Practical Stereoselective Synthesis of (2E)‐ and (2Z)‐4‐Cycloalkylidenebut‐2‐enoic Acids

Abstract

Stereoselective synthesis of α,β‐unsaturated esters 7 and 8 was achieved through Horner–Wadsworth–Emmons reaction of β,β‐disubstituted α,β‐unsaturated aldehydes. Thus, aldehydes 6 undergo olefination with phosphonate carbanion generated from triethyl phosphonoacetate 3 and lithium hydroxide or butyl lithium/DMPU to give (E)‐α,β‐unsaturated esters 7 with excellent selectivity. The treatment of 6 with the new Horner–Emmons reagents, ethyl(diphenylphosphono)acetate 4a and ethyl (di‐o‐tolyl‐phosphono) acetate 4b in the presence of benzyltrimethyl ammonium hydroxide (Triton B) afforded (Z)‐α,β‐unsaturated esters 8 with 73–89% selectivity. The esters 7 and 8 were converted to (2E)‐ and (2Z)‐4‐cycloalkylidenebut‐2‐enoic acids 9 and 10, respectively.

Keywords:

• Wittig reactions
• Phosphonate carbanions
• Stereoselective synthesis
• α,β‐Unsaturated esters
• Carboxylic acids

Acknowledgment

We gratefully acknowledge financial support from Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, Illinois, USA.