Oxidative Dimerization of (E)- and (Z)-2-Propenylsesamol with O₂ in the Presence and Absence of Laccases and Other Catalysts: Selective Formation of Carpanones and Benzopyrans under Different Reaction Conditions

Abstract

The oxidative dimerization of 2-propenylsesamol to carpanone with O(2) as the oxidant, which probably proceeds as a domino phenol oxidation/anti-β,β-radical coupling/intramolecular hetero Diels-Alder reaction, can be efficiently catalyzed by laccases. Experiments with laccases and other catalysts like a Co(salen) type catalyst and PdCl(2) clearly demonstrate that the diastereoselectivity of the carpanone formation does not depend on the catalyst but on the double-bond geometry of the substrate. With (E)-2-propenylsesamol as the substrate, carpanone and a so far unknown carpanone diastereoisomer are formed in a 9:1 ratio. When (Z)-2-propenylsesamol is used as starting material, carpanone is accompanied by two carpanone diastereoisomers unknown so far in a 5:1:4 ratio. All three carpanone diastereoisomers have been separated by HPLC, and their structures have been elucidated unambiguously by NMR spectroscopy, DFT calculations, and spin work analysis. When the oxidation of 2-propenylsesamol with O(2) is performed in the absence of any catalyst two diastereoisomeric benzopyrans are formed, probably as the result of a domino oxidation/intermolecular hetero Diels-Alder reaction. Under these conditions, carpanone is formed in trace amounts only.

Selective Catalytic Oxidation of CH Bonds with Molecular Oxygen

“…Since a pioneering study the oxidative dimerization of 2‐propenylsesamol ( 107 ) to carpanone ( 109 a )175 has received considerable attention. Recently, the coupling of 107 to 109 a , which probably proceeds as a domino phenol oxidation/anti‐β,β‐radical coupling/intramolecular hetero Diels–Alder reaction, was found to be efficiently catalyzed by laccases using O 2 as the oxidant 176. Experiments with laccases and other catalysts like a Co II salen and PdCl 2 clearly demonstrate that the diastereoselectivity of the carpanone formation does not depend on the catalyst but on the double bond geometry of the substrate.…”

Diastereoselective Synthesis of Benzoxanthenones

“…The Beifuss group has also done extensive studies of oxidation of the cis and trans carpanone monomer and showed the diastereomeric outcomes under different oxidative conditions. With the trans starting material, the diastereomer corresponding to natural carpanone is formed almost exclusively . Recently, an automated flow reactor has been utilized to synthesize carpanone as well as other members of the benzoxanthenone scaffold .…”

“…Notably, the major product ( 2 ) arose from an unexpected exo Diels‐Alder reaction after the initial C−C dimerization. The structure and spectroscopic properties of 2 were determined based on prior studies by the Beifuss group . DFT calculations (B3LYP/6‐31G) reveal that the endo product ( 1 ) is 9.1 kcal/mol more stable than the exo product ( 2 ) in terms of free energy (see SI for details).…”

“…As a consequence, this stronger catalyst binding to the substrate leads to the higher asymmetric induction during the C−C bond forming event. Participation of the catalyst in the subsequent Diels‐Alder cyclization is highly probable given the perturbation of the selectivity towards the exo product (endo product is favored with outer sphere oxidants that do not bind the substrates) . The vanadium (IV) catalyst disassociates upon the formation of 12 .…”

“…With the trans starting material, the diastereomer corresponding to natural carpanone is formed almost exclusively. [10] Recently, an automated flow reactor has been utilized to synthesize carpanone as well as other members of the benzoxanthenone scaffold. [11] The mechanistic paradigm behind oxidative formation of diasteromeric benzoxanthenones has remained consistent.…”