Synthesis of Tri-substituted, Aliphatic and 13C-Labelled α,β-Unsaturated Carboxylic Acids via Wittig CO2 Utilisation Reactions

Abstract

Phosphonium carboxylate ylides are formed through CO₂ activation by phosphonium ylides. These can undergo Wittig reactions with carbonyl compounds, thereby enabling formation of both the C—CO₂ bond and the two bonds of the C=C double bond of an α,β-unsaturated carboxylic acid in a one-pot transformation. In this work, we have developed methodology to enable the synthesis of very useful trisubstituted alkene-containing products. Secondly, the protocol allows for the use of base-sensitive aliphatic aldehydes (avoiding the occurrence of aldol self-condensation). The key design element that allowed for these tranformations exploited the increased reactivity of a more nucleophilic ylide. Thirdly, we show that this methodology enables production of a labelled α,β-unsaturated carboxylic acid using ¹³C-labelled CO₂.