Three-hindered quadrant phosphine ligands with an aromatic ring backbone for the rhodium-catalyzed asymmetric hydrogenation of functionalized alkenes

Article abstract of DOI:10.1021/jo300454n

The three-hindered quadrant phosphine ligands (R)-1-tert- butylmethylphosphino-2-(di-tert-butylphosphino)benzene ((R)-3H-BenzP*) and (R)-2-tert-butylmethylphosphino-3-(di-tert-butylphosphino)quinoxaline ((R)-3H-QuinoxP*) exhibited good to excellent enantioselectivities in the rhodium-catalyzed asymmetric hydrogenation of selected dehydroamino acid derivatives, enamides, and ethenephosphonates.

Full text of DOI:10.1021/jo300454n

Note
pubs.acs.org/joc
Three-Hindered Quadrant Phosphine Ligands with an Aromatic Ring
Backbone for the Rhodium-Catalyzed Asymmetric Hydrogenation of
Functionalized Alkenes
Zhenfeng Zhang,† Ken Tamura,† Daisuke Mayama,† Masashi Sugiya,† and Tsuneo Imamoto*,†,‡
†Organic R&D Department, Nippon Chemical Industrial Co., Ltd., Kameido, Koto-ku, Tokyo 136-8515, Japan
‡Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
S
* Supporting Information
ABSTRACT: The three-hindered quadrant phosphine ligands
(R)-1-tert-butylmethylphosphino-2-(di-tert-butylphosphino)-
benzene ((R)-3H-BenzP*) and (R)-2-tert-butylmethylphosphino-
3-(di-tert-butylphosphino)quinoxaline ((R)-3H-QuinoxP*) ex-
hibited good to excellent enantioselectivities in the rhodium-
catalyzed asymmetric hydrogenation of selected dehydroamino
acid derivatives, enamides, and ethenephosphonates.
ligands to form five-membered chelates has not yet been
reported.12,13
espite the development of numerous chiral phosphine
ligands, there remains a need for highly efficient and
D
operationally convenient ligands in the field of asymmetric metal
catalysis.1 In our previous studies of the synthesis and application
of new P-stereogenic phosphine ligands, we described the
preparation of (S,S)-1,2-bis(tert-butylmethylphosphino)ethane
(t-Bu-BisP*) and (R,R)-bis(tert-butylmethylphosphino)methane
(t-Bu-MiniPHOS).2−4 These ligands were designed based on a
“quadrant diagram” concept,5 with the expectation that the two
bulky tert-butyl groups of the metal complexes would occupy the
diagonal quadrants and the two methyl groups would be located
in the other quadrants. Single crystal X-ray analysis of the
rhodium complexes clearly revealed typical C2-symmetric two-
hindered quadrant catalyst structures. As expected, the catalysts
provided high enantioselectivities in the rhodium-catalyzed
asymmetric hydrogenation of functionalized alkenes.2−4
We recently reported the preparation of the C2-symmetric
P-stereogenic phosphine ligands 1,2-bis(tert-butylmethylphos-
phino)benzene (BenzP*) and 2,3-bis(tert-butylmethylphosphino)-
quinoxaline (QuinoxP*).14−16 These ligands exhibited excellent
enantioselectivities and high catalytic activities in the rhodium-
catalyzed asymmetric hydrogenation of various functionalized
alkenes. Notably, the ligands were air-stable crystalline solids and
were useful in the production of several chiral pharmaceutical
ingredients with an amino acid or a secondary amine component.
These results prompted us to study the enantioinduction
properties of the rhodium complexes of three-hindered quadrant
phosphine ligands, such as 1-(tert-butylmethylphosphino)-2-(di-
tert-butylphosphino)benzene (3H-BenzP*)17,18 and 2-(tert-butyl-
methylphosphino)-3-(di-tert-butylphosphino)quinoxaline (3H-
QuinoxP*).
The ligand 3H-BenzP*, with an R-configuration, was prepared
according to the procedures described in the literature.17 The
ligand was obtained as a colorless oil and was immediately
converted into its cationic rhodium complex 1 by the usual
means (Scheme 1).
Another ligand with a quinoxaline backbone was prepared in
high yield from 2,3-dichloroquinoxaline via the intermediate 2
(Scheme 2). This ligand, (R)-3H-QuinoxP*, was an air-stable
crystalline solid that formed the rhodium complex 3 without
the need for special precautions.
