Air-stable P-chiral bidentate phosphine ligand with (1-adamantyl) methylphosphino group

Article abstract of DOI:10.1246/cl.2007.500

Air-stable diphosphine ligand, (R,R)-2,3-bis((1-adamantyl)-methylphosphino) quinoxaline, was prepared by the reaction of enantiomerically pure (S)-(1-adamantyl)methylphosphine-borane with 2,3-dichloroquinoxaline. The ligand exhibited excellent enantiosele

Full text of DOI:10.1246/cl.2007.500

500
Chemistry Letters Vol.36, No.4 (2007)
Air-stable P-Chiral Bidentate Phosphine Ligand with (1-Adamantyl)methylphosphino Group
Tsuneo Imamoto,ꢀ Atsushi Kumada, and Kazuhiro Yoshida
Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522
(Received January 25, 2007; CL-070093; E-mail: imamoto@faculty.chiba-u.jp)
1. (–)-sparteine/s-BuLi
Air-stable diphosphine ligand, (R,R)-2,3-bis((1-adamantyl)-
methylphosphino)quinoxaline, was prepared by the reaction of
enantiomerically pure (S)-(1-adamantyl)methylphosphine–bor-
ane with 2,3-dichloroquinoxaline. The ligand exhibited excellent
enantioselectivities in Rh-catalyzed asymmetric hydrogenation
and Pd-catalyzed asymmetric ring-opening reaction.
–78~–50 °C
ether–toluene
BH3
P
BH3
P
BzCl, pyridine
Ad
Ad
Me
CH2OH
47% after recry.
from MeOH
2. O2
Me
2
Me
60%
3
Ad: 1-adamantyl
88% ee
BH3
BH3
1. KOH, MeOH
1. n-BuLi
P
Ad
Me
P
H
Ad
CH2OBz
Optically active phosphine ligands play an important role in
transition-metal-catalyzed asymmetric reactions.1 While numer-
ous chiral phosphine ligands have been designed and synthe-
sized for almost four decades, it is still necessary to develop
new ones for the establishment of more efficient catalytic proc-
esses of various asymmetric reactions.2 Previously, we reported
new P-chiral phosphine ligands, BisPꢀ and MiniPHOS, that pos-
sess a bulky alkyl group such as tert-butyl group and the smallest
alkyl group (methyl group) on the same phosphorus atom, and
demonstrated their exceedingly high enantioselectivity in rhodi-
um-catalyzed asymmetric hydrogenation reactions.3–5 However,
the fact that these ligands are quite sensitive to air has hindered
their widespread application in various asymmetric catalyses.
In order to overcome this difficulty, we recently synthesized
an air-stable P-chiral phosphine ligand, t-Bu-QuinoxPꢀ.6 This
ligand exhibits very high to almost perfect enantioselectivities
not only in rhodium-catalyzed asymmetric hydrogenation but
also in rhodium- or palladium-catalyzed asymmetric reactions.
We are interested in examining the catalytic activity of structur-
ally analogous ligands possessing a bulkier alkyl group at the
phosphorus atoms. Here, we report the synthesis of (R,R)-2,3-
bis((1-adamantyl)methylphosphino)quinoxaline (1) (abbreviat-
ed as Ad-QuinoxPꢀ) and its enantioselectivities in representative
catalytic asymmetric reactions.
Me
2. K2S2O8/KOH
RuCl3 (5 mol %)
2. 2,3-dichloro-
quinoxaline
3. TMEDA
4
5
>99% ee
75%
>99% ee
78%
Ad Me
Ad
Me
N
N
P
Cl
Cl
N
P
P
PdCl2(cod)
Pd
P
N
Me Ad
Me Ad
1
6
>99% ee
Scheme 1.
The synthesis of Ad-QuinoxPꢀ (1) was carried out according
to the procedure that uses phosphine–boranes as key intermedi-
ates (Scheme 1). 1-Adamantyl(dimethyl)phosphine–borane (2)
was subjected to enantioselective deprotonation with (ꢁ)-spar-
teine/sec-BuLi at low temperature and the generated organo-
lithium compound was treated with oxygen gas to give optically
active hydroxy derivative 3 with 88% ee in 60% yield. In order
to increase the ee of the alcohol, it was converted into benzoyl
derivative 4, which was recrystallized from methanol two times
to afford an enantiomerically pure compound.7 Hydrolysis of
this ester and subsequent oxidative one-carbon degradation pro-
duced enantiomerically pure secondary phosphine–borane 5.8
Deprotonation with n-BuLi and subsequent substitution reaction
with 2,3-dichloroquinoxaline, followed by treatment with tetra-
methylethylenediamine to remove the boranato groups, afforded
the desired ligand 1 as an orange air-stable amorphous solid in
75% yield.9 We expected to obtain this ligand as a crystalline
solid similar to t-Bu-QuinoxPꢀ. Unfortunately, however, numer-
ous attempts at the crystallization of 1 have proved unsuccessful.
