Chiral Phosphoric Acid-Catalyzed Enantioselective Higher-Order Cycloadditions: Temperature-Dependent Periselectivity

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Higher-order cycloadditions (HOCs) are vital for complex cyclic structure synthesis.
• Existing HOC methods often suffer from low selectivity and challenging stereocontrol.

Purpose of the Study:

• To develop a highly selective chiral phosphoric acid-catalyzed HOC reaction.
• To explore novel transformations of cycloaddition products.

Main Methods:

• Chiral phosphoric acid catalysis of reactions between tropones and trifluoroacetamido-1,3-dienes.
• Thermal Cope rearrangement of intermediate cycloadducts.
• Investigating thermal transformations of substituted analogues.

Main Results:

• Efficient synthesis of bicyclo[4.4.1]undecatrienones with excellent peri-, diastereo-, and enantioselectivities.
• Regioselective Cope rearrangement to bicyclo[3.2.2]nonadienones.
• Formation of unique tetracyclic decahydro-1,5-methanoazulene motifs from 7-alkyl substituted analogues.

Conclusions:

• A versatile and highly selective catalytic method for constructing complex bridged polycyclic molecules.
• Demonstration of sequential transformations enabling access to diverse molecular architectures.
• The resulting polycyclic compounds offer valuable handles for further synthetic derivatization.