A Short and Efficient Synthesis of (R,R)-2-Methylcyclopropanecarboxylic Acid

Abstract

We report herein a short and efficient synthesis of (R,R)-2-methylcyclopropanecarboxylic acid via a Horner−Wadsworth−Emmons reaction involving commercially available (S)-propylene oxide and triethylphosphonoacetate (TEPA). The TEPA/base/propylene oxide stoichiometry was found critical to achieve high yields. We therefore studied the TEPA anion formation and stability using in situ IR spectroscopy. The reaction yield is strongly influenced by the counterion and solvent, whereas high diastereoselectivities are always obtained. Under the best experimental conditions (HexLi/MeTHF/150 °C), crude (R,R)-2-methylcyclopropanecarboxylic acid is obtained in 85−90% yield with >98% trans selectivity.