Scheme 1. Catalyst Screeninga,b
Scheme 2. Scope of Dienyl Esters: Phase-Transfer Catalytic
Hydrolytic Enantioselective Protonationa
a A screw cap vial was charged with Chiral PTC (5 mol %), CHCl3-
mesitylene (2:l, 400 μL), 2-chloroethanol (0.5 equiv), and 50% KOH aq
(100 μL). The mixture was cooled to À40 °C, dienyl ester (0.1 mmol) was
added, and the mixture was stirred for 24 h. b GC yield.
used for the synthesis of biologically active compounds.5
In addition, other transformations are also available.6À9
However, conventional approaches are limited to stoic-
hiometric reactions5aÀd,f,hÀk,10 and catalytic reactions that
(5) Numerous examples exist. Selected examples are as follows:
€
(a) Tun, M. K. M.; Wustmann, D.-J.; Herzon, S. B. Chem. Sci. 2011,
2, 2251. (b) Garnsey, M. R.; Matous, J. A.; Kwiek, J. J.; Coltart, D. M.
Bioorg. Med. Chem. Lett. 2011, 21, 2406. (c) Velthuisen, E. J.; Danishefsky,
S. J. J. Am. Chem. Soc. 2007, 129, 10640. (d) Jiang, C.-H.; Bhattacharyya, A.;
Sha, C.-K. Org. Lett. 2007, 9, 3241. (e) Kuramochi, A.; Usuda, H.;
Yamatsugu, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2005, 127,
14200. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H.; Minakawa, N.;
Rainier, J. D.; Hartz, R. A.; Cho, Y. S.; Cui, H.; Moser, W. H. J. Am.
Chem. Soc. 2003, 125, 8228. (g) Cantın, A.; Lull, C.; Primo, J.; Miranda,
a A screw cap vial was charged with 3a (2 mol %), CHCl3-mesitylene
(2 1, 400, μL), 2-chloroethanol (0.5 equiv), and 50% KOH aq (100 μL).
The mixture was cooled to À40 °C, dienyl ester (0.1 mmol) was added,
and the mixture was stirred for 24 h. Full conversion of substrates was
confirmed by TLC before the reactions were quenched. Isolated yields
are shown unless otherwise noted. b GC yield. c 5 mol % of catalyst was
used. d 2.5 mmol scale.
ꢀ
M. A.; Primo-Yufera, E. Tetrahedron: Asymmetry 2001, 12, 677.
(h) Schwaebe, M.; Little, R. D. J. Org. Chem. 1996, 61, 3240. (i) Smith,
A. B., III; Nolen, E. G., Jr.; Shirai, R.; Blase, F. R.; Ohta, M.; Chida, N.;
Hartz, R. A.; Fitch, D. M.; Clark, W. M.; Sprengeler, P. A. J. Org.
Chem. 1995, 60, 7837. (j) Iio, H.; Monden, M.; Okada, K.; Tokoroyama,
T. J. Chem. Soc., Chem. Commun. 1987, 358. (k) Audenaert, F.; De
Keukeleire, D.; Vandewalle, M. Tetrahedron 1987, 43, 5593.
lack generality.5e,11,12 Therefore, asymmetric synthesis of
the enones is regarded as an important subject.
EP is one of the potent reactions for the preparation of
the enones. To date, several distinct catalytic EP reactions
have been developed.12À16 However, only a few examples
were applied to the synthesis of the enones with limited
scopes.12 Herein, we report a highly enantioselective, gen-
eral catalytic method for the synthesis of the cyclic enones
bearing tertiary chiral centers neighboring to carbonyl
groups by asymmetric hydrolytic protonation of dienyl
(6) For reviews of Michael addition reactions of conjugate enones,
€
ꢁ
see: (a) Alexakis, A.; Backvall, J. E.; Krause, N.; Pamies, O.; M.
ꢀ
Dieguez, M. Chem. Rev. 2008, 108, 2796. (b) Harutyunyan, S. R.; den
Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev. 2008,
108, 2824. (c) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M.
Chem. Rev. 2005, 105, 933.
(7) For several examples of diastereoselective 1,4-addition of cyclo-
hexenones, see: (a) Taber, D. F.; Christos, T. E.; Rheingold, A. L.; Guzei,
I. A. J. Am. Chem. Soc. 1999, 121, 5589. (b) Barton, D. H. R.; Boivin, J.;
Gastiger, M.; Morzycki, J.; Hay- Motherwell, R. S.; Motherwell, W. B.;
Ozbalik, N.; Schwartzentruber, K. M. J. Chem. Soc., Perkin Trans. 1
1986, 947.
(11) Imai, M.; Hagihara, A.; Kawasaki, H.; Manabe, K.; Koga, K.
J. Am. Chem. Soc. 1994, 116, 8829.
(8) For a review of epoxidation reactions of enones, see: Weiß, K. M.;
Tsogoeva, S. B. Chem. Rec. 2010, 11, 18.
(12) The catalytic EP reaction applied for the synthesis of the
enones is Nazarov cyclization/protonation. This process is limited to
5-membered ring products. (a) Shimada, N.; Stewart, C.; Tius, M. A.
Tetrahedron 2011, 67, 5851. (b) Rueping, M.; Ieawsuwan, W.; Antonchick,
A. P.; Nachtsheim, B. J. Angew. Chem., Int. Ed. 2007, 46, 2097. (c) Liang,
G.; Trauner, D. J. Am. Chem. Soc. 2004, 126, 9544.
(13) For reviews of EP reactions, see: (a) Mohr, J. T.; Hong, A. Y.;
Stoltz, B. M. Nat. Chem. 2009, 1, 359. (b) Duhamel, L.; Duhamel, P.;
Plaquevent, J. C. Tetrahedron: Asymmetry 2004, 15, 3653. (c) Eames, J.;
Weerasooriya, N. Tetrahedron: Asymmetry 2001, 12, 1. (d) Yanagisawa, A.;
Yamamoto, H. In Comprehensive Asymmetric Synthesis III; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Heidelberg, 1999; p 1295. (e) Fehr, C.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2566.
(9) For everal examples including DielsÀAlder reaction, epoxidation,
reduction, and 1,2-addition, see: (a) Meng, J.; Light, M. E.; Kilburn, J. D.;
Dixon, S. Tetrahedron Lett. 2011, 52, 928. (b) Sauer, E. L. O.; Hooper, J.;
Woo, T.; Barriault, L. J. Am. Chem. Soc. 2007, 129, 2112. (c) Gauvreau, D.;
€
Barriault, L. J. Org. Chem. 2005, 70, 1382. (d) Kreiser, W.; Korner, F. Helv.
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Chim. Acta 1999, 82, 1610. (e) Solladie, G.; Hutt, J. J. Org. Chem. 1987, 52,
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Lawson, J. A.; FitzGerald, G. A.; Rokach, J. J. Am. Chem. Soc. 1998, 120,
11953. (g) Tanis, S. P.; McMills, M. C.; Herrinton, P. M. J. Org. Chem.
1985, 50, 5887.
(10) Job, A.; Janeck, C. F.; Bettray, W.; Peters, R.; Enders, D.
Tetrahedron 2002, 58, 2253.
B
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