Asymmetric Michael Addition of 5 H-Oxazol-4-ones to Vinyl Sulfones:

Stereoselective Synthesis of Monofluorinated Analogs of 2‐Tertiary Hydroxyl‐3‐Methyl‐Substituted Carboxylic Acidl Derivatives

Qian Liu, Baokun Qiao, Kek Foo Chin, Choon‐Hong Tan and Zhiyong Jiang

Advanced Synthesis and Catalysis, 2014, 356, 3777-3783

Abstract: An asymmetric Michael addition of 5H‐oxazol‐4‐ones to vinyl sulfones has been developed. In the presence of 10 mol % of quinine‐based benzyl‐substituted thiourea as catalyst at 0 °C, the products could be obtained with excellent enantio‐ and diastereoselectivity (up to>99 % ee and>20:1 dr). 1.0 mol % of catalyst also produced the corresponding adducts with similar stereoselective results when the temperature was increased to 25 °C. The obtained adducts have been demonstrated as significant synthetic fragments to conveniently access the monofluorinated analogs of biologically important 2‐tertiary hydroxyl‐3‐methyl‐substituted carboxylic acid derivatives.

Paper download: https://doi.org/10.1002/adsc.201400649