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Adv. Synth. Catal. 2004, 346, 1599 ¨C1626

Palladium-Catalyzed CN and CO Coupling ¨CA Practical
Guide from an Industrial Vantage Point†

Abstract: The palladium-catalyzed coupling of amines
with aryl halides or aryl alcohol derivatives, commonly
dubbed Buchwald¨CHartwig amination, has matured
from a synthetic laboratory procedure to a technique
that is widely used in natural product synthesis as well
as in other fields of academic interest. Furthermore,
due to the versatility and reliability of this reaction,
researchers in industrial environments have included
this methodology in their toolbox as a standard procedure
for the synthesis of amine derivatives. Therefore,
it is not surprising that first industrial processes up to
ton-scale have been performed using this cross-coupling
reaction. The authors who are involved in the
application of this reaction to industrial processes
on this scale give an overview of the recent developments
in this field of chemistry, also including fundamental
principles, with a special focus on the industrial
approach and issues to be considered relevant in
scaling-up this transition metal-catalyzed chemistry.
This review differs from the already existing excellent
academic reviews by focusing on the practical problems
arising during implementing the methodology
in an industrial environment as well as giving practical
hints to this end.
1 Introduction
2 Components of the Catalytic System
2.1 Ligands
2.2 Palladium Precursors
2.3 Bases
2.4 Solvents/Temperature
3 CN Coupling of Amines
3.1 Motivation
3.2 Description of Table 2
3.3 General Statements
3.4 Aryl Bromides
3.5 Aryl Chlorides
3.6 Aryl Iodides
3.7 Arenesulfonic Acid Esters
3.8 Pyridyl Halides
3.9 Other Heteroaromatic Halides
3.10 Catalyst Activity
3.11 Weak Bases
3.12 Low Temperatures
3.13 New Bases
3.14 Amine Nucleophiles
4 Coupling Reactions with Non-Amine Nucleophiles
4.1 Coupling of Amides, Sulfonamides, Carbamates
and Ureas
4.2 Coupling with Sulfoximines, Hydrazines and
Guanidines
4.3 Ammonia Surrogates
5 Applications of Buchwald¨CHartwig Amination
5.1 Synthesis of Natural Products and Analogues as
Active Agents
5.2 Applications in Ligand Synthesis
5.3 Applications in Material Science
6 CO Coupling
7 Contributions Elucidating the Mechanism
7.1 CN Coupling
7.2 C-Amide Coupling
7.3 CO Coupling
8 Overview of Current Review Articles
9 Conclusions
Keywords: Buchwald¨CHartwig amination; CN bond
formation; CO bond formation; cross-coupling; homogeneous
catalysis: palladium; phosphine ligands

[ Last edited by wxwdoctor on 2007-3-25 at 19:32 ]
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