This ligand was reacted with PdCl2(cod) to afford complex
ꢀ
.
Figure 1. Molecular structure of PdCl2(Ad-QuinoxP )
2CHCl3: The two chloroform molecules and hydrogen atoms
are omitted for clarity.
6.10 Its molecular structure was determined by single-crystal
X-ray analysis.11 As shown in Figure 1, the complex is rigid
owing to the quinoxaline backbone, and the five-membered pal-
ladium chelate forms an almost flat plane. Also worth noting is
that the two Pd–Cl bonds deviate by approximately 16ꢂ from the
chelate plane due to steric repulsion between the chlorine
atom and the bulky adamantyl group. Side views of the X-ray
structure clearly show that the second and forth quadrants
are effectively shielded by the adamantyl groups and the
other diagonal quadrants are occupied by the methyl groups.
This imposed asymmetric environment would lead to excellent
enantioselectivity in asymmetric catalysis.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.4 (2007)
501
S. Li, Q.-L. Zhou, J. Am. Chem. Soc. 2006, 128, 12886. k) T.
´
The enantioinduction ability of the ligand was examined in
the typical Rh-catalyzed asymmetric hydrogenation. The hydro-
genations of methyl (Z)-ꢀ-acetamidocinnamate and 1-acetyl-
amino-1-phenyl-2-methylpropene afforded the corresponding
reduction products both with 99.9% ee.12 These results suggest
the high utility of this ligand for the asymmetric hydrogenation
of similar prochiral substrates.
Imamoto, K. Yashio, K. V. L. Crepy, K. Katagiri, H.
Takahashi, M. Kouchi, I. D. Gridnev, Organometallics 2006,
25, 908.
3
T. Imamoto, J. Watanabe, Y. Wada, H. Masuda, H. Yamada, H.
Tsuruta, S. Matsukawa, K. Yamaguchi, J. Am. Chem. Soc.
1998, 120, 1635.
Y. Yamanoi, T. Imamoto, J. Org. Chem. 1999, 64, 2988.
I. D. Gridnev, Y. Yamanoi, N. Higashi, H. Tsuruta, M. Yasutake,
T. Imamoto, Adv. Synth. Catal. 2001, 343, 118.
T. Imamoto, K. Sugita, K. Yoshida, J. Am. Chem. Soc. 2005, 127,
4
5
[Rh(nbd)2]BF4/1 (1 mol%)
COOMe
COOMe
Ph
Ph
(1)
H2 (3 atm), MeOH, rt, 2 h
6
7
NHCOMe
NHCOMe
11934.
99.9% ee
22
Colorless crystals: mp 98–99 ꢂC, ½ꢀꢃ
¼ ꢁ25:1 (c 1.07,
D
CHCl3); 1H NMR (CDCl3) ꢁ 0.0–0.9 (br q, 3H), 1.33 (d,
JHP ¼ 9:9 Hz, 3H), 1.7–2.1 (m, 15H), 4.69 (dd, J ¼ 14:0 Hz,
[Rh(nbd)2]BF4/1 (1 mol %)
Ph
Ph
(2)
H2 (3 atm), MeOH, rt, 2 h
2JHP ¼ 1:0 Hz, 1H), 4.76 (dd, J ¼ 14:0 Hz, JHP ¼ 2:2 Hz, 1H),
2
NHCOMe
NHCOMe
7.46–7.50 (m, 2H), 7.63–7.59 (m, 1H), 8.04 (d, J ¼ 7:7 Hz,
2H); 13C NMR (CDCl3) ꢁ 1.8 (d, JCP ¼ 18:0 Hz), 27.5 (d,
3JCP ¼ 7:2 Hz), 30.5 (d, JCP ¼ 25:6 Hz), 36.2, 36.3, 57.0 (d,
JCP ¼ 28:8 Hz), 128.6, 129.0, 129.7, 133.5, 165.8; IR (KBr)
3070, 2915, 2365, 1720, 1450, 1320, 1245, 1110, 1065,
710 cmꢁ1; HRMS (FAB) calcd for C19H27BO2P ([M–1]þ)
329.1842, found 329.1845. The ee of this product was 99%
(Chiralcel OJ–H, hexane/2-propanol = 90:10, flow rate = 0.5
mL/min, wavelength = 254 nm, Retention times: 17.6 min ((S)
enantiomer, 22.0 min ((R) enantiomer)).
99.9% ee
This ligand was successfully used also in the palladium-
catalyzed asymmetric ring-opening reaction.13 Thus, reactions
using a premixing catalyst with PdCl2(cod) and 1 provided
products with 96–98% ee in almost quantitative yields.14 It is
worthy to note that the ee’s obtained in this study are about
1% higher than the ee’s by the use of t-Bu-QuinoxPꢀ.6 The
excellent enantioselectivities indicate the high utility of this
ligand in this class of asymmetric catalyses.
