Iridium/f‐Amphol‐catalyzed Efficient Asymmetric Hydrogenation of Benzo‐fused Cyclic Ketones

Abstract

Iridium/f-Amphol-catalyzed asymmetric hydrogenation of various benzo-fused five to sevenmembered cyclic ketones was successfully developed, affording a series of chiral benzo-fused cyclic alcohols with excellent results (75%-99% yields, 93%-> 99% ee, and TON up to 297 000). The enantioenriched products can be employed as key intermediates or motifs for the synthesis of some important biologically active compounds, such as rasagiline mesylate TVP-1012 used for the treatment of Parkinson's disease, the enantiomer of anticonvulsant drug eslicarbazepine acetate (BIA 2-093).

Design of Ru(II)-NHC-Diamine Precatalysts Directed by Ligand Cooperation: Applications and Mechanistic Investigations for Asymmetric Hydrogenation

“…Moreover, various benzo-fused cyclic ketones underwent the hydrogenation smoothly in the current catalytic system, giving the corresponding chiral alcohols with high e.r. values ( 6d – j ) …”

Recent Progress and Applications of Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

“…In 2018, Zhang, Dong, and co-workers investigated the stereoselective hydrogenation of Ir-mediated AH of racemic benzo-fused cyclic ketones via a DKR process using a new family of chiral ferrocene-based amino phosphine alcohol (f-Amphol) ligands. 10 The f-Amphol ligand L2 with a 3,5-ditert-butylphenyl group was identified as the optimal ligand, giving the targeted chiral benzo-fused cyclic alcohols in 75-96% yields and consistently excellent 99% ee. However, and as depicted in Scheme 3, the diastereomeric ratios of the reaction proved to be highly dependent on the size of the benzo-fused ring.…”

Biocatalytic asymmetric synthesis of (R)‐1‐tetralol using Lactobacillus paracasei BD101

“…10 To date, many chemical catalysts have been used for asymmetric reduction of 1-tetralone (1) and its derivatives, such as iridiumcatalyzed ligands, oxazaborolidine, amino acid-based ligands, and lutidine-based ligands. [11][12][13][14][15] In the literature, various chemical catalysts were tested for asymmetric reduction of substrate 1. However, to our knowledge, the use of biocatalyst for reduction of 1 has limited.…”

“…These products containing tetralone ring are of great interest in the drug industry 10 . To date, many chemical catalysts have been used for asymmetric reduction of 1‐tetralone ( 1) and its derivatives, such as iridium‐catalyzed ligands, oxazaborolidine, amino acid‐based ligands, and lutidine‐based ligands 11–15 …”