C O M M U N I C A T I O N S
Table 2. Diels-Alder Reactions of â-substituted Enones 10-13 with
Cyclopentadiene
Supporting Information Available: Complete experimental pro-
cedures, determination of stereoisomeric mixtures, 1H and 13C spectra,
and HPLC chromatograms. This material is available free of charge
for ordering information and Web access instructions.
References
b
enone
R
cat. T, °C
1a -20
t, h
endo:exoa product yield, % ee, %
(1) Reviews: (a) Jurczak, J.; Bauer, T.; Chapuis, C. In StereoselectiVe
Synthesis (Houben-Weyl); Helmchen, G., Hoffmann, R. W., Mulzer, J.,
Schaumann, E., Eds.; Thieme: Stuttgart, 1996; Vol. E21/5, pp 2735-
2871. (b) Fringueli, F.; Taticchi, A. The Diels-Alder Reaction. Selected
Practical Methods; John Wiley: New York, 2002. (c) Cycloaddition
Reactions in Organic Synthesis; Kobayashi, S., Jørgensen, K. A., Eds.;
Wiley-VCH: 2002.
(2) (a) Evans, D. A.; Johnson, J. S. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfatz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999;
Vol. III, pp 1177-1235. (b) Corey, E. J. Angew. Chem., Int. Ed. 2002,
41, 1650-1667.
10
Et
6
95:5
>98:2
91:9
14
15
93
90
90
86
85
94
>99
>99
90
>99
>99
>99
1d -78 21
11
Ph
1a
1d
1d
25
0
8
14
2.5
24
94:6
12
13
4-ClPh
0
95:5
16
17
4-MeOPhc 1d
0
94:6
a Determined by 13C NMR. b Determined by HPLC. c Using 10 equiv.
of diene.
(3) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G.
Angew. Chem., Int. Ed. 2002, 41, 1668-1698.
(4) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc.
2000, 122, 4243-4244.
ing the reaction at -20 °C. The result was most impressive when
catalyst 1d was used, which led to >99:1 regioisomeric ratio and
94% ee.18 Similar levels of selectivity were obtained with other
difficult dienes such as 2,3-dimethyl butadiene and piperylene,
catalyst 1d again being the most effective. Remarkably, lowering
the catalyst loading from 10% to only 2% resulted in no significant
loss of either regioselectivity or enantioselectivity for isoprene and
2,3-dimethylbutadiene and reaction times were only slightly longer.
Observations that supported the 1,4-metal binding activation of
these enones were further attained in the reactions of â-substituted
enones 10-1319 with cyclopentadiene.20 As shown in Table 2,
selectivities and ee values remained high for both â-alkyl and â-aryl
substituted enones, even at the high temperatures required for the
less reactive substrates. In addition, the reaction appears to be quite
regular regardless of the electron-neutral, electron-rich or electron-
poor nature of aryl substituents.
The excellent enantioselectivity observed in these reactions is
also of particular interest since carbonyl addition and subsequent
diol cleavage provides ketone adducts such as 18 and 19 (eq 1),
formally derived from the Diels-Alder reaction of alkyl vinyl
ketones. Similarly, treatment of adducts 5 and 15 (eq 2) with cerium
ammonium nitrate (CAN) gave the corresponding carboxylic acids
20 and 21 in high yields and ee’s.14 Moreover, in these transforma-
tions acetone is the only byproduct formed, an additional aspect of
the approach that is of practical interest.
(5) (a) Northrup, A. B.; McMillan, D. W. C. J. Am. Chem. Soc. 2002, 124,
2458-2460. (b) Thayumanavan, R.; Dhevalapally, B.; Sakthivel, K.;
Tanaka, F.; Barbas, C. F., III. Tetrahedron Lett. 2002, 43, 3817-3820.
(6) (a) Evans, D. A.; Miller, S. J.; Lectka, T. J. Am. Chem. Soc. 1993, 115,
6460-6461. (b) Evans, D. A.; Miller, S. J.; Lectka, T.; von Matt, P. J.
Am. Chem. Soc. 1999, 121, 7559-7573. (c) Evans, D. A.; Barnes, D. M.;
Johnson, J. S.; Lectka, T.; von Matt, P.; Miller, S. J.; Murry, J. A.;
Norcross, R. D.; Shaughnessy, E. A.; Campos, K. R. J. Am. Chem. Soc.
1999, 121, 7582-7594.
(7) For the use of acrylic acid-derived hydroxamates in enantioselective Diels-
Alder reactions, see: (a) Corminboeuf, O.; Renaud, P. Org. Lett. 2002,
4, 1731-1733. (b) Corminboeuf, O.; Renaud, P. Org. Lett. 2002, 4, 1735-
1738.
