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ChemComm
1.1 equiv.
Hirama, Org. Lett. 2008, 10, 3413; (h) Y. Murata, D. Yamashita, K.
50
cf.
DOI: 10.1039/C5CC05508C
H2
N
OMe
3f (10 mol%)
4 (3.0 equiv.)
O
O
O
O
Ed. 2009, 48, 1400; (i) M. Enomoto, A. Morita, S. Kuwahara, Angew.
Chem. Int. Ed. 2012, 51, 12833; (j)Y. Tang, J.-T. Liu, P. Chen, M. C.
Lv, Z. Z. Wang, Y.-K. Huang, J. Org. Chem. 2014, 79, 11729.
For reviews of catalytic enantioselective desymmetrization, see: (a) R.
S. Ward, Chem. Soc. Rev. 1990, 19, 1; (b) K. Fuji. Chem. Rev. 1993,
93, 2037; (c) K. Mikami, A. Yoshida, J. Synth. Org. Chem., Jpn. 2002,
60, 732; (d) Rovis, T. In New Frontiers in Asymmetric Catalysis;
Mikami, K., Lautens, M., Eds.; Wiley: Hoboken, NJ, 2007; p 275.
(a) X.-M. Zhang, M. Wang, Y.-Q. Tu, C.-A. Fan, Y.-J. Jiang, S.-Y.
Zhang, F.-M. Zhang, Synlett 2008, 2831; (b) G. Guillena, C. Nájera, S.
F. Viózquez, Synlett 2008, 3031; (c) D. B. Ramachary, M. Kishor, J.
Org. Chem. 2007, 72, 5056; (d) D. Almazi, D. A. Alonso, A.-N.
BAlaguer, C. Nájera, Adv. Synth. Catal. 2009, 351, 1123; (e) B.
Bradshaw, G. Etxebarria-Jardi, J. Bonjoch, S. F. Viozquez, G.
Guillena, C. Nájera, Adv. Synth. Catal. 2009, 351, 2482; (f) B.
Brradshow, G. Etxebarria-Jardi, . Bonjoch, J. Am. Chem. Soc. 2010,
132, 5966; (g) R. Pedrosa, J. M. Andrés, R. Manzano, C. Pérez-López,
Tetrahedron Lett. 2013, 54, 3101.
(a) S. G. Davies, R. L. Sheppard, A. D. Smith, J. E. Thomson, Chem.
Commun. 2005, 3802; (b) S. G. Davies, A. J. Russell, R. L. Sheppard,
A. D. Smith, J. E. Thompson, Org. Biomol. Chem. 2007, 5, 3190.
(a) K. Kriis, T. Kanger, M. Laars, T. Kailas, A.-M. Müürisepp, T.
Pehk, M. Lopp, Synlett 2006, 1699; (b) M. Limbach, Tetrahedron Lett.
2006, 47, 3843; (c) T. Kanger, K. Kriis, M. Laars, T. Kailas, A.-M.
Müürisepp, T. Pehk, M. Lopp, J. Org. Chem. 2007, 72, 5168.
V. D’Elia, H. Zwicknagl, O. Reiser, J. Org. Chem. 2008, 73, 3262.
(a) C. Xu, L. Zhang, P. Zhou, S. Luo, J.-P. Cheng, Synthesis, 2013, 45,
1939; (b) C. Xu, L. Zhang, P. Zhou, S. Luo, J. Org. Chem. 2014, 79,
11517.
O
toluene
MS3Å
N
N
50 °C, 2 d
4
1a
55
23%, 8% ee
OMe
8
OH
2ac
56%, 79% ee
O
O
H
N
5
60
H
O
O
H
O
P
O
O
*
Proposed transition state model
Scheme 2. Importance of bifunctionality of the chiral phosphoric acid and
65
70
75
the proposed transition state model.
In summary, we have developed a highly enantioselective
synthesis of fused piperidine and pyrrolidine derivatives with
all-carbon stereogenic centers by chiral phosphoric acid
catalyzed symmetry breaking. Using this method, several
important substructures, such as 5-6 and 5-5 fused
polyheterocycles with contiguous stereogenic centers, were
10 synthesized with good to excellent enantioselectivities (up to
98% ee). Further investigations of its application to natural
product synthesis are under way in our laboratory.
5
6
7
8
9
Acknowledgements
80 10 Á. L. Fuentes de Arriba, D. G. Seisdedos, L. Simón, V. Alcázar, C.
Raposo, J. R. Morán, J. Org. Chem. 2010, 75, 8303.
11 For selected reviews on chiral phosphoric acid catalysis, see: T.
Akiyama, Chem. Rev. 2007, 107, 5744; (b) M. Terada, Synthesis,
2010, 1929; (c) D. Parmar, E. Sugiono, S. Raja, M. Rueping, Chem.
This work was partially supported by a Grant-in-Aid for
15 Scientific Research on Innovative Areas “Advanced
Transformation Organocatalysis” from MEXT, Japan.
85
90
Rev. 2014, 114, 9047. For seminal works of chiral phosphoric acid,
see: (d) T. Akiyama, J. Itoh, K. Yokota, K. Fuchibe, Angew. Chem.
Int. Ed. 2004, 43, 1566; (e) D. Uraguchi, M. Terada, J. Am. Chem.
Soc. 2004, 126, 5356.
