Dynamic Parallel Kinetic Resolution of α-Ferrocenyl Cation Initiated by Chiral Brønsted Acid Catalyst

The dynamic parallel kinetic resolution (DPKR) of an α-ferrocenyl cation intermediate under the influence of a chiral conjugate base of a chiral phosphoric acid catalyst has been demonstrated in an...

Mutual kinetic resolution: probing enantiorecognition phenomena and screening for kinetic resolution with racemic reagents

This review highlights recent examples of mutual kinetic resolutions and describes how this approach can be used as a powerful tool to screen for efficient kinetic/parallel kinetic resolution protocols.

Oxazaborolidine-catalyzed reductive parallel kinetic resolution of ketones from β-nitro-azabicycles for the synthesis of chiral hypoestestatins 1, 2

A novel approach for the synthesis of 13a-methyl tylophora alkaloids has been reported. The key features included two different synthetic pathways targeted at transforming the β-nitro-azabicycle to the phenanthrene core....

Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent

Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.

Catalytic Asymmetric Transformations of Racemic Aziridines

The catalytic asymmetric ring-opening transformations of aziridines represent an important strategy for the construction of various chiral nitrogen-containing molecular architectures. This short review covers the progress achieved in the catalytic asymmetric transformation of racemic aziridines, focusing on the catalytic strategies employed for each different type of such aziridines.1 Introduction2 Reaction of Racemic 2-Vinylaziridines3 Reaction of Racemic 2-Alkylaziridines3.1 Regiodivergent Parallel Kinetic Resolution3.2 Kinetic Resolution4 Reaction of Racemic 2-(Hetero)arylaziridines4.1 Kinetic Resolution4.2 Enantioconvergent Transformation5 Reaction of Racemic Donor–Acceptor-Type Aziridines6 Conclusion and Outlook

11-Step Asymmetric Synthesis of (–)-Bilobalide

The <i>Ginkgo biloba </i>metabolite bilobalide (BB) is widely ingested but poorly understood. However, its antagonism of <i>gamma</i>-aminobutyric acid A receptors (GABA_AR) has been tied to rescue of cognitive deficits in mouse models of Down syndrome. Prior syntheses required multistep redox strategies to mitigate competing reactions of functional groups—emergent properties of the BB scaffold that cause unexpected reactivity. Here we exploit the unusual reactivity of bilobalide to affect a late-stage ‘inside-out’ oxidation that symmetrizes the molecular core and allows oxidation states to be embedded in the starting material, resulting in an 11-step synthesis. The stereochemically dense scaffold is accessed in asymmetric fashion through a novel catalytic enantioselective Reformatsky reaction and a solvent-dependent radical hydration. Steric compression and a parallel kinetic resolution result in the diastereoselective formation of a remarkably acid-stable oxetane acetal that proves crucial to relay stereochemical information.