Iridium-Catalyzed Asymmetric Hydrogenation of γ- and δ-Ketoacids for Enantioselective Synthesis of γ- and δ-Lactones

Abstract

A highly efficient asymmetric hydrogenation of γ- and δ-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active γ- and δ-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.

Visible Light-Driven, Copper-Catalyzed Aerobic Oxidative Cleavage of Cycloalkanones

“…ε-Keto acid 2a also underwent the oxidative decarboxylation reaction smoothly to give the 5-fluoro-1-phenylpentan-1-one 5a and 5-azido-1-phenylpentan-1-one 5b in moderate yields . In addition, δ-keto acid 3a could be reduced with NaBH 4 , and then made to undergo intramolecular esterification to deliver the lactone 7a in 77% yield …”

“…9 In addition, δ-keto acid 3a could be reduced with NaBH 4 , and then made to undergo intramolecular esterification to deliver the lactone 7a in 77% yield. 10 To elucidate the mechanism, control experiments were conducted (Scheme 5). When 2.0 equiv of TEMPO was added into the reaction of 1a, the reaction was completely inhibited, and the TEMPO-adduct could be detected by highresolution mass spectrometry (Scheme 5, eq 1).…”

“…Spectral data match those previously reported. 10 5-(4-Chlorophenyl)-5-oxopentanoic Acid (3b). Reaction conditions A.…”

Bifunctional Homogeneous Catalysts Based on Ruthenium, Rhodium and Iridium in Asymmetric Hydrogenation

“…AH of ketones, lactones and -ketoesters using an iridium catalyst based on a P(NH)N spiro ligand by Zhou, Xie and co-workers. [219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234] This method provides one of the most impressive recent applications of Ir-bifunctional catalysts in asymmetric hydrogenation, in terms of both catalytic efficiency, enantioselectivity, substrate scope and synthetic potential. It is worth to note that Zhang, Yin and co-workers reported in parallel the synthesis of rather similar oxaspirocyclic chiral ligands and applied them to iridium-catalyzed direct asymmetric hydrogenation of Bringmann's lactones (Scheme 73a).…”

“…[225][226][227][228][229][230][231][232] A recent application to the AH/Dynamic kinetic resolution of racemic α-arylamino-γ-lactones and α-arylamino-δlactones led to the corresponding chiral 2-amino diols with high yields and enantioselectivities (Scheme 72d). [233][234] According to theoretical studies, the hydride and proton transfer step proceeds via a cyclic 6membered transition state. The calculated transition state of lowest energy leads to the (S)-2-amino-diol, as observed experimentally.…”