In 2004, Hoge et al. described the preparation of the
enantiopure di-tert-butylphosphino(tert-butylmethylphosphino)-
methane (Trichickenfootphos), a C1-symmetric three-hindered
quadrant diphosphine ligand, demonstrating its utility as a chiral
ligand in the context of rhodium-catalyzed asymmetric hydro-
genation toward the production of useful optically active
compounds.6,7 Thereafter, several new three-hindered quadrant
phosphine ligands were prepared and successfully utilized in
rhodium-catalyzed asymmetric hydrogenation reactions.8−11 All
of these ligands consisted of a bis(dialkylphosphino)methane
molecular framework that formed four-membered metal com-
plexes. To our knowledge, the use of three-hindered quadrant
Received: March 2, 2012
Published: March 23, 2012
© 2012 American Chemical Society
4184
dx.doi.org/10.1021/jo300454n | J. Org. Chem. 2012, 77, 4184−4188

The Journal of Organic Chemistry
Note
tested using other (Z)-β-dehydroamino acid ester substrates
having an alkyl or an aryl substituent at the β-position (entries
17−28). The substrates possessing a n-propyl group or an
isopropyl group were hydrogenated in good to high enantio-
selectivities (entries 17−20). It is noted that the isopropyl
derivative 4j underwent hydrogenation under 10 atm H2 in the
presence of 1 to furnish the product with 94.4% ee. The β-aryl-
substituted β-dehydroamino acid esters were also hydrogenated
to give the corresponding products with good to high
enantiomeric excesses (entries 21−28). Notably, compound
4n was converted with a high enantioselectivity into a key
intermediate for the synthesis of the VLA-4 antagonist S9059.20
Entries 29−42 show the hydrogenation results of prochiral
enamides. In a series of α-aryl-substituted enamides, the catalyst
3, with a less electron-rich ligand 3H-QuinoxP*, gave
remarkably higher enantioselectivities than the catalyst 1, with
an electron-rich ligand 3H-BenzP*, except for the hydro-
genation of the phenyl-substituted enamide 4o. Hydrogenation
of the tert-butyl-substituted enamide 4t provided very low
enantioselectivities (9 and 15%) (entries 39 and 40). These
results sharply contrasted with those obtained through the use
of the C2-symmetric BenzP* and QuinoxP*, which gave 96.6
and 99.0% ee, respectively.16 On the other hand, a β-keto
enamide 4u was hydrogenated into the corresponding product
with considerably high enantiomeric excesses (entries 41 and 42),
though the ee values are not comparable to the highest ones
reported previously.21
Scheme 1. Preparation of Rhodium Complex 1
Scheme 2. Preparation of (R)-3H-QuinoxP* and Its
Rhodium Complex 3
The enantioselective hydrogenation of enol phosphonates
and enamido phosphonates provides an efficient approach to
the synthesis of optically active amino and hydroxy phosphoric
acids, which are of widespread utility as pharmaceuticals and
agrochemicals.22 Our results (95.6−98.4% ee) for the hydro-
genation of the model substrates 4v and 4w were comparable
to the highest enantioselectivities reported previously, suggest-
ing that the catalysts 1 and 3 may be useful for the
hydrogenation of similar ethenephosphonates.
In conclusion, rhodium complexes of the three-hindered
quadrant phosphine ligands (R)-1-tert-butylmethylphosphino-
2-(di-tert-butylphosphino)benzene ((R)-3H-BenzP*) and
(R)-2-tert-butylmethylphosphino-3-(di-tert-butylphosphino)-
quinoxaline ((R)-3H-QuinoxP*) were prepared, and their
catalytic performances were evaluated with respect to the
hydrogenation of representative dehydroamino acid derivatives,
enamides, and ethenephosphonates. The enantioselectivities
varied widely, depending on the substrate and catalyst;
however, the results were promising and indicated that the
catalysts are potentially useful in the asymmetric hydrogenation
of other prochiral substrates.
The enantioinduction capabilities of the rhodium catalysts 1
and 3 were evaluated with respect to the hydrogenation of
representative dehydroamino acid derivatives, enamides, and
ethenephosphonates. The results are summarized in Table 1.
