COMMUNICATIONS
DOI: 10.1002/adsc.202001564
Salicylic Acid-Promoted Three-Component Annulation of
Benzimidazoles, Aryl Nitroalkenes and Elemental Sulfur
Ruhuai Mei,a Feng Xiong,a Chenrui Yang,a and Jinwu Zhaob,*
a
Key Laboratory of Coarse Cereal Processing,
Ministry of Agriculture and Rural Affairs,
Chengdu University,
Chengdu 610106, People’s Republic of China
School of Pharmacy,
b
Guangdong Medical University,
Dongguan 523808, People’s Republic of China
E-mail: jwzhao@gdmu.edu.cn
Manuscript received: December 17, 2020; Revised manuscript received: January 11, 2021;
Version of record online: Februar 5, 2021
On the other hand, sulfur-containing frameworks
widely exist in pharmaceuticals. Among the molecules
Abstract: Herein, a three-component cyclization
reaction of benzimidazoles, aryl nitroalkenes and
in the table of top 200 pharmaceuticals by US
elemental sulfur has been developed. Cheap and
prescription in 2012, for examples, more than 20% of
easily available salicylic acid found to be an
them contain at least one sulfur atom.[3] Considering
efficient mediator for the present transformation.
the pharmaceutical importance of sulfur compounds,[4]
This protocol provides a facile access to structurally
significant imidazo[2,1-b]thiazole skeleton from
efficient methods for their construction has been
intensively studied.[5] Elemental sulfur is a cheap,
simple raw materials with a range of compatible
bench-stable, user-friendly sulfur reagent that was
synthetically useful functionalities. Furthermore,
recently exploited to produce sulfur compounds includ-
gram-scale preparation of this method is effective,
ing some valuable sulfur heterocycles such as
which enables potential applications of it in broader
thiophenes,[6] thiazoles,[7] benzothiazoles,[8] and among
fields of molecule synthesis. Mechanistically, a
others.[9] Remarkably, the multi-component reactions
reaction cascade involving sequential aza-Michael
addition, nucleophilic sulfuration, and deaminative
through direct CÀ H sulfuration with elemental sulfur
found to be versatile to give atom- and step-economic
aromatization was proposed.
entries to complex sulfur-containing molecules. For
example, Deng and coworkers have developed three-
component heterocyclization of indoles, ketones, and
Keywords: multi-component reaction; elemental sul-
fur; benzimidazoles; nitroalkenes; imidazo[2,1-b]
elemental sulfur, which affords a novel access to
indole-fused (benzo)thiophenes.[10] On the basis of this
thiazole
result, the same group utilized alkenes or alkynes as
the coupling partner instead of ketones to construct the
same heterocycle skeleton under metal-free
One-pot multi-component cascade assembly represents conditions.[11] Complementarily, Fu et al. discovered
an advanced technique in modern synthesis that that acrylic acids were also capable to engage into this
provides an efficient platform for rapid preparation of three-component assembly and this reaction proceeded
complex molecules from simple raw materials.[1] This smoothly under additive-free conditions because of the
strategy has also been extensively exploited in medic- acidity of reactant (Figure 1, a).[12]
inal chemistry, total synthesis of naturally occurring
Given the structurally nucleophilic resemblance
products, and materials science.[2] In spite of the great between indoles and benzimidazoles, we speculated
progress, novel multi-component cascade reactions benzimidazoles could be used to replace indoles in the
especially under facile reaction conditions remain three-component assembly with elemental sulfur.
desirable for method development in synthetic Hence, a range of coupling partners such as acetopho-
chemistry.
none, phenylacetylene, styrene, cinnamic acid, and β-
nitrostyrene were initially screened as the third
Adv. Synth. Catal. 2021, 363, 1861–1866
1861
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