Palladium-Catalyzed Synthesis of Amidines viatert-Butyl isocyanide Insertion

Abstract

Para -substituted iodobenzenes were reacted with tert -butyl isocyanide and piperidine as nucleophiles in the presence of palladium–diphosphine catalysts. Both single and double insertion of the isocyanide was observed and the corresponding amidines and ketimine–amidines were obtained in yields of practical interest. With the increase of the tert -butyl isocyanide/iodobenzene ratio, 100% chemoselectivity toward the ketimine–amidine was achieved. The formation of the products was rationalized on the basis of a catalytic cycle analogous to that of the aminocarbonylation reactions. Clear connection was found between the activity and the electronic structure of the proposed catalyst Pd(diphosphine) by computational studies, as the more negative partial charge on palladium resulted in higher conversion. Among five isocyanide substrates, only tert -butyl isocyanide was proved to be active.

Recent Advances in Palladium-Catalyzed Isocyanide Insertions

“…This reaction is fully compatible with tertiary, secondary, and aromatic isocyanides, but fails to afford any product 81 when primary aliphatic or α-acidic isocyanides are employed. In an intermolecular variant of this double insertion, the group of Kègl investigated the substituent effects of aryl halides 83 on the imidoylative cross-coupling with tert-butyl isocyanide 3 and secondary amines 82 [58]. Typically, this imidoylative Buchwald-Hartwig type multicomponent reaction affords the ketimine-amidine 85 in good yields, although in most cases a mixture of 85 and the amidine 84 is formed (Scheme 27).…”

Divergent and Selective Synthesis of 3-Alkylidene Oxindoles Using Pd-Catalyzed Multicomponent Reaction

“…Recently, Xia et al reported the synthesis of amidines via cobalt-catalyzed MCR consisting of diazo ester, isocyanides, and amines (Scheme f) . Besides, palladium-catalyzed MCRs consisting of the diazo compound, isocyanide, along with amine have been investigated to construct heterocyclic compounds . By drawing encouragement from the attractive therapeutic applications of 3- alkylidene oxindole and our previous work on the metal-catalyzed reaction of diazo compounds, herein, we reported a multicomponent approach for the diverse synthesis of E -selective 3-alkylidene oxindole derivatives via Pd-catalyzed reaction of 3-diazo oxindole, isocyanide, and aniline (Scheme g).…”