8
9
K. Nagata, S. Matsukawa, T. Imamoto, J. Org. Chem. 2000, 65,
4185.
R22Zn
OH
R1
27
Ad-QuinoxPꢀ: orange amorphous solid, ½ꢀꢃ
¼ ꢁ248 (c 0.33,
R1
R1
R2
D
PdCl2(cod)2/1 (5 mol %)
O
CHCl3); 1H NMR (CDCl3) ꢁ 1.39–1.41 (m, 6H), 1.53–1.85 (m,
30H), 7.73 (dd, J ¼ 6:3 Hz, 4.4 Hz, 2H), 8.11 (dd, J ¼ 6:3 Hz,
4.4 Hz, 2H). IR (KBr) 3060, 2900, 2845, 1450, 1300, 1075,
1005, 870, 760 cmꢁ1; HRMS (FAB): calcd for C30H40N2P2
(Mþ) 490.2667, found. 490.2643. The ee of this product was
>99:9% (Chiralcel OD–H, pentane, flow rate = 0.2 mL/min,
wavelength = 254 nm, Retention times: 26.4 min [(S,S) enan-
tiomer], 32.0 min [(R,R) enantiomer], 33.9 min [meso isomer]).
This compound was neither oxidized nor epimerized at the P-ster-
eogenic phosphorus atoms on standing in air at room temperature
R1
CH2Cl2, rt, 2 h
(3)
R1 = H, R2 = Me: 86%, 96.4% ee
R
R
1 = H, R2 = Et: 67%, 98.5% ee
1 = F, R2 = Me: 69%, 95.2% ee
In summary, we have prepared a new air-stable P-chiral di-
phosphine ligand possessing adamantyl groups (Ad-QuinoxPꢀ)
and demonstrated extremely high enantioselectivity in rhodi-
um-catalyzed hydrogenation and palladium-catalyzed ring-
opening reaction.
for more than 6 months.
24
10 Mp > 300 ꢂC (decomp.). ½ꢀꢃ
¼ ꢁ121 (c 0.99, CHCl3).
D
11 Single crystals of 6 suitable for X-ray crystallographic analysis
were grown from CHCl3/pentane. Crystal data for
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
6
.
(C32H42Cl8N2P2Pd (6 2CHCl3): Mr ¼ 906:62, T ¼ 173 K, tri-
˚
˚
clinic space group P1, a ¼ 9:4461ð10Þ A, b ¼ 10:4572ð11Þ A,
ꢂ
ꢂ
˚
c ¼ 11:0933ð11Þ A, ꢀ ¼ 68:6450ð10Þ , ꢂ ¼ 75:9880ð10Þ , ꢃ ¼
67:1510ð10Þꢂ, V ¼ 933:98ð17Þ A3, Z ¼ 1, ꢄcalcd ¼ 1:612 g cmꢁ3
,
¼
This paper is dedicated to Professor Teruaki Mukaiyama on
the occasion of his 80th birthday.
5281 reflections collected, R1 ¼ 0:022 for I > 2ꢅðIÞ, Rw
0:061 for all data, GOF = 1.176, CCDC-633549.
12 Conditions for the determination of the ee’s by HPLC analysis.
N-Acetylphenylalanine methyl ester: Chiralcel OJ, hexane/
2-propanol = 9:1, 0.5 mL/min, wavelength = 254 nm, retention
times: 22.3 min (R), 31.7 min (S); 1-phenyl-1-acetylamino-2-
methylpropane: Chiralcel AD, hexane/2-propanol = 9:1, 0.5
mL/min, wavelength = 254 nm, retention times: 9.7 min (S),
11.9 min (R).
References and Notes
1
For representative reviews, see: a) W. Tang, X. Zhang, Chem.
´
Rev. 2003, 103, 3029. b) K. V. L. Crepy, T. Imamoto, Top. Curr.
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2
For recent representative examples, see: a) G. Hoge, H.-P. Wu,
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and references cited therein.
14 Conditions for the determination of the ee’s by HPLC analysis.
R1 = H, R2 = Me: Chiralcel OD–H, hexane/2-propanol =
199:1, 1 mL/min, wavelength = 254 nm, retention times: 28.5
min (minor), 30.6 min (major); R1 = H, R2 = Et: Chiralcel
OD–H, hexane/2-propanol = 199:1, 1 mL/min, wavelength =
254 nm, retention times: 26.0 min (minor), 29.6 min (major);
R1 = F, R2 = Me: Chiralcel OD–H (two columns), hexane/2-
propanol = 199:1, 0.5 mL/min, wavelength = 254 nm, retention
times: 126.5 min (major), 132.6 min (minor).
`
´
Int. Ed. 2005, 44, 1118. g) O. Pamies, M. Dieguez, C.
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Published on the web (Advance View) March 3, 2007; doi:10.1246/cl.2007.500