TY - JOUR
T1 - Enantioconvergent 6π Electrocyclization Enabled by Photoredox Racemization
AU - Ričko, Sebastijan
AU - Bitsch, René Slot
AU - Kaasik, Mikk
AU - Otevrel, Jan
AU - Højgaard Madsen, Mikkel
AU - Keimer, Anna
AU - Jørgensen, Karl Anker
PY - 2023/9/12
Y1 - 2023/9/12
N2 - This study presents a novel photoredox-enabled enantioconvergent catalytic strategy used to construct chiral 2H-1,3-benzoxazines via an unprecedented oxa-6π electrocyclization utilizing racemic α-substituted glycinates as substrates. The approach leverages a cobalt-based chiral Lewis acid catalyst, which promotes the transformation under thermal or photoredox conditions. While the thermal reaction selectively converts only the (S)-configured glycinates into enantioenriched 2H-1,3-benzoxazines (up to 96:4 e.r.), the addition of 0.5 mol % of a commercially available iridium photocatalyst under visible light irradiation transforms the reaction into an enantioconvergent process. Detailed mechanistic and time course studies of optically pure α-deuterated substrates revealed the presence of an enantiospecific kinetic isotope effect, which helped to clarify the role of both the photo- and chiral Lewis acid catalyst in the reaction sequence. In this dual catalytic system, the photocatalyst promotes a dynamic interconversion between the substrate enantiomers─a process not accessible via ground-state chemistry─while the chiral Lewis acid selectively transforms only the (S)-configured substrates. Further mechanistic evidence for the proposed mechanism is provided by linear free energy relationship analysis, which suggests that the stereodetermining step involves a 6π electrocyclization under both thermal and photoredox conditions.
AB - This study presents a novel photoredox-enabled enantioconvergent catalytic strategy used to construct chiral 2H-1,3-benzoxazines via an unprecedented oxa-6π electrocyclization utilizing racemic α-substituted glycinates as substrates. The approach leverages a cobalt-based chiral Lewis acid catalyst, which promotes the transformation under thermal or photoredox conditions. While the thermal reaction selectively converts only the (S)-configured glycinates into enantioenriched 2H-1,3-benzoxazines (up to 96:4 e.r.), the addition of 0.5 mol % of a commercially available iridium photocatalyst under visible light irradiation transforms the reaction into an enantioconvergent process. Detailed mechanistic and time course studies of optically pure α-deuterated substrates revealed the presence of an enantiospecific kinetic isotope effect, which helped to clarify the role of both the photo- and chiral Lewis acid catalyst in the reaction sequence. In this dual catalytic system, the photocatalyst promotes a dynamic interconversion between the substrate enantiomers─a process not accessible via ground-state chemistry─while the chiral Lewis acid selectively transforms only the (S)-configured substrates. Further mechanistic evidence for the proposed mechanism is provided by linear free energy relationship analysis, which suggests that the stereodetermining step involves a 6π electrocyclization under both thermal and photoredox conditions.
UR - http://www.scopus.com/inward/record.url?scp=85172918627&partnerID=8YFLogxK
U2 - 10.1021/jacs.3c06227
DO - 10.1021/jacs.3c06227
M3 - Journal article
C2 - 37753541
AN - SCOPUS:85172918627
SN - 0002-7863
VL - 145
SP - 20913
EP - 20926
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 38
ER -