Rhodium-catalyzed asymmetric arylation of azomethine imines

Article abstract of DOI:10.1021/ol101700v

A rhodium-catalyzed addition of sodium tetraarylborates to azomethine imines has been described. Highly efficient asymmetric catalysis has also been achieved by employing a chiral diene ligand to give 1-(diarylmethyl)pyrazolidin- 3-ones with high enantioselectivity.

Full text of DOI:10.1021/ol101700v

ORGANIC
LETTERS
2010
Vol. 12, No. 18
4106-4109
Rhodium-Catalyzed Asymmetric
Arylation of Azomethine Imines
Ryo Shintani,* Ying-Teck Soh, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
shintani@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Received July 21, 2010
ABSTRACT
A rhodium-catalyzed addition of sodium tetraarylborates to azomethine imines has been described. Highly efficient asymmetric catalysis has
also been achieved by employing a chiral diene ligand to give 1-(diarylmethyl)pyrazolidin-3-ones with high enantioselectivity.
Azomethine imines are a class of 1,3-dipoles typically em-
ployed in the [3 + 2] cycloadditions with alkenes or alkynes
Table 1. Rhodium-Catalyzed Addition of Phenylboron Reagents
to give five-membered nitrogen heterocycles,1 and some effec-
to Azomethine Imine 1a: Effect of Catalyst and Nucleophile
tive asymmetric variants by using chiral catalysts have also been
reported.2 Among the known azomethine imines in the litera-
ture, 2-alkylidene-5-oxopyrazolidin-2-ium-1-ides (e.g., 1a in
Table 1) derived from pyrazolidin-3-ones and aldehydes have
been most widely utilized primarily because of their stability
and ease of handling,3 and the cycloadducts thus obtained
constitute a family of compounds with interesting biological
activity.4 Despite the high utility of these azomethine imines
in cycloaddition reactions, their use as substrates for the catalytic
asymmetric addition of organometallic reagents has been
entry
Rh-catalyst
Ph-B
yield (%)
1
2
3
4
5
6
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(binap)]2
PhB(OH)2
0
0
a
PhB(OR)2
(PhBO)3
Ph4BNa
PhBF3K
Ph4BNa
1
13b
77
0
(1) For a review, see: (a) Schantl, J. G. Sci. Synth. 2004, 27, 731. For
recent examples, see: (b) Maiti, D. K.; Chatterjee, N.; Pandit, P.; Hota,
S. K. Chem. Commun. 2010, 46, 2022. (c) Keller, M.; Sido, A. S. S.; Pale,
P.; Sommer, J. Chem.sEur. J. 2009, 15, 2810. (d) Pezdirc, L.; Cerkovnik,
J.; Pirc, S.; Stanovnik, B.; Svete, J. Tetrahedron 2007, 63, 991.
(2) For a review, see: (a) Stanley, L. M.; Sibi, M. P. Chem. ReV. 2008,
108, 2887. For recent examples, see: (b) Hashimoto, T.; Maeda, Y.; Omote,
M.; Nakatsu, H.; Maruoka, K. J. Am. Chem. Soc. 2010, 132, 4076. (c) Sibi,
M.; Rane, D.; Stanley, L. M.; Soeta, T. Org. Lett. 2008, 10, 2971. (d) Chen,
W.; Du, W.; Duan, Y.-Z.; Wu, Y.; Yang, S.-Y.; Chen, Y.-C. Angew. Chem.,
Int. Ed. 2007, 46, 7667. (e) Suga, H.; Funyu, A.; Kakehi, A. Org. Lett.
2007, 9, 97. (f) Sua´rez, A.; Downey, C. W.; Fu, G. C. J. Am. Chem. Soc.
2005, 127, 11244.
0
a (OR)2 ) OCH2CMe2CH2O. Determined by H NMR of the crude
material.
b
scarcely explored. In fact, although uncatalyzed addition of
Grignard reagents to these dipoles was reported more than 30
years ago,5 only one recent report by Shibata and co-workers
addressed this issue to date, achieving asymmetric trifluorom-
ethylation under phase transfer catalysis.6,7 In this context,
(3) (a) Dorn, H.; Otto, A. Chem. Ber. 1968, 101, 3287. (b) Dorn, H.;
Otto, A. Angew. Chem., Int. Ed. Engl. 1968, 7, 214.
(4) (a) Claramunt, R. M.; Elguero, J. Org. Prep. Proced. Int. 1991, 23,
273. (b) Ternansky, R. J.; Holmes, R. A. Drugs Future 1990, 15, 149. (c)
Jungheim, L. N.; Sigmund, S. K. J. Org. Chem. 1987, 52, 4007.
(5) Dorn, H.; Graubaum, H. J. Prakt. Chem. 1976, 318, 253.
10.1021/ol101700v  2010 American Chemical Society
Published on Web 08/17/2010

