 7.21 – 7.27 (m, 3H), 7.31 – 7.36 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ = 25.4, 32.6, 41.0, 44.6, 48.8, 126.4, 126,5, 128.5, 144.2,
5
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210.9. IR (neat): 3061, 3028, 2937, 2866, 1713, 1603, 1497, 1452, 1421, 1344, 1315,
28.1
1250, 1223, 1030, 756, 700, 538 cmꢀ1. [α]D
= +19.8 (c 1.0, CHCl3). HPLC (Daicel
Chiralcel ODꢀ3, detected at 254 nm, hexane/2ꢀpropanol = 99/1, flow rate = 0.7
mL/min): tR of (S)ꢀ3; 27.6 min. (0.2%), tR of (R)ꢀ3; 29.8 min. (99.8%).
General procedure for the 1,4ꢀaddition of arylboronic acid (2) to maleimides (6)
Procedure for the 1,4ꢀaddition of phenylboronic acid (2a) to Nꢀmethylmaleimide
(6a) to obtain (R)ꢀ1ꢀmethylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7aa).16b
A 20 mL Schlenk flask was flushed with argon and charged with (R)ꢀ4 (4.2 mg, 5.3
ꢁmol), [RhOH(cod)]2 (1.2 mg, 2.6 ꢁmol) and deoxygenated dichloromethane (0.5 mL).
The mixture was stirred at room temperature for 10 minutes, and then the solvent was
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removed under reduced pressure. After addition of phenylboronic acid (2a) (635 mg,
5.20 mmol), Nꢀmethylmaleimide (6a) (116 mg, 1.04 mmol), deoxygenated diethyl ether
(2.0 mL), and deoxygenated water (0.3 mL), the resulting mixture was stirred at ꢀ10 °C
for 3 hours. and then sat. NaHCO3 aq. was added. After extraction with ethyl acetate,
the organic layer was dried over MgSO4, filtrated with suction, and then concentrated
under reduced pressure. The residue was purified by silica gel column chromatography
(hexane/acetone = 3/1) to give 184 mg of 7aa (94% yield, 92% ee) as a white solid. M.p.
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3
= 72 – 73 °C. 1H NMR (400 MHz, CDCl3): δ 2.83 (dd, J = 18.5 Hz, J = 4.7 Hz, 1H),
3.07 (s, 3H), 3.11 (dd, 2J = 18.5 Hz, 3J = 9.6 Hz, 1H), 4.03 (dd, 3J = 9.6 Hz and 4.7 Hz,
1H), 7.20 – 7.24 (m, 2H), 7.29 – 7.64 (m, 1H), 7.34 – 7.40 (m, 2H). 13C NMR (100
MHz, CDCl3): δ 25.3, 37.2, 46.1, 127.5, 128.1, 129.3, 137.2, 176.4, 177.9. IR (KBr):
3441, 3032, 2937, 1774, 1693, 1433, 1383, 1279, 1121, 951, 810, 752, 704, 648 cmꢀ1.
[α]D21.4 = ꢀ83.7 (c 1.01, CHCl3) {lit16b [α]D20 = +67.7 (c 1.08, CHCl3) for (S)ꢀenantiomer,
88% ee}. HPLC (Daicel Chiralcel ADꢀH, detected at 254 nm, hexane/2ꢀpropanol = 9/1,
flow rate = 1.0 mL/min): tR of (R)ꢀ7aa; 12.7 min. (96%), tR of (S)ꢀ7aa; 15.2 min. (4%).
