LETTER
Organocatalytic Hetero-Diels–Alder Reactions of Activated Ketones
2349
Encouraged by these results, we further examined the ap-
plication of the present method to cyclic ketone systems
such as benzofuran-2,3-dione (3i) and N-Boc-isatin (3j)
as an unprecedented carbonyl-dienophile component
(Table 3).
Acknowledgment
This work was supported in part by grants for Scientific Research
on Priority Areas from MEXT, as well as by a Special Research
Grant for Green Science from Kochi University. We are also grate-
ful to the JSPS Sakura Program for support of international collabo-
rations.
Table 3 HDA Reactions of Benzofuran-2,3-dione (3i) and N-Boc-
isatin (3j)a
References and Notes
OMe
OMe
(1) High-Pressure Organic Chemistry, Part 35. For Part 34, see:
Azad, S.; Kobayashi, T.; Nakano, K.; Ichikawa, Y.; Kotsuki,
H. Tetrahedron Lett. 2009, 50, 48.
(2) Istvan, E. S.; Deisenhofer, J. Science 2001, 292, 1160.
(3) Reviews: (a) Collins, I. J. Chem. Soc., Perkin Trans. 1 1999,
1377. (b) Boucard, V.; Broustal, G.; Campagne, J. M. Eur. J.
Org. Chem. 2007, 225.
O
catalyst 1a (30 mol%)
O
+
X
O
X
O
2a
3i: X = O
4k: X = O
3j: X = NBoc
4l: X = NBoc
(4) Selected recent examples: (a) Perez, L. J.; Micalizio, G. C.
Synthesis 2008, 627. (b) Habel, A.; Boland, W. Org.
Biomol. Chem. 2008, 6, 1601. (c) Evans, D. A.; Burch, J. D.;
Hu, E.; Jaeschke, G. Tetrahedron 2008, 64, 4671. (d) Jung,
W.-H.; Guyenne, S.; Riesco-Fagundo, C.; Mancuso, J.;
Nakamura, S.; Curran, D. P. Angew. Chem. Int. Ed. 2008, 47,
1130. (e) Crimmins, M. T.; Dechert, A.-M. R. Org. Lett.
2009, 11, 1635. (f) Su, Y.; Xu, Y.; Han, J.; Zheng, J.; Qi, J.;
Jiang, T.; Pan, X.; She, X. J. Org. Chem. 2009, 74, 2743.
(5) Selected recent examples: (a) Wu, F.; Hong, R.; Khan, J.;
Liu, X.; Deng, L. Angew. Chem. Int. Ed. 2006, 45, 4301.
(b) Pichlmair, S.; de Lera Ruiz, M.; Vilotijevic, I.; Paquette,
L. A. Tetrahedron 2006, 62, 5791. (c) Kumar, I.; Rode, C.
V. Tetrahedron: Asymmetry 2007, 18, 1975. (d) Hanessian,
S.; Auzzas, L. Org. Lett. 2008, 10, 261.
(6) Selected recent examples: (a) Shibahara, S.; Fujino, M.;
Tashiro, Y.; Takahashi, K.; Ishihara, J.; Hatakeyama, S. Org.
Lett. 2008, 10, 2139. (b) Akaike, H.; Horie, H.; Kato, K.;
Akita, H. Tetrahedron: Asymmetry 2008, 19, 1100.
(c) Chandrasekhar, S.; Rambabu, Ch.; Reddy, A. S.
Tetrahedron Lett. 2008, 49, 4476. (d) Ding, F.; Jennings,
M. P. J. Org. Chem. 2008, 73, 5965.
Entry Ketone 3 Conditions
Yield (%)b
in toluene
0.1 MPa, r.t., 72 hc 21d
in CH2Cl2
17d
1
2
3
4
5
6
7
8
3i
0.1 MPa, r.t., 36 h
0.8 GPa, r.t., 12 hc
0.8 GPa, r.t., 12 h
63
90
74
12e
79
23e
3j
0.1 MPa, r.t., 72 hc 6d
13d
0.1 MPa, r.t., 36 h
1.0 GPa, r.t., 10 hc
1.0 GPa, r.t., 10 h
62
60
82
94
95
62
a Unless otherwise noted, all reactions were carried out using 2a (1.0
mmol) and 3i or 3j (0.25 mmol) in the presence of 30 mol% of 1a in
toluene or CH2Cl2 (ca. 2.5 mL).
b Isolated yield. The product was obtained as a mixture (ca. 1:1) of di-
astereomers determined by 1H NMR analysis.
c No 1a catalyst was used.
