One-Pot Alkynylation/Isomerization Cascade of β-Formylated Enoates to Functionalized Ynones

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Catalysis

Background:

• γ-hydroxy esters with propargylic and allylic alcohol groups are valuable synthetic intermediates.
• Classical synthesis of related carbonyl compounds often requires multiple steps, including oxidation-reduction sequences.

Purpose of the Study:

• To develop a novel, efficient, and metal-free method for synthesizing γ-hydroxy esters and their subsequent conversion to γ-keto esters.
• To explore a cascade transformation for the direct synthesis of functionalized ynones.

Main Methods:

• Reaction of β-formylated enoates with terminal alkynes to form γ-hydroxy esters.
• Base-catalyzed allylic isomerization of γ-hydroxy esters to γ-keto esters under metal-free conditions.
• Density functional theory (DFT) calculations to investigate the reaction mechanism.

Main Results:

• Successfully synthesized previously unknown γ-hydroxy esters bearing both propargylic and allylic alcohol moieties.
• Achieved chemoselective allylic isomerization to γ-keto esters in a single step.
• Demonstrated a metal-free, base-catalyzed protocol for cascade transformations.

Conclusions:

• The developed protocol offers a streamlined, one-step synthesis of functionalized ynones from readily available precursors.
• This method provides an alternative to traditional multi-step oxidation-reduction sequences for carbonyl compound synthesis.
• DFT calculations provided insights into the mechanism of the cascade reaction.