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.     

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.     

Ligand‐Enabled β‐C–H Arylation of α‐Amino Acids Without Installing Exogenous Directing Groups

Herein we report acid‐directed β‐C(sp³)‐H arylation of α‐amino acids enabled by pyridine‐type ligands. This reaction does not require the installation of an exogenous directing group, is scalable, and enables the preparation of Fmoc‐protected unnatural amino acids in three steps. The pyridine‐type ligands are crucial for the development of this new C(sp³)‐H arylation.     

One‐Pot Multicomponent Synthesis of β‐Amino Amides

Multicomponent reactions are excellent tools for rapid generation of small molecules with broad chemical diversity and molecular complexity. Herein, a novel one‐pot multicomponent synthesis of β‐amino amides from aldehydes, anilines, carboxylic acids and ynamides has been successfully developed. This process is practical and efficient to unravel synthetic utility and scalability. Moreover, an isotope labeling reaction was conducted to elucidate a plausible reaction mechanism.