pubs.acs.org/joc
antiallergic,4 and inhibitory5 (tazobactam) activities. Tri-
Facile Entry into Triazole Fused Heterocycles via
Sulfamidate Derived Azido-alkynes
azolobenzodiazepines6 have shown high affinity toward
benzodiazepine receptors. They are also emerging as power-
ful pharmacophores in their own right. Copper-catalyzed
cycloaddition is mainly used for conjugation7 or ligation
between two molecules or in an intramolecular fashion to
generate macrocycles.8 In parallel, there has been consider-
able interest shown toward the synthesis of novel condensed
triazoles using intramolecular version of Huisgen cycloaddi-
tion.9 Tailor-made molecules possessing alkyne and azide
moieties disposed in the same molecule when heated undergo
intramolecular Huisgen cycloaddition to furnish novel, 1,5-
substituted triazole fused heterocyclic systems. We have
recently demonstrated this in the synthesis of 4,5,6,7-
tetrahydro[1,2,3]triazolo[1,5-a]pyrazin-6-ones from primary
amines and amino acids comprising a three-step protocol
employing intramolecular [2 þ 3] cycloaddition as the key
step.10 In our continued interest toward the synthesis of
novel triazole fused systems, we report herein an elegant
and high-yielding synthesis of diversely substituted nitrogen-
rich triazole fused compounds via azido-alkynes derived
from a variety of sulfamidates. The choice of azido-alkynes
for the cycloaddition was quite broad, ranging from simple
azido-alkynes to novel substrates derived from amino
acids and carbohydrates. Constrained intramolecular
[3þ2] cycloaddition between azide and alkyne was used as
a pivotal reaction.
V. Sai Sudhir, N. Y. Phani Kumar, R. B . Nasir Baig, and
Srinivasan Chandrasekaran*,†
Department of Organic Chemistry, Indian Institute of Science,
Bangalore-560012, Karnataka, India. †Honorary Professor,
Jawaharlal Nehru Center for Advanced Scientific Research,
Jakkur, Bangalore.
Received July 31, 2009
Direct synthesis of condensed triazoles from diverse
sulfamidates by ring opening of sulfamidates with sodium
azide followed by one-pot propargylation and cycloadd-
ition furnished title compounds. The methodology in
general has been demonstrated on diverse sulfamidates
derived from amino acids, amino acid derivatives, and
carbohydrates to obtain diverse triazole fused scaffolds.
In one example, a condensed triazole containing amino
acid has been synthesized by ring opening of a sulfami-
date derivative with propargyl amine.
Our strategy involved ring opening of diverse sulfamidates
with sodium azide to furnish the corresponding azido
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Published on Web 09/02/2009
DOI: 10.1021/jo9016748
r
2009 American Chemical Society