Amination of N-aryl prolinol via ring expansion and contraction: Application to the chiral ligand for the catalytic asymmetric reaction

Article abstract of DOI:10.1021/jo0479967

(Chemical Equation Presented) Chiral diaminophosphines 4 were prepared from (S)-prolinol-derived aminophosphine oxide 5 by bromination with ring expansion followed by animation with ring contraction and reduction, using trichlorosilane. In the presence of

Full text of DOI:10.1021/jo0479967

SCHEME 1. Preparation of Diaminophosphine
Amination of N-Aryl Prolinol via Ring
Expansion and Contraction: Application to
the Chiral Ligand for the Catalytic
Asymmetric Reaction
Takashi Mino,* Akio Saito, Youichi Tanaka,
Shintaro Hasegawa, Yutaka Sato,
Masami Sakamoto, and Tsutomu Fujita
Department of Applied Chemistry and Biotechnology,
Faculty of Engineering, Chiba University, 1-33, Yayoi-cho,
Inage-ku, Chiba 263-8522, Japan
tmino@faculty.chiba-u.jp
Received November 11, 2004
and 2,6 and investigated the effect of the terminal groups
of the side chain on the ligand in palladium-catalyzed
asymmetric allylic alkylation. Recently, Kondo reported
on the preparation of chiral diaminophosphine 37 and
investigation of its application to asymmetric7b,d or
regioselective7c reactions. In this case, 3 (III: R, R′ )
-(CH)4-) was prepared from the corresponding diamine
II, such as (S)-1-(2-pyrrolidinylmethyl)pyrrolidine with
phosphine oxide I, by using the nucleophilic aromatic
substitution (SNAr) reaction as a key step. This route
(Route A in Scheme 1) did not provide a convenient way
of tuning on the terminal groups of the side chain on the
diaminophosphine unlike the case of tuning on the
phosphine site and benzene backbone,5,6 and necessitated
the preparation of various corresponding diamines II
from proline over several steps.8 Here, we report the more
straightforward preparation of various chiral diamino-
phosphines 49 (III: R ) OMe, R′ ) H) by bromination
Chiral diaminophosphines 4 were prepared from (S)-prolinol-
derived aminophosphine oxide 5 by bromination with ring
expansion followed by amination with ring contraction and
reduction, using trichlorosilane. In the presence of 4 as a
ligand, palladium-catalyzed asymmetric allylic alkylation of
1,3-diphenyl-2-propenyl acetate (11) with a dialkyl mal-
onate-BSA-LiOAc system was successfully carried out with
good enantioselectivities (up to 98% ee).
Palladium-catalyzed allylic alkylation is a widely used
process in organic synthesis,1 and the development of
efficient enantioselective catalysis for this reaction is
awaited.2 It has been found that chiral 2-(phosphinoaryl)-
oxazoline can induce high enantiomeric excesses in this
reaction.3 Following this pioneering study, aminophos-
phines have been used as ligands for this reaction.
Especially, pyrrolidinyl-containing aminophosphines were
found to be efficient chiral sources.4 Previously, we
reported the preparation of chiral aminophosphines 15
(4) (a) Farrell, A.; Goddard, R.; Guiry, P. J. J. Org. Chem. 2002, 67,
4209. (b) Okuyama, Y.; Nakano, H.; Hongo, H. Tetrahedron: Asymmetry
2000, 11, 1193. (c) Suzuki, Y.; Abe, I.; Hiroi, K. Heterocycles 1999, 50,
89. (d) Hiroi, K.; Suzuki, Y.; Abe, I. Tetrahedron: Asymmetry 1999,
10, 1173. (e) Cahill, J. P.; Cunneen, D.; Guiry, P. J. Tetrahedron:
Asymmetry 1999, 10, 4157. (f) Hattori, T.; Komuro, Y.; Hashizaka, N.;
Takahashi, H.; Miyano, S. Enantiomer 1997, 2, 203.
(5) (a) Mino, T.; Tanaka, Y.; Akita, K.; Anada, K.; Sakamoto, M.;
Fujita, T. Tetrahedron: Asymmetry 2001, 12, 1677. (b) Mino, T.;
Tanaka, Y.; Sakamoto, M.; Fujita, T. Heterocycles 2000, 53, 1485.
(6) (a) Tanaka, Y.; Mino, T.; Akita, K.; Sakamoto, M.; Fujita, T. J.