herein we describe the development of a rhodium-catalyzed
asymmetric arylation of azomethine imines by the use of
sodium tetraarylborates as the nucleophile in the presence
of a readily available chiral diene ligand.
Initially, we conducted a reaction of azomethine imine 1a
with phenylboronic acid (2.0 equiv) in the presence of [Rh(OH)-
(cod)]2 (5 mol % Rh) in anhydrous dioxane at 90 °C, but no
addition product 2a was observed under these conditions with
partial decomposition of 1a and full consumption of phenyl-
boronic acid (Table 1, entry 1). The use of phenylboronic acid
neopentylglycol ester instead of phenylboronic acid also resulted
in no formation of 2a (entry 2). Although the reaction did
proceed by using phenylboroxine as the nucleophile, compound
2a was obtained in only 13% yield (entry 3). In contrast, the
desired phenylation smoothly took place by employing sodium
tetraphenylborate8 under the catalysis of [RhCl(cod)]2, giving
2a in 77% yield (entry 4).9 In comparison, the use of potassium
phenyltrifluoroborate10 as the nucleophile (entry 5) or [RhCl-
(binap)]211 as the catalyst (entry 6) did not promote this reaction
under otherwise the same conditions as in entry 4.
Figure 1. X-ray crystal structure of 1a-BPh3 adduct (hydrogen
atoms are omitted for clarity).
As we previously proposed in the 1,4-addition to ꢀ,ꢀ-
disubstituted R,ꢀ-unsaturated ketones,12 the uniquely high
reactivity of sodium tetraphenylborate under the Rh/cod catalyst
system may be attributed to the activation of substrate 1a by
Lewis acidic triphenylborane,13 which is presumably generated
upon transmetalation of a phenyl group from tetraphenylborate
to rhodium. To support this hypothesis, we conducted the
following two experiments. (1) A stoichiometric reaction of 1a
with Rh(cod)(η6-C6H5)BPh3 (3), which is readily prepared from
[RhCl(cod)]2 and sodium tetraphenylborate,14 smoothly pro-
ceeded to give 2a in 77% yield after aqueous workup (eq 1).
(2) In addition, a rapid and clean formation of stable 1:1 adduct
of 1a and triphenylborane was observed in THF-d8 at room
temperature by mixing these two components, and the structure
of this adduct was confirmed by X-ray crystallographic analysis
as depicted in Figure 1.
nylborate is illustrated in Scheme 1. Thus, complex 3,
initially formed by the reaction of [RhCl(cod)]2 with sodium
Scheme 1. Proposed Catalytic Cycle for the Rhodium-Catalyzed
Addition of Sodium Tetraphenylborate to 1a ([Rh] ) Rh(cod),
Ar ) 2-FC6H4)
tetraphenylborate, undergoes transmetalation to give a phe-
nylrhodium species 4 and triphenylborane. Subsequent
activation of 1a with Lewis acidic triphenylborane toward
phenylation by 4 gives intermediate 5. Ligand exchange of
this intermediate with sodium tetraphenylborate then releases
the phenylated product along with regeneration of complex
3 to complete the cycle.
On the basis of the above consideration, a proposed
catalytic cycle for the reaction of 1a with sodium tetraphe-
(6) Kawai, H.; Kusuda, A.; Nakamura, S.; Shiro, M.; Shibata, N. Angew.
Chem., Int. Ed. 2009, 48, 6324.
(7) Skucas, E.; Ngai, M.-Y.; Komanduri, V.; Krische, M. J. Acc. Chem.
Res. 2007, 40, 1394.
(8) For examples of the use of sodium tetraarylborates in rhodium-
catalyzed addition reactions, see: (a) Ueda, M.; Miyaura, N. J. Organomet.
Chem. 2000, 595, 31. (b) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami,
M. J. Am. Chem. Soc. 2005, 127, 1390. (c) Ueura, K.; Miyamura, S.; Satoh,
T.; Miura, M. J. Organomet. Chem. 2006, 691, 2821. (d) Shintani, R.; Isobe,
S.; Takeda, M.; Hayashi, T. Angew. Chem., Int. Ed. 2010, 49, 3795.
(9) Only a trace amount of 2a was formed when the reaction was
conducted in the presence of water or methanol (2.0 equiv).
(10) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett. 1999, 1,
1683. (b) Pucheault, M.; Darses, S.; Genet, J.-P. Tetrahedron Lett. 2002,
43, 6155.
(11) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am.
Chem. Soc. 2002, 124, 5052.
(12) Shintani, R.; Tsutsumi, Y.; Nagaosa, M.; Nishimura, T.; Hayashi,
T. J. Am. Chem. Soc. 2009, 131, 13588.
(13) (a) Tolman, C. A.; Seidel, W. C.; Druliner, J. D.; Domaille, P. J.
Organometallics 1984, 3, 33. (b) Brunkan, N. M.; Brestensky, D. M.; Jones,
W. D. J. Am. Chem. Soc. 2004, 126, 3627. (c) Nakao, Y.; Yada, A.; Ebata,
S.; Hiyama, T. J. Am. Chem. Soc. 2007, 129, 2428. (d) Yamashita, Y.;
Gopalarathnam, A.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7508.
Org. Lett., Vol. 12, No. 18, 2010
4107