Notes and references
a
Department of Chemistry, Faculty of Science Gakushuin University, 1-
12 K. Mori, T. Katoh, T. Suzuki, T. Noji, M. Yamanaka, T. Akiyama,
Angew. Chem. Int. Ed. 2009, 48, 9652.
5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan, E-mail:
20 takahiko.akiyama@gakushuin.ac.jp; Fax: (+81) 3-5992-1029; Tel: (+81)
3-3986-0221.
13 E. M. Phillips, J. M. Roberts, K. A. Scheidt, Org. Lett. 2010, 12, 2830.
14 For pioneering works of chiral phosphoric acid catalyzed transfer
hydrogenation, see: (a) M. Rueping, E. Sugiono, C. Azap, T.
Theissmann, M. Bolte, Org. Lett. 2005, 7, 3781; (b) S. Hoffmann, A.
Seayad, B. List, Angew. Chem. Int. Ed. 2005, 44, 7424; (c) R. I.
Storner, D. E. Carrera, Y. Ni, D. W. C. MacMillan, J. Am. Chem. Soc.
2006, 128, 84.
b
Department of Applied Chemistry, Graduate School of Engineering,
Tokyo University of Agriculture and Technology, 2-24-16 Nakacho
Koganei, Tokyo 184-8588, Japan.
25 † Electronic Supplementary Information (ESI) available: Experimental
procedures, characterization data for all new compounds. See
DOI: 10.1039/b000000x/
95
15 Our group has recently developed chiral Brønsted acid catalyzed
transfer hydrogenation of imines using benzothiazoline derivatives as
hydrogen donor, see: (a) C, Zhu, T. Akiyama, Org. Lett. 2009, 11,
4180; (b) C. Zhu, T. Akiyama, Adv. Synth. Catal. 2010, 352, 1846; (c)
C. Zhu, T. Akiyama, Synlett 2011, 1251; (d) A. Henseler, M. Kato, K.
Mori, T. Akiyama, Angew. Chem., Int. Ed. 2011, 50, 8180; (e) K.
Saito, T. Akiyama, Chem. Commun. 2012, 48, 4573; (f) C. Zhu, T.
Akiyama, Tetrahedron Lett. 2012, 53, 416; (g) T. Sakamoto, K. Mori,
T. Akiyama, Org. Lett. 2012, 14, 3312; (h) T. Sakamoto, K.
Horiguchi, K. Saito, K. Mori, T. Akiyama, Asian. J. Org. Chem. 2013,
2, 943; (i) K. Saito, K. Horiguchi, Y. Shibata, M. Yamanaka, T.
Akiyama, Chem. Eur. J. 2014, 20, 7616. See also: (j) D. Enders, J. X.
Liebich, G. Raabe, G. Chem. Eur. J. 2010, 16, 9763; (k) C. Zhu, J. R.
Falck, ChemCatChem 2011, 3, 1850; (k) C. Zhu, K. Saito, M.
Yamanaka, T. Akiyama, Acc. Chem. Res. 2015, 48, 388.
‡ Footnotes should appear here. These might include comments relevant
to but not central to the matter under discussion, limited experimental and
30 spectral data, and crystallographic data.
100
105
110
115
1
(a) U. Eder, G. Sauer, R. Wiechert, Angew. Chem. Int. Ed. Engl. 1971,
10, 496; (b) Z. G. Hajos, D. R. Parrish, J. Org. Chem. 1974, 39, 1615;
(c) R. A. Micheli, Z. G. Hajos, N. Cohen, D. R. Parrish, L. A. Poland,
W. Sciamanna, M. A. Scott, P. A. Wehrli, J. Org. Chem. 1975, 40,
675; (d) Z. G. Hajos, D. R. Parrish, Org. Synth. 1985, 63, 26..
For the synthesis of Wieland – Miescher ketone; (e) P. Wieland, K.
Miescher, Helv. Chim. Acta 1950, 33, 2215; (f) J. Gutzwiller, A.
Buchschacher, A. Furst, Synthesis 1977, 167; (g) S. Ramachandran, M.
S. Newman, Org. Synth. 1961, 41, 38.
35
2
40 3 For selected references, see: a) E. J. Corey, M. Ohno, R. B. Mitra, P.
A. Vatakencherry, J. Am. Chem. Soc. 1964, 86, 478; (b) E. J. Corey,
M. Ohno, R. B. Mitra, R. A. Vatakencherry, J. Am. Chem. Soc. 1964,
86, 478; (c) J. E. McMurry, S. J. Isser, J. Am. Chem. Soc. 1972, 94,
7132; (d) R. C. A. Isaacs, R. M. J. Di Grandi, S. J. Danishefsky, J.
16 The reaction with benzothiazoline15 failed. The main product was
benzylamine 10, which was produced by the acid hydrolysis of 8
followed by the reductive amination of the resulting aldehyde with m-
hydroxyaniline.
45
Org. Chem. 1993, 58, 3938; (e) L. A. Paquette, T.-Z. Wang, M. R.
Sivik, J. Am. Chem. Soc. 1994, 116, 11323; (f) D. M. Coltart, S. J.
Danishefsky, Org. Lett. 2003, 5, 1289; (f) T. J. Reddy, G. Bordeau, L.
Trimble, Org. Lett. 2006, 8, 5585; (g) S. Yamashita, K. Iso, M.
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