Org. Chem. 2004, 69, 6679. (b) Mino, T.; Tanaka, Y.; Akita, K.;
Sakamoto, M.; Fujita, T. Heterocycles 2003, 60, 9. (c) Mino, T.; Tanaka,
Y.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2001, 12, 2435.
(7) (a) Horibe, H.; Fukuda, Y.; Kondo, K.; Okuno, H.; Murakanmi,
Y.; Aoyama, T. Tetrahedron 2004, 60, 10701. (b) Sakamoto, Y.; Kondo,
K.; Tokunaga, M.; Kazuta, K.; Fujita, H.; Murakami, Y.; Aoyama, T.
Heterocycles 2004, 63, 1345. (c) Horibe, H.; Kazuta, K.; Kotoku, K.;
Kondo, K.; Okuno, H.; Murakami, Y.; Aoyama, T. Synlett 2003, 2047.
(d) Kondo, K.; Kazuta, K.; Saitoh, A.; Murakami, Y. Heterocycles 2003,
59, 97. (e) Kondo, K.; Kazuta, K.; Fujita, H.; Sakamoto, Y.; Murakami,
Y. Tetrahedron 2002, 58, 5209.
* To whom correspondence should be addressed. Phone: +81-43-
290-3385. Fax: +81-43-290-3401.
(1) (a) Tsuji, J.; Minami, I. Acc. Chem. Res. 1987, 20, 140. (b) Trost,
B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford,
UK, 1982; Vol. 8, p 799. (c) Trost, B. M. Acc. Chem. Res. 1980, 13, 385.
(2) (a) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1 (b) Trost, B. M.;
Lee, C. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; VCH
Publishers: New York, 2000; p 893. (c) Helmchen, G. J. Organomet.
Chem. 1999, 576, 203. (d) Pfaltz, A.; Lautens, M. In Comprehensive
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer, Tokyo, Japan, 1999; Vol. 2, p 833 and references therein.
(3) (a) Dawson, J. G.; Frost, C. G.; Williams, J. M. J.; Coote, S. J.
Tetrahedron Lett. 1993, 34, 3149. (b) Von Matt, P.; Pfaltz, A. Angew.
Chem., Int. Ed. Engl. 1993, 32, 566. (c) Sprinz, J.; Helmchen, G.
Tetrahedron Lett. 1993, 34, 1769.
(8) (a) Amedikouh, M.; Ahlberg, P. Tetrahedron: Asymmetry 2002,
13, 2229. (b) Asami, M.; Ohno, H.; Kobayashi, S.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1978, 51, 1869.
10.1021/jo0479967 CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/05/2005
J. Org. Chem. 2005, 70, 1937-1940
1937

SCHEME 3. Bromination of N-Aryl Prolinol 5
with Ring Expansion
with ring expansion and amination using the correspond-
ing amines with ring contraction on the pyrrolidine ring
(Route B).
TABLE 1. Halogenation of 5 with Ring Expansion
under Various Conditions
Initially, we tried the Mitsunobu-type reaction with
pyrrolidine using DEAD for direct amination of the
hydroxyl group10 at the terminal side chain of prolinol-
derived aminophosphine oxide 5.6 We could not isolated
a desired product. The desired product was trace under
this reaction checked by TLC, because the diphenyl
phosphinoyl group of 5 was sterically hindered. Under
the condition using carbon tetrabromide-triphenylphos-
phine with pyrrolidine, 1-(2-pyrrolidinylmethyl)pyrroli-
dine type diaminophosphine oxide 6a was directly ob-
tained from 5 in a 47% yield accompanied by 3-(1-
pyrrolidinyl)piperidine type diaminophosphine oxide 7a
as a byproduct in a 23% yield.
yield of yield of
entry
X
conditions
8 (%)a
9 (%)a
1
2
3
4
I
I2, PPh3, imidazole, THF, rt, 3 h
95
30
56
51
Cl CCl4, PPh3,b MeCN, rt, 24 h
Cl MsCl, Et3N,c THF, ∆, 3 h
Cl SOCl2, Et3N,d CHCl3, rt, 2 h
15
21
31
a Isolated yields. b Reference 13. c Reference 14. d Reference 15.
SCHEME 4. Ring Expansion Rearrangement of 9c
This reaction mechanism was investigated step by step.
