Nef isocyanide reaction explained

The Nef isocyanide reaction is an addition reaction that takes place between isocyanides and acyl chlorides to form imidoyl chloride products, a process first discovered by John Ulrich Nef.^{[1] [2]} The product imidoyl chloride can be hydrolyzed to give the amide, trapped with other nucleophiles, or undergo halide abstraction with silver salts to form an acyl nitrilium intermediate.^[3]

The reaction is of some theoretical interest, as kinetic measurements^[4] and DFT studies^[5] have indicated that the addition occurs in one step, without the intermediacy of a tetrahedral intermediate that is commonly proposed for carbonyl addition reactions.

See also

• Carbene
• Insertion reaction

Notes and References

1. Nef. J. U.. 1892. Ueber das zweiwerthige Kohlenstoffatom. Justus Liebig's Annalen der Chemie. en. 270. 3. 267–335. 10.1002/jlac.18922700302. 0075-4617.
2. Tron. Gian. El Kaïm. Laurent. La Spisa. Fabio. 2014-03-05. The Nef Reaction of Isocyanides. Synthesis. en. 46. 7. 829–841. 10.1055/s-0033-1338596. 0039-7881.
3. Westling. Mark. Smith. Richard. Livinghouse. Tom. April 1986. A convergent approach to heterocycle synthesis via silver ion mediated .alpha.-ketoimidoyl halide-arene cyclizations. An application to the synthesis of the erythrinane skeleton. The Journal of Organic Chemistry. 51. 8. 1159–1165. 10.1021/jo00358a001. 0022-3263.
4. Ugi. Ivar. Fetzer. Uwe. April 1961. Isonitrile, III. Die Addition von Carbonsäurechloriden an Isonitrile. Chemische Berichte. de. 94. 4. 1116–1121. 10.1002/cber.19610940433. 0009-2940.
5. Chéron. Nicolas. El Kaïm. Laurent. Grimaud. Laurence. Fleurat-Lessard. Paul. 2011-09-08. A Density Functional Theory Study of the Nef-Isocyanide Reaction: Mechanism, Influence of Parameters and Scope. The Journal of Physical Chemistry A. en. 115. 35. 10106–10112. 10.1021/jp205909d. 21786773. 2011JPCA..11510106C. 1089-5639.