H-bonded reusable template assisted para-selective ketonisation using soft electrophilic vinyl ethers

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Enzymatic pathways naturally form C_aryl-C(O) bonds site-selectively.
• Synthetic methods often require prefunctionalized substrates and are limited by substrate electronics and reaction conditions.

Purpose of the Study:

• To develop a directed para-selective ketonisation technique for arenes.
• To overcome limitations of existing electrophilic routes, such as substrate scope and product selectivity.

Main Methods:

• Utilized hard-soft interaction principles and in situ activation.
• Employed a polar protic solvent to facilitate the reaction.
• Investigated mechanistic pathways through experimental and computational studies.

Main Results:

• Achieved para-selective ketonisation of arenes, overriding electronic bias and structural congestion.
• Demonstrated a method that functions effectively in polar protic solvents.
• Suppressed competitive reaction pathways through controlled activation.

Conclusions:

• The developed protocol offers a general and broadly applicable method for C_aryl-C(O) bond formation.
• The technique is valuable for the formal synthesis of drugs, drug cores, and bioactive molecules.
• Mechanistic insights support the proposed reaction pathway and highlight the strategy's robustness.