Metal-Controlled Enantiodivergent Tandem Rearrangement to Synthesize 2H-Azirines.

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Organometallic Chemistry

Background:

• Chiral 2H-azirines are valuable synthetic intermediates.
• Developing methods for enantioselective synthesis of 2H-azirines remains a challenge.
• Metal-catalyzed rearrangements offer potential pathways to complex chiral molecules.

Purpose of the Study:

• To develop a metal-controlled enantiodivergent rearrangement of α-diazo-β-keto oxime ethers.
• To achieve access to both enantiomers of chiral 2H-azirines and their derivatives.
• To investigate the influence of different metal catalysts on asymmetric induction.

Main Methods:

• Utilized α-diazo-β-keto oxime ethers as substrates.
• Employed cobalt(II) and iron(II) metal catalysts with an identical ligand.
• Conducted mechanistic studies including kinetic experiments and density functional theory (DFT) calculations.

Main Results:

• Successfully developed an enantiodivergent rearrangement controlled by metal catalysts.
• Switching the metal catalyst from Co(II) to Fe(II) completely reversed the asymmetric induction.
• Achieved high efficiency with the cobalt-based catalyst, even at 0.05 mol% loading.
• Demonstrated accessibility of both enantiomers of chiral 2H-azirines under thermal or photolytic conditions.

Conclusions:

• The study presents a novel metal-controlled enantiodivergent rearrangement for synthesizing chiral 2H-azirines.
• Distinct electronic properties of cobalt and iron catalysts modulate intermediate conformations, dictating enantioselectivity.
• This work provides a versatile platform for accessing diverse chiral azirine derivatives.