Transition-metal-free chemo- and regioselective vinylation of azaallyls

Abstract

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.

The Persistent Radical Effect in Organic Synthesis

“…As the starting imines are accessed from the corresponding benzylic amines, the overall transformation is a method for the α‐arylation/α‐alkylation of benzylamines. As an extension, α‐vinylation with vinyl bromides as well as α‐arylations of benzylic amines with cyanoarenes were developed using the same approach, and cascades comprising radical cyclizations applying this strategy were also disclosed …”

Transition-Metal-Free Radical C(sp3)–C(sp2) and C(sp3)–C(sp3) Coupling Enabled by 2-Azaallyls as Super-Electron-Donors and Coupling-Partners

“…We found that deprotonation of triaryl ketimines to generate semi-stabilized 2-azaallyl anions also resulted in the formation of radical species that were detected by EPR. 9 This unexpected observation led us to speculate that the 2-azaallyl anion and neutral ketimine are in equilibrium with the 2-azaallyl radical and ketimine radical anion (Scheme 2b). This hypothesis was supported by DFT computational studies, but experimental evidence for the intermediacy of radicals in the coupling reactions was elusive.…”

Synthesis of BCP Benzylamines From 2‐Azaallyl Anions and [1.1.1]Propellane

“…Other possible mechanisms include direct nucleophilic addition of A1 to 1 to generate B1,orcleavage of the central bond in [1.1.1]propellane by an azaallyl radical generated by SET between anion A1 and ketimines 2 (see the Supporting Information, S22-24, for schemes and details). [32] As noted above,t reatment of 1 with organolithium reagents at room temperature often initiates anionic polymerization to [n]staffane oligomers. [6,27,35] To explain why no oligomerization products of B1 are observed, we hypothesize that protonation of B1 by ketimines 2 or HN(SiMe 3 ) 2 is faster than oligomerization.…”