(ꢀ)ꢀ3ꢀ(2ꢀFluorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ab)
(ꢀ)ꢀ3ꢀ(2ꢀFluorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ab) was obtained from (R)ꢀ4
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(0.53 mg, 0.66 ꢁmol), [RhOH(cod)]2 (0.15 mg, 0.33 ꢁmol), Nꢀmethylmaleimide (6a)
(14.4 mg, 0.13 mmol), 2ꢀfluorophenylboronic acid (2b) (90.9 mg, 0.65 mmol),
deoxygenated diethyl ether (0.4 mL), and deoxygenated water (0.1 mL) at 0 °C for 24
hours by the general procedure described above. White solid (26.4 mg, 99% yield, 91%
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ee). M.p. = 63 – 64 °C. H NMR (400 MHz, CDCl3): δ 2.77 (dd, 2J = 18.4 Hz, 3J = 5.3
2
3
3
Hz, 1H), 3.10 (s, 3H), 3.21 (dd, J = 18.4 Hz, J = 9.8 Hz, 1H), 4.12 (dd, J = 9.8 Hz
and 5.3 Hz, 1H), 7.06 – 7.17 (m, 2H), 7.19 – 7.25 (m, 1H), 7.28 – 7.35 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 25.4, 36.8, 41.8, 116.2 (d, 2JFꢀC = 21.5 Hz), 124.8 (d, 3JFꢀC
=
14.2 Hz), 126.8 (d, 4JFꢀC = 3.7 Hz), 130.1 (d, 2JFꢀC = 24.7 Hz), 130.2 (d, 3JFꢀC = 12.5 Hz),
160.9 (d, 1JFꢀC = 247 Hz), 176.0, 177.4 19F NMR (376 MHz, CDCl3): ꢀ118.0 – ꢀ117.9 (m,
1F). IR (KBr): 3447, 3088, 2961, 2934, 1778, 1697, 1493, 1435, 1385, 1288, 1232,
27.5
1117, 1061, 953, 845, 762, 700, 638 cmꢀ1. [α]D
= ꢀ32.0 (c 1.04, CHCl3). HPLC
(Daicel Chiralcel ADꢀ3, detected at 254 nm, hexane/2ꢀpropanol = 9/1, flow rate = 1.0
mL/min): tR of (ꢀ)ꢀ7ab; 14.5 min. (95.5%), tR of (+)ꢀ7ab; 17.8 min. (4.5%). Anal. calc.
for C11H10FNO2: C, 63.76; H, 4.86; N, 6.76. Found: C, 63.82; H, 4.64; N, 6.76.
(ꢀ)ꢀ3ꢀ(2ꢀMethoxyphenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ac)
(ꢀ)ꢀ3ꢀ(2ꢀMethoxyphenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ac) was obtained from (R)ꢀ4
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(0.53 mg, 0.66 ꢁmol), [RhOH(cod)]2 (0.15 mg, 0.33 ꢁmol), Nꢀmethylmaleimide (6a)
(14.4 mg, 0.13 mmol), 2ꢀmethoxyphenylboronic acid (2c) (98.8 mg, 0.65 mmol),
deoxygenated diethyl ether (0.4 mL), and deoxygenated water (0.1 mL) at 0 °C for 36
hours by the general procedure described above. White solid (27.6 mg, 97% yield, 95%
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ee). M.p. = 98 – 99 °C. H NMR (400 MHz, CDCl3): δ 2.75 (dd, 2J = 18.2 Hz, 3J = 5.1
Hz, 1H), 3.08 (s, 3H), 3.76 (dd, 2J = 18.2 Hz, 3J = 9.8 Hz, 1H), 3.75 (s, 3H), 3.94 (dd, 3J
= 9.8 Hz and 5.1 Hz, 1H), 6.82 – 6.89 (m, 1H), 6.92 – 6.97 (m, 1H), 7.16 – 7.19 (m, 1H),
7.27 – 7.33 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 25.1, 36.5, 44.1, 55.6, 111.3, 121.1,
125.9, 129.6, 130.9, 157.0, 177.1, 178.9. IR (KBr): 3447, 3063, 2947, 2845, 1773, 1678,
1587, 1496, 1439, 1408, 1383, 1335, 1285, 1248, 1115, 1024, 951, 829, 802, 696, 644
28.3
cmꢀ1. [α]D
= ꢀ29.5 (c 1.11, CHCl3). HPLC (Daicel Chiralcel ADꢀ3, detected at 254
nm, hexane/2ꢀpropanol = 9/1, flow rate = 1.0 mL/min): tR of (ꢀ)ꢀ7ac; 16.0 min. (97.5%),
tR of (+)ꢀ7ac; 19.7 min. (2.5%). Anal. calc. for C12H13NO3: C, 65.74; H, 5.98; N, 6.39.
Found: C, 65.90; H, 6.01; N, 6.32.
