Palladium(0)‐Catalyzed Single and Double Isonitrile Insertion: A Facile Synthesis of Benzofurans, Indoles, and Isatins

Abstract

A palladium(0)-catalyzed cascade process consisting of isonitrile insertion and α-Csp(3)-H cross-coupling can be achieved for the synthesis of benzofurans and indoles. The construction of isatins by a Pd-catalyzed cascade reaction incorporating double isonitrile insertion, amination, and hydrolysis has also been achieved. The key features of this work include diverse heterocycle synthesis, phosphine-ligand-free reaction conditions, a one-pot procedure, simple and commercially available starting materials, broad functional-group compatibility, and moderate to good reaction yields.

Ketenimines from Isocyanides and Allyl Carbonates: Palladium‐Catalyzed Synthesis of β,γ‐Unsaturated Amides and Tetrazoles

“…[1] Isoelectronic with carbon monoxide,i socyanides possess additional advantages of being tunable both electronically and sterically,a nd are easy to handle.F ollowing the seminal contribution by Whitby and co-workers on the palladiumcatalyzed three-component reaction of isocyanides,a ryl halides,a nd amines, [2] at in-free version of the synthesis of amidines as described by Kosugi, Migita, and co-workers, [3] many elegant transformations have been reported. [4,5] All these reactions involved the generation of aryl or vinyl imidoylpalladium species,f ollowed by ligand exchange and reductive elimination with the formation of ak ey C(sp 2 ) À C(sp 2 )b ond. Tr ansformations leading to the formation of aC (sp 3 ) À C(sp 2 )b ond via an alkyl imidoylpalladium intermediate,however, remain scarce.…”

Synthesis of Fused‐Pyrazines via Palladium‐Catalyzed Double Benzyl Isocyanide Insertion and Cross‐Dehydrogenative Coupling

“…In the recent past, we also developed the synthesis of isatins from o ‐iodoanilines through double isocyanide insertion via the formation of 3 H ‐indolo‐3‐imines ,. Herein, we used this strategy to synthesize ( E )‐ N ‐benzyl‐3‐(benzylimino)‐3 H ‐indol‐2‐amine 4aa′ with o ‐iodoaniline 4a and benzyl isocyanide 2a under the standard conditions of Table for 2 h. The desired intermediate 4aa′ was formed as a major yellow spot on TLC (Scheme c).…”

“…A similar mechanism was proposed for the formation of 5 H ‐pyrrolo[2,3‐ b ]indoles and 3‐benzyl‐2‐phenyl‐3,4‐dihydroimidazo[4,5‐ b ]indole as shown in Scheme . Oxidative addition of o ‐iodoaniline derivatives 4 to palladium (0) would afford the palladium(II) intermediate J . Migratory double isocyanide insertion of intermediate J will produce the imidoyl intermediate L .…”

Advances in the Synthesis of Isatins: A Survey of the Last Decade

“…52 Another no less versatile method involves the Pd-catalyzed reaction of substituted anilines 39 with tert-butyl isonitrile, which gave differently substituted isatins in moderate yields (Scheme 25). 53 It is not clear and is surprising why these easy and cheap synthetic pathways have not been developed yet. The lowest yield (10%) was observed in the case of methyl 4-aminobenzoate.…”