The hydrogenation of several α-dehydroamino acid derivatives
(4a−f) provided largely varied results, depending on the sub-
strate and the catalyst. Typical benchmark substrates, such as
α-acetamidocinnamic acid derivatives and methyl 2-acetamidoacrylate
(4a−d), afforded very high ee values of up to 99.9% (entries 1−8),
but the ee values were slightly lower than those obtained through
the use of BenzP* and QuinoxP*.16 In contrast, remarkably lower
enantioselectivities were observed in the reactions of 2-furyl
and β-dimethyl-substituted compounds (entries 9−12).
The enantioinduction capabilities of the catalysts 1 and 3
toward both (E)- and (Z)-β-dehydroamino acid esters were of
particular interest because most previous studies reported that
the (E)-isomers gave rise to higher enantioselectivities than
the (Z)-isomers.19 Hydrogenation of the model substrates 4g
and 4h afforded high ee values of 95% (entries 14−16), except
for the hydrogenation of 4g with 1 (entry 13). These results
suggested that the three-hindered catalysts 1 and 3 were readily
applicable to (Z)-derivatives as well. The catalysts were then
EXPERIMENTAL SECTION
■
General Methods. All anaerobic and moisture-sensitive manipu-
lations were conducted using standard Schlenk techniques under
1
argon. H NMR, 13C NMR, and 31P NMR spectra were obtained at
500, 125, and 200 MHz, respectively. Anhydrous tetrahydrofuran,
diethyl ether, and dichloromethane were used as received from
commercial suppliers.
( R ) - 1 - ( t e r t - B u t y l m e t h y l p h o s p h i n o ) - 2 - ( d i - t e r t -
butylphosphino)benzene(1,5-cyclooctadiene)rhodium(I) Hex-
afluoroantimonate (1). A solution of (R)-1-(tert-butylmethylphos-
phino)-2-(di-tert-butylphosphino)benzene (64.9 mg, 0.200 mmol) in
dichloromethane (1 mL) was added dropwise to a solution of
[Rh(cod)2]SbF6 (101.0 mg, 0.182 mmol) in dichloromethane (5 mL)
at 0 °C under argon. After stirring at room temperature for 1 h, the
solution was concentrated under reduced pressure to 0.5 mL, followed
4185
dx.doi.org/10.1021/jo300454n | J. Org. Chem. 2012, 77, 4184−4188

The Journal of Organic Chemistry
Note
Table 1. Asymmetric Hydrogenation of Functionalized Alkenes Using [Rh((R)-3H-BenzP*)(cod)]SbF6 (1) or [Rh((R)-3H-
QuinoxP*)(cod)]SbF6 (3)
ab
,
entry
substrate
catalyst
S/C
H2 (atm)
product
ee (%) (config.)
1
2
3
4
5
6
7
8
4a: R1 = Ph, R2 = H, R3 = CO2Me, X = NHAc
4a: R1 = Ph, R2 = H, R3 = CO2Me, X = NHAc
4b: R1 = Ph, R2 = H, R3 = CO2H, X = NHAc
4b: R1 = Ph, R2 = H, R3 = CO2H, X = NHAc
4c: R1 = 3-FC6H4, R2 = H, R3 = CO2H, X = NHAc
4c: R1 = 3-FC6H4, R2 = H, R3 = CO2H, X = NHAc
4d: R1 = R2 = H, R3 = CO2Me, X = NHAc
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1
3
1000
1000
1000
1000
1000
1000
1000
1000
200
3
3
5a
5a
5b
5b
5c
5c
5d
5d
5e
5e
5f
99.2 (R)
98.4 (R)
c
3
91.6 (R)
c
3
97.6 (R)
c
3
97.7 (R)
c
3
97.1 (R)
3
93.6 (R)
99.9 (R)
