4 Conclusions
Since a decade, impressive progressions have been accomplished for the coppercatalyzed formation of C(sp
2 )–N bonds. Both Ullmann and Chan–Lam reactions
have permitted the coupling of a wide array of nitrogen nucleophiles with aryl/vinyl
halides and boronic acids, respectively. The simplicity of the ligands, when necessary, their commercial availability and the low cost of copper make these reactions
very attractive compared to palladium cross coupling, though the latter are considered complementary one to another.
Nevertheless, Cu-catalyzed cross-coupling methodologies display several
drawbacks.
Compared to the well-established C–N coupling catalyzed by palladium, the
copper systems present lower turnover numbers and frequencies. This is particularly
the case for the Chan–Lam-type reaction which often still requires stoichiometric
amounts of metal. A lot of additives like the oxidant and bases, and sometimes
co-oxidants, are also often needed in stoichiometric or higher quantities.
In the catalytic version of the Ullmann reaction the situation is different, the
challenge being to obtain acceptable turnover frequencies at low temperatures
(25–80
C).
In both reactions, the goal is the reduction of metallic waste and the residual
levels of copper in final products. The same objective could be also reached by the
development of recyclable and reusable catalytic systems.
The copper systems are especially efficient with the aryl iodides or bromides.
The arylation of N-nucleophiles from the less reactive but also much less expensive
aryl chlorides in mild conditions remains a stimulating challenge.
As far as the industrial application of this copper chemistry is concerned, it is
difficult to gather some information. However, at least the Rhodia and the Shasun
Chemical companies tested the Ullmann reaction in its catalytic version and
produced several tones of various target compounds.
Finally, a very important challenge for copper-catalyzed C–N bond formation and
in a general point of view for all types of Cu-catalyzed carbon nucleophile (O, C, S)
coupling is a better understanding of the mechanism. In comparison, one of the
reasons which permitted the palladium-catalyzed reaction to become the method of
choice for C(sp
2
)–N bond formation is the clear description of the different steps in
the catalytic cycle. We hope to be able in the near future to correlate some mechanistic understanding with this exciting area of copper chemistry.
References
1. Ullmann F (1903) Ber Dtsch Chem Ges 36:2382
2. Ullmann F, Illgen E (1914) Ber Dtsch Chem Ges 47:380
3. Ullmann F (1904) Ber Dtsch Chem Ges 37:853
4. Ullmann F, Sponagel P (1905) Ber Dtsch Chem Ges 38:2211
Copper-Catalyzed C(aryl)–N Bond Formation
197
Since a decade, impressive progressions have been accomplished for the coppercatalyzed formation of C(sp
2 )–N bonds. Both Ullmann and Chan–Lam reactions
have permitted the coupling of a wide array of nitrogen nucleophiles with aryl/vinyl
halides and boronic acids, respectively. The simplicity of the ligands, when necessary, their commercial availability and the low cost of copper make these reactions
very attractive compared to palladium cross coupling, though the latter are considered complementary one to another.
Nevertheless, Cu-catalyzed cross-coupling methodologies display several
drawbacks.
Compared to the well-established C–N coupling catalyzed by palladium, the
copper systems present lower turnover numbers and frequencies. This is particularly
the case for the Chan–Lam-type reaction which often still requires stoichiometric
amounts of metal. A lot of additives like the oxidant and bases, and sometimes
co-oxidants, are also often needed in stoichiometric or higher quantities.
In the catalytic version of the Ullmann reaction the situation is different, the
challenge being to obtain acceptable turnover frequencies at low temperatures
(25–80
C).
In both reactions, the goal is the reduction of metallic waste and the residual
levels of copper in final products. The same objective could be also reached by the
development of recyclable and reusable catalytic systems.
The copper systems are especially efficient with the aryl iodides or bromides.
The arylation of N-nucleophiles from the less reactive but also much less expensive
aryl chlorides in mild conditions remains a stimulating challenge.
As far as the industrial application of this copper chemistry is concerned, it is
difficult to gather some information. However, at least the Rhodia and the Shasun
Chemical companies tested the Ullmann reaction in its catalytic version and
produced several tones of various target compounds.
Finally, a very important challenge for copper-catalyzed C–N bond formation and
in a general point of view for all types of Cu-catalyzed carbon nucleophile (O, C, S)
coupling is a better understanding of the mechanism. In comparison, one of the
reasons which permitted the palladium-catalyzed reaction to become the method of
choice for C(sp
2
)–N bond formation is the clear description of the different steps in
the catalytic cycle. We hope to be able in the near future to correlate some mechanistic understanding with this exciting area of copper chemistry.
References
1. Ullmann F (1903) Ber Dtsch Chem Ges 36:2382
2. Ullmann F, Illgen E (1914) Ber Dtsch Chem Ges 47:380
3. Ullmann F (1904) Ber Dtsch Chem Ges 37:853
4. Ullmann F, Sponagel P (1905) Ber Dtsch Chem Ges 38:2211
Copper-Catalyzed C(aryl)–N Bond Formation
197