Yi-Yong Huang

An aza-Michael addition protocol to fluoroalkylated β-amino acid derivatives and enantiopure trifluoromethylated N-heterocycles

The aza-Michael reaction with β-fluoroalkylated acrylates provided the corresponding fluoroalkylated β-amino acid derivatives in up to 99% yield under catalyst- and solvent-free conditions. An enantioenriched β-trifluoromethylated β-amino acid was obtained in good yield through a scale-up diastereoselective aza-Michael addition, which facilitated the installation of enantiopure trifluoromethylated analogues of β-lactam and dihydroquinolin-4-one.

Asymmetric synthesis of chiral trifluoromethylated heliotridane via highly catalytic asymmetric Friedel–Crafts alkylation with β-trifluoromethylated acrylates and pyrroles

Chiral Ph-dbfox (Ph-dbfox = (R,R)-4,6-dibenzofurandiyl-2,2′-bis(4-phenyloxazoline))/Zn(NTf2)2 catalyzed enantioselective Friedel–Crafts reactions of β-CF3 acrylates with pyrroles and indoles have been investigated, which afforded the corresponding chiral trifluoromethyl pyrrole and indole derivatives in high yields (90–99%) with a range of 66–99% ee values. With the aid of the chiral adduct of the asymmetric Friedel–Crafts reaction, the chiral trifluoromethylated heliotridane has been successfully constructed in good total yield.

Petasis-Type gem-Difluoroallylation Reactions Assisted by the Neighboring Hydroxyl Group in Amines

A three-component Petasis-type gem-difluoroallylation reaction of using pinacol gem-difluoroallylboronates, aldehydes or isatin, and β-amino alcohols enabled by the neighboring hydroxyl group in amine is reported, affording various racemic and chiral gem-difluorohomoallylamine derivatives with good to excellent results. Based on the control experiment and stereochemistry of the product, a proposed reaction pathway is illustrated to clarify the origin of regio- and stereoselectivity under protic solvent conditions.

Enantioselective Synthesis of 1,3-Disubstituted 1,3-Dihydroisobenzofurans via a Cascade Allylboration/Oxo-Michael Reaction of o-Formyl Chalcones Catalyzed by a Chiral Phosphoric Acid

The first chiral Brønsted acid-catalyzed asymmetric cascade allylboration/oxo-Michael reaction between o-formyl chalcones and allylboronate has been successfully discovered, which afforded chiral 1,3-disubstituted 1,3-dihydroisobenzofurans with a yield, diastereoselective ratio (dr) and enantioselective excess (ee) up to 94%, 2.5:1, and 98%, respectively. In addition, 2,3-dienylboronic pinacol ester was also applied into this cascade reaction with good catalytic results.

Air- and Light-Stable S-(Difluoromethyl)sulfonium Salts: C-Selective Electrophilic Difluoromethylation of β-Ketoesters and Malonates

Air- and light-stable electrophilic difluoromethylating reagents, S-(difluoromethyl)- S-phenyl- S-(2,4,6-trialkoxyphenyl) sulfonium salts were successfully developed, and the introduction of intramolecular hydrogen bonds plays a crucial role for the stabilities and reactivities of these reagents. C-selective difluoromethylation of a broad range of β-ketoesters and malonates proceeded smoothly under mild reaction conditions to give good to excellent yields with excellent C/O regioselectivities.