Efficient kinetic resolution in the asymmetric transfer hydrogenation of 3-aryl-indanones: applications to a short synthesis of (+)-indatraline and a formal synthesis of (R)-tolterodine?

RSC Advances Pub Date: 2021-06-30 DOI: 10.1039/D1RA04538E

Abstract

Efficient kinetic resolution (KR) occurs in asymmetric transfer hydrogenation (ATH) reactions of racemic 3-aryl-1-indanones using commercial (R,R)- or (S,S)-Ts-DENEB as a catalyst, a 1?:?5 mixture of HCO2H and Et3N as a hydrogen source and MeOH as solvent. This process at room temperature produces near equal yields of cis-3-arylindanols with high dr and ee, and unreacted 3-arylindanones with excellent ee. Stereoselective transformations of 3-arylindanols and 3-arylindanones, generated by using the ATH-KR protocol, were carried out to form (+)-indatraline and synthetically valuable (R)-6-methyl-4-phenylcoumarine, which is a key intermediate in the preparation of (R)-tolterodine, (S)-4-aryl-3,4-dihydroquinoline-2(1H)-one and (S)-4-aryl-3,4-dihydroisoquinoline-1(2H)-one.

Graphical abstract: Efficient kinetic resolution in the asymmetric transfer hydrogenation of 3-aryl-indanones: applications to a short synthesis of (+)-indatraline and a formal synthesis of (R)-tolterodine
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