Hypervalent Iodine(III)‐Mediated Regioselective Cyanation of Quinoline N‐Oxides with Trimethylsilyl Cyanide

Abstract

A regioselective cyanation of quinoline N-oxides with trimethylsilyl cyanide was developed by using (Diacetoxyiodo) benzene (PIDA) as mediated hypervalent iodine(III) reagent under metal-free and base-free reaction conditions to obtain 2-cyanoquinolines. The efficient PIDA reagent could play the role of an activator of the substrates and an accelerator of NÀO bond cleavage. The reaction system featured a wide range of substrate suitability and high yields. The procedure was enlarged gram-scale to synthesize the tuberculosis (TB) inhibitor. Finally, according to some experimental results, a plausible mechanism for the cyanation reaction is proposed.

Regioselective Cyanation of Six‐Membered N‐Heteroaromatic Compounds Under Metal‐, Activator‐, Base‐ and Solvent‐Free Conditions

“…of trimethylsilyl cyanide in dichloroethane (DCE) at room temperature. We observed no conversion after refluxing overnight (Table , entries 1 and 2) which was consistent with the reported literature . However, when dimethylformamide (DMF) was employed as the solvent rather than DCE, the conversion was slightly improved and the desired product was obtained with a modest 12% yield (entry 3).…”

“…Various reagents like dimethyl sulphate, [17] N,N-dimethylcarbamoyl chloride, [18] ethyl chloroformate, [19] benzoyl halides, [20] acetic anhydrides, [21] and MsCl, [22] have been used as activators for this purpose [more recently, Sun and coworkers used hypervalent iodine (III) [23] as an activating agent]. Various reagents like dimethyl sulphate, [17] N,N-dimethylcarbamoyl chloride, [18] ethyl chloroformate, [19] benzoyl halides, [20] acetic anhydrides, [21] and MsCl, [22] have been used as activators for this purpose [more recently, Sun and coworkers used hypervalent iodine (III) [23] as an activating agent].…”

“…The heteroaromatic N ‐oxide class would seemingly be a suitable alternative to overcome the issue of selectivity, as the electrophilic character at the C‐2 position is enhanced by the coordination of an activating agent to the N ‐oxide. Various reagents like dimethyl sulphate, N,N ‐dimethylcarbamoyl chloride, ethyl chloroformate, benzoyl halides, acetic anhydrides, and MsCl, have been used as activators for this purpose [more recently, Sun and co‐workers used hypervalent iodine (III) as an activating agent]. Despite considerable progress, these protocols suffer from several limitations such as longer reaction times and excess use of reagents or activators.…”

“…In addition, these reagents are often hazardous, toxic, and sensitive towards air and moisture, which stiffen easy handling. In many cases the competing additions of the activator counter‐ion also become problematic . And bases are generally required with a super‐stoichiometric amount to facilitate the full conversion at the final re‐aromatization step .…”

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

“…Sun and coworkers found that the reaction with quinoline N ‐oxides can be activated by the eco‐friendly and inexpensive hypervalent reagent PhI(OAc) 2 (PIDA, Scheme 95). [127] The reaction proceeds quickly, but is not efficient enough for pyridine N ‐oxides. Das's group successfully prepared 2‐cyanated pyridines and quinolines 317 under neat conditions at high temperatures either by conventional heating or microwave treatment (Scheme 96).…”