Kinetic Resolution and Chemoenzymatic Dynamic Kinetic Resolution of Functionalized γ-Hydroxy Amides

Abstract

[reaction: see text] An efficient kinetic resolution of racemic gamma-hydroxy amides 1 was performed via Pseudomas cepacia lipase (PS-C)-catalyzed transesterification. The enzyme PS-C tolerates both variation in the chain length and different functionalities giving good to high enantioselectivity (E values of up to >250). The combination of enzymatic kinetic resolution with a ruthenium-catalyzed racemization led to a dynamic kinetic resolution. The use of 2,4-dimethyl-3-pentanol as a hydrogen source to suppress ketone formation in the dynamic kinetic resolution yields the corresponding acetates in good yield and good to high enantioselectivity (ee's up to 98%). The synthetic utility of this procedure was illustrated by the practical synthesis of the versatile intermediate gamma-lactone (R)-5-methyltetrahydrofuran-2-one.

Easy preparation of enantiomerically enriched heteroaromatic alcohols through lipase-catalyzed acylation with succinic anhydride under unconventional activation

“…D. Yu and colleagues have showed the same effect for resolution of (R,S)-2-octanol with vinyl acetate through transesterification, the microwave irradiation acted as activator to both of (R)-and (S)-2-octanol during the reaction except for the variation of the activation degree [52]. The choice of solvent is important, as it can influence the enantioselectivity observed for a given reaction [53,54]. In our case, diethyl ether is an efficient solvent compared to toluene, with respect to the enantiopurity of the products obtained.…”

Tuning of the Electronic Properties of a Cyclopentadienylruthenium Catalyst to Match Racemization of Electron‐Rich and Electron‐Deficient Alcohols

“…After chromatography the fractions were pooled, evaporated to dryness and dried in vacuo. 1 6 ]DMSO d C = 39.5 ppm). High resolution mass spectra (HRMS) were recorded on a Bruker MicroTOF ESI-TOF mass spectrometer.…”

“…This protocol was later extended to functionalized secondary alcohols such as hydroxyacid derivatives, [5,6] various bsubstituted alcohols, [ 2a] and diols. [7] Shvos catalyst has also been applied to DKR of primary amines, [8] in which the catalyst was also subject for electronic modifications, showing that electron-rich substituents on the catalyst lead to more efficient racemization.…”

Biocatalysis: Synthesis of Chiral Intermediates for Drugs

“…The use of 2,4 -dimethyl -3 -pentanol as a hydrogen source to suppress ketone formation in the dynamic kinetic resolution yields the corresponding acetates in good yield and good to high enantioselectivity (ee ' s to Corynebacterium C12 98%). The synthetic utility of this procedure was illustrated by the practical synthesis of the versatile intermediate γ -lactone ( R ) -5 -methyltetrahydrofuran -2 -one (Fransson et al , 2005 ). Chiral γ -lactones are important structural synthons for the synthesis of natural products and biologically active compounds (Benincori et al , 2004 ).…”