C O M M U N I C A T I O N S
Table 1. Catalytic Asymmetric Amination with Ln/(S)-7 Complexa
the following recrystallization gave 3 in optically pure form. 3 was
subjected to modified Clauson-Kaas pyrrole synthesis to give 8
in 85% yield.19 Installation of a trichloroacetyl group and subsequent
treatment with 4-bromo-2-fluorobenzylamine gave rise to a pyr-
rolopyrazine core, affording (-)-1.20
In summary, we achieved a catalytic asymmetric synthesis of
Lanthanide Screening (x ) 10)b
(
-)-1 via catalytic asymmetric amination promoted by a newly
La: y. 66%, 43% ee
Gd: y. 11%, 28% ee
Nd: y. 15%, 16% ee
Dy: y. 8%, -5% ee
Sm: y. 21%, 0% ee
Er: y. 88%, 3% ee
developed La/amide (R)-7 complex. Ligand 7 was synthesized from
inexpensive starting materials without chromatographic purifica-
tion.16 A novel combination of Ln/amide will provide for a new
type of chemistry as the La/7 complex is effective for the
asymmetric amination of 4, unlike other catalyst types. The
amination product was successfully transformed into (-)-1 on a
multigram scale. We anticipate that this route may be useful for
enhancing the prospective future supply of (-)-1, a highly potent
aldose reductase inhibitor under development for the treatment of
diabetic complications.
Solvent Screening (x ) 10)c
THF: y. 66%, 43% ee
DMF: y. 85%, 7% ee
ether: y. 64%, 46% ee
toluene: y. 31%, 31% ee CHCl3: y. 96%, 57% ee AcOEt: y. 86%, 76% ee
Catalyst Loadingd
in AcOEt
in CHCl3
x ) 10, -40 °C: y. 86%, 76% ee, 24 h x ) 10, -40 °C: y. 96%, 57% ee, 24 h
1
4
14
x ) 1, -40 °C: y. 96%, 89% ee, 57 h
x ) 1, -40 °C: y. 99%, 68% ee, 32 h
a
Determined by H NMR analysis. In THF at -40 °C for 24 h. c Ln
1
b
Acknowledgment. Financial support was provided by a Grant-
in-Aid for Specially Promoted Research of MEXT. N.K. thanks
Grant-in-Aid for Start-up. We thank Drs. Sanae Furusho and
Akihiro Sato at JASCO international for technical support in ESI-
QFT MS analysis.
d
)
La, at -40 °C for 24 h. Ln ) La.
Table 2. aCatalytic Asymmetric Amination with La/(S)-7 Complex
with DMA
Supporting Information Available: Experimental details and
characterization data for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
temp
C)
time
(h)
yieldb
(%)
ee
(%)
References
entry
x
y
solvent
(
°
(
1) (a) Yabe-Nishimura, C. Pharmacol. ReV. 1998, 50, 21. (b) Oka, M.; Kato,
N. J. Enzyme Inhib. 2001, 16, 465.
1c
2
1
1
1
1
1
1
2
0.5
0
AcOEt
AcOEt
AcOEt
-40
-40
0
-40
-40
0
57
29
4
32
20
3
96
>99
99
>99
>99
>99
99
89
87
89
68
76
82
90
74
10
10
0
10
10
20
5
(
2) Kinoshita, J. H.; Nishimura, C. Diabetes Metab. ReV. 1988, 4, 323.
3
4
(3) Gonz a´ lez, R, G.; Barnett, P.; Aguayo, J.; Cheng, H. M.; Chylack, L. T.
c
CHCl
CHCl
CHCl
CHCl
CHCl
3
3
3
3
3
J. Diabetes 1984, 33, 196.
(
4) (a) Green, D. A.; Latimmer, S. A. Diabetes 1983, 33, 712. (b) Hamada,
5
6
7
Y.; Kitoh, R.; Raskin, P. Diabetes 1991, 40, 1233.
(
(
(
5) Cameron, N. E.; Cotter, M. A.; Hohman, T. C. Diabetologia 1996, 39, 172.
0
0
0.5
9
6) Green, D. A.; Sima, A. A. F. Diabet. Med. 1993, 10, 31.
d
8
>99
7) (a) Sestanj, K.; Bellini, F.; Fung, S.; Abraham, N.; Treasurywala, A.;
Humber, L.; Simard-Duquesne, N.; Dvornik, D. J. Med. Chem. 1984, 27,
255. (b) Kador, P. F.; Kinoshita, J. H.; Sharpless, N. E. J. Med. Chem.
a
.4 mmol scale. b Determined by H NMR analysis. Reaction under
1
c
0
1
985, 28, 841. (c) Lee, Y. S.; Pearlstein, R.; Kador, P. F. J. Med. Chem.
994, 37, 787. (d) Malamas, M. S.; Hohman, T. C.; Millen, J. J. Med.
Ar. d 0.8 mmol scale.
1
Chem. 1994, 37, 2043. (e) Ishii, A.; Kotani, T.; Nagaki, Y.; Shibayama,
Y.; Toyomaki, Y.; Okukada, N.; Ienaga, K.; Okamoto, K. J. Med. Chem.
1
Scheme 2. Catalytic Asymmetric Synthesis of AS-3201 ((-)-1)a
996, 39, 1924.
