Palladium-Catalyzed Nucleophilic Isocyanation for the Synthesis of α-Aryl-α-Isocyanoacetoamide Derivatives

α-Aryl-α-isocyanoacetoamide derivatives were synthesized through palladium-catalyzed nucleophilic isocyanation. Diethylphosphates derived from N,N-disubstituted mandelamide derivatives reacted with trimethylsilyl cyanide in the presence of a catalytic amount of Pd(OAC)2 to afford the titled isonitri...

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Bibliographic Details
Published in:Bulletin of the Chemical Society of Japan 2021-09, Vol.94 (9), p.2155-2161
Main Authors: Yurino, Taiga, Tange, Yuji, Ohkuma, Takeshi
Format: Article
Language:English
Subjects:
Aromatic compounds
Carbonyls
Catalysts
Chemical synthesis
Lewis acid
Oxazole
Palladium
Reaction mechanisms
Reagents
Substrates
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Summary:α-Aryl-α-isocyanoacetoamide derivatives were synthesized through palladium-catalyzed nucleophilic isocyanation. Diethylphosphates derived from N,N-disubstituted mandelamide derivatives reacted with trimethylsilyl cyanide in the presence of a catalytic amount of Pd(OAC)2 to afford the titled isonitriles (13 examples) in moderate to high yield. The silyl cyanopalladate complex formed in situ was a proposed catalyst, which behaved as a Lewis acid promoting elimination of the phosphate group and also the N-nucleophilic cyanide reagent. The isocyanation was applied to a gram-scale reaction with 0.2 mol% of the catalyst. The obtained isocyanoacetoamide was employable for the further transformation into the trisubstituted oxazole without any purification procedure. DFT calculation suggested that the neighboring group effect of the carbonyl moiety in the substrate amide group assisted the elimination of phosphate and stabilized the carbocation intermediate. A plausible reaction mechanism of the isocyanation is also described.
ISSN:0009-2673
1348-0634
DOI:10.1246/bcsj.20210214