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

Abstract

The past decade has witnessed the rapid development of radical generation strategies and their applications in C–C bond-forming reactions. Most of these processes require initiators, transition metal catalysts or organometallic reagents. Herein, we report the discovery of a simple organic system (2-azaallyl anions) that enables radical coupling reactions under transition-metal-free conditions. Deprotonation of N-benzyl ketimines generates semi-stabilized 2-azaallyl anions that behave as “super-electron-donors” (SEDs) and reduce aryl iodides and alkyl halides to aryl and alkyl radicals. The SET process converts the 2-azaallyl anions into persistent 2-azaallyl radicals, which capture the aryl and alkyl radicals to form C–C bonds. The radical coupling of aryl and alkyl radicals with 2-azaallyl radicals makes possible the synthesis of functionalized amine derivatives without the use of exogenous radical initiators or transition metal catalysts. Radical clock studies and 2-azaallyl anion coupling studies provide mechanistic insight for this unique reactivity.

The Persistent Radical Effect in Organic Synthesis

“…The coupling of N ‐benzyldiphenylimine 53 with aryl or alkyl halides is an interesting example of the PRE (Figure ) . With a strong base, imine 53 is deprotonated to generate the azaallyl anion 54 , which, as a strong reducing reagent, transfers an electron (ET) to an aryl or alkyl halide, leading to the corresponding transient radical R .…”

“…Thec oupling of N-benzyldiphenylimine 53 with aryl or alkyl halides is an interesting example of the PRE (Figure 15). [72] With as trong base,i mine 53 is deprotonated to generate the azaallyl anion 54,which, as astrong reducing reagent, transfers an electron (ET) to an aryl or alkyl halide, leading to the corresponding transient radical RC along with the longer-lived azaallyl radical 55.I nt he product-forming step,t he transient alkyl or aryl radical selectively crosscouples with 55 to give 56.Asthe starting imines are accessed from the corresponding benzylic amines,t he overall transformation is am ethod for the a-arylation/a-alkylation of benzylamines.A sa ne xtension, a-vinylation [73] with vinyl bromides as well as a-arylations [74] of benzylic amines with cyanoarenes were developed using the same approach, and cascades comprising radical cyclizations applying this strategy were also disclosed. [75] Figure 13.…”

“…Coupling of imine 53 with aryl and alkyl halides. [72] Angewandte Chemie Reviews 82 www.angewandte.org…”

Der “Persistent Radical Effect” in der organischen Chemie

“…Ein interessantes Beispiel des PRE ist die Kupplung von N ‐Benzyldiphenyliminen 53 mit Aryl‐ oder Alkylhalogeniden (Abbildung ) . Mit einer starken Base werden die Imine 53 zu den Azaallyl‐Anion 54 deprotoniert, welche starke Reduktionsmittel sind.…”

“…Ein interessantes Beispiel des PRE ist die Kupplung von N-Benzyldiphenyliminen 53 mit Aryl-oder Alkylhalogeniden (Abbildung 15). [72] Mit einer starken Base werden die Imine 53 zu den Azaallyl-Anion 54 deprotoniert, welche starke Reduktionsmittel sind. Durch den Elektronentransfer (ET) auf Aryl-oder Alkylhalogenide werden transiente Radikale RC und langlebige Azaallyl-Radikale 55 erzeugt.…”