occurred in applying triazole building blocks as either
bioactive components in drug discovery or special func-
tional groups in new materials synthesis.6 Recently, several
interesting studies that utilized 1,2,3-triazoles as ligands
in transition metal catalysis have been reported.7,8 The
fast growing research applications of this heterocycle neces-
sitate the development of effective methods for the prepara-
tion of diverse 1,2,3-triazole derivatives. Herein, we report
the successful use of Fe(III)-catalyzed C-O bond activation
as an efficient strategy in post-triazole propargylation and
its application for the preparation of asymmetric N-C type
1,1-bis-triazole compounds.
bis-triazole compounds could be summarized as three
different classes: N-N type,12 C-C type,13 and N-C type
(Scheme 1).
Scheme 1. Three Different Types of Bis-triazole Compounds
Our interest in studying 1,2,3-triazole compounds was
initiated by the recent success of Lewis base-catalyzed
nitroalkene activation.9 With this method, various 4,5-
disubstituted NH-triazoles were prepared in good yields.10
Moreover, the post-triazole N-2 functionalization was de-
veloped,11 where alkylation, arylation, and vinylation of
1,2,3-triazoles have been successfully achieved with good
yields and regioselectivity.
During the last two years, our group has been working
on the investigation of 1,2,3-triazole derivatives as ligands
in transition metal catalysis.8 These triazole compounds
have shown significant influence on the metal catalyst
reactivity by serving as effective nitrogen σ-donor. To
further extend our studies of triazole-metal coordination,
we aimed at the bis-triazole compounds as potential
interesting bidentate ligands to coordinate with transition
metal cations. Considering the substitution pattern, the
While the N-N and C-C type bis-triazoles have been
successfully synthesized from either post-triazole al-
kylation11a or click chemistry (Scheme 1, A and B), the
N-C type bis-triazoles have not been reported. These
unsymmetrical N-C type bis-triazoles, especially the 1,1-
bis-triazoles, are particularly interesting because of the
presence of the stereocenter. A brief synthetic design of
this type of compounds is shown in Scheme 1C, where
the two triazole moieties are introduced by click chemistry
and post-triazole propargylation sequentially. Although the
retrosynthesis design looked straightforward, the actual
preparation was much more challenging than we expected
(Vide infra), especially the post-triazole propargylation.
(5) (a) Chemama, M.; Fonvielle, M.; Arthur, M.; Valery, J. M.; Etheve-
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1067. (c) Michaels, H. A.; Murphy, C. S.; Clark, R. J.; Davidson, M. W.;
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In general, the propargylation could be challenging since
the nucleophiles would potentially attack the propargyl
position as well as the triple bonds, to give corresponding
allene intermediates that further convert into other prod-
ucts (such as Meyer-Schuster rearrangement).14,15 There-
fore, the performance of this transformation usually depends
on the nature of the substrates (i.e., the stability of leaving
groups and steric hindrance of alkynes). With simple
propargyl bromide 2a, effective triazole propargylation could
be achieved in excellent yields (Scheme 2A). However, the
direct substitution failed to work for substituted alkynes. For
example, reaction between triazole 1a and propargyl acetate
2b gave no reaction with Cs2CO3 as the base. Treating the
substrates under harsher conditions (DMSO and strong base)
led to the formation of complex reaction mixtures with no
desired propargyl triazole 3b observed (Scheme 2B). More-
over, attempts in converting propargyl alcohol 4a into
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