(
8) (a) Negoro, T.; Murata, M.; Ueda, S.; Fujitani, B.; Ono, Y.; Kuromiya,
A.; Suzuki, K.; Matsumoto, J.-I. J. Med. Chem. 1998, 41, 4118. (b)
Kurono, M.; Fujiwara, I.; Yoshida, K. Biochemistry 2001, 40, 8216. (c)
Bril, V.; Buchanan, R. A. Diabetes Care 2004, 27, 2369. (d) Kurono,
M.; Fujii, A.; Murata, M.; Fujitani, B.; Negoro, T. Biochem. Pharmacol.
2
006, 71, 338. (e) Giannoukakis, N. Curr. Opin. InVest. Drugs 2006, 7, 916.
(
9) (a) Diels, O. Justus Liebigs Ann. Chem. 1922, 429, 1. (b) Diels, O.;
Behncke, H. Chem. Ber. 1924, 57, 653.
(
10) For selected examples, see: (a) Marigo, M.; Juhl, K.; Jørgensen, K. A.
Angew. Chem., Int. Ed. 2003, 42, 1367. (b) Sabby, S.; Bella, M.; Jørgensen,
K. A. J. Am. Chem. Soc. 2004, 126, 8120. (c) Pihko, P. M.; Pohjakallio,
A. Synlett 2004, 2115. (d) Ma, S.; Jiao, N.; Zheng, Z.; Ma, Z.; Lu, Z.;
Ye, L.; Deng, Y.; Chen, G. Org. Lett. 2004, 6, 2193. (e) Liu, X.; Li, H.;
Deng, L. Org. Lett. 2005, 7, 167. (f) Foltz, C.; Stecker, B.; Marconi, G.;
Bellemin-Laponnaz, S.; Wadepohl, H.; Gabe, L. H. Chem. Commun. 2005,
5115. (g) Xu, X.; Yabuta, T.; Yuan, P.; Takemoto, Y. Synlett 2006, 137.
a
Key: (a) HCl (g), toluene, 0 °C, 99%; (b) Raney-Ni, H2, EtOH, rt,
(
h) Kim, Y. K.; Kim, D. Y. Tetrahedron Lett. 2006, 47, 4565. (i) Terada,
recrystallization, 66%; (c) 2,5-dihydroxytetrahydrofuran, THF-H2O, 40 °C,
5%; (d) CCl3COCl, 80 °C, 90%; (e) 4-bromo-2-fluorobenzylamine, DMF,
rt, 71%.
M.; Nakano, M.; Ube, H. J. Am. Chem. Soc. 2006, 128, 16044. (j)
Comelles, J.; Pericas, AÅ .; Moreno-Ma n˜ as, M.; Vallribera, A.; Drudis-Sol e´ ,
G.; Lledos, A.; Parella, T.; Roglans, A.; Garc ´ı a-Granda, S.; Roces-
Fern a´ ndez, L. J. Org. Chem. 2007, 72, 2077.
8
would substantially disrupt the asymmetric environment. Higher
reaction temperature had a beneficial effect on the enantioselectivity,
affording 6 in higher enantiomeric excess in either ethyl acetate or
chloroform (entries 2 vs 3 and 5 vs 6).18 The highest enantiomeric
excess (90% ee) was observed in chloroform with 2 mol % of
catalyst (entry 7). The reaction is not sensitive to oxygen, and
laboratory scale experiments have been performed under air.
With the efficient catalytic asymmetric amination protocol of 4
in hand, we attempted the asymmetric synthesis of (-)-1 (Scheme
): 10 g of succinimide 4 was subjected to catalytic asymmetric
amination with 2 mol % of La/(R)-7 complex at 0 °C to give
3.4 g of (-)-6 in >99% yield and 92% ee. Boc groups were
quantitatively removed by treatment with HCl in toluene at 0 °C.
N-N bond cleavage proceeded smoothly with Raney nickel, and
(
11) For a recent review of asymmetric aminations of carbonyl compounds,
see: Greck, C.; Drouillat, B.; Thomassigny, C. Eur. J. Org. Chem. 2004,
1377 and references cited therein.
(
12) Wang, W.; Huang, Y.; Tang, N. Spectrochim. Acta Part A 2007, 66, 1058.
(13) For the synthesis of ligand 7, see Supporting Information.
(
14) The reason of the higher ee in the case of x ) 1 is not clear at the moment
and is under investigation.
(
15) Gross, M. L.; Rempel, D. L. Science 1984, 226, 261.
(16) For details, see Supporting Information.
(
17) Although the catalyst solution is cloudy after the addition of 4, clear
reaction mixture is developed with catalytic amount of DMA, suggesting
that DMA is much more effective to fragment the catalyst assembly.
18) Although the reason is not clear, the reaction at 0 °C gave better ee.
19) Gourlay, B. S.; Molesworth, P. P.; Ryan, J. H.; Smith, J. A. Tetrahedron
Lett. 2006, 47, 799.
(
(
2
2
(20) The synthetic route from 3 to (-)-1 was improved from that reported in
ref 8a.
JA0752585
J. AM. CHEM. SOC.
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VOL. 129, NO. 37, 2007 11343