Enzyme-like Regiodivergent Behavior of a Flavopeptide Catalyst in Aerobic Baeyer-Villiger Oxidation.

We recently developed a flavopeptide immobilized on polystyrene resin, Fl-Pep-PS, that could realize the first N5-unmodified neutral flavin (Fl)-catalyzed aerobic oxygenation reactions under non-enzymatic conditions. Although a key active species is assumed to be the corresponding 4a-hydroperoxyflavin (Fl4aOOH) from the unprecedented activity and unique chemoselectivity, further circumstantial support would be helpful to be sure since spectroscopic evidence is difficult to obtain due to the compound's insolubility. In this article, we report that the aerobic Baeyer-Villiger oxidation of a fused cyclobutanone, (±)-cis-bicyclo[3.2.0]hept-2-en-6-one (1), can be promoted with Fl-Pep-PS in a FMO-like chemoselectivity and regiodivergent manner via Fl-related catalytic intermediates, which delivers strong evidence of the involvement of Fl4aOOH as an active species in Fl-Pep-PS-catalyzed aerobic oxygenation reactions.

Enantioselective synthesis of 3-(N-indolyl)quinolines containing axial and central chiralities.

Quinoline and indole are important core structures in biologically active compounds and materials. Atropisomeric biaryls consisting of quinoline and indole are a unique class of axially chiral molecules. We report herein enantioselective synthesis of 3-(N-indolyl)quinolines having both C-N axial chirality and carbon central chirality by a photoredox Minisci-type addition reaction catalyzed by a chiral lithium phosphate/Ir-photoredox complex. The catalytic system enabled access to a unique class of 3-(N-indolyl)quinolines with high chemo-, regio-, and stereoselectivities in good yields through the appropriate choice of an acid catalyst and a photocatalyst. This is the first example of the synthesis of 3-(N-indolyl)quinoline atropisomers in a highly enantioselective manner.

Creation of a Chiral All-Carbon Quaternary Center Induced by CF3 and CH3 Substituents via Cu-Catalyzed Asymmetric Conjugate Addition.

Cu-catalyzed asymmetric construction of a chiral quaternary center bearing CH3 and CF3 groups was achieved with high to excellent enantioselectivity using our originally developed ligands. The asymmetric conjugate addition of Me3Al to ß-CF3-substituted enones and unsaturated ketoesters proceeded efficiently. The use of unsaturated ketoesters gives optically active furanones in high yields with high enantioselectivities. The perfluoroalkyl-substituted enone does not seem to be favorable in the present reaction.

Design of peptide-containing N5-unmodified neutral flavins that catalyze aerobic oxygenations.

Simulation of the monooxygenation function of flavoenzyme (Fl-Enz) has been long-studied with N5-modified cationic flavins (FlEt+ ), but never with N5-unmodified neutral flavins (Fl) despite the fact that Fl is genuinely equal to the active center of Fl-Enz. This is because of the greater lability of 4a-hydroperoxy adduct of Fl, FlOOH , compared to those of FlEt+ , FlEtOOH , and Fl-Enz, FlOOH-Enz. In this study, Fl incorporated into a short peptide, flavopeptide (Fl-Pep), was designed by a rational top-down approach using a computational method, which could stabilize the corresponding 4a-hydroperoxy adduct (FlOOH-Pep) through intramolecular hydrogen bonds. We report catalytic chemoselective sulfoxidation as well as Baeyer-Villiger oxidation by means of Fl-Pep under light-shielding and aerobic conditions, which are the first Fl-Enz-mimetic aerobic oxygenation reactions catalyzed by Fl under non-enzymatic conditions.