N-Boc-L-valine-connected amidomonophosphane rhodium(I) catalyst for asymmetric arylation of N-tosylarylimines with arylboroxines

Article abstract of DOI:10.1021/ja0475398

A catalytic asymmetric arylation of sterically tuned imines with arylboroxines was developed by using N-Boc-L-valine-connected amidomonophosphane rhodium(I) catalyst in n-PrOH. The TMS group used for the steric tuning of imines is convertible to other fun

Full text of DOI:10.1021/ja0475398

Published on Web 06/15/2004
N-Boc-L-Valine-Connected Amidomonophosphane Rhodium(I) Catalyst for
Asymmetric Arylation of N-Tosylarylimines with Arylboroxines
Masami Kuriyama, Takahiro Soeta, Xinyu Hao, Qian Chen, and Kiyoshi Tomioka*
Graduate School of Pharmaceutical Sciences, Kyoto UniVersity, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Received April 28, 2004; E-mail: tomioka@pharm.kyoto-u.ac.jp
The asymmetric synthesis of diarylmethylamines is very impor-
tant because these amines are subunits of some biologically
significant compounds.1 However, the efficient asymmetric syn-
thesis of these amines is rather limited.2-4 Despite many reports,
only two examples of the catalytic asymmetric additions of
arylmetallic reagents to arylimine derivatives have been reported.5
Hayashi developed a chiral MOP-based phosphane rhodium(I)-
catalyzed addition of arylstannanes to N-sulfonylimines.6 A di-
phenylzinc addition to masked N-formylimines employing a
paracyclophane-based ketimine catalyst was reported by Bra¨se.7
From the viewpoint of green chemistry, however, the catalytic
asymmetric reaction of imines with less toxic arylation reagents is
desirable.8,9 We selected arylboron reagents10 as an aryl source and
succeeded in the development of the efficient asymmetric arylation
of imines. The key points to the success were (1) L-valine-connected
amidomonophosphane as a chiral ligand to rhodium(I), (2) steric
tuning of arylimines, and (3) arylboroxines instead of arylboronic
acids.
Figure 1. Chiral phosphane ligands 1-7.
Scheme 1. Asymmetric Arylation of N-Tosylarylimine 8 with
Phenylboron 9 and 11a, Giving 10
We started our arylation approach with hemilabile chiral amido-
monophosphanes 1 and 2 (Figure 1), which were proven to be
effective in two different types of asymmetric addition reactions.
The less bulky phosphane 1-rhodium(I) catalyzes the conjugate
addition of arylboronic acids to enones,11 and the more bulky
2-copper(I) mediates the 1,2-addition of dialkylzinc reagents to
alkyl- and arylimines.12 Unfortunately, both phosphanes were
ineffective in the asymmetric rhodium(I)-catalyzed arylation of
4-tolylaldehyde N-toluenesulfonylimine 8a with phenylboronic acid
9 at 100 °C for 1 h in dioxane, giving N-tosyl-diarylmethylamide
10a in marginal stereoselectivity (Scheme 1; Table 1, entries 1 and
2). BINAP was also not the good ligand, giving 10a with 67:33 er
(entry 3).
The replacement of the pivaloyl group of 1 and 2 by a readily
available chiral R-amino acid is the advantage of the phosphane
scaffold. Although N-Boc-D- and L-valine-connected bulky amido-
phosphanes 4 and 5 were less effective, giving 10a with 53:47 er
and 62:38 er in low chemical yields, less bulky 6 and 7 gave better
reactivity (over 90% yield within 1 h) and selectivity (70:30 er
and 76:24 er (entries 4-7)).
Table 1. Asymmetric Arylation of N-Tosylarylimine 8 with
Phenylboron 9 and 11a Catalyzed by 1-7 and Rhodium(I)
4
entry
imine 8
R
1−7
boron
solvent
yield (%)
era
1
2
3
4
5
6
7
8
9
8a
8a
8a
8a
8a
8a
8a
8b
8c
8d
8d
8d
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
3-Me
2-Me
2-TMS
2-TMS
2-TMS
1
2
3
4
5
6
7
7
7
7
7
7
9
9
9
9
9
9
9
9
9
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
n-PrOH
n-PrOH
80
20
88
26
24
91
95
99
99
91
72
95
51:49
53:47
67:33
53:47
62:38
70:30
76:24
78:22
87:13
89:11
90:10
90:10
10
11
12
9
9
11a
a
Determined by HPLC (Supporting Information).
of 10d with 90:10 er was improved to 95% by using phenylboroxine
((PhBO)3) 11a in n-PrOH at 60 °C for 3 h (entry 12).
It was an unexpected pleasure to find that the arylation of 8d
with substituted phenylboroxines 11b-11f gave 10 with higher
enantioselectivity up to 97:3 (Scheme 2). For example, 3-chloro-
phenylation of 8d with 11f gave 10df14 with 97:3 er quantitatively
(Table 2, entry 9). The electron-donating 3-methoxyphenyl group
was introduced to 8d with 11e, giving 10de with 95:5 er in 87%
yield (entry 8). 4-Methoxy- and 4-chlorophenyl groups were also
introduced to 8d with 11c and 11d, giving 10dc and 10dd with
94:6 er (84%) and 95:5 er (97%) (entries 6 and 7). 4-Phenylphenyl-
boroxine 11b was also a good donor to give 10db with 96:4 er in
98% yield (entry 4).
