Asymmetric Synthesis of Propargylic alfa-Chiral Tertiary Amines by Reductive Alkynylation of Tertiary Amides Using Ir/Cu Tandem Catalysis

The development of an asymmetric protocol for the reductive alkynylation of amides to access important alfa-chiral tertiary propargylic amines is reported using tandem Ir-catalyzed hydrosilylation/enantioselective Cu-catalyzed alkynylation. The reaction utilizes a Cu/PyBox catalyst system in the alkynylation step to achieve asymmetry and affords excellent yields with moderate to good levels of enantiocontrol while employing low Ir-catalyst loadings (0.5 mol %).

Chemoselective reduction of tertiary amides by 1,3-diphenyldisiloxane (DPDS)

A convenient procedure for the chemoselective reduction of tertiary amides at room temperature in the presence of air and moisture using 1,3-diphenyldisiloxane (DPDS) has been developed. The reaction conditions are tolerant of a great number of functional groups including esters, nitriles, secondary amides, carbamates, sulfoxides, sulfones, sulfonyl fluorides, halogens, aryl-nitro groups, and arylamines. The conditions reported are the mildest to date and utilize EtOAc, a preferred solvent given its excellent safety profile and lower environmental impact. The ease of set up and broad chemoselectivity make this method attractive for organic synthesis. These results further demonstrate the utility of DPDS as a selective reducing agent.

Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive Reformatsky reaction

The synthesis of medicinally relevant α-difluoroalkylated amines by an iridium-catalyzed reductive alkylation of tertiary amides and lactams with difluoro-Reformatsky reagents, is described. This report features the introduction of various geminal difluoro-acetates and -acetamides as well as late stage derivatization of APIs, gram scale synthesis and downstream functionalizations.