In the bromination of aminophosphine oxide 5 with
carbon tetrabromide-triphenylphosphine11 at room tem-
perature, chiral 3-bromopiperidine derivative 8a (see
Figure S1 in Supporting Information) was obtained with
ring expansion in a 92% yield (Scheme 3).
bromination (entry 1 in Table 1). Although chlorination
of 5 proceeded slowly, this reaction gave 3-chloropiperi-
dine derivative 8c (see Figure S2 in Supporting Informa-
tion) with 2-chloromethylpyrrolidine 9c as a byproduct
under various methods (entries 2-4). 2-Chloromethyl-
pyrrolidine 9c was easily converted to 8c in chloroform
at 50 °C (Scheme 4).
SCHEME 2. Amination of N-Aryl Prolinol 5
A plausible mechanism for this halogenation with ring
expansion is given below.15,16 Treatment of 5 with halo-
genated reagents led to 2-halomethylpyrrolidine A
(Scheme 5). This intermediate A was easily rearranged
to 2-halomethylpyrrolidine derivative C via aziridine B,
followed by ring opening by a concerted attack of halo-
genated anion without racemization (see Supporting
Information) similar to ring expansion reactions reported
by Ori13 and Cossy.14
The amination of 3-bromopiperidine derivative com-
pound 8a via aziridinium ion intermediate A17 was
employed in the preparation of 6 (Route A in Scheme 6).
Using pyrrolidine as an amine, diaminophosphine oxide
We tried halogenation of 5 under various conditions.
Iodination of 5 with the iodine-triphenylphosphine-
imidazole method12 gave chiral 3-iodopiperidine deriva-
tive 8b in a good yield similar to that achieved by the
(9) Preliminary communication: Mino, T.; Tanaka, Y.; Sato, Y.;
Saito, A.; Sakamoto, M.; Fujita, T. Tetrahedron Lett. 2003, 44, 4677;
Tetrahedron Lett. 2003, 44, 5759.
(12) Park, S.-H.; Kang, H.-J.; Ko, S.; Park, S.; Chang, S. Tetrahedron:
Asymmetry 2001, 12, 2621.
(10) For some recent papers on Mitsunobu-type amination, see: (a)
Amos, D. T.; Renslo, A. R.; Danheiser, R. L. J. Am. Chem. Soc. 2003,
125, 4970. (b) Danstrup, D. M.; VanBrunt, M. P.; Weinreb, S. M. J.
Org. Chem. 2003, 68, 4112. (c) Rew, Y.; Goodman, M. J. Org. Chem.
2002, 67, 8820. (d) Lau, J. F.; Hansen, T. K.; Kilburn, J. P.; Fryden-
vang, K.; Holsworth, D. D.; Ge, Y.; Uyeda, R. T.; Judge, L. M.;
Andersen, H. S. Tetrahedron 2002, 58, 7339.
(13) Ori, M.; Toda, N.; Takami, K.; Tago, K.; Kogen, H. Angew.
Chem., Int. Ed. 2003, 42, 2540.
(14) Cossy, J.; Dumas, C.; Pardo, D. G. Eur. J. Org. Chem. 1999,
1693.
(15) (a) Hammer, C. F.; Weber J. D. Tetrahedron 1981, 37, 2173.
(b) Hammer, C. F.; Heller, S. R.; Craig, J. H. Tetrahedron 1972, 28,
239.
(11) Kocienski, P. J.; Cernigliaro, G.; Feldstein, G. J. Org. Chem.
1977, 42, 353.
(16) Nagle, A. S.; Salvatore, R. N.; Chong, B.-D.; Jung, K. W.
Tetrahedron Lett. 2000, 41, 3011.
1938 J. Org. Chem., Vol. 70, No. 5, 2005

TABLE 3. Preparation of Diaminophosphine 4a-h
SCHEME 5. A Plausible Mechanism for
Halogenation with Ring Expansion
yield of
yield of
yield of
6 (%)a
7 (%)a
4 (%)a
SCHEME 6. A Plausible Mechanism for Amination
with Ring Contraction
entry
amine
1
2
3
4
5
6
7
pyrrolidine
59 (6a)
54 (6b)
55 (6c)
82 (6d)
54 (6e)
61 (6f)
32 (6g)
39 (7a)
40 (7b)
34 (7c)
ndb (7d)
43 (7e)
26 (7f)
6 (7g)
84 (4a)
88 (4b)
87 (4c)
87 (4d)
77 (4e)
79 (4f)
23 (4g)
piperidine
morpholine
dicyclohexylamine
N-ethylethanol amine
diethanol amine
diethyl iminoacetate
a Isolated yields. b Not detected.
TABLE 4. Preparation of Diaminophosphine 4h and 4i
yield of 4
yield of 10
entry
amine
indoline
N-ethylbenzylamine
from 8a (%)a
from 8a (%)a
1
2
41 (4h)
54 (4i)
42 (10h)
26 (10i)
a Isolated yields.
