The presence of an acyl trapping agent was crucial, since the unprotected
cycloadduct can rapidly trigger oxidative fragmentation to undesired products.
Other protecting groups including Boc and Fmoc were examined, but they resulted
in diminished yields. The Pt in the system was proposed to inhibit back electron
transfer to the indole by acting as an electron sponge, resulting in a more efficient
catalytic system. The reaction tolerates a wide range of electron-donating or
electron-withdrawing functionality at the C5 and C6 positions of the indole ring.
Halides, as well as a pinacolboron group, were also unreactive, opening the
door to further functionalization of the cycloaddition product. It was observed
that nitro- and azaindoles did not participate in this reaction. Centrifugation could
be used to separate catalyst from reaction mixture, whereupon its drying under
vacuum allowed for reuse in subsequent reactions. However, loss in activity was
observed, most likely due to poisoning by the indole derivatives.
5 Copper
Opportunities to apply relatively inexpensive organocopper chemistry [41] in
the form of nanoparticles as catalysts have also been the focus of several recent
investigations. Significant efforts have been dedicated to improving the efficiency of
copper located within NPs, notably toward reducing metal loading ( 1,000 ppm) as
well as developing an alternative to more toxic and/or precious metals. One driving
force behind reducing the loading of copper can be seen in the case of biologically
relevant couplings, such as the copper(I)-catalyzed alkyne-azide cycloaddition
(CuAAC) or other click reactions, where excess metal may interfere with applications of the triazole products. Additionally, valuable transformations such as C-C or
C-heteroatom formation as well as reduction [41] or oxidation [42] processes have
been reported.
Historically, alkyne-azide cycloaddition (AAC) reactions usually lead to
mixtures of 1,4- and 1,5-disubstituted triazoles. Work by Sharpless and Meldal,
in 2002 [43, 44], highlighted the positive impact of adding Cu(I) to the pot,
leading to regiocontrol strongly favoring the 1,4-isomer. In this regard, the
emergence of CuNPs as recoverable and recyclable catalysts has begun to address
the sustainability aspects of this important reaction. Radivoy et al. described
both unsupported and supported CuNPs for the CuAAC reaction [45]. In the case
of unsupported CuNPs, despite superior activities compared to commercial copper
catalysts, the NPs had the tendency to dissolve under optimal conditions, posing
a problem for recycling and residual metal to be found in the final product [46].
Later, the same group reported on supported NPs, using carbon or MagSilica.
Isolation and manipulation of the organic azide needed for the Cu-catalyzed
AAC could be avoided by its in situ generation via a multicomponent process
from anilines, aryldiazonium salts, alkenes [47], epoxides [48], or halides [49].
Thus, both waste reduction and safer processes were achieved. Simultaneously,
the CuAAC reaction could be effected in the presence of 0.5–5 mol% of CuNPs
on carbon or MagSilica at 70
C in water or acetonitrile [50]. Applications of
Earth-Abundant and Precious Metal Nanoparticle Catalysis
97
cycloadduct can rapidly trigger oxidative fragmentation to undesired products.
Other protecting groups including Boc and Fmoc were examined, but they resulted
in diminished yields. The Pt in the system was proposed to inhibit back electron
transfer to the indole by acting as an electron sponge, resulting in a more efficient
catalytic system. The reaction tolerates a wide range of electron-donating or
electron-withdrawing functionality at the C5 and C6 positions of the indole ring.
Halides, as well as a pinacolboron group, were also unreactive, opening the
door to further functionalization of the cycloaddition product. It was observed
that nitro- and azaindoles did not participate in this reaction. Centrifugation could
be used to separate catalyst from reaction mixture, whereupon its drying under
vacuum allowed for reuse in subsequent reactions. However, loss in activity was
observed, most likely due to poisoning by the indole derivatives.
5 Copper
Opportunities to apply relatively inexpensive organocopper chemistry [41] in
the form of nanoparticles as catalysts have also been the focus of several recent
investigations. Significant efforts have been dedicated to improving the efficiency of
copper located within NPs, notably toward reducing metal loading ( 1,000 ppm) as
well as developing an alternative to more toxic and/or precious metals. One driving
force behind reducing the loading of copper can be seen in the case of biologically
relevant couplings, such as the copper(I)-catalyzed alkyne-azide cycloaddition
(CuAAC) or other click reactions, where excess metal may interfere with applications of the triazole products. Additionally, valuable transformations such as C-C or
C-heteroatom formation as well as reduction [41] or oxidation [42] processes have
been reported.
Historically, alkyne-azide cycloaddition (AAC) reactions usually lead to
mixtures of 1,4- and 1,5-disubstituted triazoles. Work by Sharpless and Meldal,
in 2002 [43, 44], highlighted the positive impact of adding Cu(I) to the pot,
leading to regiocontrol strongly favoring the 1,4-isomer. In this regard, the
emergence of CuNPs as recoverable and recyclable catalysts has begun to address
the sustainability aspects of this important reaction. Radivoy et al. described
both unsupported and supported CuNPs for the CuAAC reaction [45]. In the case
of unsupported CuNPs, despite superior activities compared to commercial copper
catalysts, the NPs had the tendency to dissolve under optimal conditions, posing
a problem for recycling and residual metal to be found in the final product [46].
Later, the same group reported on supported NPs, using carbon or MagSilica.
Isolation and manipulation of the organic azide needed for the Cu-catalyzed
AAC could be avoided by its in situ generation via a multicomponent process
from anilines, aryldiazonium salts, alkenes [47], epoxides [48], or halides [49].
Thus, both waste reduction and safer processes were achieved. Simultaneously,
the CuAAC reaction could be effected in the presence of 0.5–5 mol% of CuNPs
on carbon or MagSilica at 70
C in water or acetonitrile [50]. Applications of
Earth-Abundant and Precious Metal Nanoparticle Catalysis
97