Cyanation is the substitution or

attachment of cyanide group on various

substrates.

Compounds with cyanide group “CN” are

called nitriles.

Nitriles have vast applications in the

synthesis of natural products, materials,

pharmaceuticals, agricultural chemicals,

and dyes.

In earlier days, metal complexes of Zinc,

Copper, Nickel etc. was used for cyanation.

For example, Sandmeyer reaction,

Rosenmund–von Braun reaction, Leimgruber-

Batcho indole synthesis etc.

Advancement in this regard is the use of

palladium catalyst with high yield and less

harsh conditions.

First Pd-catalyzed cyanation method was

reported by Takagi et al. 40 years ago.

Ushkov and Grushin uses reducing agents or

exploit low solubility of NaCN, KCN and

Zn(CN)2 in organic solvents to prevent

poisoning of cyanide group.

Beller and Weissman discovered K4[Fe(CN)6],

a nontoxic food additive, as cyanide source for

Pd-catalyzed coupling reactions.

Firstly, Aryl amines was oxidative dehydrated with ammonia to

produce armatic nitriles.

Jiao and co-workers developed a Cu-catalyzed transformation of

para substituted toluenes into the corresponding aromatic nitriles,

with NaN3 as the nitrogen source and an excess amount of

phenyliodoniumdiacetate (PIDA) as the oxidant.

In reported, a palladium-catalyzed ammoxidation of methyl

arenes with tert-butyl nitrite (TBN) as both the nitrogen source and

the oxidant.

Palladium-Catalyzed Cyanoalkenylation of Indoles

Indoles are heterocyclic compounds consisting

on benzene ring fused to a five member

nitrogen containing ring.

Palladium catalyzed

cynaoalkenylation of N-substituted

indoles in the presence of

K4[Fe(CN)6] as cyanating agent.

3-iodo-1-alkyl indole reacts with alkynes in the presence ofPdCl2 (catalyst), K4Fe(CN)6 (cynating agent), NaHCO3 (base),DMF:H2O (solvent) at 120 0C for 1h and gives

3-(1-alkyl-3-indolyl)-2,3-dialkylacrylonitrile as product.

General Mechanism:

Indoles exhibits a broad range of usefulpharmacological effects, including antibiotic, anti-inflammatory, antihypertensive, and antitumoractivities. Aromatic nitriles have application in a variety offields as both synthetic intermediates and finaltargets. For example, the antineoplastic (Letrozole),antidepressant (Citalopram), and anti-HIV drug(Etravirine).