2.  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.

3.  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.

4.  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.

6.  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.

8. 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.

9.  3-iodo-1-alkyl indole reacts with alkynes in the presence of
PdCl2 (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.

10. General Mechanism:

11.  Indoles exhibits a broad range of useful
pharmacological effects, including antibiotic, anti-
inflammatory, antihypertensive, and antitumor
activities.
 Aromatic nitriles have application in a variety of
fields as both synthetic intermediates and final
targets. For example, the antineoplastic (Letrozole),
antidepressant (Citalopram), and anti-HIV drug
(Etravirine).