Recent Advances in Palladium-Catalyzed Isocyanide Insertions

Abstract

Isocyanides have long been known as versatile chemical reagents in organic synthesis. Their ambivalent nature also allows them to function as a CO-substitute in palladium-catalyzed cross couplings. Over the past decades, isocyanides have emerged as practical and versatile C1 building blocks, whose inherent N-substitution allows for the rapid incorporation of nitrogeneous fragments in a wide variety of products. Recent developments in palladium catalyzed isocyanide insertion reactions have significantly expanded the scope and applicability of these imidoylative cross-couplings. This review highlights the advances made in this field over the past eight years.

A New Saddle-Shaped Aza Analog of Tetraphenylene: Atroposelective Synthesis and Application as a Chiral Acylating Reagent

“…By trapping the imidoyl palladium intermediate with an intramolecular functionality following isocyanide insertion to a Pd(II) species, a variety of 5-7-membered nitrogen-containing heterocycles could be generated. [27][28][29][30][31][32] In addition, N-heterocycles bearing central and planar as well as axial chirality have been successfully constructed by applying this strategy, opening an avenue for isocyanide in transition-metal-catalyzed asymmetric synthesis. [33][34][35][36][37][38] Particularly, the chemistry of using 2-isocyano-1,1'biphenyl for the synthesis of 6-arylphenanthridine inspires the hypothesis that a structurally similar 2,2'-diisocyano-1,1'-biphenyl would proceed through an unprecedented double isocyanide insertion followed by termination with an intermolecular nucleophile (Figure 1b).…”

The Dark Side of Isocyanides: Visible-Light Photocatalytic Activity in the Oxidative Functionalization of C(sp3)–H Bonds

“…Accordingly, their unique reactivity features have been widely exploited in isocyanide-based multicomponent reactions − (nucleophile/carbene reactivity, Figure a) and in Lewis acid-catalyzed migratory insertions into nucleophiles − (electrophile reactivity, Figure b). Furthermore, their ability to form complexes with π-electron-releasing transition metals has been shown as key to promote imidoylative cross couplings, with isocyanides undergoing 1,1-migratory insertions into either σ- or π-bonds. − On the other hand, the presence of a lone pair on the (carbenic) isocyanide carbon atom makes them excellent geminal radical acceptors in reactions involving the formation of open-shell species (somophile reactivity, Figure c). − …”

Divergent Conversion of Double Isocyanides with Alkenyl Bromide to Polysubstituted Pyrroles and 4-Imino-4,5-dihydropyrrolo[3,4-b]pyrrol-6(1H)-one Derivatives by Pd-Catalyzed Tandem Cyclization Reactions

“…Isocyanides have been recognized as an active organic reagent for the formation of heterocarbon bonds in multicomponent reactions, insertion reactions, and other cascade cyclization processes . There is no doubt that reactions of isocyanides using Pd catalysts are particularly prominent in the strategy of organic synthesis . In sharp contrast to the popularity of reactions with one isocyanide molecule, reactions with more than one isocyanide have rarely been developed .…”