(R)ꢀ3ꢀ(3ꢀFluorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ad)16i
(R)ꢀ3ꢀ(3ꢀFluorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ad) was obtained from (R)ꢀ4
(0.53 mg, 0.66 ꢁmol), [RhOH(cod)]2 (0.15 mg, 0.33 ꢁmol), Nꢀmethylmaleimide (6a)
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(14.4 mg, 0.13 mmol), 3ꢀfluorophenylboronic acid (2d) (90.9 mg, 0.65 mmol),
deoxygenated diethyl ether (0.4 mL), and deoxygenated water (0.1 mL) at 0 °C for 36
hours by the general procedure described above. White solid (26.4 mg, 99% yield, 91%
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ee). M.p. = 78 – 79 °C. H NMR (400 MHz, CDCl3): δ 2.82 (dd, 2J = 18.4 Hz, 3J = 4.9
2
3
3
Hz, 1H), 3.08 (s, 3H), 3.23 (dd, J = 18.4 Hz, J = 9.6 Hz, 1H), 4.04 (dd, J = 9.6 Hz
and 4.9 Hz, 1H), 6.94 – 6.98 (m, 1H), 6.98 – 7.06 (m, 2H), 7.31 – 7.38 (m, 1H). 13C
4
2
NMR (100 MHz, CDCl3): δ 25.4, 37.0, 45.7 (d, JFꢀC = 1.5 Hz), 114.8 (d, JFꢀC = 22.4
2
4
3
Hz), 115.2 (d, JFꢀC = 21.7 Hz), 123.2 (d, JFꢀC = 3.0 Hz), 130.9 (d, JFꢀC = 8.22 Hz),
3
1
19
139.4 (d, JFꢀC = 7.5 Hz), 163.2 (d, JFꢀC = 248 Hz), 175.9, 177.3. F NMR (376 MHz,
CDCl3): ꢀ112.8 – ꢀ112.7 (m, 1F). IR (KBr): 3441, 3076, 3020, 2939, 1776, 1678, 1614,
1589, 1487, 1437, 1376, 1362, 1140, 1119, 1049, 957, 901, 881, 878, 752, 696, 640 cmꢀ1.
[α]D24.8 = ꢀ62.2 (c 1.02, CHCl3) {lit16i [α]D25 = ꢀ57.1 (c 0.98, CHCl3) for 89% ee}. HPLC
(Daicel Chiralcel ADꢀ3, detected at 254 nm, hexane/2ꢀpropanol = 9/1, flow rate = 0.7
mL/min): tR of (R)ꢀ7ad; 22.0 min. (96%), tR of (S)ꢀ7ad; 24.9 min. (4%).
(R)ꢀ3ꢀ(3ꢀChlorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ae)16i
(R)ꢀ3ꢀ(3ꢀChlorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ae) was obtained from (R)ꢀ4
(0.53 mg, 0.66 ꢁmol), [RhOH(cod)]2 (0.15 mg, 0.33 ꢁmol), Nꢀmethylmaleimide (6a)
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(14.4 mg, 0.13 mmol), 3ꢀchlorophenylboronic acid (2e) (163 mg, 1.04 mmol),
deoxygenated diethyl ether (0.4 mL), and deoxygenated water (0.1 mL) at 0 °C for 48
hours by the general procedure described above. White solid (28.5 mg, 98% yield, 92%
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ee). M.p. = 89 – 90 °C. H NMR (400 MHz, CDCl3): δ 2.81 (dd, 2J = 18.4 Hz, 3J = 4.9
2
3
3
Hz, 1H), 3.08 (s, 3H), 3.22 (dd, J = 18.4 Hz, J = 9.6 Hz, 1H), 4.01 (dd, J = 9.6 Hz
and 4.9 Hz, 1H), 7.10 – 7.15 (m, 1H), 7.22 – 7.24 (m, 1H), 7.28 – 7.34 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ 25.4, 37.0, 45.6, 125.8, 127.8, 128.4, 130.6, 135.1, 139.0,
175.8, 177.2. IR (KBr): 3452, 3057, 2982, 2945, 1780, 1690, 1497, 1574, 1479, 1414,
1385, 1288, 1227, 1196, 1119, 1063, 1040, 959, 893, 804, 785, 687, 646, 631 cmꢀ1.
[α]D26.6 = ꢀ61.6 (c 1.04, CHCl3) {lit16i [α]D25 = ꢀ54.1 (c 1.09, CHCl3) for 87% ee}. HPLC
(Daicel Chiralcel ADꢀ3, detected at 254 nm, hexane/2ꢀpropanol = 7/3, flow rate = 0.4
mL/min): tR of (S)ꢀ7ae; 18.7 min. (96%), tR of (R)ꢀ7ae; 20.2 min. (4%).