4d: R1 = R2 = H, R3 = CO2Me, X = NHAc
3
d
e
9
4e: R1 = 2-Furyl, R2 = H, R3 = CO2Me, X = NHCbz
4e: R1 = 2-Furyl, R2 = H, R3 = CO2Me, X = NHCbz
4f: R1 = R2 = Me, R3 = CO2Me, X = NHAc
4f: R1 = R2 = Me, R3 = CO2Me, X = NHAc
4g: R1 = H, R2 = CO2Me, R3 = Me, X = NHAc
4g: R1 = H, R2 = CO2Me, R3 = Me, X = NHAc
4h: R1 = CO2Me, R2 = H, R3 = Me, X = NHAc
4h: R1 = CO2Me, R2 = H, R3 = Me, X = NHAc
4i: R1 = CO2Me, R2 = H, R3 = Pr, X = NHAc
4i: R1 = CO2Me, R2 = H, R3 = Pr, X = NHAc
4j: R1 = CO2Et, R2 = H, R3 = i-Pr, X = NHAc
4j: R1 = CO2Et, R2 = H, R3 = i-Pr, X = NHAc
4k: R1 = CO2Me, R2 = H, R3 = Ph, X = NHAc
4k: R1 = CO2Me, R2 = H, R3 = Ph, X = NHAc
4l: R1 = CO2Et, R2 = H, R3 = 4-MeOC6H4, X = NHAc
4l: R1 = CO2Et, R2 = H, R3 = 4-MeOC6H4, X = NHAc
4m: R1 = CO2Me, R2 = H, R3 = 3,5-Cl2C6H3, X = NHAc
4m: R1 = CO2Me, R2 = H, R3 = 3,5-Cl2C6H3, X = NHAc
4n: R1 = CO2Et, R2 = H, R3 = 3,4-(MeO)2C6H3, X = NHAc
4n: R1 = CO2Et, R2 = H, R3 = 3,4-(MeO)2C6H3, X = NHAc
4o: R1 = R2 = H, R3 = Ph, X = NHAc
4
76 (R)
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
200
4
84 (R)
d
200
3
64 (S)
d
200
3
5f
40 (S)
1000
1000
1000
1000
1000
1000
500
3
5g
5g
5h
5h
5i
86 (R)
3
94.5 (R)
94.8 (R)
95.0 (R)
92.1 (R)
90 (R)
3
3
5
5
5i
10
10
3
5j
94.4 (S)
72 (S)
f
500
5j
1000
1000
200
5k
5k
5l
96.8 (S)
91.4 (S)
96.4 (S)
92.6 (S)
76 (S)
3
5
200
5
5l
200
4
5m
5m
5n
5n
5o
5o
5p
5p
5q
5q
5r
200
4
89 (S)
500
10
10
3
94.1 (S)
92.8 (S)
71 (R)
500
1000
1000
1000
1000
1000
200
4o: R1 = R2 = H, R3 = Ph, X = NHAc
3
71 (S)
4p: R1 = R2 = H, R3 = 2-Naph, X = NHAc
4
43 (R)
4p: R1 = R2 = H, R3 = 2-Naph, X = NHAc
4
96.4 (R)
58 (R)
4q: R1 = R2 = H, R3 = 3-AcOC6H4, X = NHAc
4q: R1 = R2 = H, R3 = 3-AcOC6H4, X = NHAc
4r: R1 = R2 = H, R3 = 4-O2NC6H4, X = NHAc
4r: R1 = R2 = H, R3 = 4-O2NC6H4, X = NHAc
4s: R1 = R2 = H, R3 = 3,5-(F3C)2C6H3, X = NHAc
4s: R1 = R2 = H, R3 = 3,5-(F3C)2C6H3, X = NHAc
4t: R1 = R2 = H, R3 = t-Bu, X = NHAc
4
4
96.3 (R)
92.8 (R)
98.6 (R)
73 (R)
1000
200
4
4
5r
1000
1000
300
4
5s
5s
5t
4
96.1 (R)
9 (S)
5
4t: R1 = R2 = H, R3 = t-Bu, X = NHAc
300
5
5t
15 (S)
4u: R1 = PhCO, R2 = H, R3 = Me, X = NHAc
4u: R1 = PhCO, R2 = H, R3 = Me, X = NHAc
4v: R1 = R2 = H, R3 = P(O)(OMe)2, X = OBz
4v: R1 = R2 = H, R3 = P(O)(OMe)2, X = OBz
4w: R1 = R2 = H, R3 = P(O)(OEt)2, X = NHAc
4w: R1 = R2 = H, R3 = P(O)(OEt)2, X = NHAc
200
5
5u
5u
5v
5v
5w
5w
89 (+)
g
200
5
86 (+)
1000
1000
200
5
98.0 (S)
96.8 (S)
95.6 (S)
98.4 (S)
5
4
200
4
a
b
All reactions were carried out in methanol at room temperature over 18 h, and the conditions were not optimized. The reactions were completed
c
d
under the conditions, unless otherwise noted. The ee values were determined after conversion of the product into its methyl ester. The
hydrogenation was carried out in dichloromethane. The hydrogenation in methanol provided the corresponding product with 47% ee. Conversion
of the reaction: 50%. Conversion of the reaction: 42%.