Because the present transformation is effectively catalyzed
by a Rh/cod complex, we examined chiral diene ligands15-17
to develop an asymmetric addition of sodium tetraphenylbo-
rate to azomethine imine 1a. The use of (R,R)-Ph-bod*18 as
the ligand gave 2a in 66% yield with 95% ee (eq 2), and
higher yield and ee were achieved by changing the substit-
uents on the olefins from phenyl to benzyl ((R,R)-Bn-bod*;18b
80% yield, 98% ee). Further improvements on both yield
and enantioselectivity were realized by using ester-attached
chiral diene (R)-L1 (84% ee, >99.5% ee), which can be
readily synthesized from commercially available (R)-R-
phellandrene in a stereoselective manner.19
Table 2. Rhodium-Catalyzed Asymmetric Addition of Sodium
Tetraarylborates to Azomethine Imines 1: Scope
yield
product (%)
ee
(%)a
entry
1 (Ar1)
Ar2
1
2
3
4
5
6
1a (2-FC6H4)
Ph
Ph
Ph
Ph
(R)-2a
(R)-2b
(R)-2c
(R)-2d
(R)-2e
(R)-2f
(S)-2f
84
75
82
83
85
75
63
79
50
84
80
>99.5
99
98
>99.5
99
99
98
98
96
98
1b (2-MeC6H4)
1c (3-ClC6H4)
1d (3-MeOC6H4)
1e (4-MeO2CC6H4) Ph
1f (4-MeC6H4)
1g (Ph)
1g
1g
Ph
4-MeC6H4
4-(i-Pr)C6H4 (S)-2g
4-MeOC6H4 (S)-2h
3-MeC6H4
3-MeC6H4
7b
8b
9c
10b 1g
(S)-2i
(R)-2j
11
1a
>99.5
a Determined by chiral HPLC with hexane/2-propanol. b 8 mol % of
catalyst was used. c 10 mol % of catalyst was used.
shown in entry 11 (80% yield, >99.5% ee). The absolute
configuration of 2c obtained in entry 3 was determined to
be R by X-ray crystallographic analysis after recrystallization
from EtOAc/pentane (Figure 2).20
Under the conditions using [RhCl((R)-L1)]2, several steri-
cally and electronically different aryl groups are tolerated at
the imine portion of substrates 1 to give the corresponding
phenylation products 2 in high yield with excellent enanti-
oselectivity (75-85% yield, g98% ee; Table 2, entries 1-6).
With regard to the nucleophilic component, not only phenyl
but also some other aryl groups can be effectively installed
with similarly high enantioselectivity (50-84% yield, 96-98%
ee; entries 7-10). Preparation of addition products having
substituents on both of the aryl groups is also possible as
(14) (a) Schrock, R. R.; Osborn, J. A. Inorg. Chem. 1970, 9, 2339. See
also: (b) Oro, L. A.; Pinilla, E.; Tenajas, M. L. J. Organomet. Chem. 1978,
148, 81. (c) Aresta, M.; Quaranta, E.; Albinati, A. Organometallics 1993,
12, 2032
.
(15) For reviews, see: (a) Shintani, R.; Hayashi, T. Aldrichimica Acta
2009, 42, 31. (b) Defieber, C.; Gru¨tzmacher, H.; Carreira, E. M. Angew.
Chem., Int. Ed. 2008, 47, 4482
.
(16) For examples of asymmetric reactions using chiral diene ligands,
see: (a) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem.
Soc. 2004, 126, 1628. (b) Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.;
Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 10850. (c) La¨ng, F.; Breher,
