Method for Regio- and Stereoselective Synthesis of (E)-β,γ-Unsaturated Acids from Aldehydes Under Solvent-Free Conditions

Abstract

Synthesis of (E)-β,γ-unsaturated acids from aldehydes with malonic acid has been explored under solvent-free conditions. The modified Knoevenagel condensation reaction with N-methyl morpholine (NMM) as catalyst exhibits highly β,γ-regioselectivity and exclusively E-stereoselectivity. A mechanism accounting for both regio- and stereoselectivity has been proposed and preliminarily studied.

Keywords:

• Knoevenagel reaction
• regioselectivity
• solvent-free
• stereoselectivity
• β,γ-unsaturated acid

Notes

^a Yields refer to isolated combined product of β,γ- and α,β-hexenoic acids.

^b Determined by ¹H NMR analysis of the crude product.

^c Ratio of E:Z refers to β,γ-hexenoic acids, and >99:1 means only one isomer was observed.

^a Yields refer to isolated combined product of β,γ- and α,β-unsaturated acids.

^b Determined by ¹H NMR analysis of the crude product.

^c Ratio of E:Z refers to β,γ-unsaturated acids, and >99:1 means only one isomer was observed.

^d Data in parantheses refer to the results of reaction with Et₃N instead of NMM.

^a Yields refer to isolated combined product of β,γ- and α,β-isomers.

^b Determined by ¹H NMR analysis of crude product.

^c Ratio of E:Z refers to β,γ-isomers, and >99:1 means only one isomer was observed.