e
f
g
by the addition of diethyl ether (5 mL). The precipitated solid was
collected on a glass filter and washed with diethyl ether to afford
orange microcrystals (120 mg, 86%): H NMR (500 MHz, CDCl3) δ
1.21 (d, J = 14.9 Hz, 9H), 1.26 (d, J = 13.8 Hz, 9H), 1.46 (d, J = 13.7
Hz), 1.61 (d, J = 8.6 Hz), 2.16−2.24 (m, 3H), 2.24−2.32 (m, 1H),
2.42−2.51 (m, 2H), 2.68−2.75 (m, 2H), 4.47 (m, 1H), 5.45 (m, 1H),
5.57 (m, 1H), 6.45 (m, 1H), 7.68−7.75 (m, 2H), 7.76−7.75 (m, 1H),
8.13−8.17 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 5.2 (d, J = 24.0
Hz), 26.0 (d, J = 24.0 Hz), 29.4 (s), 31.21 (s), 31.5 (s), 35.8 (d, J =
22.8 Hz), 37.4 (d, J = 28.8 Hz), 39.6 (d, J = 7.2 Hz), 41.8 (d, J = 14.4 Hz),
1
4186
dx.doi.org/10.1021/jo300454n | J. Org. Chem. 2012, 77, 4184−4188

The Journal of Organic Chemistry
Note
95.1 (s), 100.0 (s), 100.6 (m), 109.1 (s), 131.5 (d, J = 23.9), 132.6
(d, J = 16.8 Hz), 134.2 (d, J = 15.6 Hz); 31P NMR (202 MHz, CDCl3)
δ 59.3 (d, J = 149.8 Hz), 83.6 (d, J = 160.7 Hz); HRMS-TOF
(m/z) [M − SbF6 − C8H12 (COD)]+ calcd for C19H34P2Rh+,
427.1191; found, 427.1190.
solution was concentrated under reduced pressure to 0.5 mL, followed by
the addition of diethyl ether (3 mL). The precipitated solid was collected
on a glass filter and washed with diethyl ether to give (R)-2-(tert-
butylmethylphosphino)-3-(di-tert-butylphosphino)quinoxaline(1,5-
cyclooctadiene)rhodium(I) hexafluoroantimonate (74 mg, 90%) as a
brown microcrystalline solid: 1H NMR (500 MHz, CDCl3) δ 1.26 (d, J =
14.9 Hz, 9H), 1.31 (d, J = 14.1 Hz, 9H), 1.55 (d, J = 14.3 Hz, 9H), 1.78
(d, J = 8.6 Hz, 3H), 2.16−2.38 (m, 4H), 2.44−2.60 (m, 2H), 2.66−2.84
(m, 2H), 4.65−4.75 (m, 1H), 5.56−5.66 (m, 1H), 5.66−5.72 (m, 1H),
6.51−6.61 (m, 1H), 7.96−8.10 (m, 2H), 8.22−8.35 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 4.6 (d, J = 24.0 Hz), 26.2 (d, J = 16.8 Hz), 29.3 (d,
J = 3.6 Hz), 30.8 (d, J = 4.8 Hz), 31.2 (d, J = 4.8 Hz), 35.7 (dd, J = 36.0,
3.6 Hz), 38.6 (d, J = 27.6 Hz), 40.4 (d, J = 8.4 Hz), 43.2 (d, J = 13.2 Hz),
85.2 (dd, J = 14.4, 7.2 Hz), 94.2 (dd, J = 12.0 Hz, 6.0 Hz), 102.5 (dd, J =
9.6, 3.6 Hz), 130.2, 108.8 (t, J = 6.0 Hz), 133.1, 141.4 (d, J = 8.4 Hz),
141.9 (d, J = 7.2 Hz), 155.8 (dd, J = 55.7, 45.7 Hz), 157.1 (dd, J = 49.3,
40.9 Hz); 31P NMR (202 MHz, CDCl3) δ 44.2 (d, J = 141 Hz), 62.3 (d,
J = 122 Hz); HRMS-ESI (m/z) [M − SbF6]+ calcd for C29H46N2P2Rh+,
587.2191; found, 587.2190.
