Palladium-Catalyzed C(sp²)–H Cyanation Using Tertiary Amine Derived Isocyanide as a Cyano Source

Abstract

An unprecedented palladium-catalyzed cyanation of aromatic C-H bonds by using tertiary amine derived isocyanide as a novel cyano source was developed. Cu(TFA)(2) was used as a requisite stoichiometric oxidant. Mechanistic studies suggest that a tertiary carbon cation-based intermediate is involved following the C-N bond breakage.

Transition Metal‐Catalyzed CH Activation of Indoles

“…Reaction Couplingpartner/reagentC atalyst References 1a rylation aryl halides Pd [101,102,104,105] 2b enzoic acids Pd [107] 3a rylhydrazines Pd [108] 4c yclohexanones Pd [109] 5d iaryliodonium salts Cu [110] 6N -heterocyclic compounds Pd [111][112][113][114] 7a lkynylation alkynes Au [115] 8b enzylation benzylic alcohols Au [116] 9o lefination alkenes Pd [117,118] 10 acylation benzaldehydes Pd [119] 11 TMEDA Cu [120] 12 nitrilesP d [121] 13 CO and alcohols Rh [122] 14 a-amino carbonyl compounds Cu [123] 15 Pd [124] 16 synthesis of bisindoles alcohols Pd [141,142] 17 aldehydes Ag [143] 18 amines Pd [144] 19 annulation alkenes Pd 21 cyanation CuCN Pd [150] 22 K 4 [Fe(CN) 6 ]P d [151] 23 t-BuNC Pd [152] 24 NH 4 HCO 3 and DMSOP d [153] 25 amidation isocyanides Pd [154] Scheme 44. Pd-catalyzedarylation.…”

“…Relatively non-toxic reactionp rotocols that achieve cyanation in the absence of cyanometal saltsh ave also been reported utilizing isonitriles, [152] and am ixture of ammonium bicarbonate andD MSO. [153] Amidation at the C-3p osition of indolesh aveb een achieved by employing isonitrilesa sc oupling partners,( Scheme 71).…”

Synthesis, Crystal Structures, and DFT Calculations of Three New Cyano(phenylsulfonyl)indoles and a Key Synthetic Precursor Compound

“…In connection with our interest in developing novel indole chemistry [1], and in view of the enormous recent interest in the synthesis and biological activity of 2-and 3-cyanoindoles [2][3][4][5], we have synthesized three cyano-1-(phenylsulfonyl)indoles (I-III) and the synthetic precursor (IV) (Figure 1) and characterized them with NMR, single-crystal X-ray diffraction, and DFT molecular orbital calculations. These three compounds and the heteroaryl and aryl nitriles are key precursors of aldehydes, amines, amidines, tetrazoles, amides, and other carbonyl compounds [6,7] and are often employed in the synthesis of pharmaceuticals, dyes, agrochemicals, and natural products [8,9].…”

Copper-catalyzed, oxidative sp2 C-H cyanation: facile synthesis of aromatic carbonitriles

“…Meanwhile, Cheng found DMSO contributes to the formation of final nitrile. 24 Very recently, Zhu 25 and Xu 26 communicated the cyanation of C-H using a Pd/isocyanide system. Pdfree examples of C-H cyanation are comparatively few.…”