Organocatalytic Asymmetric Aldol Reaction of Ketones with β,γ‐Unsaturated α‐Keto Esters: An Efficient Access to Chiral Tertiary Alcohol Skeletons

This update describes a highly efficient organocatalytic aldol reaction of ketones and β,γ‐unsaturated α‐keto esters for constructing the chiral tertiary alcohol motif. With the application of 9‐amino(9‐deoxy)epi‐Cinchona alkaloid and an acidic additive as catalysts, both acyclic and cyclic ketones react with β,γ‐unsaturated α‐keto esters smoothly to afford aldol adducts in good to excellent yields and asymmetric induction. This protocol offers a new pathway for the construction of adjacent chiral carbon centers and the synthesis of chiral β‐hydroxy carbonyl compounds.     

An Efficient Approach to Chiral Ferrocene‐Based Secondary Alcohols via Asymmetric Hydrogenation of Ferrocenyl Ketones

P‐Phos‐ruthenium‐DPEN precatalysts have been found to be efficient for the asymmetric hydrogenation of various ferrocenyl ketones. The use of (R)‐xylyl‐P‐PhosRuCl₂(R,R)‐DPEN generated chiral ferrocenylethanol in 99.3% e.e. with >99% conversion in a 150‐g scale.     

Highly Enantioselective Catalytic Alkynylation of Ketones – A Convenient Approach to Optically Active Propargylic Alcohols

The development of highly enantioselective catalysts involving Cu(OTf)₂ and chiral camphorsulfonamides for the alkynylation of ketone is described. The influences of Lewis acids, reaction conditions and chiral ligands on the outcome of the reaction are discussed. The best enantioselectivity (up to 97 % ee) was obtained in the alkynylation of 2′‐chloroacetophenone. The scope of the reaction is also examined.     

A General Approach to the Synthesis of β2‐Amino Acid Derivatives via Highly Efficient Catalytic Asymmetric Hydrogenation of α‐Aminomethylacrylates

A new strategy was developed for the synthesis of a valuable class of α‐aminomethylacrylates via the Baylis–Hillman reaction of different aldehydes with methyl acrylate followed by acetylation of the resulting allylic alcohols and S_N2′‐type amination of the allylic acetates. Asymmetric hydrogenation of these diverse olefinic precursors using rhodium(Et‐Duphos) catalysts provided the corresponding β²‐amino acid derivatives with excellent enantioselectivities and exceedingly high reactivities (up to >99.5% ee and S/C=10,000). The first hydrogenation of (Z)‐configurated substrates was studied for the synthesis of β²‐amino acid derivatives. The high influence of the substrate geometry and steric hindrance on the reactivity and enantioselectivity was also disclosed for this reaction. This protocol provides a highly practical, facile and scalable method for the preparation of optically pure β²‐amino acids and their derivatives under mild reaction conditions.     

Machine Learning Enables Selection of Epistatic Enzyme Mutants for Stability Against Unfolding and Detrimental Aggregation

Machine learning (ML) has pervaded most areas of protein engineering, including stability and stereoselectivity. Using limonene epoxide hydrolase as the model enzyme and innov'SAR as the ML platform, comprising a digital signal process, we achieved high protein robustness that can resist unfolding with concomitant detrimental aggregation. Fourier transform (FT) allows us to take into account the order of the protein sequence and the nonlinear interactions between positions, and thus to grasp epistatic phenomena. The innov'SAR approach is interpolative, extrapolative and makes outside-the-box, predictions not found in other state-of-the-art ML or deep learning approaches. Equally significant is the finding that our approach to ML in the present context, flanked by advanced molecular dynamics simulations, uncovers the connection between epistatic mutational interactions and protein robustness.     

Fields, forces, and performance equations of air-core linerself-synchronous motor with rectangular current control

An analytical field approach to determine the permanent magnetic field distribution in a flat air-core self-synchronous linear motor with a permanent magnet mover is reported. Thrust and normal forces are calculated for idealized rectangular-current inverter control. Notable thrust and normal force time pulsations are shown through a numerical example. The performance equations with an on-off current controller are developed with the motor fed from a voltage source transistor inverter. The analysis represents a reliable tool for refined design and control of permanent magnet air-core linear self-synchronous motors