pubs.acs.org/joc
potential biological activity to allergens, share the same core
A Strategy to Synthesize Taxol Side Chain
and (-)-epi Cytoxazone via Chiral Brønsted
Acid-Rh2(OAc)4 Co-catalyzed Enantioselective
Three-Component Reactions†
structure as that of chiral β-amino-R-hydroxyl acid deriva-
tives (Scheme 1). Therefore, numerous efforts have been
made to develop enantioselective methodologies to synthe-
size optically active β-amino-R-hydroxyl acids. Successful
approaches include 1,3-dipolar cycloadditions,4 Sharpless
aminohydroxylation,5 and the ring-opening of epoxides and
aziridines6 with appropriate nucleophiles. Furthermore, organo-
catalytic asymmetric Mannich-type reactions7 toward pro-
Yu Qian,† Xinfang Xu,† Liqin Jiang,‡ Dipak Prajapati,§ and
Wenhao Hu*,‡
†Department of Chemistry, East China Normal University,
Shanghai, 200062 China, ‡Institute of Drug Discovery and
Development, East China Normal University, Shanghai,
200062 China, and, §Medicinal Chemistry Division,
North East Institute of Science and Technology,
Jorhat - 785 006, Assam, India
ducing chiral β-amino-R-hydroxyl acids have been devel-
7b
oped independently by List7a and Cordova.
ꢀ
SCHEME 1. Structure of a Taxol Side Chain and (-)-epi-
Cytoxazone
Received August 12, 2010
The development of highly efficient reactions that yield
complex molecules from simple starting materials has re-
ceived considerable attention in recent years.8 Multicompo-
nent reactions (MCRs)9 are considered as powerful strate-
gies to form multiple chemical bonds from three or more
starting materials in one step with a high yield. Recently, as
an effective strategy to enhance reaction selectivity and
reactivity, cooperative catalysis in asymmetric tandem, multi-
component reactions has been reported to produce chiral
molecules with improved synthetic efficiency.10
A new approach to synthesize optically active β-amino-
R-hydroxyl acid derivatives via chiral Brønsted acid-Rh2-
(OAc)4 cocatalyzed three-component reactions of diazo
acetates with alcohols and imines is reported. A matched
reaction system was identified to give the products in
moderate diastereoselectivity and good enantioselectiv-
ity. Application of this methodology is demonstrated in
the efficient synthesis of a taxol side chain and (-)-epi-
cytoxazone.
(4) (a) Torssell, S.; Kienle, M.; Somfai, P. Angew. Chem., Int. Ed 2005, 44,
3096. (b) Torssell, S.; Somfai, P. Adv. Synth. Catal. 2006, 348, 2421.
(5) Li, G.; Chang, H.; Sharpless, B. K. Angew. Chem. Int. Ed. Engl. 1996,
118, 7420.
(6) (a) Liu, W.; Lv, B.; Gong, L. Angew. Chem., Int. Ed. 2009, 48, 6503.
(b) Bergmeter, S. C. Tetrahedron 2000, 56, 2561. (c) Olofsson, B.; Somfai,
P. J. Org. Chem. 2002, 67, 8574.
(7) For selected examples of Mannich-type reaction: (a) Yang, J. W.;
Stadler, M.; List, B. Angew. Chem., Int. Ed. 2007, 46, 609. (b) Dziedzic, P.;
ꢀ
Schyman, P.; Kullberg, M.; Cordova, A. Chem, Eur, J 2009, 15, 4044.
(c) Matsunaga, S.; Kumagai, N.; Harada, N.; Harada, S.; Shibasaki, M.
J. Am. Chem. Soc. 2003, 125, 4712. (d) Trost, B. M.; Jaratjaroonphong, J.;
Reutrakul, U. J. Am. Chem. Soc. 2006, 128, 2778. (e) Hayashi, Y.; Okano, T.;
Itoh, T.; Urushima, T.; Ishikawa, H.; Uchimaru, T. Angew. Chem., Int. Ed.
2008, 47, 9053.
(8) (a) Bruce, A. A. Chem.;Eur. J. 2009, 15, 302. (b) Trost, B. M. Acc.
Chem. Res. 2002, 35, 695. (c) Kolb, H. C.; Finn, M. G.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2001, 40, 2004. (d) Wasilke, J. C.; Obrey, S. J.; Baker,
R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001. (e) Lee, J. M.; Na, Y.; Han,
H.; Chang, S. Chem. Soc. Rev. 2004, 33, 302. (f) Tietze, L. F.; Brasche, G.;
Gericke, K. Domino Reactions in Organic Synthesis; Wiley: New York, 2006.
(g) Padwa, A.; Weingarten, M. D. Chem. Rev. 1996, 96, 223.
Chiral β-amino-R-hydroxyl acid derivatives are not only
frequently used as building blocks in natural product
synthesis1 and as chiral ligands2 in asymmetric catalysis,
but also are frequently present in pharmaceutical related
compounds.1a,3 For example, a side chain of the anticancer
drug Taxol3a,b and (-)-epi-cytoxazone,3c,d which showed
ꢀ
(9) For representative reviews: (a) Zhu, J.; Bienayme, H. Multicomponent
Reactions; Wiley-VCH: Weinheim, 2005. (b) Wasilke, J. C.; Obrey, S. J.
€
Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001. (c) Domling, A.
Chem. Rev. 2006, 106, 17. (d) Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109,
ꢀ
† Dedicated to Professor Albert B. C. Chan on the occasion of his 60th birthday.
(1) For reviews see: (a) Liu, M.; Sibi, M. P. Tetrahedron 2002, 58, 7991.
(b) Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996, 25, 117.
(2) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835.
(3) For selected examples: (a) Kinston, D. G. I. Chem. Commun. 2001,
867. (b) Horwitz, S. B. J. Natural Prod. 2004, 67, 136. (c) Birman, V. B.; Jiang,
H.; Li, X.; Guo, L.; Uffman, E. W. J. Am. Chem. Soc. 2006, 128, 6536.
(d) Davies, S. G.; Hughes, D. G.; Nicholson, R. L.; Smith, A. D.; Wright,
A. J. Org. Biomol. Chem. 2004, 2, 1549. (e) Kudyba, I.; Raczko, J.; Jurczak, J.
Tetrahedron Lett. 2003, 44, 8685.
4439. (e) Wessjohann, L. A.; Rivera, D. G.; Vercillo, O. E. Chem. Rev. 2009,
109, 796. (f) Grondal, C.; Jeanty, M.; Ender, D. Nature 2010, 445, 167.
(10) For selected examples of cooperative catalysis asymmetric reactions:
(a) Hu, W.; Xu, X.; Zhou, J.; Liu, W.; Huang, H.; Hu, J.; Yang, L.; Gong,
L. Z. J. Am. Chem. Soc. 2008, 130, 7782. (b) Xu, X.; Zhou, J.; Yang, L.; Hu,
W. Chem. Commun. 2008, 6564. (c) Ko, S.; Kang, B.; Chang, S. Angew.
Chem., Int. Ed. 2005, 44, 455. (d) Guan, X.; Yang, L.; Hu., W. Angew. Chem.,
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Chem. Soc. 2008, 130, 5652. (f) Liu, H.; Dagousset, G.; Masson, G.;
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DOI: 10.1021/jo101559p
r
Published on Web 10/12/2010
J. Org. Chem. 2010, 75, 7483–7486 7483
2010 American Chemical Society