Aromatization-Driven Cascade [1,5]-Hydride Transfer/Spirocyclization Promoted by Fluorinated Alcohols

Area of Science:

• Organic Chemistry
• Synthetic Methodology

Background:

• Para-quinone methides are versatile intermediates in organic synthesis.
• Developing efficient and mild synthetic routes is crucial for accessing complex molecular architectures.

Purpose of the Study:

• To develop novel aromatization-driven cascade reactions starting from para-quinone methides.
• To synthesize valuable azaspirocyclohexadienones and ortho-benzylated anilines.

Main Methods:

• Development of a cascade [1,5]-hydride transfer/spirocyclization reaction.
• Development of a cascade [1,5]-hydride transfer/hydrolysis reaction.
• Utilizing 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a solvent.

Main Results:

• Successful synthesis of azaspirocyclohexadienones via spirocyclization.
• Successful synthesis of ortho-benzylated anilines via hydrolysis.
• Achieved good to high yields under mild reaction conditions.
• Demonstrated room temperature, additive-free protocols with good functional group tolerance.

Conclusions:

• The developed cascade reactions provide efficient access to important heterocyclic and aromatic compounds.
• These methods offer a practical and versatile approach for organic synthesis.
• The mild and functional-group-tolerant nature of the protocols enhances their applicability.