C=N Bond Formation, CN Bond Formation >

Synthesis of Isonitriles

Related:

Recent Literature

Treatment of N-substituted formamides with chlorophosphate compounds and tertiary amine bases produced the corresponding isocyanides in high yields. This method can be used to prepare various alkyl and aryl isocyanides.
G. Kobayashi, T. Saito, Y. Kitano, Synthesis, 2011, 3225-3234.

Treatment of N-substituted formamides with triphenylphosphine and molecular iodine quickly produces the corresponding isocyanides in high yields under ambient conditions in the presence of a tertiary amine. This convenient synthetic procedure employs readily available and low-cost reagents and mild reaction conditions for the synthesis of various alkyl and aryl isocyanides.
X. Wang, Q.-G. Wang, Q.-L. Luo, Synthesis, 2015, 47, 49-54.

Difluorocarbene, generated in situ from chlorodifluoroacetate via decarboxylation, reacts efficiently with primary amines to produce isocyanides. Various primary amines can be converted, including aryl, heteroaryl, benzyl, and alkyl amines, as well as amine residues in amino acids and peptides. Late-stage functionalization of biologically active amines is also demonstrated.
Y.-X. Si, P.-F. Zhu, S.-L. Zhang, Org. Lett., 2020, 22, 9086-9090.

A facile conversion of both aliphatic and aromatic formamides to isonitriles under very mild conditions and microwave irradiation is described.
A. Porcheddu, G. Giacomelli, M. Salaris, J. Org. Chem., 2005, 70, 2361-2363.

An electrochemical method for the preparation of isocyanides from easily accessible aminotetrazole derivatives tolerates an unprecedented range of functional groups. A chemical rather than electrochemical approach was also demonstrated. Flow electrochemistry enables a convenient scale-up.
M. C. Leech, A. Petti, N. Tanbouza, A. Mastrodonato, I. C. A. Goodall, T. Ollevier, A. P. Dobbs, K. Lam, Org. Lett., 2021, 23, 9373-9375.