Dynamic Kinetic Resolution of rac‐2‐Hydroxy‐1‐indanone by using a Heterogeneous Ru(OH)₃/Al₂O₃ Racemization Catalyst and Lipase

Abstract

Kinetic resolution and dynamic kinetic resolution, in particular, provide practical tools for synthesis of enantiomerically pure compounds. In the present work, the resolution of rac‐2‐hydroxy‐1‐indanone and racemization of (S)‐2‐hydroxy‐1‐indanone were investigated. Immobilized lipase AK (Pseudomonas fluorescens) was found as the best enzyme catalyst for kinetic resolution and ruthenium supported on Al2O3 as a potential heterogeneous catalyst for racemization of the starting material. By combining the two reactions, a simple dynamic kinetic resolution of rac‐2‐hydroxy‐1‐indanone producing (R)‐1‐oxo‐indan‐2‐yl butanoate was developed. Under optimal conditions, the product was obtained in 92 % ee at approximately 90 % conversion.

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…In fact, there are few examples of heterogeneous and immobilized racemization catalysts compatible with lipases (Akai et al, 2010;Egi et al, 2013;Han et al, 2010a;Långvik et al, 2010;Nieguth et al, 2014;Wieczorek et al, 2011). The development of these catalysts, which are in general reusable and more suitable for industrial applications, is still a challenge.…”

ChemInform Abstract: Heterogeneous Chemoenzymatic Catalyst Combinations for One‐Pot Dynamic Kinetic Resolution Applications

“…[72] Moreover,s ome examples have been reported in which ah eterogeneousR u-based racemization catalyst has been used in combination with an immobilized lipase for development of heterogeneously catalyzed DKR reactions. [73,74] Our group has studied the kinetics of Ru(OH) x /Al 2 O 3 for racemization in DKR applications for both 1-phenylethanol and the structurally more interesting 2-hydroxy-1-indanone. [73,74] The racemization rate in the heterogeneously catalyzed DKR reactions is inhibited by the esters present,however, the use of rac-2-hydroxy-1-indanone as the startingm aterial provided the acylated product with reasonably high conversions (90 %) and moderate ee values (92 %) of the acylated product (Scheme 10).…”

“…[73,74] The racemization rate in the heterogeneously catalyzed DKR reactions is inhibited by the esters present,however, the use of rac-2-hydroxy-1-indanone as the startingm aterial provided the acylated product with reasonably high conversions (90 %) and moderate ee values (92 %) of the acylated product (Scheme 10). [73]…”

“…DKR of rac-2-hydroxy-1-indanone using lipaseAK/Celite and Ru(OH) x /Al 2 O 3 . [73] ChemCatChem 2015, 7,4004 -4015 www.chemcatchem.org matic DKR, startingf rom ap rochiral ketone or ketoxime, yielding in an optimal case enantiomerically pure products are rare. [74][75][76][77][78][79] In the production of ac hiral amine the first step involves ap alladium-catalyzed,n onstereoselective reduction of ab enzylic ketoxime using H 2 as the hydrogen source to yield ap rimary amine.…”

Heterogeneous Chemoenzymatic Catalyst Combinations for One‐Pot Dynamic Kinetic Resolution Applications

“…Although this heterogeneous Ru catalyst suffered from a lower racemization rate in the presence of ester moieties, the catalyst appeared to be reasonably fast in the presence of ethyl acetate, possibly enabling further development of efficient DKR processes . Moreover, some examples have been reported in which a heterogeneous Ru‐based racemization catalyst has been used in combination with an immobilized lipase for development of heterogeneously catalyzed DKR reactions . Our group has studied the kinetics of Ru(OH) x /Al 2 O 3 for racemization in DKR applications for both 1‐phenylethanol and the structurally more interesting 2‐hydroxy‐1‐indanone .…”