(7) Selected recent examples: (a) Lucas, B. S.;
Gopalsamuthiram, V.; Burke, S. D. Angew. Chem. Int. Ed.
2007, 46, 769. (b) Jensen, K. H.; Sigman, M. S. Angew.
Chem. Int. Ed. 2007, 46, 4748. (c) Dilger, A. K.;
d Incomplete reaction.
e The reaction gave a complex mixture of products.
Gopalsamuthiram, V.; Burke, S. D. J. Am. Chem. Soc. 2007,
129, 16273. (d) Yu, Z.; Liu, X.; Dong, Z.; Xie, M.; Feng, X.
Angew. Chem. Int. Ed. 2008, 47, 1308. (e) Yang, X.-B.;
Feng, J.; Zhang, J.; Wang, N.; Wang, L.; Liu, J.-L.; Yu,
X.-Q. Org. Lett. 2008, 10, 1299. (f) Lin, L.; Chen, Z.; Yang,
X.; Liu, X.; Feng, X. Org. Lett. 2008, 10, 1311. (g) Tiseni,
P. S.; Peters, R. Org. Lett. 2008, 10, 2019.
Interestingly, 3i and 3j were sufficiently reactive even at
atmospheric pressure and under 1a-catalyzed conditions
the corresponding spirocyclic adducts 4k and 4l were ob-
tained, albeit slowly, while the uncatalyzed systems were
again useless (Table 3, entries 1, 2, 5, 6).17 On the other
hand, at 0.8–1.0 GPa, the reactions proceeded quite
smoothly for both substrates regardless of the use of cata-
lyst 1a (Table 3, entries 3, 4, 7, 8).
(8) Reviews of HDA reactions: (a) Cycloaddition Reactions in
Organic Synthesis; Kobayashi, S.; Jørgensen, K. A., Eds.;
Wiley-VCH: Weinheim, 2002. (b) Jørgensen, K. A. Angew.
Chem. Int. Ed. 2000, 39, 3558. (c) Carmona, D.; Lamata,
M. P.; Oro, L. A. Coord. Chem. Rev. 2000, 200-202, 717.
(d) Jørgensen, K. A. Eur. J. Org. Chem. 2004, 2093.
(e) Gouverneur, V.; Reiter, M. Chem. Eur. J. 2005, 11,
5806. (f) Lin, L.; Liu, X.; Feng, X. Synlett 2007, 2147.
(9) Recent examples: (a) Moreau, X.; Bazán-Tejeda, B.;
Campagne, J.-M. J. Am. Chem. Soc. 2005, 127, 7288.
(b) Broustal, G.; Ariza, X.; Campagne, J.-M.; Garcia, J.;
Georges, Y.; Marinetti, A.; Robiette, R. Eur. J. Org. Chem.
2007, 4293. (c) Chen, I.-H.; Oisaki, K.; Kanai, M.;
Shibasaki, M. Org. Lett. 2008, 10, 5151.
In summary, we have developed a new efficient method
for the HDA reaction of a variety of activated ketones
with dienes in the presence of 1a as an organocatalyst un-
der high pressure. Notably, since HDA products 4 can be
easily oxidized to the corresponding d-lactone deriva-
tives,18 the overall process constitutes a rapid means for
preparing this important family of compounds. Further-
more, it may be easy to extend the present method to
asymmetric versions using chiral thiourea catalysts,11 and
further studies along these lines are now in progress in our
laboratory.
Synlett 2009, No. 14, 2346–2350 © Thieme Stuttgart · New York