(R)ꢀ3ꢀ(3ꢀMethoxyphenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7af)16i
(R)ꢀ3ꢀ(3ꢀMethoxyphenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7af) was obtained from (R)ꢀ4
(1.4 mg, 1.8 ꢁmol), [RhOH(cod)]2 (0.40 mg, 0.88 ꢁmol), Nꢀmethylmaleimide (6a) (38.9
mg, 0.35 mmol), 3ꢀmethoxyphenylboronic acid (2f) (425 mg, 2.8 mmol), deoxygenated
diethyl ether (0.7 mL), and deoxygenated water (0.1 mL) at ꢀ10 °C for 24 hours by the
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general procedure described above. White solid (73.7 mg, 96% yield, 94% ee). M.p. =
5
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7
8
75 – 76 °C. 1H NMR (400 MHz, CDCl3): δ 2.35 (s, 3H), 2.82 (dd, 2J = 18.6 Hz, 3J = 4.7
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Hz, 1H), 3.08 (s, 3H), 3.20 (dd, J = 18.6 Hz, J = 9.6 Hz, 1H), 3.98 (dd, J = 9.6 Hz
and 4.7 Hz, 1H), 6.75 – 6.81 (m, 1H), 6.83 – 6.87 (m, 1H), 7.26 – 7.31 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 25.4, 37.2, 46.1, 55.4, 113.2, 113.7, 119.6, 130.4, 138.7,
160.2, 176.4, 177.8. IR (KBr): 3443, 3063, 2947, 2839, 1776, 1678, 1597, 1494, 1435,
1383, 1325, 1252, 1176, 1121, 1065, 1036, 953, 889, 862, 878, 750, 633 cmꢀ1. [α]D
=
28.0
25
ꢀ83.1 (c 1.06, CHCl3) {lit3 [α]D = ꢀ47.7 (c 0.65, CHCl3) for 90% ee}. HPLC (Daicel
Chiralcel IA, detected at 254 nm, hexane/2ꢀpropanol, flow rate = 1.0 mL/min): tR of
(S)ꢀ7af; 26.1 min. (2.4%), tR of (R)ꢀ7af; 29.3 min. (97.6%).
(R)ꢀ1ꢀMethylꢀ3ꢀ(3ꢀmethylphenyl)ꢀ 2,5ꢀpyrrolidinedione (7ag)16i
(R)ꢀ1ꢀMethylꢀ3ꢀ(3ꢀmethylphenyl)ꢀ 2,5ꢀpyrrolidinedione (7ag) was obtained from (R)ꢀ4
(2.1 mg, 2.6 ꢁmol), [RhOH(cod)]2 (0.60 mg, 1.3 ꢁmol), Nꢀmethylmaleimide (6a) (57.8
mg, 0.52 mmol), 3ꢀmethylphenylboronic acid (2g) (353 mg, 2.6 mmol), deoxygenated
diethyl ether (1.0 mL), and deoxygenated water (0.15 mL) at ꢀ10 °C for 5 hours by the
general procedure described above. White solid (97.2 mg, 92% yield, 94% ee). M.p. =
93 – 94 °C. 1H NMR (400 MHz, CDCl3): δ 2.35 (s, 3H), 2.82 (dd, 2J = 18.6 Hz, 3J = 4.7
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Hz, 1H), 3.08 (s, 3H), 3.20 (dd, J = 18.6 Hz, J = 9.6 Hz, 1H), 3.98 (dd, J = 9.6 Hz
and 4.7 Hz, 1H), 6.95 – 7.02 (m, 2H), 7.11 – 7.14 (m, 1H), 7.23 – 7.28 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 21.5, 25.4, 46.1, 124.5, 128.2, 128.9, 129.2, 137.2, 139.1,
176.5, 178.1. IR (KBr): 3443, 2949, 1776, 1682, 1493, 1433, 1387, 1288, 1121, 1061,
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953, 818, 779, 752, 692, 650 cmꢀ1. [α]D = ꢀ67.3 (c 1.02, CHCl3) {lit16i [α]D = ꢀ62.3
(c 1.06, CHCl3) for 91% ee}. HPLC (Daicel Chiralcel ADꢀH, detected at 254 nm,
hexane/2ꢀpropanol = 9/1, flow rate = 0.7 mL/min): tR of (R)ꢀ7ag; 17.1 min. (97%), tR of
(S)ꢀ7ag; 20.0 min. (3%).
