A unified strategy for an efficient and high diastereoand enantioselective synthesis of (−)-chloramphenicol, (−)-azidamphenicol, (+)-thiamphenicol, and (+)-florfenicol based on a key catalytic syn-selective Henry reaction is reported. The stereochemistry of the ligand-enabled copper(II)-catalyzed aryl aldehyde Henry reaction of nitroethanol was first explored to forge a challenging syn-2-amino-1,3-diol structure unit with vicinal stereocenters with excellent stereocontrol. Multistep continuous flow manipulations were carried out to achieve the efficient asymmetric synthesis of this family of amphenicol antibiotics.

The catalytic enantioselective alkynylation of isatins, catalyzed by a Zn(OCOCF 3 ) 2 /chiral bis(sulfonamide)-diamine (BSDA) catalyst under mild condition, has been developed. The desired chiral 3-alkynyl-3-hydroxy-2-oxindoles were ob-tained in moderate to excellent yields (up to 96%) and good to excellent enantioselectivites (up to 97% ee). The reaction is broad in scope with respect to aryl-substituted terminal alkynes and substituted isatins.

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