(8) (a) Bull, S. D.; Davies, S. G.; Epstein, S. W.; Ouzman, J. V. A. Chem.
Commun. 1998, 659-660. (b) Corminboeuf, O.; Quaranta, L.; Renaud,
P.; Liu, M.; Jasperse, C. P.; Sibi, M. P. Chem. Eur. J. 2003, 9, 28-35.
(9) (a) Sibi, M. P.; Venkatraman, L.; Liu, M.; Jasperse, C. P. J. Am. Chem.
Soc. 2001, 123, 8444-8445. (b) Quaranta, L.; Corminboeuf, O.; Renaud,
P. Org. Lett. 2002, 4, 39-42.
(10) For a remarkable exception, see: (a) Corey, E. J.; Shibata, T.; Lee, T.
W., J. Am. Chem. Soc. 2002, 124, 3808-3809. (b) Ryu, D. H.; Corey, E.
J. J. Am. Chem. Soc. 2003, 125, 6388-6390.
(11) For other chelating ketone dienophiles employed in Diels-Alder cycload-
ditions, see: (a) Honda, Y.; Date, T.; Hiramatsu, H.; Yamaguchi, M. Chem.
Commun. 1997, 1411-1412. (b) Wada, E.; Pei, W.; Kanemasa, S., Chem.
Lett., 1994, 2345-2348. (c) Otto, S.; Engberts, J. B. F. N. J. Am. Chem.
Soc. 1999, 121, 6798-6806. (d) Schuster, T.; Bauch, M.; Durner, G.;
Gobel, M. W. Org. Lett. 2000, 2, 179-181. Nitrone cycloadditions: (e)
Kanemasa, S.; Uemura, T.; Wada, E. Tetrahedron lett. 1992, 33, 7889-
7892.
(12) (a) Choy, W.; Reed, L. A., III.; Masamune, S. J. Org. Chem. 1983, 48,
1137-1139. (b) Masamune, S.; Reed, L. A., III.; Davis, J. T.; Choy, W.
J. Org. Chem. 1983, 48, 4441-4444.
(13) Aldol additions: (a) Palomo, C.; Gonza´lez, A.; Garc´ıa, J. M.; Landa, C.;
Oiarbide, M.; Rodr´ıguez, S.; Linden, A. Angew. Chem., Int. Ed. 1998,
37, 180-182. Mannich reactions: (b) Palomo, C.; Oiarbide, M.; Landa,
A.; Gonza´lez-Rego, M. C.; Garc´ıa, J. M.; Gonza´lez, A.; Odriozola, J.
M.; Mart´ın-Pastor, M.; Linden, A. J. Am. Chem. Soc. 2002, 124, 8637-
8643.
(14) Palomo, C.; Oiarbide, M.; Garc´ıa, J. M.; Gonza´lez, A.; Lecumberri, A.;
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(15) This five-membered organizational arrangement may present a more biased
chiral enviroment as compared with the 1,5-metal binding pattern found
upon complexation of N-enoylimides I. See ref 6, and Thorhauge, J.;
Roberson, M.; Hazell, R. G.; Jørgensen, K. A. Chem. Eur. J. 2002, 8,
1888-1898.
(16) For such a determination in thermal Diels-Alder reactions of related
ketols, see: Stammen, B.; Berlage, U.; Kindermann, R.; Kaiser, M.;
Gu¨nther, B.; Sheldrick, W. S.; Welzel, P.; Roth, W. R. J. Org. Chem.
1992, 57, 6566-6575.
In conclusion, we have documented a complementary approach
to enantiocontrol in Diels-Alder reactions that is based upon an
efficient 1,4-metal binding complexation in R′-hydroxy enones.
Extension of this metal-binding principle to other enantioselective
transformations can be predicted and work in that direction is active
in our laboratories.
(17) Hoff, S.; Brandsma, L.; Arens, J. F. Rec. TraV. Chim. 1968, 87, 1179-
1185.
(18) In the case of isoprene, the remaining catalysts 1b, 1c, and 2-3 were
inferior (catalyst; ee: 1b; 8%. 1c; 18%. 2a; 24%. 2b; 32%. 3a; 26%).
(19) Enones 10-13 were readily prepared by aldol condensation of the
commercially available 3-hydroxy-3-methyl-2-butanone with the respective
aldehyde. See Supporting Information for details.
Acknowledgment. We thank The University of the Basque
Country and Ministerio de Ciencia y Tecnologia (Spain) for
financial support. A grant to E. Arceo from UPNA is acknowledged.
(20) Other less reactive dienes such as isoprene and 2,3-dimethylbutadiene
did not react with â-substituted enones under the conditions tested.
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