Organocatalytic Enantioselective Michael Additions of Malonates to 2-Cyclopentenone

Abstract

The Michael reaction of a dialkyl malonate with a cyclic enone using a chiral diamine-acid combination catalyst gave the desired Michael adduct in high yield with excellent enantiomeric excess in a protic solvent such as methanol and ethanol. The methanol molecule participates in a proton relay system in which the dialkyl malonate is activated through hydrogen bonding to afford the Michael adduct with excellent enantioselectivity.

Key words

enone - malonate - Michael addition - organocatalysis - proton relay

References and Notes

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8

http://www.msg.ameslab.gov/GAMESS/. See also Supporting Information.

14

Typical Procedure for the Direct Michael Reaction of the Malonate 15 with the Enone 14 Using Catalyst 12 (Table 3, entry 1): A catalyst stock solution (1.0 M in MeOH) was prepared as a mixture of (S)-(+)-1-(2-pyrrolidinyl-methyl)pyrrolidine (11, 0.5 mmol) and trifluoroacetic acid (0.5 mmol) in anhyd MeOH (0.5 mL) before use. 2-Cyclopentenone (14c, 0.5 mmol) was dissolved in MeOH (0.45 mL) and dibenzyl malonate (15a, 0.6 mmol) was added. To the mixture the catalyst stock solution (1.0 M in MeOH, 50 µL, 0.05 mmol) was added at 25 ˚C. After stirring for 48 h, the reaction mixture was directly purified by column chromatography (silica gel 5 g, hexanes-EtOAc, 90:10) to afford the Michael product 16a (98% yield, 94% ee). The enantiomeric excess (ee) of Michael products was determined by chiral-phase HPLC analysis and/or ^¹³C NMR (see Supporting Information). The absolute configuration of Michael products was determined by comparison of the reported specific optical rotation and HPLC data.