Triple-Consecutive Isocyanide Insertions with Aldehydes: Synthesis of 4-Cyanooxazoles

Abstract

An efficient TMSOTf-promoted selective triple consecutive insertions of tert-butyl isocyanide into aldehydes has been developed, affording pharmacological interesting 4-cyanooxazoles in high yields in a one pot manner. The given method encompasses a wide range of substrates with tert-butyl isocyanide serving as sources of critical “CN” and “C–NC” moieties. The versatile transformations of the resulting 4-cyanooxazoles were demonstrated. The key reaction intermediates for plausible mechanisms were determined.

Cyanation with isocyanides: recent advances and perspectives

“…Xu and co-workers reported efficient TMSOTf-promoted cyanation of isocyanides with aldehydes, cultivating a one pot synthesis of pharmacologically interesting 4-cyanooxazoles with high yields (Scheme 22). 34 The transformation was realized through synergetic triple consecutive isocyanide insertion, with tert-butyl isocyanide acting as sources of critical ''CN'' and ''C-NQC'' moieties. Based on their preliminary data, a possible mechanism was proposed.…”

“…Their versatility has been witnessed in transition-metal-catalyzed isocyanide insertion, 10 isocyanide-based multicomponent reactions, 11 and radical isocyanide chemistry, 12 resulting in the rise of imidoylation, 13 ketenimination, 14 and cyanation. 15–53 Among the innumerable applications of isocyanides, the most striking feature is their ability to act as a “cyano” source, where they show advantages over other sources in being nontoxic, commercially available, easy to handle, and environmentally benign. In general, three types of cyanation with isocyanides have been established.…”

Recent Advancements in Strategies for the Synthesis of Imidazoles, Thiazoles, Oxazoles, and Benzimidazoles

“…Very recently, Xu et al created a method for promoting the insertion of tert-butyl isocyanide into aldehydes 18 that generates high yields of 4-cyanooxazoles 122 that are pharmacologically intriguing. [91] Tert-butyl isocyanide 121 served as the source of the crucial "CN" and "CÀ N=C" groups, enabling the transformation to be achieved by the synergistically isocyanide insertion. The provided approach has a straightforward operating setup, metal-free conditions, and a wide range of substrate scopes.…”

Synthesis of N-fused polycyclic indoles via a Pd-catalyzed multicomponent cascade reaction consisting of an amide-directed [3+1+1] annulation reaction of 3-diazo oxindole and isocyanides

“…10 Another efficient approach towards consecutive triple isocyanide insertion into aldehydes to synthesize a broad library of 4-cyano oxazole derivatives was reported by Xu and co-workers. (Scheme 1d–f) 11 Also, we have developed a Pd-catalysed one-pot cascade reaction to access benzoxazine-fused 1,2,3-triazoles using N -aryl-α-(tosylhydrazone)acetamides with isocyanide. 12 In continuation of our efforts to develop novel cascade reactions by the use of isocyanide and diazo compounds (Scheme 1g), 13 herein, we have developed a Pd-catalysed multicomponent cascade reaction of 3-diazo oxindole, isocyanide, and H 2 O to generate tricyclic oxazolo[3,2- a ]indole scaffolds (Scheme 1h).…”