The document discusses palladium-catalyzed cyanation reactions. Specifically, it describes how palladium catalysts can be used to attach cyanide groups to various substrates under milder conditions compared to traditional metal complexes. It then provides examples of palladium-catalyzed cyanation of aromatic amines and methyl arenes. Finally, it summarizes a palladium-catalyzed cyanoalkenylation reaction of N-substituted indoles using K4[Fe(CN)6] as the cyanide source.

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).