C O M M U N I C A T I O N S
Scheme 1. Reductive Cleavage of the N-N Bond
a base compatible with a Lewis acid catalyst. As summarized in
Table 3, the reaction could be conducted under otherwise identical
conditions to give a couple of cycloadducts 6 (entries 1-4),14
although the use of R,ꢀ-disubstituted enals led to low conversion
(data not shown). In the case of ꢀ-unsubstituted enals, the reaction
predominantly gave the endo isomer with uniformly high enanti-
oselectivities (entries 5-9).
In summary, we successfully demonstrated that C,N-cyclic
azomethine imines can be utilized as a promising 1,3-dipole in
asymmetric 1,3-DC. As the synthetic utility of azomethine imines
has been moving beyond archetypal 1,3-DCs,15 uncovering a new
class of useful azomethine imines would also offer new opportuni-
ties in these growing fields.
Table 2. Asymmetric 1,3-DC of C,N-Cyclic Azomethine Iminesa
Acknowledgment. This work was partially supported by a
Grant-in-Aid for Scientific Research from the MEXT, Japan.
entry
R1
R2
R3
yield (%)b
exo/endoc
ee(%)d
Supporting Information Available: Experimental details and
characterization data for new compounds. This material is available
1
2
3
4
5
6
7
8
9
10
11
12
13e
5-Me (1b)
6-Me (1c)
7-Me (1d)
8-Me (1e)
6-MeO (1f)
6-Br (1g)
7-Br (1h)
H (1a)
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Pr
85 (2b)
99 (2c)
93 (2d)
94 (2e)
96 (2f)
93 (2g)
92 (2h)
86 (2i)
94 (2j)
85 (2k)
93 (2l)
98 (2m)
97 (2n)
>95:5
>95:5
>95:5
84:16
>95:5
>95:5
>95:5
>95:5
>95:5
95:5
89
92
H
H
H
H
H
H
H
H
Me
92
62/22e
82
References
95
93
85
99
(1) For recent reviews, see: (a) Pellissier, H. Tetrahedron 2007, 63, 3235. (b)
Stanley, L. M.; Sibi, M. P. Chem. ReV. 2008, 108, 2887. (c) Hashimoto,
T.; Maruoka, K. In Handbook of Cyclization Reactions; Ma, S., Eds.; Wiley-
VCH: Weinheim, Germany, 2009; Chapter 3, p 87.
Ph
Me
(2) (a) Shintani, R.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 10778. (b) Sua´rez,
A.; Downey, C. W.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 11244. (c)
Chen, W.; Yuan, X.-H.; Li, R.; Du, W.; Wu, Y.; Ding, L.-S.; Chen, Y.-C.
AdV. Synth. Catal. 2006, 348, 1818. (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) Sibi, M. P.;
Rane, D.; Stanley, L. M.; Soeta, T. Org. Lett. 2008, 10, 2971. (g) Kato, T.;
Fujinami, S.; Ukaji, Y.; Inomata, K. Chem. Lett. 2008, 37, 342.
(3) (a) Godtfredsen, W. O.; Vangedal, S. Acta Chem. Scand. 1955, 9, 1498.
(b) Howard, J. C.; Gever, G.; Wei, P. J. Org. Chem. 1963, 28, 868. (c)
Dorn, H.; Otto, A. Angew. Chem., Int. Ed. 1968, 7, 214. (d) Dorn, H.;
Otto, A. Chem. Ber. 1968, 101, 3287.
88
-(CH2)3-
Me
H
92:8
50:50
61:39
89/86e
96/98e
62/74e
H
H
a Performed with
1 (0.50 mmol) and aldehyde (1.0 mmol).
c
b Combined yield of exo/endo isomers. Determined by the H NMR of
the crude mixture. d Determined by chiral HPLC after reduction of 2.
e Ee value of the endo isomer.
1
(4) (a) Oppolzer, W. Tetrahedron Lett. 1970, 11, 2199. (b) Oppolzer, W.
Tetrahedron Lett. 1970, 11, 3091.
Table 3. Asymmetric 1,3-DC of in Situ Generated C,N-Cyclic
Azomethine Iminesa
(5) Chiral Lewis acid catalyzed [3+2]-cycloaddition of hydrazones with olefins
may be regarded as a relevant strategy; see: (a) Kobayashi, S.; Shimizu,
H.; Yamashita, Y.; Ishitani, H.; Kobayashi, J. J. Am. Chem. Soc. 2002,
124, 13678. (b) Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2004,
126, 11279. (c) Shirakawa, S.; Lombardi, P. J.; Leighton, J. L. J. Am. Chem.