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(ꢀ)ꢀ3ꢀ(3,5ꢀDimethylphenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ah)
(ꢀ)ꢀ3ꢀ(3,5ꢀDimethylphenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ah) was obtained from
(R)ꢀ4 (0.53 mg, 0.66 ꢁmol), [RhOH(cod)]2 (0.15 mg, 0.33 ꢁmol), Nꢀmethylmaleimide
(6a) (14.4 mg, 0.13 mmol), 3,5ꢀdimethylphenylboronic acid (2h) (156 mg, 1.04 mmol),
deoxygenated diethyl ether (0.4 mL), and deoxygenated water (0.1 mL) at 0 °C for 48
hours by the general procedure described above. White solid (27.7 mg, 98% yield, 94%
1
2
ee). M.p. = 100 – 102 °C. H NMR (400 MHz, CDCl3): δ 2.30 (s, 6H), 2.81 (dd, J =
3
2
3
18.4 Hz, J = 4.5 Hz, 1H), 3.08 (s, 3H), 3.18 (dd, J = 18.4 Hz, J = 9.6 Hz, 1H), 3.94
(dd, J = 9.6 Hz and 4.5 Hz, 1H), 6.79 – 6.81 (m, 2H), 6.93 – 6.95 (m, 1H). 13C NMR
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(100 MHz, CDCl3): δ 21.4, 25.4, 37.5, 46.1, 125.3, 129.8, 137.2, 139.0, 176.6, 178.2. IR
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6
7
8
(KBr): 2936, 2854, 1767, 1697, 1452, 1393, 1375, 1340, 1144, 750, 702, 652 cmꢀ1.
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26.4
[α]D
= ꢀ109.6 (c 0.68, CHCl3). HPLC (Daicel Chiralcel ADꢀ3, detected at 254 nm,
hexane/2ꢀpropanol = 9/1, flow rate = 0.7 mL/min): tR of (ꢀ)ꢀ7ah; 13.9 min. (97%), tR of
(+)ꢀ7ah; 16.0 min. (3%). Anal. calc. for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found:
C, 72.01; H, 6.91; N, 6.36.
(R)ꢀ3ꢀ(4ꢀFluorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ai)16i
(R)ꢀ3ꢀ(4ꢀFluorophenyl)ꢀ1ꢀmethylꢀ2,5ꢀpyrrolidinedione (7ai) was obtained from (R)ꢀ4
(1.4 mg, 1.8 ꢁmol), [RhOH(cod)]2 (0.40 mg, 0.88 ꢁmol), Nꢀmethylmaleimide (6a) (38.9
mg, 0.35 mmol), 4ꢀfluorophenylboronic acid (2i) (392 mg, 2.80 mmol), deoxygenated
diethyl ether (0.7 mL), and deoxygenated water (0.15 mL) at 0 °C for 48 hours by the
general procedure described above. White solid (71.1 mg, 98% yield, 95% ee). M.p. =
100 – 101 °C. 1H NMR (400 MHz, CDCl3): δ .2.79 (dd, 2J = 18.4 Hz, 3J = 4.8 Hz, 1H),
3.09 (s, 3H), 3.21 (dd, 2J = 18.4 Hz, 3J = 9.6 Hz, 1H), 4.10 (dd, 3J = 9.6 Hz and 4.8 Hz,
1H), 6.95 – 7.10 (m, 2H), 7.17 – 7.24 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 25.4,
37.2, 45.3, 116.3 (d, 2JFꢀC = 21.2 Hz), 129.2 (d, 3JFꢀC = 8.2 Hz), 132.8 (d, 4JFꢀC = 3.8 Hz),
162.5 (d, JFꢀC = 248 Hz), 176.1, 177.7. 19F NMR (376 MHz, CDCl3): ꢀ121.0 – ꢀ120.6
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(m, 1F). IR (KBr): 3442, 3068, 2955, 1776, 1693, 1601, 1514, 1437, 1404, 1352, 1288,
5
6
7
8
1221, 1155, 1123, 947, 854, 833, 692, 527 cmꢀ1. [α]D = ꢀ65.1 (c 1.01, CHCl3) {lit16i
26.6
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[α]D = ꢀ57.8 (c 0.94, CHCl3) for 87% ee}. HPLC (Daicel Chiralcel ADꢀ3, detected at
254 nm, hexane/2ꢀpropanol = 9/1, flow rate = 1.0 mL/min): tR of (R)ꢀ7ai; 14.8 min.
