Palladium-Catalyzed Access to Benzocyclobutenone-Derived Ketonitrones via C(sp²)–H Functionalization

Abstract

The palladium-catalyzed C(sp 2 )–H functionalization of bromoaryl aldonitrones leading to benzocyclobutenone-derived ketonitrones is described. This method allows for the preparation of a wide range of strained, four-membered ketonitrones with broad functional group tolerance. Downstream transformations of the formed products were readily demonstrated, illustrating the synthetic utility of the obtained benzocyclobutenone-derived nitrones for the construction of polycyclic nitrogen-containing scaffolds.

Synthesis of Isoindole N-Oxides by Palladium-Catalyzed C–H Functionalization of Aldonitrones

“…A relatively low value k H / k D = 1.22 observed suggests that C–H bond activation is not the rate-determining step. On the basis of the mechanistic studies and our previous results in nitrone C–H activation, a plausible mechanism is proposed as shown in Scheme . First, the oxidative addition of aryl bromide 1a to palladium(0) takes place, generating the arylpalladium­(II) species I .…”

“…Nevertheless, these strategies mostly rely upon the formation of a new C–N bond and require highly prefunctionalized substrates. Recently, our group has been interested in the palladium-catalyzed C­(sp 2 )–H activation of aldonitrones for their direct conversion into ketonitrones with formation of a new C–C bond . In this unique approach, we demonstrated the possibility to form strained benzocyclobutenone-derived ketonitrones in a simple manner starting from aldonitrones (Scheme c) .…”

Asymmetric Synthesis of Scillascillin-Type Homoisoflavonoid

“…Our strategy for asymmetric synthesis of benzocyclobutene was based on Baudoin et al’s construction of the four-membered ring through C–H activation of inactivated methyl group, and the benzylic all-carbon quaternary center was accessed through catalytic reductive desymmetrization of malonic esters, which was recently developed by Huang and co-workers (Scheme ). As enantioselective formation of the all-carbon quaternary center through α-alkylation from benzocyclobutenones is not accessible, this proposed synthetic strategy through the construction of chiral centers of acyclic substrates followed by ring closure would provide a general asymmetric method to access this moiety.…”

Palladium-Catalyzed Alkenyl C–H Activation/Diamination toward Tetrahydrocarbazole and Analogs Using Hydroxylamines as Single-Nitrogen Sources

“…In classic aziridine chemistry, [2 + 1] annulations of O-substituted hydroxylamines and olefins have been well developed . Through sequential nucleophilic and electrophilic aminations, stepwise synthetic strategies for building larger N-heterocycles with O-substituted hydroxylamines, such as azetidines, pyrrolidines, and other more extensive cyclic amine derivatives, are generally adopted (Scheme a). Our group focused on exploring new O-substituted hydroxylamine reagents as single-nitrogen sources for direct synthetic approaches to various nitrogen heterocyclic compounds.…”