We demonstrate that well-known transition metal catalysts can be transformed into high-performance versions by the simple use of a fluoride anion source. In situ fluoride-activated catalysts are hi...

Straightforward Access to High-Performance Organometallic Catalysts by Fluoride Activation: Proof of Principle on Asymmetric Cyanation, Asymmetric Michael Addition, CO2 Addition to Epoxide, and Reductive Alkylation of Amines by Tetrahydrofuran

Epilepsy is a chronic neurological disorder in the brain, affecting individuals of all age groups. Nearly 1% of the world population is affected by seizure disorder, of which 80% of the patients are observed in underdeveloped and developing countries. The predominant treatment option for epilepsy includes an antiepileptic drug named brivaracetam. This drug emerged as an unusual success of rational drug discovery in clinical development by exhibiting magnificent affinity toward synaptic vesicle glycoprotein as compared to conventional drug levetiracetam and piracetam. Given its efficiency in limiting the progression of epilepsy, this drug has drawn considerable attention of researchers to devise novel routes of its synthesis. The present review encapsulates the reported literature on synthetic strategies for brivaracetam, which will assist medicinal chemists in the further progress of its synthesis.

https://pubs.acs.org/doi/pdf/10.1021/acsomega.1c05378

Synthetic Approaches toward the Synthesis of Brivaracetam: An Antiepileptic Drug

Functionally substituted sulfones with stereogenic centers are valuable reagents in organic synthesis and key motifs in some bioactive compounds. The asymmetric Michael addition of β-ketosulfones to conjugated nitroalkenes in the presence of Ni(II) complexes with various chiral vicinal diamines was studied. This reaction provides convenient access to non-racemic 4-nitro-2-sulfonylbutan-1-ones with two stereocenters with high yield and excellent enantioselectivity (up to 99%). It has been established that the catalytic Michael reaction itself was carried out with high diastereoselectivity, but the Michael adducts may epimerize at the C-2 position at a significant rate. Conditions for the preparation of individual diastereomers were found.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-15-127.pdf

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones.

The biocatalytic stereoselective synthesis of lactams with two chiral centers by a dynamic kinetic resolution strategy is demonstrated. Five transaminases were examined for the transamination of chemically synthesized substituted γ‐ or δ‐keto esters. The application of (R)‐ and (S)‐selective enzymes led to the corresponding chiral amines with moderate to high diastereomeric ratios and excellent enantiomeric excess, followed by the formation of γ‐ or δ‐lactams in some cases. Reaction conditions including pH, co‐solvent and ratio of amine donor vs. acceptor were optimised. The stereoselective biotransaminations were performed at semi‐preparative scale, successfully generating the corresponding lactams or amine in 46–70 % isolated yields, up to 99 : 1 diastereomeric ratios and >99 % ee values. This study represents a promising approach to the biocatalytic synthesis of important γ‐ and δ‐lactams with two chiral centers.

Leonid E. Kapranov

Papers

Nitroalkenes in the Ni(II) Catalyzed Asymmetric Michael Addition. Convenient Route to the Key Intermediate of Brivaracetam