Remote Enantioselective [4 + 1] Annulation with Copper-Vinylvinylidene Intermediates

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Developing novel synthetic methodologies for complex molecule construction is crucial.
• Enantioselective annulation reactions are vital for accessing chiral compounds.
• Remote stereocontrol strategies offer unique advantages in complex synthesis.

Purpose of the Study:

• To achieve the first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds.
• To establish a remote stereocontrol strategy for regioselective nucleophilic substitution.
• To synthesize diverse spirocycles with high levels of selectivity.

Main Methods:

• Utilized a novel chiral copper-vinylvinylidene species generated from yne-allylic esters.
• Employed a remote stereocontrol strategy for ε regioselective nucleophilic substitution.
• Performed detailed mechanistic studies to elucidate the reaction pathway.

Main Results:

• Successfully realized the first copper-catalyzed enantioselective [4 + 1] annulation.
• Achieved highly regioselective and enantioselective synthesis of diverse spirocycles.
• Demonstrated excellent chemo-, regio-, and enantioselectivities in the annulation.

Conclusions:

• The developed method provides a powerful route to diverse spirocycles via remote stereocontrol.
• The reaction proceeds through an yne-allylic substitution and Conia-ene cascade pathway.
• This work expands the scope of asymmetric catalysis and spirocycle synthesis.