General Procedure for Asymmetric Hydrogenation. The
rhodium precatalyst (0.002 mmol), substrate (2 mmol), and a
magnetic stir bar were introduced into a hydrogenation bottle. The
system was then evacuated and filled with hydrogen. After repeating
this operation several times, degassed methanol (5 mL) was added,
and the hydrogen pressure was adjusted to 3 atm. After stirring for
18 h, the reaction mixture was evaporated under reduced pressure, and
the residue was passed through a short column of silica gel using ethyl
acetate/hexane (1:1) as the eluent to remove the rhodium catalyst.
The solvent was removed under reduced pressure, and the product
was dried under vacuum. The enantiomeric excess of the product was
determined by HPLC or GC analysis using chiral columns.
2-(Di-tert-butylphosphino)-3-chloroquinoxaline (2). To a
solution of di-tert-butylphosphine−borane (2.40 g, 15.0 mmol) in
THF (30 mL) was added n-BuLi (9.4 mL of a 1.6 M hexane solution,
15.0 mmol) under argon at −5 °C. The resulting yellow-green solution
was slowly added to a solution of 2,3-dichloroquinoxaline (1.99 g,
10.0 mmol) in THF (40 mL) over 10 min. After stirring for an
additional 30 min, water (50 mL) was added, the organic layer was
separated, and the aqueous layer was extracted with hexane (25 mL).
The combined organic extracts were washed with water (25 mL × 2)
and brine (50 mL), dried over Na2SO4, and evaporated to give a pasty
oil. TMEDA (10 mL) and ethyl acetate (20 mL) were added, and
the solution was kept for 2 h until the deboronation reaction had
completed. The reaction mixture was diluted with ethyl acetate
(30 mL) and washed successively with water, 5% aqueous HCl
solution, water, and brine, followed by drying over Na2SO4. The
solvent was removed on a rotary evaporator to give a yellow pasty oil,
which was purified by silica gel column chromatography (hexane/ethyl
acetate = 30/1) to afford 2-(di-tert-butylphosphino)-3-chloroquinoxa-
line as a yellow solid (2.98 g, 96%): mp 71−72 °C, Rf = 0.23 (silica gel,
hexane/ethyl acetate = 30/1); 1H NMR (500 MHz, CDCl3) δ 1.26 (d,
J = 12.0 Hz, 18H), 7.71−7.79 (m, 2H), 7.95−8.00 (m, 1H), 8.10−8.15
(m, 1H); 13C NMR (125 MHz, CDCl3) δ 30.2 (d, J = 14.4 Hz), 34.4
(d, J = 22.8 Hz), 128.4, 129.5, 130.0, 131.4, 140.6, 141.2, 153.4 (d, J =
38.5 Hz), 160.9 (d, J = 34.9 Hz); 31P NMR (202 MHz, CDCl3) δ 26.5
(brs); HRMS-ESI (m/z) [M + H]+ calcd for C16H23ClN2P+, 309.1287;
found, 309.1270.