(97.4%), tR of (S)ꢀ7ai; 19.9 min. (2.6%).
(R)ꢀ1ꢀBenzylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7ba)16a
(R)ꢀ1ꢀBenzylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7ba) was obtained from (R)ꢀ4 (4.2 mg, 5.3
ꢁmol), [RhOH(cod)]2 (1.2 mg, 2.6 ꢁmol), Nꢀbenzylmaleimide (6b) (195 mg, 1.04
mmol), phenylboronic acid (2a) (380 mg, 3.12 mmol), deoxygenated diethyl ether (2.0
mL), and deoxygenated water (0.3 mL) at ꢀ10 °C for 3 hours by the general procedure
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described above. White solid (262 mg, 95% yield, 95% ee). M.p. = 59 – 60 °C. H
NMR (400 MHz, CDCl3): δ 2.80 (dd, 2J = 18.6 Hz, 3J = 4.9 Hz, 1H), 3.18 (dd, 2J = 18.6
Hz, 3J = 9.6 Hz, 1H), 4.03 (dd, 3J = 9.6 Hz and 4.9 Hz, 1H), 4.68 (d, 2J = 14.1 Hz, 1H),
4.74 (d, 2J = 14.1 Hz, 1H), 7.15 (d, 3J = 7.2 Hz, 2H), 7.24 – 7.37 (m, 6H), 7.40 (d, 3J =
7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 37.3, 42.8, 46.0, 127.5, 128.0, 128.1,
128.8, 128.9, 129.3, 135.9, 137.3, 175.9, 177.5. IR (KBr): 3442, 3061, 3030, 2918, 1773,
1709, 1499, 1429, 1404, 1340, 1165, 932, 698, 646 cmꢀ1. [α]D
= ꢀ48.6 (c 1.06,
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CHCl3) {lit16a [α]D = ꢀ33.7 (c 1.20, CHCl3) for 88% ee}. HPLC (Daicel Chiralcel
ODꢀH, detected at 254 nm, hexane/2ꢀpropanol = 9/1, flow rate = 1.0 mL/min): tR of
(S)ꢀ7ba; 23.3 min. (2.3%), tR of (R)ꢀ7ba; 28.3 min. (97.7%).
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(R)ꢀ1ꢀCyclohexylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7ca)16a
(R)ꢀ1ꢀCyclohexylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7ca) was obtained from (R)ꢀ4 (4.2 mg,
5.3 ꢁmol), [RhOH(cod)]2 (1.2 mg, 2.6 ꢁmol), Nꢀcyclohexylmaleimide (6c) (186 mg,
1.04 mmol), phenylboronic acid (2a) (507 mg, 4.16 mmol), deoxygenated diethyl ether
(2.0 mL), and deoxygenated water (0.3 mL) at ꢀ10 °C for 5 hours by the general
procedure described above. White solid (260 mg, 96% yield, >99% ee). M.p. = 83 –
84 °C. 1H NMR (400 MHz, CDCl3): δ 1.18 – 1.39 (m, 3H), 1.60 – 1.69 (m, 3H), 1.80 –
1.87 (m, 2H), 2.12 – 2.26 (m, 2H), 2.74 (dd, 2J = 18.4 Hz, 3J = 4.5 Hz, 1H), 3.13 (dd, 2J
3
3
3
= 18.4 Hz, J = 9.6 Hz, 1H), 3.93 (dd, J = 9.6 Hz and 4.5 Hz, 1H), 4.04 (tt, J = 12.3
Hz and 3.9 Hz, 1H), 7.19 (d, 3J = 7.2 Hz, 2H), 7.27 – 7.32 (m, 1H), 7.36 (t, 3J = 7.2 Hz,
2H). 13C NMR (100 MHz, CDCl3): δ 25.1, 25.91, 25.93, 29.0, 37.2, 45.7, 52.1, 127.3,
127.9, 129.3, 137.9, 176.5, 177.9. IR (KBr): 3443, 2936, 2854, 1767, 1697, 1452, 1393,
23.1
20
1375, 1340, 1144, 750, 702, 652 cmꢀ1. [α]D
= ꢀ38.2 (c 1.01, CHCl3) {lit16a [α]D
=
ꢀ34.0 (c 0.82, CHCl3) for 87% ee}. HPLC (Daicel Chiralcel ODꢀH, detected at 254 nm,
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hexane/2ꢀpropanol = 9/1, flow rate = 1.0 mL/min): tR of (S)ꢀ7ca; 13.5 min. (0%), tR of
(R)ꢀ7ca; 16.0 min. (100%).
