Double Insertion of Isocyanides into Dihydropyridines: Direct Access to Substituted Benzimidazolium Salts

Link: http://www3.interscience.wiley.com/cgi-bin/abstract/114182360/ABSTRACT

From Prof. Rodolfo Lavilla's group at Institute for Research in Biomedicine, Barcelona Science Park, and University of Barcelona, Barcelona, Spain

This paper in ACIEE EarlyView deals with the use of isocyanide in a novel reaction. This is the type of reaction which could be a good mechanism question. Basically, dihydropyridines or DHPs could react with isocyanide in the presence of Br2 or I2 to give new products, depending on the halogens employed.

The reaction of interest in this paper is the case where I2 is used in the reaction. This is because the reaction led to the formation of the benzimidazolium salt, for example 4a in the scheme above. This is significant as imidazolium salts are a precursor of N-heterocyclic carbenes (NHCs), which have found increasing applications as ligands in transition metal catalysis process. Additionally, imidazolium salts may find uses as ionic liquids in various processes. By using a series of C13- and H2-isotopic studies, the mechanism of this process, even though not fully established, has been proposed to be as followed.

The authors suggested the followings:

"The subtle distinction between the nucleophilicity and nucleofugacity of bromide and iodide may account for the different stabilization of the nitrilium intermediates, as well as the capacity to promote the ring opening and recyclization from intermediates C and D, respectively."

The established method was applied to various combinations of DHP and isocyanide derivatives, which gave access to several benzimidazolium salts 4. The results on scope of the reaction are summarized in Table 1. It is noteworthy that when the amide and formyl derivatives of DHP were used (entries 11 and 12), no desired product was formed. This was contributed to the oxidative interferences of the amido and formyl groups during the oxidation process.

Although several yields are not that great, nonetheless, this paper still presented a unique way of accessing benzimidazolium salts 4, an increasingly important class of compounds through a quite novel reaction pathway.