Pd-catalyzed asymmetric allylic amination using aspartic acid derived P-chirogenic diaminophosphine oxides: DIAPHOXs

Article abstract of DOI:10.1021/ol051748v

(Chemical Equation Presented) A Pd-catalyzed asymmetric allylic amination using aspartic acid derived P-chirogenic diaminophosphine oxides (DIAPHOXs) is described. Asymmetric allylic amination of both linear and cyclic substrates proceeded at room temperature to give the chiral allylic amines in 72-99% ee.

Full text of DOI:10.1021/ol051748v

ORGANIC
LETTERS
2
005
Vol. 7, No. 20
447-4450
Pd-Catalyzed Asymmetric Allylic
Amination Using Aspartic Acid Derived
P-Chirogenic Diaminophosphine
Oxides: DIAPHOXs
4
Tetsuhiro Nemoto, Takamasa Masuda, Yuichi Akimoto, Takashi Fukuyama, and
Yasumasa Hamada*
Graduate School of Pharmaceutical Sciences, Chiba UniVersity, Yayoi-cho, Inage-ku,
Chiba, 263-8522, Japan
hamada@p.chiba-u.ac.jp
Received July 23, 2005
ABSTRACT
A Pd-catalyzed asymmetric allylic amination using aspartic acid derived P-chirogenic diaminophosphine oxides (DIAPHOXs) is described.
Asymmetric allylic amination of both linear and cyclic substrates proceeded at room temperature to give the chiral allylic amines in 72
−99%
ee.
Considerable effort has been directed toward the catalytic
asymmetric synthesis of R-chiral amines because of the
ubiquity of the chiral amine unit in biologically active
compounds. Various approaches, involving asymmetric
tigated. Among them, a transition-metal-catalyzed asym-
metric allylic amination reaction is a powerful method for
4
the synthesis of chiral allylic amines. Several reactions of
5
6
7
this type using Pd, Ir, or other transition metal catalysts
have been reported.
1
hydrogenation, as well as asymmetric addition of carbon
2
3
nucleophiles and nitrogen nucleophiles, have been inves-
(
3) (a) Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc.
(
1) For a review, see: Ohkuma, T.; Kitamura, M.; Noyori, R. Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York,
000; pp 1-110.
2) For recent representative examples, see: (a) Strecker reaction:
2003, 125, 16178-16179. (b) Hamashima, Y.; Somei, H.; Shimura, Y.;
Tamura, T.; Sodeoka, M. Org. Lett. 2004, 6, 1861-1864 and references
therein.
(4) For reviews, see: (a) Trost, B. M. Chem. Pharm. Bull. 2002, 50,
1-14. (b) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921-
2943.
(5) (a) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.;
Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301-6311. (b) Trost, B. M.;
Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089-4090. (c) Evans, D. A.;
Campos, K. R.; Tedrow, J. S.; Michael, F. E.; Gagn e´ , M. R. J. Org. Chem.
1999, 64, 2994-2995. (d) You, S.-L.; Zhu, X.-Z.; Lou, Y.-M.; Hou, X.-L.;
Dai, L.-X. J. Am. Chem. Soc. 2001, 123, 7471-7472. (e) Zablocka, M.;
Koprowski, M.; Donnadieu, B.; Majoral, J.-P.; Achard, M.; Buono, G.
Tetrahedron Lett. 2003, 44, 2431-2415. (f) Uozumi, Y.; Tanaka, H.;
Shibatomi, K. Org. Lett. 2004, 6, 281-283. (g) Faller, J. W.; Wilt, J. C.
Org. Lett. 2005, 7, 633-636.
2
(
Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10012-10014
and references cited therein. (b) Reissert reaction: Ichikawa, E.; Suzuki,
M.; Yabu, K.; Albert, M.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
004, 126, 11808-11809 and references therein. (c) Mannich-type reac-
tion: Yoshida, T.; Morimoto, H.; Kumagai, N.; Matsunaga, S.; Shibasaki,
2
M. Angew. Chem., Int. Ed. 2005, 44, 3470-3474 and references therein.
(
1
1
d) Boezio, A. A.; Charette, A. B. J. Am. Chem. Soc. 2003, 125, 14260-
4261. (e) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126,
0558-10559. (f) Ogawa, C.; Sugiura, M.; Kobayashi, S. Angew. Chem.,
Int. Ed. 2004, 43, 6491-6493. (g) Ooi, T.; Kameda, M.; Taniguchi, M.;
Maruoka, K. J. Am. Chem. Soc. 2004, 126, 9685-9694. (h) Momiyama,
N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5360-5361.
1
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© 2005 American Chemical Society
Published on Web 09/08/2005

