Nickel-Catalyzed Reductive Cascade Arylalkylation of Alkenes with Alkylpyridinium Salts

Abstract

Herein, we describe a nickel-catalyzed reductive deaminative arylalkylation of tethered alkenes with pyridinium salts as C(sp 3 ) electrophiles. This two-component dicarbofunctionalization reaction enables the efficient synthesis of various benzenefused cyclic compounds bearing all-carbon quaternary centers. The approach presented in this paper proceeds under mild conditions, tolerating a wide variety of functional groups and heterocycles. It has been used to functionalize complicated molecules at a late stage.

Synthesis of Vicinal Carbocycles by Intramolecular Nickel-Catalyzed Conjunctive Cross-Electrophile Coupling Reaction

“… 9 An additional strategy, tethering one electrophile and alkene together to afford a two-component reaction, also significantly addresses the selectivity challenges and at the same time constructs cyclic fragments ( Scheme 1 b). 10 − 12 We envisioned a fully intramolecular nickel-catalyzed conjunctive XEC reaction to provide vicinal ring systems ( Scheme 1 c). 13 , 14 This manifold engages two unactivated electrophiles and an internal olefin, and generates two carbocycles in a single step.…”

“…Building upon the mechanistic insights from XEC reactions, , several strategies have been established to achieve selectivity, including mechanistic differentiation of the electrophiles or employing an excess of one reagent. − In addition, the use of directing groups can also favor regio- and chemoselective reactions and allow for the use of unactivated conjunctive reagents . An additional strategy, tethering one electrophile and alkene together to afford a two-component reaction, also significantly addresses the selectivity challenges and at the same time constructs cyclic fragments (Scheme b). − We envisioned a fully intramolecular nickel-catalyzed conjunctive XEC reaction to provide vicinal ring systems (Scheme c). , This manifold engages two unactivated electrophiles and an internal olefin, and generates two carbocycles in a single step. Vicinal 3,5-carbocyclic motifs are present in a number of biologically active compounds and natural products, and cyclopropanes themselves are common in medicinal chemistry (Scheme d). − We sought to prepare vicinal 3,5-carbocyclic motifs by a nickel-catalyzed conjunctive XEC reaction, where a single cascade reaction would construct both carbocyclic moieties.…”

N-Arylation of Amino Acid Esters via an I2-Mediated Metal-Free Multicomponent Benzannulation Strategy

“…Meanwhile, the construction of benzene skeletons has received a great deal of attention from synthetic chemists since substituted benzene frameworks are present in numerous natural products and pharmaceuticals, which are of immense biological importance. − Traditional synthetic strategies to access substituted benzene are mainly based on Diels–Alder reactions of common dienophiles with dienes involving furans. , The dominant methods are transition-metal-catalyzed benzannulation of alkynes or alkenes to construct the functionalized benzenes. − Recent work has enabled benzene skeleton construction to be performed with a growing number of simple acyclic precursors, such as electron-deficient olefins, α,β-unsaturated ketones, chlorocyclopropane, and active methylene compounds . In addition, some convergent reaction strategies were also used to construct the aryl framework, such as tandem reactions and organocatalytic benzannulation reactions. − On the other hand, amino acids are derived from renewable resources, and their racemic or natural forms are cheap and readily available in varieties.…”