Encouraged by the enantioselectivity improvement with 7, we
then turned our attention to the steric tuning of the imine.
Enantioselectivity was found to be dependent on the position of a
substituent on the phenyl ring. Tolylaldehyde imines 8b and 8c
bearing 3- and 2-methyl substituents were converted to 10b and
10c using 3 mol % of 7-Rh(I) catalysis with better 78:22 er and
87:13 er (entries 8 and 9). Since a trimethylsilyl (TMS) group on
a phenyl ring is easily convertible to a proton or halogen, the
arylation was examined with 2-TMS-benzaldehyde13 imine 8d. The
enantioselectivity was improved to 89:11 er to give 10d (entry 10).
The 7-Rh(I)-catalyzed arylation of 8d with phenylboronic acid
9 in dioxane, THF, and n-PrOH at 60 °C gave 10d with the same
90:10 er in 8, 20, and 72% yields (entry 11). The chemical yield
Other than 2-TMS-phenylimine 8d, 2-, 3-, and 4-tolylimines 8a-
8c were converted, upon treatment with 4-phenylphenylboroxine
9
8128
J. AM. CHEM. SOC. 2004, 126, 8128-8129
10.1021/ja0475398 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Asymmetric Arylation of 8 with 11, Giving 10
In conclusion, a catalytic asymmetric arylation of sterically tuned
imines with arylboroxines was developed by using N-Boc-L-valine-
connected amidomonophosphane rhodium(I) catalyst in n-PrOH.
It is also important to note that further modification of the
amidophosphane is possible with use of other natural R-amino acids.
The TMS group used for the steric tuning of the imine is convertible
to other functionalities that are applicable as a key foothold for the
carbon-carbon bond forming coupling reactions.
Acknowledgment. This research was supported by the 21st
Century Center of Excellence Program “Knowledge Information
Infrastructure for Genome Science” and a Grant-in-Aid for Scientific
Research on Priority Areas (A) “Exploitation of Multi-Element
Cyclic Molecules”, from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. M.K. thanks the JSPS for a
fellowship.
Table 2. Rhodium(I)-7-Catalyzed Asymmetric Arylation of
N-Tosylarylimines 8 with Arylboroxines 11 in n-PrOH, Giving 10
temp
(°C)
yield
(%)
entry
8
Ar1
11
Ar2
era
1
2
3
4
5
6
7
8
9
8a 4-MeC6H4
8b 3-MeC6H4
11b 4-PhC6H4
11b 4-PhC6H4
11b 4-PhC6H4
60
60
60
60
60
80
80
60
60
100
86
90
97
98
83
84
97
87
99
88
86:14
88:12
93:7
96:4
83:17
94:6
95:5
95:5
97:3
96:4
8c
2-MeC6H4
Supporting Information Available: Experimental procedure,
characterization data, NMR spectra, and HPLC traces (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
8d 2-TMSC6H4 11b 4-PhC6H4
8e Ph 11b 4-PhC6H4
8d 2-TMSC6H4 11c 4-MeOC6H4
8d 2-TMSC6H4 11d 4-ClC6H4
8d 2-TMSC6H4 11e
8d 2-TMSC6H4 11f
3-MeOC6H4
3-ClC6H4
11b 4-PhC6H4
References
(1) For example, see: (a) Spencer, C. M.; Foulds, D.; Peters, D. H. Drugs
1993, 46, 1055-1080. (b) Bishop, M. J.; McNutt, R. W. Bioorg. Med.
Chem. Lett. 1995, 5, 1311-1314. (c) Sakurai, S.; Ogawa, N.; Suzuki, T.;
Kato, K.; Ohashi, T.; Yasuda, S.; Kato, H.; Ito, Y. Chem. Pharm. Bull.
1996, 44, 765-777.
(2) For recent synthesis of diarylmethylamines through resolution, see: (a)
Opalka, C. J.; D’Ambra, T. E.; Faccone, J. J.; Bodson, G.; Cossement, E.
Synthesis 1995, 766-768. (b) Pflum, D. A.; Wilkinson, H. S.; Tanoury,
G. J.; Kessler, D. W.; Kraus, H. B.; Senanayake, C. H.; Wald, S. A. Org.
Process Res. DeV. 2001, 5, 110-115.
10 8f
1-Naphthyl
a
Determined by HPLC or NMR (Supporting Information).
Scheme 3. Protodesilylation, Iododesilylation, and Detosylation
(3) Examples of asymmetric synthesis of diarylmethylamines using chiral
auxiliaries: (a) Pridgen, L. N.; Mokhallalati, M. K.; Wu, M. J. J. Org.
