A CO2-Mediated Conjugate Cyanide Addition to Chalcones

Abstract

Carbon dioxide is an intrinsically stable molecule; however, it can readily react with various nucleophilic reagents. In the presence of a cyanide source, CO2 was proven to be useful to promote addition reactions. Here we report the use of CO2 to facilitate 1,4-conjugate cyanide addition reaction to chalcones to generate organonitriles. Nitriles are key component in organic synthesis due to their utility in numerous functional group transformation, however, conjugation addition of cyanide has been a challenge in this substrate class due to side reactions. To mitigate this, we employed simple ammonium and metal cyanide sources as nucleophiles under carbon dioxide atmosphere where high selectivity toward the desired product was obtained. The presented reaction is not feasible under inert atmosphere, which highlights the important role of CO2, as a Lewis and Brøndsted acidic catalyst. Further derivatization of organonitriles compounds were performed to showcase the utility of the reaction, while an unprecedented dimerization reaction was identified and characterized, affording a cyclopentanone scaffold.

γ-Hydroxy-γ-butyrolactams as 1,2-bis-electrophiles in a Brønsted/Lewis acid-free synthesis of condensed nitrogen heterocycles

“…Previously, we have reported a convenient method for the preparation of (het)aryl substituted 3-pyrrolin-2-ones 1 26 and 2 28 from the readily available chalcones 3 29,30 through transformations of 3-cyanoketones 4 31 (Scheme 3). This approach has proven to be quite useful, for instance, in the synthesis of LSD-like polynuclear indole moieties (Scheme 2c), where the key step is the in situ formation of the corresponding N -acyliminium intermediate discussed above.…”