TABLE 2. Amination of 8 with Pyrrolidine
in Table 3, the phosphine oxide 6a was converted into
the desired chiral diaminophosphine 4a18 by using tri-
chlorosilane-triethylamine in a good yield without race-
mization (see Supporting Information). The diamino-
phosphines 4b-g were prepared in the same manner
with the various corresponding diamines (entries 2-7).
Unfortunately, the mixture of products from indoline and
N-ethylbenzylamine could not easily be separated by
silica gel column chromatography. However, the mixture
of isomers was directly converted into the desired chiral
diaminophosphines 4h,i and 10h,i by using trichlorosi-
lane-triethylamine and separated in good yields (Table
4). We also prepared piperidine type diaminophosphines
10a (77% yield) and 10b (58% yield) by the reduction of
7a and 7b using the trichlorosilane-triethylamine method.
We successfully conducted X-ray crystallographic analy-
sis of 4b and 10b. The ORTEP drawings are shown in
Figures S3 and S4 (see Supporting Information). Al-
though we previously reported the compound 10b was
an atorpisomeric diastereomer of 4b on the C-N bond
in a preliminary communication,9 the correct structure
of 10b was 3-(1-piperidinyl)piperidine type phosphine.
Acetylation of diaminophosphines 4e and 4f with acetyl
chloride and triethylamine gave the corresponding di-
aminophosphines 4j (86%) and 4k (94%).
reaction
time (h)
ratio of
yield of
entry
X
6a:7aa
6a and 7a (%)b
1
2
3
Br (8a)
I (8b)
Cl (8c)
7
5.5
30
60:40
60:40
63:37
95
93
68
a Determined by 1H NMR analysis. b Isolated yields.
6a was obtained with 3-(1-pyrrolidinyl)piperidine type
diaminophosphine oxide 7a as a byproduct (Route B). The
ratio of 6a and 7a was estimated to be about 60:40 by
1H NMR analysis (entry 1 in Table 2). Although the
reaction rate was different, this ratio was similar to that
for the reaction of 3-iodopiperidine 8b or 3-chloropiperi-
dine 8c instead of 8a (entries 2 and 3). Both isomers were
stable under the reaction conditions without rearrange-
ment.
The diaminophosphine oxide 6a was separated from
3-(1-pyrrolidinyl)piperidine type phosphine oxide 7a by
silica gel column chromatography. As shown in entry 1
The chiral diaminophosphines 4, 10a, and 10b were
applied to the chiral ligands for the palladium-catalyzed
asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl
(17) (a) Graham, M. A.; Wadsworth, A. H.; Thornton-Pett, M.;
Rayner, C. M. Chem. Commun. 2001, 966. (b) Connor, D. T.; Unangst,
P. C.; Schwender, C. F.; Sorenson, R. J.; Carethers, M. E.; Puchalski,
C.; Brown, R. E.; Finkel, M. P. J. Med. Chem. 1989, 32, 683.
(18) Recently Kondo independently reported the preparation of 4a
via Route A in Scheme 1 and the application to the asymmetric
Kumada cross coupling reaction: see refs 7a and 7b.
J. Org. Chem, Vol. 70, No. 5, 2005 1939

TABLE 6. Palladium-Catalyzed Asymmetric Allylic
Alkylation with 4aa
acetate (11) with dimethyl malonate (12a) as a model
reaction. This reaction was carried out in the presence
of 2 mol % of [Pd(η3-C3H5)Cl]2, 4 mol % of diaminophos-
phine, and a mixture of N,O-bis(trimethylsilyl)acetamide
(BSA) and 2 mol % of metal acetate (Table 5).19
entry
malonate
yield (%)b
ee (%)c
configc
1
12a
12b
12c
12d
12b
12b
99
96
84
91
93
71
95
95
91
95
96
98
S
S
TABLE 5. Palladium-Catalyzed Asymmetric Allylic
Alkylation with Diaminophosphinea
2
3
4
R
S
S
5d
6d,e
a All reactions were carried out for 24 h. b Isolated yields.
c Determined by chiral HPLC analysis. d This reaction was carried
out with 10 mol % catalyst at -40 °C for 72 h. e This reaction was
carried out with 4j instead of ligand 4a.
