Direct C(sp3)–C(sp2) bond-formation under transition-metal-free conditions offers an atom-economical, inexpensive, and environmentally benign alternative to traditional transition metal-catalyzed cross-coupling reactions. A new chemo- and regioselective coupling protocol between 3-aryl-substituted-1,1-diphenyl-2-azaallyl derivatives and vinyl bromides has been developed. This is the first transition-metal-free cross-coupling of azaallyls with vinyl bromide electrophiles and delivers allylic amines in excellent yields (up to 99%). This relatively simple and mild protocol offers a direct and practical strategy for the synthesis of high-value allylic amine building blocks that does not require the use of transition metals, special initiators, or photoredox catalysts. Radical clock experiments, EPR studies and DFT calculations point to an unprecedented substrate-dependent coupling mechanism. Furthermore, an EPR signal was observed when the N-benzyl benzophenone ketimine was subjected to silylamide base, supporting formation of radical species upon deprotonation. The unique mechanisms outlined herein could pave the way for new approaches to transition-metal-free C–C bond formations.

An efficient deuteration process of β-amino C─H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B(C 6 F 5 ) 3 and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d 6 to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then leads to the formation of β-deuterated bioactive amines with up to 99% deuterium incorporation.

An efficient and highly enantioselective Conia-ene-type process has been developed. Reactions are catalyzed by a combination of B(C 6 F 5) 3 , an N-alkylamine and a BOX-ZnI 2 complex. Specifically, through cooperative action of B(C 6 F 5) 3 and amine, ketones with poorly acidic α-C-H bonds can be converted in situ to the corresponding enolates. Subsequent enantioselective cyclization involving a BOX-ZnI 2-activated alkyne leads to the formation of various cyclopentenes in up to 99% yield and 99:1 er.

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.

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