Nicoletta Gaggero

A practical four-step sequence for the synthesis of α,δ-dioxoesters with high enantiomeric excess was developed. It makes use of a regio- and stereoselective Michael addition of a chiral ketimine to ethyl 2-(phenylthio)-2-propenoate as a key transformation. The synthetic elaboration of the Michael adduct provides the new ethyl 3-(1-methyl-2-oxo-cyclohexyl)-2-oxopropanoate, bearing a quaternary stereocenter with 95% ee and high yield.

3,4-dihydropyridin-2-ones are of considerable importance due to the large number of these core structures exhibiting a diverse array of biological and pharmacological activities. The Michael-type addition of 1,3-dithiane-2-carbothioates to α,β-unsaturated N-tosyl imines, followed by intramolecular annulation driven by a sulfur leaving group, provides a practical reaction cascade for the synthesis of a variety of substituted 3,4-dihydropyridin-2-ones. In this work, the reaction was carried out under solid–liquid phase transfer catalysis (SL-PTC) conditions at room temperature, in short reaction times in the presence of cheap Bu₄N⁺HSO₄^– and solid KOH. The new PTC method exhibited adequate functional group tolerance, proving to be a green and reliable method and easy to scale up to furnish rapid access to 3,4-dihydropyridin-2-ones after desulfurization from simple, readily available starting materials.

Cascade reactions catalyzed by immobilized multi enzymatic systems are emerging as a tool to address the increasing need for green and sustainable chemistry. In this regard, the carrier-free immobilization strategy of combined cross-linked enzymes aggregates (combi- CLEAs) is of great interest. In a combi-CLEAs two or more enzymes are co-immobilized into a single unit where they are accommodated in close proximity in order to minimize the intermediates diffusion in the reaction medium, at the same time allowing the access of substrates and coenzymes to the active sites. The use of CLEAs provides a simple and low cost methodology that enhances operational and storage enzyme stability and facilitates biocatalyst recovery and recycle. Some significant applications of cascade reactions catalyzed by combi- CLEAs are reported in this mini-review. These examples have been applied on a multigram scale and have furnished practical steps towards the implementation of enzymes on an industrial scale.

A highly stereoselective synthesis of anl-Oic-analogue bearing a tetrasubstituted sterocenter is reported.

Quaternary stereocenters are privileged structural motifs, widely distributed in natural products and in pharmaceutically active compounds. Asymmetric methods for the efficient construction of these prominent frameworks are rapidly increasing. Biocatalysis represents an alternative to the existing methods of using hazardous metals and chemicals. Enzymes discussed in this mini‐review involve thiamine‐bisphosphate (ThDP)‐dependent lyases, aldolases and hydroxynitrile lyases. The chiral products, (α‐alkyl‐α‐hydroxy ketones, α‐alkyl‐α‐hydroxy‐β‐diketones, β‐hydroxy ketones, ketone cyanohydrins) obtained by these enzymes, are valuable intermediates suitable for further transformations affording a variety of multi‐functionalized useful building blocks bearing a tetrasubstituted stereocenter, such as amino alcohols, diols, α‐hydroxy carboxylic acids, β‐hydroxy‐α‐amino acids to cite only a few.

The N-heterocyclic carbene(NHCs)-catalyzed aza-benzoin condensation reaction is an efficient, single step strategy which employs easily available substrates, such as aldehydes and imines, to provide α-amino ketones. The multifunctionality and high reactivity of α-amino ketones makes these structures attractive for medicinal chemistry and as precursors of a variety of amine derivatives. The different electrophilic characteristics of aldehydes and imines ensure a high regioselective reaction. Enantiomerically-enriched α-amino ketones have been synthesized through stereoselective couplings promoted by chiral N-heterocyclic carbenes. One-pot domino procedures, including an aza-benzoin step, allow valuable complex molecules to be accessed.

2,3-Dihydro-1,5-benzothiazepines have been obtained through a domino process involving a Michael addition of 2-aminothiophenols to chalcones, followed by in situ cyclization. Up to 98% chemical yields have been obtained at room temperature under essentially neutral conditions by using hexafluoro-2-propanol as an efficient medium.

An exhaustive and critical overview of synthetically relevant methods for intermolecular cross-acyloin condensation reactions is reported.

An efficient organocatalytic methodology has been developed to perform the stereoselective addition of 2-carboxythioesters-1,3-dithiane to nitroalkenes. Under mild reaction conditions γ-nitro-β-aryl-α-keto esters with up to 92% ee were obtained, realizing a formal catalytic stereoselective conjugate addition of the glyoxylate anion synthon. The reaction products are versatile starting materials for further synthetic transformations; for example, the simultaneous reduction of the nitro group and removal of the dithiane ring was accomplished, allowing the preparation of a GABA_B receptor agonist baclofen.

Albumin emerged as a biocatalyst in 1980 and the continuing interest in this protein is proved by numerous papers.