Page 1067 - Advanced Organic Chemistry Part B - Reactions & Synthesis

CH 3 CH 3 1043
Br CN
DMF
+ CuCN SECTION 11.3
Δ
93% Ref. 138 Transition
Metal–Catalyzed
Aromatic Substitution
Reactions
CN
Br NMP
+ CuCN
200°C
95% Ref. 139
A general mechanistic description of the copper-promoted nucleophilic substi-
tution involves an oxidative addition of the aryl halide to Cu(I) followed by collapse
of the arylcopper intermediate with a ligand transfer (reductive elimination). 140

Ar X + Cu(I)Z Ar Cu(III) Z Ar Z + CuX
X = halide X
Z = nucleophile

Several other kinds of nucleophiles can be arylated by copper-catalyzed substitution.
Among the reactive nucleophiles are carboxylate ions, 141 alkoxide ions, 142 amines, 143
phthalimide anions, 144 thiolate anions, 145 and acetylides. 146 In some of these reactions
there is competitive reduction of the aryl halide to the dehalogenated arene, which is
attributed to protonolysis of the arylcopper intermediate. Most of these reactions are
carried out at high temperature under heterogeneous conditions using copper powder
or copper bronze as the catalyst. The general mechanism suggests that these catalysts
act as sources of Cu(I) ions. Homogeneous reactions can be carried out using soluble
Cu(I) salts, particularly Cu(I)O SCF . 147 These reactions occur under milder conditions
3
3
than those using other sources of copper. The range and effectiveness of coupling aryl
halides and phenolates to give diaryl ethers is improved by use of with CsCO . 148
3
Reaction occurs in refluxing toluene.
CH 3 CuO SCF CH 3
3
Cs CO 3 3
2
I + – O O CH 3
toluene
CH 3 105°C CH 3 80%
Some reactions of this type are accelerated further by use of naphthoic acid as an
additive. This effect is believed to result from formation of a mixed anionic cuprate

138
L. Friedman and H. Shechter, J. Org. Chem., 26, 2522 (1961).
139 M. S. Newman and H. Bode, J. Org. Chem., 26, 2525 (1961).
140
T. Cohen, J. Wood, and A. G. Dietz, Tetrahedron Lett., 3555 (1974).
141 T. Cohen and A. H. Lewin, J. Am. Chem. Soc., 88, 4521 (1966).
142 R. G. R. Bacon and S. C. Rennison, J. Chem. Soc. C, 312 (1969).
143
A. J. Paine, J. Am. Chem. Soc., 109, 1496 (1987).
144 R. G. R. Bacon and A. Karim, J. Chem. Soc., Perkin Trans. 1, 272 (1973).
145
H. Suzuki, H. Abe, and A. Osuka, Chem. Lett., 1303 (1980); R. G. R. Bacon and H. A. O. Hill, J. Chem.
Soc., 1108 (1964).
146
C. E. Castro, R. Havlin, V. K. Honwad, A. Malte, and S. Moje, J. Am. Chem. Soc., 91, 6464 (1969).
147 T. Cohen and J. G. Tirpak, Tetrahedron Lett., 143 (1975).
148
J. F. Marcoux, S. Doye, and S. L. Buchwald, J. Am. Chem. Soc., 119, 10539 (1997).