Asmic

Asmic, short for o-anisylsulfanylmethyl isocyanide, is a relatively newly developed reagent for introducing the isocyanide (isonitrile) group in organic synthesis.

Asmic first came to light in 2015 in world patent application WO2015127226 by Fraser Fergusson Fleming and Jesús Armando Lujan-Montelongo at Duquesne University (Pittsburgh). The first line in the applications reads, “This invention relates to novel isonitriles, including arylthio isonitriles, and methods for their preparation.”

In 2018, Fleming, now at Drexel University (Philadelphia), and co-workers followed up by describing Asmic as a building block for isocyanide alkylations. In particular, the authors found that the o-anisylsulfanyl group is critical for facilitating the initial deprotonation–alkylation step and providing a nucleophilic site for promoting the n-butyllithium¹ removal of the sulfanyl moiety. The overall reaction can be used to synthesize methyl isocyanides with as many as three substituents.

In subsequent years, Fleming et al. expanded on the synthetic advantages of Asmic. In 2020, they reported that the reagent is useful for addition reactions with carbonyl compounds to synthesize dihydrooxazoles and dihydroimidazoles. The reaction, which forms four new bonds, is mediated by the boron trifluoride–diethyl ether² adduct.

Similarly, in 2023, the research group described base-catalyzed one-pot syntheses of oxazoles from Asmic, an alkyl halide, and an acid chloride and of imidazoles from Asmic, an alkyl halide, and a nitrile. In both cases, the products can contain up to two substituents. The authors point out that 59% of US Food and Drug Administration–approved small-molecule drugs contain nitrogen heterocycles such as can be produced by Asmic ring-forming reactions.

Currently, no hazard information is available for Asmic.

1. CAS Reg. No. 109-72-8.
2. CAS Reg. No. 109-63-7.