Streamlined asymmetric α-difunctionalization of ynones

Area of Science:

• Organic Chemistry
• Asymmetric Synthesis
• Catalysis

Background:

• Ynones are versatile structural motifs with significant potential in organic synthesis.
• Chiral ynones, especially those with an alpha-stereogenic center, are desirable for creating complex molecules.
• Existing methods for asymmetric alpha-functionalization of ynones are limited, and double functionalization remains a challenge.

Purpose of the Study:

• To develop a streamlined strategy for asymmetric alpha-difunctionalization of ynones.
• To establish a novel gold-catalyzed multicomponent reaction for generating key intermediates.
• To achieve high enantioselectivity in the synthesis of chiral fluorinated alkynes.

Main Methods:

• A gold-catalyzed multicomponent condensation reaction involving a ynone, an amine, and an electrophilic alkynylating reagent.
• Formation of a stable and isolable 1,2-dialkynyl enamine intermediate.
• Asymmetric fluorination of the intermediate catalyzed by a chiral phosphoric acid derivative.

Main Results:

• Successful synthesis of chiral ynones with an alpha-quaternary carbon, incorporating both fluorine and alkyne functionalities.
• High yields and high enantiomeric excess (ee) were achieved for the target compounds.
• Demonstrated synthetic utility through the preparation of enantioenriched tri(hetero)arylmethyl fluorides.

Conclusions:

• The developed method provides an efficient route for asymmetric alpha-difunctionalization of ynones.
• The strategy enables access to valuable chiral building blocks containing fluorine and alkyne moieties.
• This work expands the synthetic toolbox for creating enantiomerically enriched complex organic molecules.