Table 1. Pd-Catalyzed Asymmetric Allylic Amination
1
2
b
c
entry
substrate
HNR R
Pd catalyst (mol %)
solvent
preligand
product
time (h)
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
BnNH2
furfurylamine
n-BuNH2
cyclohexylamine
i-PrNH2
morpholine
morpholine
N-methylaniline
BnNH2
2
2
2
2
2
2
1
2
5
5
5
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
3a
3b
3c
3d
3e
3f
24
24
60
24
12
7
12
24
23
23
23
23
91
92
79
87
99
92
90
nrd
63
72
75
76
98 (R)
96
99
98
94
95
97
3f
3g
3h
3h
3h
3h
35
52
48
29
1
1
1
0
1
2
BnNH2
BnNH2
BnNH2
a
η3-C3H5PdCl)2 was used. b Isolated yield. c Determined by HPLC analysis. d No reaction.
(
We recently developed aspartic acid derived air- and
moisture-stable pentavalent phosphorus preligands: P-
chirogenic diaminophospine oxides 1a-d (Figure 1). These
ternary stereocenters through Pd-catalyzed asymmetric allylic
alkylation. These results led us to expect that the present
catalyst system could be extended to carbon-nitrogen bond-
forming reactions. Herein, we report Pd-catalyzed asym-
metric allylic amination reactions using P-chirogenic di-
8
9
aminophosphine oxides.
We first examined asymmetric allylic amination of 1,3-
diphenylallyl acetate 2a with benzylamine using (S,R )-Ph-
P
DIAPHOX 1a. The reaction was performed under conditions
similar to the case of asymmetric allylic alkylation of 2a
8
b
with dimethyl malonate, and the best reactivity and
enantioselectivity were obtained when CH Cl was used as
2
2
the solvent (Table 1). Various amine nucleophiles were
applied to this type of asymmetric allylic amination. Using
1-2 mol % of Pd catalyst and 2-4 mol % of 1a, asymmetric
allylic amination of 2a with both primary and secondary
amines proceeded at room temperature to give the corre-
sponding products 3a-f in good yield with high stereo-
selectivity. No reaction, however, occurred when aniline
Figure 1. Aspartic acid derived P-chirogenic diaminophosphine
oxides: (S,R )-DIAPHOXs.
P
preligands were activated in situ by N,O-bis(trimethylsilyl)-
acetamide (BSA) induced P(V) to P(III) transformation to
afford trivalent phosphorus ligands and were successfully
applied to stereoselective construction of tertiary and qua-
1
0
derivatives were utilized as the nucleophiles. This catalyst
system was also applied to asymmetric allylic amination of
1
,3-dialkyl-substituted allyl carbonate 2b. The reaction
was performed using 1a in CH CN, affording the corre-
sponding product in moderate yield with low enantiomeric
3
(
6) (a) Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 15164-
1
5165. (b) Kiener, C. A.; Shu, C.; Incarvito, C.; Hartwig, J. F. J. Am. Chem.
Soc. 2003, 125, 14272-14273. (c) Shu, C.; Leiner, A.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2004, 43, 4797-4800. (d) Tissot-Croset, K.; Polet, D.;
Alexakis, A. Angew. Chem., Int. Ed. 2004, 43, 2426-2428. (e) Lipowsky,
G.; Helmchen, G. Chem. Commun. 2004, 116-117. (f) Welter, C.; Dahnz,
A.; Bruner, B.; Steiff, S.; D u¨ bon, P.; Helmchen, G. Org. Lett. 2005, 7,
(9) For representative examples of transition metal catalysis with
pentavalent phosphorus preligands, see: (a) Li, G. Y. Angew. Chem., Int.
Ed. 2001, 40, 1513-1516. (b) Jiang, X.-B.; Minnaard, A. J.; Hessen, B.;
Feringa, B. L.; Duchateau, A. L. L.; Andrien, J. G. O.; Boogers, J. A. F.;
de Vries, J. G. Org. Lett. 2003, 5, 1503-1506. (c) Ackermann, L.; Born,
R. Angew. Chem., Int. Ed. 2005, 44, 2444-2447. (d) Bigeault, J.; Giordano,
L.; Buono, G. Angew. Chem., Int. Ed. 2005, 44, 4753-4757 and references
therein.
1
239-1242. (g) Polet, D.; Alexakis, A. Org. Lett. 2005, 7, 1621-1624.
(7) (a) Ru catalyst: Matsushima, Y.; Onitsuka, K.; Kondo, T.; Mitsudo,
T.; Takahashi, S. J. Am. Chem. Soc. 2001, 123, 10405-10406. (b) Ni
catalyst: Bekowitz, D. B.; Maiti, G. Org. Lett. 2004, 6, 2661-2664. (c)
Enantiospecific allylic amination using Rh catalyst: Evans, P. A.; Robinson,
J. E.; Nelson, J. D. J. Am. Chem. Soc. 1999, 121, 6761-6762.
(10) When benzylamine and morpholine were treated with 1 equiv of
1
(8) (a) Nemoto, T.; Matsumoto, T.; Masuda, T.; Hitomi, T.; Hatano, K.;
BSA in CDCl3, N-trimethylsilylation was observed in each case by H NMR.
Hamada, Y. J. Am. Chem. Soc. 2004, 126, 3690-3691. (b) Nemoto, T.;
This fact indicates that N-trimethylsilylated amines would be the actual
nucleophiles in this reaction system. In contrast, no trimethylsilylation
occurred in the case of N-methylaniline. These results appear to suggest
that N-trimethylsilylation might be important for the reaction.
Masuda, T.; Matsumoto, T.; Hamada, Y. J. Org. Chem. 2005, 70, 7172-
7
178. (c) Nemoto, T.; Fukuda, T.; Matsumoto, T.; Hitomi, T.; Hamada, Y.
AdV. Synth. Catal. In press.
4448
Org. Lett., Vol. 7, No. 20, 2005

