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

Abstract

The reaction of allyl ethyl carbonates with isocyanides in the presence of a catalytic amount of Pd(OAc) provided ketenimines through β-hydride elimination of the allyl imidoylpalladium intermediates. The insertion of the isocyanide into the π-allyl Pd complex proceeded via an unusual η -allyl Pd species. The resulting ketenimines were hydrolyzed to β,γ-unsaturated carboxamides during purification by flash column chromatography on silica gel or converted in situ into 1,5-disubstituted tetrazoles by [3+2] cycloaddition with hydrazoic acid or trimethylsilyl azide.

Recent Advances in Palladium-Catalyzed Isocyanide Insertions

“…While the authors report that the reaction is compatible with secondary and even aromatic isocyanides, these examples were not included in the initial publication. The first intermolecular cross-coupling involving a π-allylpalladium complex and isocyanides was reported by Zhu et al in 2016 [72]. They used allylic carbonates 130 to facilitate isocyanide insertion to give the corresponding vinylic ketenimines 133 (Scheme 39), which were subjected to hydration or formal [3 + 2] cycloaddition with azides in a one pot fashion to afford β,γ-unsaturated amides 131 or tetrazoles 132, respectively.…”

“…The se isomerization processes can also be catalyzed by palladium [77]. [71][72][73]75,76]. The authors make no mention of a possible hydride transfer.…”

Transition Metal and Inner Transition Metal Catalyzed Amide Derivatives Formation through Isocyanide Chemistry

“…Various C-vinylketenimines 54 68 were synthesized by the reaction of isocyanides and allyl ethyl carbonates 53 catalyzed by Pd(OAc) 2 (Scheme 19). 69 The oxidative addition of allyl ethyl carbonate 53 and isocyanide with palladium with decarboxylation generates -allyl-Pd complex 57 which after migratory insertion of isocyanide and -hydride elimination delivers ketenimine 54. Furthermore, intermediate 54 was hydrolyzed by silica gel on flash column chromatography to form ,-unsaturated carboxamides 55.…”

Formal [4+1] Cycloaddition of o‐Aminobenzyl Chlorides with Isocyanides: Synthesis of 2‐Amino‐3‐Substituted Indoles

“…[43] More relevant to the present topic, a number of valuable synthetic methodologies have also been developed for the synthesis of indoles using arylisocyanides as starting materials. [44] Our group has a long-term interest in isocyanide chemistry [45][46][47][48][49][50][51][52] and has reported an AlCl 3 -catalyzed formal [4 + 1] cycloaddition of 2-cyano-1-azadienes with isocyanides for the synthesis of 2-amino-5cyanopyrroles. [53] As a continuation of this research program, we report herein a novel synthesis of 2aminoindoles 3 by a base-promoted (NaHCO 3 ) reaction of N-tosyl-2-aminobenzyl chlorides 1 with isocyanides 2 (Scheme 1,g).…”