Reaction of Nitrogen‐Radicals with Organometallics Under Ni‐Catalysis: N‐Arylations and Amino‐Functionalization Cascades

Abstract

Herein, we report a strategy for the generation of nitrogen‐radicals by ground‐state single electron transfer with organyl–Ni I species. Depending on the philicity of the N‐radical, two types of processes have been developed. In the case of nucleophilic aminyl radicals direct N‐arylation with aryl organozinc, organoboron, and organosilicon reagents was achieved. In the case of electrophilic amidyl radicals, cascade processes involving intramolecular cyclization, followed by reaction with both aryl and alkyl organometallics have been developed. The N‐cyclization–alkylation cascade introduces a novel retrosynthetic disconnection for the assembly of substituted lactams and pyrrolidines with its potential demonstrated in the short total synthesis of four venom alkaloids.

Intermolecular radical carboamination of alkenes

“…For example, carboamination comprising an N-radical cyclization followed by an intermolecular C-C bond formation to provide pyrrolidine or pyrrolidin-2-one scaffolds has been intensively explored using redox catalysis. [26][27][28][29][30][31][32][33] As compared to these cyclizing carboaminations, intermolecular vicinal radical alkene carboamination is more challenging and accordingly less well explored. Based on the nature of the initially attacking species, intermolecular alkene radical carboamination can be categorized into three different classes: (1) initial formation of the C-N bond through intermolecular addition of an N-centered radical to an alkene followed by C-radical trapping; (2) initial formation of the C-C bond through addition of a C-radical to an alkene followed by C-amination; (3) single-electron-transfer (SET) oxidation of the alkene to generate a radical cation that gets trapped with an N-nucleophile resulting in a C-radical that eventually engages in a C-C bond forming step (Scheme 1).…”

Nitrogen radical-triggered trifunctionalizing ipso-spirocyclization of unactivated alkenes with vinyl azides towards new spiroaminal frameworks

“…Substrate scope on the amidyl radical-triggered trifunctionalizing ipso-spirocyclization. Encouraged by the success of the unprecedented trifunctionalizing ipso-spirocyclization enabled by the iminyl radical-triggered CTTC cascade, we speculated that the high electrophilic amidyl radical 41,42 could also trigger such CTTC cascade to achieve the desired trifunctionalizing ipso-spirocyclization of unactivated alkenes for rapid construction of another new spiroaminal framework. Excitingly, upon the facile screening of parameters, amidyl radical precursor olefinic amides were indeed capable partners and readily underwent such photocatalytic trifunctionalizing ipso-spirocyclization (Table 4).…”

Philip‐Leverhulme‐Preise in Chemie 2019

“…Die Gewinner sind Silvia Vignolini (University of Cambridge), die kürzlich in einer Advanced‐Materials ‐Zuschrift über chiral‐nematische photonische Filme auf Cellulosebasis berichtete, sowie Kim Jelfs (Imperial College London) und Daniele Leonori (University of Manchester) die 2018 je einen Harrison‐Meldola‐Preis der Royal Society of Chemistry gewannen . Beide waren jüngst in der Angewandten Chemie vertreten: Jelfs berichtete in einem Forschungsartikel über organische Mehrkomponentenkäfige durch soziale Selbtsortierung, und Leonori beschrieb in einer Zuschrift nickelkatalysierte Reaktionen von Stickstoffradikalen mit Organometallspezies . Die beiden verbleibenden Preisträger sind neu in dieser Rubrik.…”