of cyclic substrates. Asymmetric allylic amination of 2-sub-
stituted cycloalkenyl alcohol derivatives affords versatile
adducts for the synthesis of nitrogen-containing natural
products. Despite its usefulness, the success of this type of
Table 2. Effect of Solvent in Pd-Catalyzed Asymmetric Allylic
Amination of 5a with Benzylamine
1
2
reaction is limited. Therefore, we examined asymmetric
allylic amination of 2-phenylcyclohexenyl alcohol derivatives
with benzylamine (Table 2). Although no reaction occurred
when 2-phenylcyclohexenyl acetate 4 was used as the
substrate, allylic amination reaction of 2-phenylcyclohexenyl
carbonate 5a proceeded in the presence of 2 mol % of the
catalyst at room temperature, affording the corresponding
product 6a in 75% yield and 93% ee. Examination of the
solvent effect revealed that the reaction medium dramatically
affected reactivity rather than enantioselectivity, and the best
a
b
entry
substrate
solvent
time (h)
yield (%)
ee (%)
1
2
3
4
5
6
4
CH2Cl2
CH2Cl2
THF
DMF
toluene
CH3CN
24
48
48
48
48
17
nrc
75
33
71
39
93
5a
5a
5a
5a
5a
93
92
92
90
96
results were obtained when CH
3
CN was used as the solvent.13
The scope and limitation of different substrates were
further examined under optimized conditions (Table 3).
When 2 mol % of Pd catalyst and 4 mol % of 1a were used,
asymmetric allylic amination of 2-phenyl cyclohexenyl
carbonates using primary and secondary amines proceeded
at room temperature to provide the corresponding products
in good yield with high enantioselectivity (95-97% ee).
Other cyclic substrates with a five-membered ring and a
seven-membered ring were also applicable to this reaction,
a
Isolated yield. b Determined by HPLC analysis. c No reaction.
excess.11 There was a slight improvement in the enantio-
selectivity when (S,R )-1-Np-DIAPHOX 1b was used as the
P
preligand.
The satisfactory results in the conventional reaction system
led us to turn our attention to asymmetric allylic amination
Table 3. Pd-Catalyzed Asymmetric Allylic Amination of 2-Substituted Cycloalkenyl Carbonates
a
η3-C3H5PdCl)2 was used. b Isolated yield. c Determined by HPLC analysis. d 5 mol % of Pd catalyst and 10 mol % of 1a were used. e The number in
(
parentheses indicates recovered starting material.
Org. Lett., Vol. 7, No. 20, 2005
4449

