Design and Enantioselective Construction of Axially Chiral Naphthyl‐Indole Skeletons

The first enantioselective construction of a new class of axially chiral naphthyl‐indole skeletons has been established by organocatalytic asymmetric coupling reactions of 2‐naphthols with 2‐indolylmethanols (up to 99 % yield, 97:3 e.r.). This approach not only affords a new type of axially chiral heterobiaryl backbone, but also provides a new catalytic enantioselective strategy for constructing axially chiral biaryl scaffolds by making use of the C3‐electrophilicity of 2‐indolylmethanols.     

Isolable Silylene Ligands Can Boost Efficiencies and Selectivities in Metal‐Mediated Catalysis

A significant number of isolable silylenes are currently known. They have quickly developed from laboratory curiosities to useful ligands in metal‐mediated homogeneous catalysis. This includes their utilization in various catalytic transformations, such as C?C cross‐coupling, cyclotrimerization, hydroformylation, borylation, deuteration, hydrosilylation, amination, hydrogenation, and transfer semi‐hydrogenation reactions. Recent studies suggest that the silylene ligands surpass the steering properties of their phosphine and N‐heterocyclic carbene (NHC) analogues and provide excellent chemo‐, regio‐, and stereoselectivites. Mechanistic studies suggest that their promoted performance of metal‐mediated catalytic transformations results from a strong σ‐donor character along with cooperative effects of their Si^II centers. This Minireview covers the most recent advances in the field.     

Stereospecific α‐Sialylation by Site‐Selective Fluorination

Sialic acids are ubiquitous components of mammalian cell membranes and key regulators of cellular recognition events. Located at the non‐reducing termini of bioactive gangliosides, these essential building blocks are fused to the polysaccharide core via a characteristic α‐linkage, and rarely occur in the monomeric form. Effective chemical strategies to enable α‐sialylation are urgently required to construct well‐defined tools for glycomics. To complement existing chemoenzymatic strategies, an α‐selective process has been devised based on the site‐selective introduction of fluorine at C3 (more than 20 examples, up to 90 % yield). Predicated on localized particle charge inversion (C?H^δ+→C?F^δ?), fluorine insertion simultaneously augments the anomeric effect, enhances electrophilicity at C2 and mitigates elimination. A stereochemical induction model is postulated that spans the S_N continuum and validates the role of the C?F bond in orchestrating α‐selectivity.     

Turning Regioselectivity into Stereoselectivity: Efficient Dual Resolution of P‐Stereogenic Phosphine Oxides through Bifurcation of the Reaction Pathway of a Common Intermediate

Synthetic routes that provide facile access to either enantiomeric form of a target compound are particularly valuable. The crystallization‐free dual resolution of phosphine oxides that gives highly enantioenriched materials (up to 94 % ee) in excellent yields is reported. Both enantiomeric oxides have been prepared from a single intermediate, (R_P)‐alkoxyphosphonium chloride, which is formed in the course of a selective dynamic kinetic resolution using a single enantiomer of menthol as the chiral auxiliary. The origin of the dual stereoselectivity lies in bifurcation of the reaction pathway of this intermediate, which works as a stereochemical railroad switch. Under controlled conditions, Arbuzov‐type collapse of this intermediate proceeds through C O bond fission with retention of the configuration at the phosphorus center. Conversely, alkaline hydrolysis of the P O bond leads to the opposite S_P enantiomer.     

An In‐tether Chiral Center Modulates the Helicity,Cell Permeability,and Target Binding Affinity of a Peptide

The addition of a precisely positioned chiral center in the tether of a constrained peptide is reported, yielding two separable peptide diastereomers with significantly different helicity, as supported by circular dichroism (CD) and NMR spectroscopy. Single crystal X‐ray diffraction analysis suggests that the absolute configuration of the in‐tether chiral center in helical form is R, which is in agreement with theoretical simulations. The relationship between the secondary structure of the short peptides and their biochemical/biophysical properties remains elusive, largely because of the lack of proper controls. The present strategy provides the only method for investigating the influence of solely conformational differences upon the biochemical/biophysical properties of peptides. The significant differences in permeability and target binding affinity between the peptide diastereomers demonstrate the importance of helical conformation.     

Diastereo‐ and Enantioselective Synthesis of β‐Aminoboronate Esters by Copper(I)‐Catalyzed 1,2‐Addition of 1,1‐Bis[(pinacolato)boryl]alkanes to Imines

Reported herein is an efficient copper(I)‐catalytic system for the diastereo‐ and enantioselective 1,2‐addition of 1,1‐bis[(pinacolato)boryl]alkanes to protected imines to afford synthetically valuable enantioenriched β‐aminoboron compounds bearing contiguous stereogenic centers. The reaction exhibits a broad scope with respect to protected imines and 1,1‐bis[(pinacolato)boryl]alkanes, thus providing β‐aminoboronate esters with excellent diastereo‐ and enantioselectivity. The synthetic utility of the obtained β‐aminoboronate ester was also demonstrated.