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Research + Discoveries

Malcolmson Lab Demonstrates New Route to Alpha-Trifluoromethyl Amines

The Malcolmson lab has recently shown that gem-difluoroazadienes can serve as a novel building block for the synthesis of chiral alpha-trifluoromethyl amines via the vicinal fluoro-functionalization of its alkene. Alpha-trifluoromethyl amines are important medicinal motifs as the CF3 group serves as a proteolysis-resistant surrogate for an amide. In this work, the research team has demonstrated that AgF addition across the azadiene is catalyzed by a phosphine, leading to a metastable alpha-CF3 azaallyl–silver intermediate that has been characterized spectroscopically, a rarity for an alkyl–silver complex. In the same pot, the silver complex engages in Pd-catalyzed cross-coupling with aryl iodides to generate benzylic amine products. The authors demonstrate the method’s utility in a short synthesis of a reported HDAC6 inhibitor. Read more about this research here in ACS Catalysis.

Malcolmson 2018