affording the chiral allylic amines with good to excellent
enantioselectivity (83-99% ee). Furthermore, asymmetric
allylic amination of cyclohexenyl carbonates with various
substituents at the 2-position were examined using benzyl-
amine as the nucleophile. Aryl groups with an electron-
withdrawing functionality, as well as an electron-donating
functionality, were tolerant to this reaction, giving the
products with high enantioselectivity (91-98% ee). Sub-
strates with alkyl, alkenyl, and alkynyl substituents were also
applicable to this reaction, and the corresponding products
were obtained in moderate to good enantiomeric excess (72-
Scheme 1. Catalytic Asymmetric Synthesis of (S)-7
1
4
94% ee).
Thus, the present catalytic asymmetric system had broad
generality for both electrophiles and amine nucleophiles,
affording R-chiral allylic amines in up to 99% ee for both
linear and cyclic substrates.15 To demonstrate the synthetic
utility, we applied this catalyst system to the catalytic
asymmetric synthesis of (S)-7, which is the key intermediate
for Mori’s total synthesis of crinine-type alkaloids (Scheme
In conclusion, we succeeded in Pd-catalyzed asymmetric
allylic amination using aspartic acid derived P-chirogenic
diaminophosphine oxides, which afforded the chiral allylic
amines in up to 99% ee. The broad substrate generality of
the developed system resulted in a highly enantioselective
synthesis of the key intermediate for crinine-type alkaloid
synthesis.
1
2e
1). Using 5 mol % of Pd catalyst and 10 mol % of 1a,
asymmetric allylic amination of 8 with amine 9 proceeded
at room temperature, affording the chiral allylic amine 10
in 98% yield and 97% ee, which could be converted to the
key intermediate (S)-7.16
Acknowledgment. This work was supported by a Grant-
in Aid for Encouragement of Young Scientist (B) from the
Ministry of Education, Culture, Sport, Science, and Technol-
ogy, Japan, and the Banyu Award in Synthetic Organic
Chemistry, Japan.
(11) The reaction proceeded very sluggishly in other solvents such as
CH2Cl2.
(12) (a) Mori, M.; Kuroda, S.; Zhang, C.-S.; Sato, Y. J. Org. Chem.
1
1
997, 62, 3263-3270. (b) Trost, B. M.; Oslob, J. D. J. Am. Chem. Soc.
999, 121, 3057-3064. (c) Hamada, Y.; Sakaguchi, K.; Hatano, K.; Hara,
Supporting Information Available: General procedure
for Pd-catalyzed asymmetric allylic amination, compound
characterization of new compounds, and NMR charts. This
material is available free of charge via the Internet at
http://pubs.acs.org.
O. Tetrahedron Lett. 2001, 42, 1297-1299. (d) Mori, M.; Nakanishi, M.;
Kajishima, D.; Sato, Y. J. Am. Chem. Soc. 2003, 125, 9801-9807. (e)
Nishimata, T.; Sato, Y.; Mori, M. J. Org. Chem. 2004, 69, 1837-1843.
(13) We speculate that coordination of CH3CN to palladium metal might
prevent catalyst deactivation by competitive coordination of the product,
resulting in the higher reactivity compared with the cases of other solvents.
(
14) Asymmetric allylic amination of cyclohexenyl methyl carbonate with
benzylamine gave less satisfactory result under the same reation conditions
Pd catalyst (2 mol %), 1a (4 mol %), BnNH2 (3 equiv), BSA (3 equiv),
OL051748V
[
CH3CN, rt, 36 h: 57%, 35% ee]. This result indicates the importance of
the 2-substituent on the asymmetric induction.
(16) In Mori’s optimized conditions (5 mol % of Pd catalyst, 5 mol %
of (S)-BINAPO, THF, -20 °C), (S)-7 was obtained from the corresponding
vinyl carbonate in 82% yield and in 74% ee.1
(
15) For the experimental procedure of asymmetric allylic amination
2e
reactions; see Supporting Information.
4450
Org. Lett., Vol. 7, No. 20, 2005