Soc. 2005, 127, 9974.
(6) Chrzanowska, M.; Rozwadowska, M. D. Chem. ReV. 2004, 104, 3341.
(7) (a) Bailey, P. D.; Millwood, P. A.; Smith, P. D. Chem. Commun. 1998,
633. (b) Felpin, F.-X.; Lebreton, J. Eur. J. Org. Chem. 2003, 3693.
(8) Tamura, Y.; Minamikawa, J.-i.; Miki, Y.; Okamoto, Y.; Ikeda, M. Yakugaku
Zasshi 1973, 93, 648.
(9) The reactivity of 1a was examined using dimethyl acetylenedicarboxylate.
See also: Truce, W. E.; Allison, J. R. J. Org. Chem. 1975, 40, 2260.
(10) (a) Kano, T.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2005, 127,
11926. (b) Kano, T.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2006,
128, 2174. (c) Hashimoto, T.; Omote, M.; Kano, T.; Maruoka, K. Org.
Lett. 2007, 9, 4805. (d) Hashimoto, T.; Omote, M.; Hato, Y.; Kano, T.;
Maruoka, K. Chem. Asian J. 2008, 3, 407. (e) Hashimoto, T.; Omote, M.;
Maruoka, K. Org. Biomol. Chem. 2008, 6, 2263.
entry
R4
R2
R3
yield (%)b
exo/endoc
ee (%)d
1
2
3
4
5
6
7
8
9
(CH2)4 (3a)
(CH2)3 (3b)
Me (3c)
(CH2)4 (3a)
(CH2)4 (3a)
Me (3c)
(CH2)4 (3a)
(CH2)3 (3b)
Me (3c)
H
H
H
H
Me
Me
H
H
H
Me
Me
Me
Pr
H
H
H
H
H
74 (6a)
64 (6b)
65 (6c)
36 (6d)
98e (6e)
99e (6f)
98e (6g)
97e (6h)
98e (6i)
81:19
77:23
88:12
67:33
22:78
11:89
15:85
13:87
7:93
90
86
76
(11) For details, see Supporting Information.
(12) For the 1,3-DC of azomethine ylides having a similar structure, see: (a)
Pearson, W. H.; Stoy, P.; Mi, Y. J. Org. Chem. 2004, 69, 1919. (b)
Coldham, I.; Jana, S.; Watson, L.; Martin, N. G. Org. Biomol. Chem. 2009,
7, 1674.
(13) For the in situ generation of 1,3-dipoles and their use in asymmetric
catalysis, see: (a) Sibi, M. P.; Stanley, L. M.; Jasperse, C. P. J. Am. Chem.
Soc. 2005, 127, 8276. (b) Sibi, M. P.; Soeta, T.; Jasperse, C. P. Org. Lett.
2009, 11, 5366. (c) Yamamoto, H.; Hayashi, S.; Kubo, M.; Harada, M.;
Hasegawa, M.; Noguchi, M.; Sumimoto, M.; Hori, K. Eur. J. Org. Chem.
2007, 2859. (d) Ono, F.; Ohta, Y.; Hasegawa, M.; Kanemasa, S. Tetrahe-
dron Lett. 2009, 50, 2111.
(14) Use of toluene led to the poor yield due to the low solubility of 3.
(15) (a) Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, 6330. (b) Chan,
A.; Scheidt, K. A. J. Am. Chem. Soc. 2007, 129, 5334. (c) Shapiro, N. D.;
Shi, Y.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 11654. (d) Kawai, H.;
Kusuda, A.; Nakamura, S.; Shiro, M.; Shibata, N. Angew. Chem., Int. Ed.
2009, 48, 6324.
75
96/97f
98/98f
83/96f
89/96f
75/97f
a Performed with 3 (0.25 mmol) and aldehyde (0.50 mmol). b Isolated
yield of the exo isomer. c Determined by the 1H NMR of the crude
mixture. d Determined by chiral HPLC after reduction of 6. e Combined
yield of the isomers. f Ee value of the endo isomer.
Finally, SmI2-mediated ring opening of the cycloadduct 2a′ was
implemented to furnish the tetrahydroisoquinoline 7 having a side
chain with three contiguous stereogenic centers (Scheme 1).
JA100787A
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J. AM. CHEM. SOC. VOL. 132, NO. 12, 2010 4077