Ephedrine- and Pseudoephedrine-Derived Thioureas in Asymmetric Michael Additions of Keto Esters and Diketones to Nitroalkenes

Abstract

Ephedrine-derived bifunctional thioureas have been synthesized and applied as organocatalysts in Michael additions of 1,3-dicarbonyl compounds to nitroalkenes.

Key words

asymmetric organocatalysis - Michael addition - thioureas - bifunctional organocatalysts - nitroalkenes

References and Notes

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15

Typical Procedure for the Asymmetric Nitro-Michael Reaction To a stirred solution of nitroalkene 6a (29.8 mg, 0.2 mmol) and thiourea 5b (9.0 mg, 0.02 mmol) in Et₂O (1.0 mL) at 0 ˚C was added 2,4-pentanedione (7a, 41 µL, 0.4 mmol). After the nitroalkene was consumed as monitored by TLC, the reaction mixture was concentrated, and the product
was purified by column chromatography on silica gel (n-pentane-EtOAc = 9:1 to 3:1) to afford the conjugate addition product 8a in 99% yield. The er of 8a (92% ee) was determined by HPLC analysis using a chiral column (Daicel Chiralpak AS, n-heptane-2-PrOH = 80:20, 0.5 mL min^-¹, t _major = 20.3 min, t _minor = 28.3 min).

16

As competing reaction, O-alkylation occurred. For a similar observation, see ref. 11a.