Reverse Regioselective Dicarbofunctionalization via Anti-Michael-Type Addition.

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Vicinal dicarbofunctionalization of α,β-unsaturated carbonyl compounds is a key synthetic strategy.
• Traditional methods typically exhibit regioselectivity governed by alkene electronics, placing nucleophiles at the β-position and electrophiles at the α-position.

Purpose of the Study:

• To develop a novel palladium-catalyzed dicarbofunctionalization of acrylamides.
• To achieve reverse regioselectivity compared to conventional approaches, enabling α-functionalization with nucleophiles.

Main Methods:

• Palladium-catalyzed dicarbofunctionalization reaction.
• Utilized acrylamides as substrates.
• Employed an anti-Michael-type addition pathway.

Main Results:

• Successfully achieved reverse regioselectivity in the dicarbofunctionalization of acrylamides.
• Efficiently incorporated (hetero)arene nucleophiles at the α-position.
• Incorporated carbon electrophiles (iodoarenes, vinyl iodides, iodomethane) at the β-position, yielding dicarbofunctionalized amides in good yields.

Conclusions:

• The developed strategy offers a powerful new route for synthesizing dicarbofunctionalized amides with reversed regioselectivity.
• Mechanistic studies indicate the reaction proceeds via an α-addition of a nucleophile to form an alkylpalladium intermediate.