R. Pedrosa et al. / Tetrahedron Letters 54 (2013) 3101–3104
3103
O
have been shown as good organocatalysts for enantioselective Rob-
inson annulation of cyclic and acyclic triketones. Specially interest-
ing are the cyclization processes promoted by supported catalysts 6
in water or under solvent-free conditions because of the easy sepa-
ration of the catalyst and the saving of waste and solvents. The sum-
marized results also showed that prolinamides derived from amines
without additional stereogenic elements in their structures are able
to promote intramolecular aldol reactions with excellent yields and
stereoselectivities.
O
O
O
Catalyst
Solvent
O
10
O
O
11
12
Scheme 3. Regio- and enantioselective cyclization of open-chain triketone 10.
process led to a mixture of ketol 9b and dehydration product (S)-2
in ratios that are dependent on the reaction time and temperature.
When 10 mol % of catalyst 6 was used, at 20 °C, the triketone 8b
was totally transformed into a mixture (88/12 or 53/47) of 9b
and 2 after 48 or 96 h of reaction (entries 13 and 14 in Table 1).
Mixtures (34/66 and 87/13) of the same compounds were also ob-
tained in the reactions promoted by 10 mol %, at 20 °C, or 20 mol %,
at 0 °C, of catalyst 6. Both mixtures were transformed into (S)-HPK
(2) by treatment5b with catalytic pTsOH in refluxing toluene in 52%
yield (er 80/20) and 43% yield (er 78/22), respectively (entries 15
and 16 in Table 1). Once again, the best results were obtained un-
der neat conditions, because (S)-2 was isolated in 70% yield and 88/
12 er, as a single product, by stirring 8b with 10 mol % of 6 and
10 mol % of AcOH without solvent (entry 17 in Table 1).
Acknowledgements
We acknowledge the financial support by the Spanish DGICYT
(Project CTQ 2011-28487). C. P.-L. also thanks the Universidad de
Valladolid for a fellowship.
Supplementary data
Supplementary data associated with this article can be found, in
We have extended the methodology to the enantioselective
cyclization of open-chain triketone 1018 to cyclohexenone deriva-
tives (Scheme 3). This reaction has been much less studied19 than
the Robinson annulation, and it has been reported that the forma-
tion of the 3,4-disubstituted cyclohexenone 11 or the 3,6-disubsti-
tuted regioisomer 12 is dependent on the protic or aprotic nature
of the solvent and the reaction conditions.19a,20
References and notes
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´
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In summary, the novel prolylsulfonamide 4 and supported proli-
namide 6, derived from cheap and easily available ethylene diamine,
Table 2
Regio- and enantioselective cyclization of triketone 10
Entry Catalyst (%) Solvent T (°C) Time (h) Product (yield)a erb
1
2
3
4
5
6
4 (10)
4 (10)
4 (10)
6 (10)
6 (10)
6 (10)
MeCN
MeCN
H2O
MeCN
H2O
20
À18
20
20
20
48
164
164
164
64
11 (82)
11 (70)
nr
11 (57)
11 (34)
11 (74)
75:25
74:26
—
69:31
69:31
75:25
15. Dijksman, A.; Elzinga, J. M.; Li, Y.-X.; Arends, I. W. C. E.; Sheldon, R.
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17. During the revision of this paper a novel silica-supported catalyst has been
described leading to the cyclization products with up to 88%, see: Bañón-
A
neat
20
312
a
Yields determined after chromatographic purification.
Determined by chiral HPLC.
b