entry ligand
solv
temp (°C) yield (%)b ee (%)c configc
1
4a
4a
4a
4a
4a
4a
4a
4a
10a
10a
10a
10b
4b
4c
PhMe
PhMe
PhCF3
PhCF3
THF
ether
PhCF3
THF
PhMe
PhCF3
ether
PhCF3
ether
ether
ether
ether
ether
ether
ether
ether
ether
ether
rt
93
15
95
89
97
99
93
99
65
nrf
nrf
nrf
99
98
97
98
86
84
91
99
98
77
82
91
91
86
93
95
93
95
15
S
S
S
S
S
S
S
S
R
2
-10
-10
-10
-10
-10
-20
-20
rt
of 13a was inverted (entry 9). When we decreased the
reaction temperature to -10 °C, the reaction did not
occur after 24 h (entries 10 and 11). This occurred in the
case of ligand 10b (entry 12). Next, we examined AAA
reactions of various diaminophosphines 4b-k as a ligand
in ether at -10 °C (entries 13-22). Each reaction
provided a similar level of chemical yield and enantio-
selectivity to the reaction with use of 4a, except 4h and
4k. When the reaction was carried out with 4h, the
enantioselectivity of 13a was slightly decreased (entry
19). In the case of 4k, (S)-13a was obtained with a similar
level of enantioselectivity, but the reaction rate became
slow (entry 22).
In addition, we examined the AAA reactions of various
dialkyl malonates using 4a as a ligand. As shown in
Table 6, each reaction provided a similar level of chemical
yield and enantioselectivity, except dibenzyl malonate
12c. When the reaction was carried out with 12c, the
enantioselectivity of 13c was slightly decreased (entry
3).
3
4d
5
6
7e
8e
9
10
-10
-10
-10
-10
-10
-10
-10
-10
-10
-10
-10
-10
-10
11
12
13
14
15
16
17
18
19
20
21
22
92
92
95
95
92
94
86
92
95
95
S
S
S
S
S
S
S
S
S
S
4d
4e
4f
4g
4h
4i
4j
4k
a All reactions were carried out for 24 h. b Isolated yields.
c Determined by HPLC analysis, using a chiral column (Chiralcel
OD-H). d KOAc was used instead of LiOAc. e This reaction was
carried out for 48 h. f No reaction.
In summary, we successfully obtained various chiral
diaminophosphines 4 from (S)-prolinol-derived amino-
phosphine oxide 5 by bromination with ring expansion
followed by amination with ring contraction, and demon-
strated palladium-catalyzed asymmetric allylic alkylation
of 1,3-diphenyl-2-propenyl acetate (11) with malonates
using them with good enantiomeric excesses. Further
studies on optimization of the ligand and application to
other asymmetric reactions are underway.
With use of ligand 4a at room temperature in toluene,
(S)-13a was obtained in a good chemical yield, but the
enantiomeric excess was moderate (entry 1). Although
the enantioselectivity was improved to 91% ee, the
reaction rate became slow with a decrease of the reaction
temperature to -10 °C (entry 2). When the reaction was
carried out in R,R,R-trifluorotoluene at -10 °C, the
reactivity was dramatically increased without decrease
of the enantioselectivity (entry 2 vs entry 3). To improve
the enantioselectivity of 13a, we further examined the
effect of the metal of the base, the solvent, and the
reaction temperature (entries 4-8). With use of ether as
a solvent at -10 °C for 24 h, (S)-13a was obtained in a
good yield (99%) with 95% ee (entry 6). On the other
hand, when the reaction was carried out with 10a at
room temperature in toluene, the reactivity and enan-
tioselectivity of 13a were decreased and the configuration
Acknowledgment. We thank Prof. K. Ogura (Chiba
University) for generously sharing the Bruker DPX-300
system. This work was partially supported by the
Saneyoshi Scholarship Foundation.
Supporting Information Available: Figures S1-S4
showing X-ray crystal structures of 8a, 8c, 4b, and 10b, full
experimental procedures and characterization data, NMR
spectra of new compounds, copies of HPLC charts of 8a, 8c,
4a, 4b, and 13a-d, and X-ray crystallographic files (CIF) for
4b, 8a, 8c, and 10b. This material is available free of charge
via the Internet at http://pubs.acs.org.
(19) (a) Mino, T.; Shiotsuki, M.; Yamamoto, N.; Suenaga, T.;
Sakamoto, M.; Fujita, T.; Yamashita, M. J. Org. Chem. 2001, 66, 1795.
(b) Mino, T.; Imiya, W.; Yamashita, M. Synlett 1997, 583.
JO0479967
1940 J. Org. Chem., Vol. 70, No. 5, 2005