ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
One-Pot Three-Component Approach to
the Synthesis of Polyfunctional Pyrazoles
Guolin Zhang,* Hangcheng Ni, Wenteng Chen, Jiaan Shao, Huan Liu, Binhui Chen,
and Yongping Yu*
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of
Pharmaceutical Science, Zhejiang University, Hangzhou 310058, P. R. China
yyu@zju.edu.cn; guolinzhang@zju.edu.cn.
Received September 29, 2013
ABSTRACT
A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-
trisubstituted 1H-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be
tolerated in this methodology, and a possible mechanism is proposed.
Pyrazoles are one of the most important heterocyclic
compounds that possess a range of biological activities, such
as antibacterial,1 antileukemic,2 antitumor,3 antiobesity,4 and
anti-inflammatory.5 Polysubstituted pyrazoles have also been
utilized as useful ligands for some cross-coupling reactions.6
Due to pyrazoles’ important utility, numerous approaches
have been developed over the past decades including the
reaction of 1,3-diketones with hydrazine and hydrazine
derivatives,7 the coupling of N-arylhydrazones and nitro-
olefins,8 and 1,3-dipolar cycloaddition of hydrazines to
alkynes.9 However, it is still challenging to prepare polysub-
stituted pyrazoles.
Recently, vinyl azides have emerged as important syn-
thons although they were once regarded as “sleepers” of
the reactive azido species for a long time. In recent years,
our group10 and others11 have developed numerous nitro-
gen-containing heterocycles from vinyl azides. Based on
the previous result, herein, we demonstrate a simple,
multicomponent, and straightforward approach to pro-
vide 3,4,5-trisubstituted 1H-pyrazoles regioselectively in
the presence of base with good to excellent yields from
vinyl azides, benzaldehyde, and tosylhydrazine. The azido
group in vinyl azides serves as a leaving group.12
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4487. (e) Alex, K.; Tillack, A.; Schwarz, N.; Beller, M. Org. Lett. 2008,
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W.; Hu, M.; Zhang, G.; Yu, Y. Tetrahedron 2013, 69, 2070.
(11) (a) For a review of vinyl azides, see: Jung, N.; Brase, S. Angew.
Chem., Int. Ed. 2012, 51, 12169. (b) Xie, H.; Liu, J.; Wu, L.; Ding, M.
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r
10.1021/ol402810f
XXXX American Chemical Society