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(R)ꢀ1ꢀPhenylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7da)16b
(R)ꢀ1ꢀPhenylꢀ3ꢀphenylꢀ2,5ꢀpyrrolidinedione (7da) was obtained from (R)ꢀ4 (4.2 mg, 5.3
ꢁmol), [RhOH(cod)]2 (1.2 mg, 2.6 ꢁmol), Nꢀcyclohexylmaleimide (7d) (180 mg, 1.04
mmol), phenylboronic acid (2a) (635 mg, 5.20 mmol), deoxygenated diethyl ether (2.0
mL), and deoxygenated water (0.3 mL) at ꢀ10 °C for 4 hours by the general procedure
1
described above. White solid (248 mg, 95% yield, >99% ee). M.p. = 137 – 138 °C. H
NMR (400 MHz, CDCl3): δ 2.98 (dd, 2J = 18.6 Hz, 3J = 4.7 Hz, 1H), 3.35 (dd, 2J = 18.6
3
13
Hz, 3J = 9.6 Hz, 1H), 4.17 (dd, J = 9.6 Hz and 4.7 Hz, 1H), 7.27 – 7.50 (m, 10H). C
NMR (100 MHz, CDCl3): δ 37.4, 46.1, 126.6, 127.5, 128.2, 128.8, 129.3, 129.4, 132.0,
137.3, 175.3, 176.8. IR(KBr): 3442, 3057, 3028, 2941, 1776, 1705, 1499, 1456, 1387,
23.5
1178, 795, 758, 702 cmꢀ1. [α]D = ꢀ12.5 (c 1.02, CHCl3) {lit16b [α]D20 = +10.6 (c 1.03,
CHCl3) for (S)ꢀenantiomer, 90% ee}. HPLC (Daicel Chiralcel ODꢀH, detected at 254
nm, hexane/2ꢀpropanol = 9/1, flow rate = 1.0 mL/min): tR of (S)ꢀ7da; 47.8 min. (0%), tR
of (R)ꢀ7da; 55.8 min. (100%).
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(R)ꢀ3ꢀPhenylꢀ2,5ꢀpyrrolidinedione (7ea)16b
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(R)ꢀ3ꢀPhenylꢀ2,5ꢀpyrrolidinedione (7ea) was obtained from (R)ꢀ4 (5.3 mg, 6.6 ꢁmol),
[RhOH(cod)]2 (1.5 mg, 3.3 ꢁmol), maleimide (6e) (21.3 mg, 0.219 mmol),
phenylboronic acid (2a) (134 mg, 1.10 mmol), deoxygenated diethyl ether (0.3 mL),
and deoxygenated water (0.1 mL) at ꢀ50 °C for 24 hours by the general procedure
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described above. White solid (34.8 mg, 91% yield, 87% ee). M.p. = 88 – 89 °C. H
NMR (400 MHz, CDCl3): δ 2.89 (dd, 2J = 18.6 Hz, 3J = 4.9 Hz, 1H), 3.26 (dd, 2J = 18.6
3
3
Hz, J = 9.6 Hz, 1H), 4.10 (dd, J = 9.6 Hz and 4.9 Hz, 1H), 7.24 – 7.40 (m, 5H), 8.30
(br s, 1H). 13C NMR (100 MHz, CDCl3): δ 38.4, 47.5, 127.5, 128.3, 129.4, 136.7, 176.1,
177.9. IR(KBr): 3442, 3057, 3028, 2941, 1776, 1705, 1499, 1456, 1387, 1178, 795, 758,
23.5
20
702 cmꢀ1. [α]D
= ꢀ69.9 (c 1.00, EtOH) {lit16b [α]D = +77.3 (c 0.84, EtOH) for
(S)ꢀenantiomer, 93% ee}. HPLC (Daicel Chiralcel OJꢀH, detected at 254 nm,
hexane/2ꢀpropanol = 2/1, flow rate = 0.6 mL/min): tR of (R)ꢀ7ea; 38.8 min. (93.6%), tR
of (S)ꢀ7ea; 53.6 min. (6.4%).
