Asymmetric Reduction of 2‐Chloro‐3‐oxo Esters by Transfer Hydrogenation

Abstract

Asymmetric reduction of 2-chloro-3-oxo esters was achieved by catalytic transfer hydrogenation using [RuCl 2 (p-cymene)](S,S)-TsDPEN as the chiral catalyst and HCOOH-Et 3 N as the hydrogen source. Moderate to good yields (up to 85%) and good enantioselectivities (up to 98% ee) were obtained.

Asymmetric Synthesis of Diverse Glycolic Acid Scaffolds via Dynamic Kinetic Resolution of α-Keto Esters

“…Chloride addition to optically pure glycidic esters often necessitates harsh reaction conditions, suffers from non-ideal regio- and stereoselectivity, and lacks significant precedent for aliphatic substrates. 47 The dynamic kinetic resolution of α-chloro-β-keto esters has been developed for some time, 48 but the dynamic kinetic resolution of β-chloro-α-keto esters that would provide isomeric products is heretofore unknown. Thus, we sought to develop a simple, flexible synthesis of β-chloro glycolic acid derivatives employing a dynamic kinetic resolution asymmetric transfer hydrogenation (DKR-ATH) of β-chloro-α-keto esters (Figure 2).…”

Biocatalytic dynamic reductive kinetic resolution of aryl α-chloro β-keto esters: divergent, stereocontrolled synthesis of diltiazem, clentiazem, and siratiazem

“…1) are a class of molecules of paramount synthetic significance. [1][2][3] For instance, intramolecular cyclization of 1 generates the corresponding epoxyesters (2), serving as the critical intermediates to various compounds of biological or pharmaceutical interest, including the calcium channel blocker diltiazem (3a), which is clinically used for the treatment of hypertension and angina in more than 100 countries, [4][5][6] and N-benzoyl-2R,3S-3-phenyl isoserine (4), the side chain of anti-cancer drug taxol. 7 Furthermore, direct displacement of the chlorine atom of 1 by an appropriate nitrogen nucleophile would ultimately give rise to b-phenylserine derivatives (5) with activities of inhibiting the influenza virus.…”