Chem. 1992, 57, 1237-1241. (b) Delorme, D.; Berthelette, C.; Lavoie,
R.; Roberts, E. Tetrahedron: Asymmetry 1998, 9, 3963-3966. (c) Pflum,
D. A.; Krishnamurthy, D.; Han, Z.; Wald, S. A.; Senanayake, C. H.
Tetrahedron Lett. 2002, 43, 923-926. (d) Plobeck, N.; Powell, D.
Tetrahedron: Asymmetry 2002, 13, 303-310. (e) Han, Z.; Krishnamurthy,
D.; Grover, P.; Fang, Q. K.; Pflum, D. A.; Senanayake, C. H. Tetrahedron
Lett. 2003, 44, 4195-4197.
(4) For an asymmetric synthesis of diarylmethylamines using stoichiometric
amounts of chromium complexes, see: Corey, E. J.; Helal, C. J.
Tetrahedron Lett. 1996, 37, 4837-4840.
(5) For an addition of aryllithiums, see: (a) Denmark, S. E.; Nakajima, N.;
Nicaise, O. J. J. Am. Chem. Soc. 1994, 116, 8797-8798. (b) Taniyama,
D.; Hasegawa, M.; Tomioka, K. Tetrahedron Lett. 2000, 41, 5533-5536.
(c) Cabello, N.; Kizirian, J.-C.; Alexakis, A. Tetrahedron Lett. 2004, 45,
4639-4642.
(6) (a) Review: Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829-
2844. (b) Hayashi, T.; Ishigetani, M. J. Am. Chem. Soc. 2000, 122, 976-
977. (c) Hayashi, T.; Ishigetani, M. Tetrahedron 2001, 57, 2589-2595.
(7) Hermanns, N.; Dahmen, S.; Bolm, C.; Bra¨se, S. Angew. Chem., Int. Ed.
2002, 41, 3692-3694.
11b, to the corresponding diarylmethylamides 10 with 93:7 er, 88:
12 er, and 86:14 er (entries 1-3). Naphthylimine 8f was also a
good acceptor with 11b, being converted to 10fb with 96:4 er in
88% yield (entry 10).
(8) (a) Bolm, C.; Hildebrand, J. P.; Mun˜iz, K.; Hermanns, N. Angew. Chem.,
Int. Ed. 2001, 40, 3284-3308. (b) Fagnou, K.; Lautens, M. Chem. ReV.
2003, 103, 169-196.
The 2-TMS group on the phenyl ring of the product was easily
convertible to other functional groups (Scheme 3). Thus, 10db was
protodesilylated with cesium fluoride in refluxing aqueous DMF
for 25 h to afford (R)-10eb15 in 74% yield without any racemization.
This arylation of the TMS-modified imine-protodesilylation se-
quence is complementary to the less effective arylation of phenyl-
imine 8e (Table 2, entries 4 vs 5). Iododesilylation of 10dd with
iodine chloride in methylene chloride at 0 °C for 15 min gave 2-iodo
derivative 12, a useful starting material suitable for the Suzuki-
Miyaura coupling, quantitatively without any racemization. Treat-
ment of 10eb with samarium iodide in refluxing THF-HMPA for
6 h gave the corresponding detosylated (R)-1316 in 98% yield
without any loss of optical purity. The si-face attack to 8 in the
arylation was determined from the established absolute configura-
tion of 10eb and 13.16
(9) Rhodium(I)-catalyzed addition of organoboron reagents to imines was
reported as the racemic version. (a) Ueda, M.; Miyaura, N. J. Organomet.
Chem. 2000, 595, 31-35. (b) Ueda, M.; Saito, A.; Miyaura, N. Synlett
2000, 11, 1637-1639.
(10) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
(11) (a) Kuriyama, M.; Tomioka, K. Tetrahedron Lett. 2001, 42, 921-923.
(b) Kuriyama, M.; Nagai, K.; Yamada, K.; Miwa, Y.; Taga, T.; Tomioka,
K. J. Am. Chem. Soc. 2002, 124, 8932-8939.
(12) (a) Fujihara, H.; Nagai, K.; Tomioka, K. J. Am. Chem. Soc. 2000, 122,
12055-12056. (b) Nagai, K.; Fujihara, H.; Kuriyama, M.; Yamada, K.;
Tomioka, K. Chem. Lett. 2002, 8-9. (c) Soeta, T.; Nagai, K.; Fujihara,
H.; Kuriyama, M.; Tomioka, K. J. Org. Chem. 2003, 68, 9723-9727.
(13) Comins, D. L.; Brown J. D. J. Org. Chem. 1984, 49, 1078-1083.
(14) The first “d” of 10df came from 8d, and the last “f” came from 11f.
(15) Cabiddu, S.; Fattuoni, C.; Floris, C.; Gelli, G.; Melis, S.; Sotgiu, F.
Tetrahedron 1990, 46, 861-884.
(16) Botta, M.; Corelli, F.; Gasparrini, F.; Messina, F.; Mugnaini, C. J. Org.
Chem. 2000, 65, 4736-4739.
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