Direct Cyanation of Heteroaromatic Compounds Mediated by Hypervalent Iodine(III) Reagents:  In Situ Generation of PhI(III)−CN Species and Their Cyano Transfer

• Published in: Journal of organic chemistry 2007-01, Vol.72 (1), p.109-116
• Main Authors: Dohi, Toshifumi, Morimoto, Koji, Takenaga, Naoko, Goto, Akihiro, Maruyama, Akinobu, Kiyono, Yorito, Tohma, Hirofumi, Kita, Yasuyuki
• Format: Article
• Language: English
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Cyanates - chemistry; Exact sciences and technology; Free Radicals - chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydroxybenzoates - chemical synthesis; Hydroxybenzoates - chemistry; Iodine - chemistry; Kinetics and mechanisms; Ligands; Molecular Structure; Organic chemistry; Oxidation-Reduction; Phenyl Ethers - chemistry; Preparations and properties; Pyrroles - chemistry; Reactivity and mechanisms; Thiophenes - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo061820i

Hypervalent iodine(III) reagents mediate the direct cyanating reaction of a wide range of electron-rich heteroaromatic compounds such as pyrroles 1, thiophenes 3, and indoles 5 under mild conditions (ambient temperature), without the need for any prefunctionalization. Commercially available trimethylsilylcyanide is usable as a stable and effective cyanide source, and the reaction proceeds in a homogeneous system. The N-substituent of pyrroles is crucial to avoid the undesired oxidative bipyrrole coupling process, and thus a cyano group was introduced selectively at the 2-position of N-tosylpyrroles 1 in good yields using the combination of phenyliodine bis(trifluoroacetate) (PIFA), TMSCN, and BF3·Et2O at room temperature. In the reaction mechanism, cation radical intermediates of heteroaromatic compounds are involved as a result of single electron oxidation, and the key to successful transformations seems to depend on the oxidation potential of the substrates used. Thus, the reaction was also successfully extended to other heteroaromatic compounds having oxidation potentials similar to that of N-tosylpyrroles such as thiophenes 3 and indoles 5. However, regioisomeric mixtures of the products derived from the reaction at the 2- and 3-positions were obtained in the case of N-tosylindole 5a. Further investigation performed in our laboratory provided insights into the real active iodine(III) species during the reaction; the reaction is induced by an active hypervalent iodine(III) species having a cyano ligand in situ generated by ligand exchange reaction at the iodine(III) center between trifluoroacetoxy group in PIFA and TMSCN, and effective cyanide introduction into heteroaromatic compounds is achieved by means of the high cyano transfer ability of the hypervalent iodine(III)−cyano intermediates. In fact, the reaction of N-tosylpyrrole 1a with a hypervalent iodine(III)−cyano compound (e.g., (dicyano)iodobenzene 8), in the absence of TMSCN, took place to afford the 2-cyanated product 2a in good yield, and an effective preparation of the intermediates is of importance for successful transformation. 1,3,5,7-Tetrakis[4-{bis(trifluoroacetoxy)iodo}phenyl]adamantane 12, a recyclable hypervalent iodine(III) reagent, was also comparable in the cyanating reactions as a valuable alternative to PIFA, affording a high yield of the heteroaromatic cyanide by facilitating isolation of the cyanated products with a simple workup. Accordingly, after preparing the active hyperv