Enantioconvergent 6π Electrocyclization Enabled by Photoredox Racemization.

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Chiral 2H-1,3-benzoxazines are valuable heterocyclic compounds.
• Developing enantioselective synthetic methods for these structures remains a challenge.

Purpose of the Study:

• To develop a novel photoredox-enabled enantioconvergent catalytic strategy for synthesizing chiral 2H-1,3-benzoxazines.
• To utilize racemic alpha-substituted glycinates as substrates in an unprecedented oxa-6π electrocyclization.

Main Methods:

• Employing a cobalt-based chiral Lewis acid catalyst.
• Utilizing a commercially available iridium photocatalyst under visible light irradiation.
• Conducting mechanistic studies with optically pure alpha-deuterated substrates and linear free energy relationship analysis.

Main Results:

• The thermal reaction selectively converted (S)-configured glycinates into enantioenriched 2H-1,3-benzoxazines (up to 96:4 e.r.).
• The addition of an iridium photocatalyst under visible light irradiation enabled an enantioconvergent process.
• Mechanistic studies revealed an enantiospecific kinetic isotope effect and confirmed the stereodetermining 6π electrocyclization step.

Conclusions:

• A novel dual catalytic system combining photoredox and chiral Lewis acid catalysis was established for enantioconvergent synthesis of chiral 2H-1,3-benzoxazines.
• The photocatalyst facilitates dynamic enantiomer interconversion, while the chiral Lewis acid selectively reacts with the (S)-enantiomer.
• The findings provide a new route to valuable chiral heterocycles with mechanistic insights into the catalytic cycle.