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.     

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.     

Diferrocenophosphaborin: A Planar‐Chiral,Redox‐Active and Anion‐Responsive Ambiphilic Ligand

A new class of Janus‐like ambiphilic ligands is introduced. The rigid diferrocene backbone in heterocycles 4‐SnP and 4‐BP creates an unprecedented chiral environment as demonstrated by multinuclear NMR and single‐crystal X‐ray studies. In addition, the ligands are redox‐responsive and the Lewis acidic borane moiety in 4‐BP can be exploited to further tune the properties: a clear decrease in the CO stretching frequency of a Vaska‐type Rh^I complex 5‐BP is observed upon addition of fluoride ions. Thus, the Lewis acid and Lewis base sites influence each other and their strength can be modulated by redox chemistry and anion binding.     

S‐((Phenylsulfonyl)difluoromethyl)thiophenium Salts: Carbon‐Selective Electrophilic Difluoromethylation of β‐Ketoesters, β‐Diketones,and Dicyanoalkylidenes

S‐((Phenylsulfonyl)difluoromethyl)thiophenium salts were designed and prepared by a triflic acid catalyzed intramolecular cyclization of ortho‐ethynyl aryldifluoromethyl sulfanes. The thiophenium salts were found to be efficient as electrophilic difluoromehtylating reagents for introduction of a CF₂H group to sp³‐hybridized carbon nucleophiles such as of β‐ketoesters and dicyanoalkylidenes. The (phenylsulfonyl)difluoromethyl group can be readily transformed into CF₂H under mild reaction conditions. Enantioselective electrophilic difluoromethylation was also achieved in the presence of bis(cinchona) alkaloids.     

Asymmetric Strecker Reaction Arising from the Molecular Orientation of an Achiral Imine at the Single‐Crystal Face: Enantioenriched l‐ and d‐Amino Acids

Strecker synthesis has long been considered one of the prebiotic reactions for the synthesis of α‐amino acids. However, the correlation between the origin of chirality and highly enantioenriched α‐amino acids through this method remains a puzzle. In the reaction, it may be conceivable that the handedness of amino acids has been determined at the formation stage of the chiral intermediate α‐aminonitrile, that is, the enantioselective addition of hydrogen cyanide to an imine. Herein, an enantiotopic crystal surface of an achiral imine acted as an origin of chirality for the enantioselective formation of α‐aminonitriles by the addition of HCN. In conjunction with the amplification of the enantiomeric excess and multiplication of enantioenriched aminonitrile, a large amount of near enantiopure α‐amino acids, with the l ‐ and d ‐handedness corresponding to the molecular orientation of the imine, is reported.     

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.