( R ) - 2 - ( t e r t - B u t y l m e t h y l p h o s p h i n o ) - 3- ( d i -t e r t -
butylphosphino)quinoxaline ((R)-3H-QuinoxP*). To a solution
of (S)-tert-butylmethylphosphine−borane (0.72 g, 6.1 mmol) in THF
(5 mL) was added n-BuLi in hexane (3.8 mL of a 1.6 M hexane
solution, 6.1 mmol) at 0 °C under argon. After stirring for 30 min, the
solution was slowly added to a suspension of 2-di-tert-butylphosphi-
no)-3-chloroquinoxaline (1.15 g, 3.7 mmol) in DMF (20 mL) at
−5 °C, and stirring was continued for an additional 4 h at the same
temperature. Water (40 mL) was added, and the mixture was extracted
with ethyl acetate (40 mL × 2). The combined extracts were washed
with brine (40 mL) and evaporated to give a yellow pasty oil, which
was reacted with TMEDA (10 mL) in ethyl acetate (20 mL) for 1 h at
room temperature. The reaction mixture was diluted with ethyl acetate
(20 mL), and the solution was washed successively with water, a 6 M
HCl solution, water, and brine, followed by drying over Na2SO4. The
solvent was removed under reduced pressure, and the residue was
purified by silica gel column chromatography using hexane/ethyl
acetate = 30/1 as the eluent to afford (R)-2-(tert-butylmethylphos-
phino)-3-(di-tert-butylphosphino)quinoxaline (1.32 g, 95%) as a
yellow solid. Pure compound was obtained by recrystallization from
ASSOCIATED CONTENT
* Supporting Information
Conditions for determining the enantiomeric excesses of the
hydrogenation products and NMR spectra of the new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*Fax: (+81)-3-3636-8071. E-mail: imamoto@faculty.chiba-u.jp.
Notes
■
The authors declare no competing financial interest.
REFERENCES
■
(1) For representative reviews, see: (a) Zhou, Q.-L., Ed.; Privileged
Chiral Ligands and Catalysts; Wiley-VCH: Weinheim, 2011. (b) Borner,
̈
A., Ed.; Phosphorus Ligands in Asymmetric Catalysis; Wiley-VCH:
Weinheim, 2008; Vol. 1−3. (c) Tang, W.; Zhang, X. Chem. Rev. 2003,
103, 3029.
(2) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.;
Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998,
120, 1635.
(3) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 64, 2988.
(4) Gridnev, I. D.; Yamanoi, Y.; Higashi, N.; Tsuruta, H.; Yasutake,
M.; Imamoto, T. Adv. Synth. Catal. 2001, 343, 118.
(5) Knowles, W. S. Acc. Chem. Res. 1983, 16, 106.
(6) Hoge, G.; Wu, H.-P.; Kissel, W. S.; Pflum, D. A.; Greene, D. J.;
Bao, J. J. Am. Chem. Soc. 2004, 126, 5966.
hot ethyl acetate/methanol (1/5): mp 165−167 °C. Rf = 0.20 (silica
1
gel, hexane/ethyl acetate = 30/1); [α]25 −46.0 (c 0.5, EtOAc); H
D
NMR (500 MHz, CDCl3) δ 1.15 (d, J = 12.0 Hz, 9H), 1.19 (d, J =
11.5 Hz, 9H), 1.34 (d, J = 11.8 Hz, 9H), 1.41 (d, J = 5.5 Hz, 3H),
7.67−7.76 (m, 2H), 8.03−8.12 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 6.7 (d, J = 8.4 Hz), 27.7 (d, J = 13.2 Hz), 30.5 (d, J = 13.2
Hz), 30.7 (d, J = 13.2 Hz), 31.3 (dd, J = 14.4, 2.4 Hz), 34.5 (dd, J =
24.0, 4.8 Hz), 35.3 (dd, J = 22.8, 2.4 Hz), 129.5, 129.6, 129.7, 129.8,
141.1, 141.2, 166.4 (t, J = 31.2 Hz), 167.5 (dd, J = 33.7, 28.8 Hz); 31P
NMR (202 MHz, CDCl3,) δ −14.4 (dm, J = 107 Hz), 21.6 (dm, J =
+
107 Hz); HRMS-ESI (m/z) [M + H]+ calcd for C21H35N2P2 ,
377.2275; found, 377.2299.
(7) Wu, H.-P.; Hoge, G. Org. Lett. 2004, 6, 3645.
( R ) - 2 - ( t e r t - B u t y l m e t h y l p h o s p h i n o ) - 3- ( d i -t e r t -
butylphosphino)quinoxaline(1,5-cyclooctadiene)rhodium(I)
Hexafluoroantimonate (3). A solution of (R)-2-(tert-butylmethyl-
phosphino)-3-(di-tert-butylphosphino)quinoxaline (39.4 mg, 0.105
mmol) in dichloromethane (1.5 mL) was added dropwise to a solution
of [Rh(cod)2]SbF6 (55.5 mg, 0.100 mmol) in dichloromethane (2 mL)
at 0 °C under argon. After stirring at room temperature for 30 min, the
(8) Dai, Q.; Li, W.; Zhang, X. Tetrahedron 2008, 64, 6943.
