multiple catalysts and multiple components in one pot to deliver
highly functionalized molecules. Reactions of this type inspire
analogies with cellular reactions and compliment traditional
organic reactions. As we have suggested previously, the synthesis of
poly-functionalized molecules using amino acid catalysis provides
a unique and under-explored perspective on prebiotic synthesis.
We thank DST (New Delhi) for financial support. RS thanks
CSIR (New Delhi) for her research fellowship.
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Notes and references
‡ Representative experimental procedures: General procedure for the re-
duction of unsaturated cyclic enones: (S)-(+)-1-(2-Pyrrolidinylmethyl)-
pyrrolidine 4e (0.019 g, 0.125 mmol) and 70% HClO4 (8 lL, 0.125 mmol)
in dry CH3CN (1.0 mL) were stirred at 25 ◦C for 10 minutes, and then
of chiral enone 5 (0.5 mmol) in CH3CN (1.0 mL) were added slowly
and stirring was continued at the same temperature for 5 min. To the
reaction mixture was added Hantzsch ester 2 (0.253 g, 1 mmol), and
the mixture refluxed for 8 h. The crude reaction mixture was worked
up with aqueous NH4Cl or NaHCO3 solution and the aqueous layer
was extracted with dichloromethane (3 × 10 mL). The combined organic
layers were dried (Na2SO4), filtered and concentrated. Pure hydrogenated
products 6 were obtained by column chromatography (silica gel, hexane–
ethyl acetate). Amine/amino acid/acid/amine-catalyzed one-pot Michael–
Robinson annulation–hydrogenation reactions: In an ordinary glass vial
equipped with a magnetic stirring bar, to CH-acid 1 (1.0 mmol) and
triethylamine (0.30 mmol) was added of CH3CN (3.0 mL), and then freshly
distilled methyl vinyl ketone (0.25 mL, 3.0 mmol) was added and the
reaction mixture was stirred at 25 ◦C for 24 h. To the reaction mixture
was added L-proline 4a (58 mg, 0.5 mmol) and 70% HClO4 (15 lL,
0.25 mmol), and the mixture refluxed for 24 h. After confirmation of
complete conversion of the Michael adduct into the enone 5 by TLC,
(S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine 4e (38 mg, 0.25 mmol) and
Hantzsch ester 2 (506 mg, 2.0 mmol) were added and refluxing continued
for 24 h. The crude reaction mixture was worked up with aqueous
NH4Cl solution and the aqueous layer was extracted with dichloromethane
(3 × 20 mL). The combined organic layers were dried (Na2SO4), filtered
and concentrated. Pure one-pot products 6 were obtained by column
chromatography (silica gel, hexane–ethyl acetate). Many of the cascade
products 6 have been described previously, and their analytical data match
literature values; new compounds were characterized on the basis of IR,
1H and 13C NMR and analytical data (see ESI).
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2492 | Org. Biomol. Chem., 2008, 6, 2488–2492
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