Substituted Imidazolium Sulfuranes and their use as novel Electrophilic Group-Transfer Reagents

The ability of hypervalent iodine compounds to act as electrophilic group-transfer reagents has been extensively exploited during the last several years in a variety of synthetically useful transformations. These include trifluoromethylation, alkynylation, arylation, amination, halogenation, cyanation. As cyanating reagents based on hypervalent iodine reagents show strong exothermic decompositions on heating - and therefore, must be handled with appropriate knowledge and safety measures - the development of novel cyanating reagents - distinguishing themself by operational simplicity, safeness and a broad reactivity profile - would be desirable.

By submitting thioureas 1 and 2 (Scheme 1) to well known halogenation conditions, the corresponding hypervalent sulfur compounds 3−5 are obtained as solids in high yields and analytic purity. Subsequent addition of one equivalent of Me3SiCN caused the formation of the desired imidazolium thiocyanates 6−8.

Compounds 6−8 were isolated as air stable solids in excellent yields and can be stored at room temperature for months without evident decomposition. DSC analysis of 8 up to 200 °C did not detect any sharp exothermic decomposition signal.
The synthetic route toward 6−8 could be scaled to multigram quantities.

The reaction of 8 with commercially available amines with the employment of DIPEA as base in dichloromethane efficiently promoted the N-cyanation to afford the desired cyanamides 10−13 in good isolated yields and short reaction times (Chart 1). The presence of alcohol substituents, as in the case of S-diphenylprolinol, does not seem to be detrimental for the process.
The same protocol was also applicable to the cyanation of other substrates such as aromatic thiols, enolates, enamines and activated methylenes providing the corresponding aromatic thiocyanates 14−16 , β-amido or keto nitriles 17−22 , and β-cyano sulphones 23 in good to excellent yields.

To further prove the utility of the novel imidazolium sulfurane platform for the design of electrophilic group-transfer reagents, also 2-Imidazolium Thioalkynes like 34 and 35 were prepared.

In the presence of DIPEA the alkynylation of aliphatic, electron rich, and electron poor aromatic thiols proceeded in excellent yields. Several activated amides and ketoesters also afforded the desired alkynylated products.

In summary, imidazolium sulfuranes could become a platform for the development of new reagents able to promote the umpolung of synthetically useful organic groups and hence will be interesting alternatives to hypervalent I(III) reagents.

Garazi Talavera, Javier Peña, Manuel Alcarazo: "Dihalo(imidazolium)sulfuranes: A Versatile Platform for the Synthesis of New Electrophilic Group-Transfer Reagents",
J. Am. Chem. Soc. 2015, 137, 8704−8707

EP priority patent application filed in June 2015.