F.; Stein, D.; Gru¨tzmacher, H. Organometallics 2005, 24, 2997. (d) Helbig,
S.; Sauer, S.; Cramer, N.; Laschat, S.; Baro, A.; Frey, W. AdV. Synth. Catal.
2007, 349, 2331. (e) Noe¨l, T.; Vandyck, K.; Van der Eycken, J. Tetrahedron
2007, 63, 12961. (f) Gendrineau, T.; Chuzel, O.; Eijsberg, H.; Genet, J.-P.;
Darses, S. Angew. Chem., Int. Ed. 2008, 47, 7669. (g) Hu, X.; Zhuang, M.;
Cao, Z.; Du, H. Org. Lett. 2009, 11, 4744. (h) Brown, M. K.; Corey, E. J.
Org. Lett. 2010, 12, 172. (i) Luo, Y.; Carnell, A. J. Angew. Chem., Int. Ed.
Figure 2. X-ray crystal structure of (R)-2c (Flack parameter )
0.00(6)).
In addition to unsubstituted pyrazolidinone-derived azome-
thine imines 1 described so far, 4,4-dimethyl substrate 6 also
smoothly undergoes addition of sodium tetraphenylborate
under the same conditions to give product 7 in 82% yield
with 99% ee (eq 3). Furthermore, when a racemic mixture
of 3-phenyl azomethine imine 8 (1.5 equiv) is employed,
one enantiomer preferentially reacts over the other,2f giving
phenylation product 9 in 53% yield (out of 75% ideal
maximum yield) with good diastereoselectivity and excellent
enantioselectivity (eq 4).21
2010, 49, 2750
.
(17) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am.
Chem. Soc. 2003, 125, 11508. (b) Otomaru, Y.; Kina, A.; Shintani, R.;
Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673. (c) Kina, A.; Ueyama,
K.; Hayashi, T. Org. Lett. 2005, 7, 5889. (d) Shintani, R.; Ichikawa, Y.;
Takatsu, K.; Chen, F.-X.; Hayashi, T. J. Org. Chem. 2009, 74, 869. (e)
Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun.
2009, 5713
.
(18) (a) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani,
R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. (b) Otomaru, Y.;
Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503.
(19) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009,
4815.
(20) See Supporting Information for details.
4108
Org. Lett., Vol. 12, No. 18, 2010

of sodium tetraarylborates as the nucleophile. Highly efficient
asymmetric catalysis has also been realized to give chiral
1-(diarylmethyl)pyrazolidin-3-ones by employing chiral diene
(R)-L1 as the ligand.
Acknowledgment. Support has been provided in part by
a Grant-in-Aid for Scientific Research (S) (19105002), the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan. Y.-T.S. thanks JSPS for postdoctoral fellowship.
Supporting Information Available: Experimental pro-
cedures and compound characterization data and X-ray data
in CIF format. This material is available free of charge via
the Internet at http://pubs.acs.org.
In summary, we have described the development of a
rhodium-catalyzed arylation of azomethine imines by the use
(21) For the determination of stereochemistry of compound 9, see
Supporting Information.
OL101700V
Org. Lett., Vol. 12, No. 18, 2010
4109