Direct Experimental Evidence for the Epimerization of Diastereoisomers in the Enantioselective Organocatalyzed Michael Addition of Acetoacetates to Nitroolefins

Abstract

The evolution of the addition of acetoacetates to nitrostyrene catalyzed by a bifunctional thiourea has been followed by ^¹9F NMR. The results show for the first time that the diastereoselectivity varies along the reaction time and that both the major and minor diastereoisomers epimerize in the presence of the catalyst.

Key words

asymmetric synthesis - epimerization - Michael addition - organocatalysis - thioureas

References and Notes

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(3 S )-Ethyl 2-Acetyl-4-nitro-3-phenylbutanoate (4): To a stirred solution of trans-β-nitrostyrene (2; 0.30 mmol, 45.6 mg) and catalyst 1 (0.03 mmol, 12.0 mg) in toluene (0.6 mL) was added ethyl acetoacetate (3; 0.60 mmol, 0.08 mL) at
-18 ˚C. The reaction mixture was stirred until disappearance of the nitroolefin (observed by TLC). The solvent was removed in vacuo and the residue was purified by flash chromatog-raphy (hexane-EtOAc, 20:1 to 15:1 as eluent) to afford the desired product 4 (0.30 mmol, 83 mg, 99% yield, 54:46 dr, 96:4 er).

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