Acknowledgments
This work was partially supported by JSPS KAKENHI Grant Number 23550124,
24105521.
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Copies of 1H NMR, 13C NMR and HPLC data for all products. This material is available
free of charge via the Internet at http://pubs.acs.org.
References and Footnotes
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Chim. Acta 2012, 95, 1809ꢀ1817. (c) Yasukawa, T.; Miyamura, H.; Kobayashi, S. J. Am.
Chem. Soc. 2012, 134, 16963ꢀ16966. (d) Lipshutz, B. H.; Isley, N. A.; Moser, R.;
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T.; Hashimoto, M.; Uehara, K.; Naruse, Y.; Kobayashi, S.; Sakamoto, M.; Fujita, T.
Tetrahedron Lett. 2012, 53, 4562ꢀ4564. (f) Grugel, H.; Albrecht, F.; Minuth, T.; Boysen,
M. M. K. Org. Lett. 2012, 14, 3780ꢀ3783. (g) Shao, C.; Yu, H.ꢀJ.; Feng, C.ꢀG.; Wang,
R.; Lin, G.ꢀQ. Tetrahedron Lett. 2012, 53, 2733ꢀ2735. (h) Sasaki, K.; Hayashi, T.
Tetrahedron: Asymmetry 2012, 23, 373ꢀ380. (i) Zhang, D.ꢀY.; Yu, C.ꢀB.; Wang, M.ꢀC.;
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Gao, K.; Zhou, Y.ꢀG. Tetrahedron Lett. 2012, 53, 2556ꢀ2559. (j) Liu, C.ꢀC.; Janmanchi,
D.; Chen, C.ꢀC.; Wu, H.ꢀL. Eur. J. Org. Chem. 2012, 2012, 2503ꢀ2507. (k) Narui, R.;
Hayashi, S.; Otomo, H.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2012, 23,
284ꢀ293. (l) Chen, G.; Gui, J.; Cao, P.; Liao, J. Tetrahedron 2012, 68, 3220ꢀ3224. (m)
Khiar, N.; Salvador, A.; Chelouan, A.; Alcudia, A.; Fernandez, I. Org. Biomol. Chem.
2012, 10, 2366ꢀ2368. (n) Jin, S.ꢀS.; Wang, H.; Zhu, T.ꢀS.; Xu, M.ꢀH. Org. Biomol.
Chem. 2012, 10, 1764ꢀ1768. (o) Ogasawara, M.; Wu, W.ꢀY.; Arae, S.; Watanabe, S.;
Morita, T.; Takahashi, T.; Kamikawa, K. Angew. Chem., Int. Ed. 2012, 51, 2951ꢀ2955.
(p) Gavrilov, K. N.; Zheglov, S. V.; Gavrilova, M. N.; Novikov, I. M.; Maksimova, M.
G.; Groshkin, N. N.; Rastorguev, E. A.; Davankov, V. A. Tetrahedron 2012, 68,
1581ꢀ1589. (q) Gosiewska, S.; Raskatov, J. A.; Shintani, R.; Hayashi, T.; Brown, J. M.
Chem. Eur. J. 2012, 18, 80ꢀ84. (r) Allen, J. C.; KociokꢀKöhn, G.; Frost, C. G. Org.
Biomol. Chem., 2012, 10, 32ꢀ35. (s) Shu, W.; Buchwald, S. L. Angew. Chem., Int. Ed.
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(4) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125,
11508ꢀ11509.
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(5) Review: Tian, P.; Dong, H.ꢀQ.; Lin, G.ꢀQ. ACS Catalysis 2012, 2, 95ꢀ119.
(6) (a) Korenaga, T.; Osaki, K.; Maenishi, R.; Sakai, T. Org. Lett. 2009, 11, 2325ꢀ2328.
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