Chiral Phosphoric Acid and BF₃·THF Relay Catalytic System Enables a Formal Asymmetric Aza-Baeyer-Villiger...

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Synthetic Methodology

Background:

• The Baeyer-Villiger rearrangement is a key transformation for synthesizing esters and lactones.
• Developing asymmetric variants for nitrogen-containing heterocycles remains a significant challenge in organic synthesis.
• Chiral auxiliaries and catalysts are crucial for achieving high enantioselectivity in organic reactions.

Purpose of the Study:

• To develop a novel, highly enantioselective method for the asymmetric aza-Baeyer-Villiger rearrangement of cyclobutanones.
• To establish a one-pot strategy combining condensation and rearrangement steps for efficient synthesis of chiral γ-lactams.
• To investigate the transfer of axial chirality to point chirality during the reaction.

Main Methods:

• A relay catalytic system employing chiral phosphoric acid (CPA) and boron trifluoride etherate (BF₃·THF) was utilized.
• A newly designed dinaphthylphosphinyl hydroxylamine (DNPH) reagent was employed for the condensation step.
• The reaction involved an asymmetric condensation followed by a BF₃·THF-promoted Beckmann rearrangement.

Main Results:

• The developed method achieved a formal asymmetric aza-Baeyer-Villiger rearrangement of cyclobutanones.
• High enantioselectivity was observed in the CPA-catalyzed condensation step (generally >90% ee).
• The Beckmann rearrangement proceeded with excellent enantiospecificity (>98% es) via axial-to-point chirality transfer, yielding valuable γ-lactams.

Conclusions:

• The one-pot relay catalytic system offers operational simplicity and excellent enantiocontrol.
• This strategy provides an efficient route to valuable chiral γ-lactams.
• The method demonstrates successful transfer of axial chirality to point chirality in asymmetric synthesis.