Page 1068 - Advanced Organic Chemistry Part B - Reactions & Synthesis

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1044 having naphthoate as one of the ligands. The Cs salts are beneficial in maximizing
the solubility of the phenolate and naphthoates.
CHAPTER 11
It has been found that a number of bidentate ligands greatly expand the scope of
Aromatic Substitution copper catalysis. Copper(I) iodide used in conjunction with a chelating diamine is a
Reactions
good catalyst for amidation of aryl bromides. Of several diamines that were examined,

trans-N,N -dimethylcyclohexane-1,2-diamine was among the best. These conditions
are applicable to aryl bromides and iodides with either ERG or EWG substituents, as
well as to relatively hindered halides. The nucleophiles that are reactive under these
conditions include acyclic and cyclic amides. 149
CH(CH ) 5 mol% CuI CH(CH )
3 2
ligand 3 2
Br + N
N O K CO 3
2
toluene
H 110°C O 94%
ligand = trans-N,N'-dimethyl-1,2-cyclohexanediamine
This catalytic system also promotes exchange of iodide for bromide on aromatic
rings. 150 The reaction is an equilibrium process that is driven forward by the low
solubility of NaBr in the solvent, dioxane.

5 mol% CuI
10 mol% ligand
NCCH 2 Br + NaI NCCH 2 I
dioxane, 110°C
97%
ligand = trans-N,N'-dimethyl-1,2-cyclohexanediamine

The N,N-diethylamide of salicylic acid is a useful ligand in conjunction with CuI and
permits amination of aryl bromides by primary alkylamines. 151
5 mol % CuI
OCH 3 20 mol % ligand OCH 3
+ H N(CH ) CH 3
2 5
2
Br K PO , DMF NH(CH ) CH 3
2 5
3
4
90 °C
ligand = N,N-diethylsalicylamide
Copper(I) iodide with 1,10-phenanthroline catalyzes substitution of aryl iodides by
alcohols. The reaction can be done either in excess alcohol or in toluene. 152
10 mol % CuI
20 mol % ligand
CH O I + HOCH C CH 2 CH O OCH C CH 2
3
2
3
2
CsCO
3
CH 3 toluene CH 3
ligand = 1,10-phenanthroline 110 °C 78%
These copper-catalyzed reactions are generally applicable to aryl halides with either
EWG or ERG substituents. The order of reactivity is I > Br> Cl > OSO R, which is
2
consistent with an oxidative addition mechanism.
149
A. Klapars, X. Huang, and S. L. Buchwald, J. Am. Chem. Soc., 124, 7421 (2002).
150 A. Klapars and S. L. Buchwald, J. Am. Chem. Soc., 124, 14844 (2002).
151 F. Y. Kwong and S. L. Buchwald, Org. Lett., 5, 793 (2003).
152
M. Wolter, G. Nordmann, G. E. Job, and S. L. Buchwald, Org. Lett., 4, 973 (2002).