convergent, divergent or simultaneous pathway with very high
yields and purities by tuning the type of solvent and ligand
employed. The high ‘click’ rates allowed us to perform these
reactions at room temperature, a distinct advantage when
synthesizing compounds that are heat unstable. We further
demonstrated the rapid synthesis of a high yielding G3
dendrimer using the CuAAC, either ATNRC or SET-NRC
and thiol–ene ‘click’ reactions. The control of these ‘click’
reactions exemplified in this work represents a mild, versatile
and highly practical strategy for the construction of a wide
range of complex macromolecular and polymeric architectures.
The implications of these findings are being further pursued to
control not only the sequence that building blocks attach, but
also to control the type of architecture depending upon the
reaction pathway chosen.
Scheme 3 Synthetic pathways for formation of a G3 architecture
using three ‘click’ reactions (i.e. thiol–ene, CuAAC, and ATNRC or
SET-NRC).
Notes and references
planar complex when coordinated with BrÀ19 but can also
form other charged, distorted tetrahedral complexes with
solvents and monomer species.20 When in its neutral
conformation, however, the complex is more soluble and thus
more reactive in toluene. In the SET-NRC process both
solvent and ligand must combine to facilitate disproportionation
of CuI to Cu0 and CuII.17 Here, Cu0 activates the halide to its
incipient radical. Reports have demonstrated the rapid
activation by Cu0 in the presence of DMSO and Me6TREN,9
and its rapid reaction with nitroxides.6,7 The G2 architecure 12
is reversible6 through the dissociation of the alkoxyamine
bonds at high temperature (>100 1C).
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Using this knowledge, we created an architecture with three
generational layers from three ‘click’ reactions, including
CuAAC, SET-NRC or ATNRC, and thiol–ene reactions.
The G3 was created using the monomers depicted in
Scheme 3 in a two-step process since the reactants 7 and
benzyl mercaptan can also participate in the very rapid and
competing thio–bromo17 reaction. In the presence of DMSO
and Me6TREN as ligand, the thiol–ene reaction between
benzyl mercaptan and 8 to give intermediate 13 was complete
in under 3 min at 25 1C (see Fig. S35, ESIw). This reaction
mixture was then added to a DMSO solution containing 7,
9 and Me6TREN; followed by CuIBr addition. Product 14
was formed in 2 h as first 9 and 7 coupled together via the
SET-NRC reaction pathway and finally the CuAAC reaction
divergently gave the final product in a 73.7% yield and 92.5%
purity (as measured by SEC). The crude product was purified
by repeatedly dissolving in THF and precipitating into diethyl
ether, thereby increasing the purity to 97.8%. In the presence
of DMSO and PMDETA as ligand, the thiol–ene reaction to
form intermediate 13 was also complete in under 3 min at
25 1C. After addition of this reaction mixture to a solution of
7, 9 and PMDETA, followed by addition of CuIBr, product 14
formed from the simultaneous CuAAC and ATNRC reactions
in a 78.6% yield, and 91.8% purity. The purity increased to
98.2% after the crude mixture was repeatedly dissolved in
THF and precipitated into diethyl ether.
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In conclusion, we report the first procedure for controlling
the rates of two orthogonal ‘click’ reactions in one pot
by preparing a second-generation dendrimer either in a
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 4165–4167 4167