the enantioselectivity of this transformation (Table 3, entries 2–7).
Additionally, it was possible to use both heteroaromatic (Table 3,
entry 13) and aliphatic b,g-unsaturated ketoester (Table 3,
entry 14) in this reaction. Furthermore, various a-nitro ketones
were used in this reaction and 5-nitro-pent-2-enoates 3p–t were
generated in high yields (Table 3, entries 16–20, 90–98%) and
good to excellent enantioselectivities (75–94% ee).
applications of chiral 5-nitro-pent-2-enoates for the development
of synthetic useful scaffolds are currently underway.
We gratefully acknowledge the National University of
Singapore for financial support of this work (Academic Research
Grant: R143000408133, R143000408733 and R143000443112).
Notes and references
Two additional experiments had been examined using nitro-
methane instead of a-nitro ketone 1a to react with b,g-unsatu-
rated ketoester 2a in the presence of catalyst IV or a strong base,
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) [eqn (2)]. However, no
desired products were obtained in both two experiments.
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ð2Þ
With regard to the mechanism, we deduce that the inter-
mediary Michael adduct A is generated from the reaction of
b,g-unsaturated ketoester 2 and a-nitro ketone 1 (Scheme 2).
Subsequently, enolization to intermediate B followed by a
hemiketal cyclization gives rise to adduct C. Adduct C then
undergoes a retro-Henry reaction to afford the desired product
3 with the regeneration of catalyst IV. The constitution and
absolute configuration of the new products were determined
by X-ray crystal structure analysis of a suitable single crystal
(3u) (Fig. 2) (see ESIw).
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In summary, we have developed a new enantioselective
bifunctional indane amine-thiourea catalyzed cascade Michael/
hemiketalization/retro-Henry reaction of b,g-unsaturated keto-
esters with a-substituted ketones. Further investigations on the
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Scheme 2 Indane amine-thiourea catalyzed Michael/hemiketalization-/
retro-Henry reaction of b,g-unsaturated ketoester 2 with a-nitro ketone 1.
6 For some examples of our group developed bifunctional indane
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Chem., 2011, DOI: 10.1039/c1ob05404j.
Fig. 2 X-Ray crystal structure of 5-nitro-pent-2-enoate 3u.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 5819–5821 5821