American Chemical Society
ja0c08599_si_001.pdf (6.96 MB)

Direct Conversion of N‑Alkylamines to N‑Propargylamines through C–H Activation Promoted by Lewis Acid/Organocopper Catalysis: Application to Late-Stage Functionalization of Bioactive Molecules

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journal contribution
posted on 2020-09-11, 19:35 authored by Jessica Z. Chan, Ahmet Yesilcimen, Min Cao, Yuyang Zhang, Bochao Zhang, Masayuki Wasa
An efficient catalytic method to convert an α-C–H bond of N-alkylamines into an α-C–alkynyl bond was developed. In the past, such transformations were carried out under oxidative conditions, and the enantioselective variants were confined to tetrahydroisoquinoline derivatives. Here, we disclose a method for the union of N-alkylamines and trimethylsilyl alkynes, without the presence of an external oxidant and promoted through cooperative actions of two Lewis acids, B­(C6F5)3 and a Cu-based complex. A variety of propargylamines can be synthesized in high diastereo- and enantioselectivity. The utility of the approach is demonstrated by the late-stage site-selective modification of bioactive amines. Kinetic investigations that shed light on various mechanistic nuances of the catalytic process are presented.