(9) Tang, W.; Capacci, A. G.; White, A.; Ma, S.; Rodriguez, S.; Qu,
B.; Savoie, J.; Patel, N. D.; Wei, X.; Haddad, N.; Grinberg, N.; Yee, N.
K.; Krishnamurthy, D.; Senanayake, C. H. Org. Lett. 2010, 12, 1104.
(10) Huang, K.; Zhang, X.; Emge, T. J.; Hou, G.; Cao, B.; Zhang, X.
Chem. Commun. 2010, 46, 8555.
4187
dx.doi.org/10.1021/jo300454n | J. Org. Chem. 2012, 77, 4184−4188

The Journal of Organic Chemistry
Note
́ ́
(11) Reves, M.; Ferrer, C.; Leon, T.; Doran, S.; Etayo, P.; Vidal-
Ferran, A.; Riera, A.; Verdaguer, X. Angew. Chem., Int. Ed. 2010, 49,
9452.
(12) Hoge and co-workers noted that 1-(tert-butylmethylphosphi-
no)-2-(di-tert-butylphosphino)ethane showed enantioselectivities sim-
ilar to those of Trichickenhootphos in the rhodium-catalyzed
asymmetric hydrogenation of α-acetamido dehydroamino acids,
while detailed results were not described.6
(13) For examples of unsymmetric diphosphine ligands analogous to
three-hindered diphosphine ligands in the structural mode, see:
(a) Blaser, H.; Brieden, W.; Pugin, B.; Spindler, F.; Studer, M.; Togni,
A. Top. Catal. 2002, 19, 3. (b) Matsumura, K.; Shimizu, H.; Saito, T.;
Kumobayashi, H. Adv. Synth. Catal. 2003, 345, 180. (c) Ohashi, A.;
Imamoto, T. Org. Lett. 2001, 3, 373.
(14) Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005,
127, 11934.
(15) Tamura, K.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; Imamoto,
T. Org. Lett. 2010, 12, 4400.
(16) Imamoto, T.; Tamura, K.; Zhang, Z.; Horiuchi, Y.; Sugiya, M.;
Yoshida, K.; Yanagisawa, A.; Gridnev, I. D. J. Am. Chem. Soc. 2012,
134, 1754.
(17) Yamamoto, Y.; Koizumi, T.; Katagiri, K.; Furuya, Y.; Danjo, H.;
Imamoto, T.; Yamaguchi, K. Org. Lett. 2006, 8, 6103.
(18) Compound 1 was previously synthesized,17 but its enantioin-
duction ability in asymmetric catalysis has not yet been evaluated.
(19) You, J.; Drexler, H.-J.; Zhang, S.; Fischer, C.; Heller, D. Angew.
Chem., Int. Ed. 2003, 42, 913 and references cited therein.
(20) Wehner, V.; Blum, H.; Kurz, M.; Stilz, H. U. Synthesis 2002,
2023.
(21) Geng, H.; Huang, K.; Sun, T.; Li, W.; Zhang, X.; Zhou, L.; Wu,
W.; Zhang, X. J. Org. Chem. 2011, 76, 332.
(22) (a) Gridnev, I. D.; Yasutake, M.; Imamoto, T.; Beletskaya, I. P.
Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 5385. (b) Wang, D.-Y.; Hu,
X.-P.; Huang, J.-D.; Deng, J.; Yu, S.-B.; Duan, Z.-C.; Xu, X.-F.; Zheng, Z.
Angew. Chem., Int. Ed. 2007, 46, 7810. (c) Wang, D.-Y.; Huang, J.-D.;
Hu, X.-P.; Deng, J.; Yu, S.-B.; Duan, Z.-C.; Zheng, Z. J. Org. Chem.
2008, 73, 2011. (d) Zhang, J.; Li, Y.; Wang, Z.; Ding, K. Angew. Chem.,
Int. Ed. 2011, 50, 11743. (e) Zhang, J.; Dong, K.; Wang, Z.; Ding, K.
Org. Biomol. Chem. 2012, 10, 1598 and references cited therein.
4188
dx.doi.org/10.1021/jo300454n | J. Org. Chem. 2012, 77, 4184−4188