||Hiroki Hayashi, Pawel Dydio, Hanna M. Key, Douglas S. Clark, John F. Hartwig, Chemoselective, Enzymatic C−H Bond Amination Catalyzed by a
Cytochrome P450 Containing an Ir(Me)-PIX Cofactor, J. Am. Chem. Soc., 10.1021/jacs.6b11410, 139, 1750-1753, 2017.01, Cytochrome P450 enzymes have been engineered to catalyze abiological C−H bond amination reactions, but the yields of these reactions have been limited by low chemoselectivity for the amination of C−H bonds over competing reduction of the azide substrate to a sulfonamide. Here we report that P450s derived from a thermophilic organism and containing an iridium porphyrin cofactor (Ir(Me)-PIX) in place of the heme catalyze enantioselective intramolecular C−H bond amination reactions of sulfonyl azides. These reactions occur with chemoselectivity for insertion of the nitrene
units into C−H bonds over reduction of the azides to the sulfonamides that is higher and with substrate scope that is broader than those of enzymes containing iron porphyrins. The products from C−H amination are formed in up to 98% yield and ∼300 TON. In one case, the enantiomeric excess reaches 95:5 er, and the reactions can occur with divergent site selectivity. The chemoselectivity for C−H bond amination is greater than 20:1 in all cases. Variants of the Ir(Me)-PIX CYP119 displaying these properties were identified rapidly by evaluating CYP119 mutants containing Ir(Me)-PIX in cell lysates, rather than as purified enzymes. This study sets the stage to discover suitable enzymes to catalyze challenging C−H amination reactions..
||Hiroki Hayashi, Hirokazu Iwata, Muhammet Uyanik, Kazuaki Ishihara, Chiral Ammonium Hypoiodite Salt-catalyzed Enantioselective Oxidative Cycloetherification to 2-Acyl Tetrahydrofurans, Chemistry Letters, http://dx.doi.org/10.1246/cl.160004, 3, 45, 353-355, 2016.01, 2-Acyl tetrahydrofuran is a fundamental structure in natural products and pharmaceuticals. We achieved chiral quaternary ammonium hypoiodite salt-catalyzed enantioselective oxidative cycloetherification of δ-hydroxyketone derivatives. The corresponding 2-acyl tetrahydrofurans were obtained in high chemical yield with high enantioselectivity..
||Hiroki Hayashi, Muhammet Uyanik, Kazuaki Ishihara, High-Turnover Hypoiodite Catalysis for Asymmetric Synthesis of Tocopherols, Science , DOI: 10.1126/science.1254976, 6194, 345, 291-294, 2014.07, The diverse biological activities of tocopherols and their analogs have inspired considerable interest in the development of routes for their efficient asymmetric synthesis. Here, we report that chiral ammonium hypoiodite salts catalyze highly chemo- and enantioselective oxidative cyclization of γ-(2-hydroxyphenyl)ketones to 2-acyl chromans bearing a quaternary stereocenter, which serve as productive synthetic intermediates for tocopherols. Raman spectroscopic analysis of a solution of tetrabutylammonium iodide and tert-butyl hydroperoxide revealed the in situ generation of the hypoiodite salt as an unstable catalytic active species and triiodide salt as a stable inert species. A high-performance catalytic oxidation system (turnover number of ~200) has been achieved through reversible equilibration between hypoiodite and triiodide in the presence of potassium carbonate base. We anticipate that these findings will open further prospects for the development of high-turnover redox organocatalysis..