Tetrahedron Letters
Catalytic aromatization of 1,4-dihydropyridines by radical cation salt
prompted aerobic oxidation
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Xiaodong Jia , Liangliang Yu, Congde Huo, Yaxin Wang, Jing Liu, Xicun Wang
Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, China
Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Aromatization of Hantzch 1,4-dihydropyridines was achieved under radical cation salt induced condi-
tions, in which triarylamine radical cation acts as an efficient catalyst to prompt the aerobic oxidation
of 1,4-DHPs in a catalytic way.
Received 16 September 2013
Revised 28 October 2013
Accepted 5 November 2013
Available online 13 November 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
1,4-Dihydropyridines
Aromatization
Radical cation
Catalytic oxidation
Hantzsch 1,4-dihydropyridines (1,4-DHPs) as a class of excel-
lent antioxidants have received extensive research. Besides their
broad applications in the treatment of cardiovascular diseases such
as hypertension and angina pectoris,1 oxidative aromatization of
DHPs, which was used to model the biological hydride transfer
mechanism of coenzyme NADH, has attracted continuing interests
of organic and medicinal chemists and massive amount of proto-
cols has been developed.2–6 A variety of catalyst systems have been
founded for the aromatization of DHPs. In early works, stoichiom-
etric or excess amount of strong oxidants were mostly used, such
as Zr(NO3)4, CAN, CrO2, HNO3, MnO2, NaIO4, and Mn(OAc)3.2
Recently, more attention has been paid to catalytic aromatization
of DHPs using molecular oxygen as a clean source of oxidant. Since
oxygen itself does not oxidize 1,4-DHP effectively, an appropriate
catalyst prompted condition is necessary. For this purpose, aerobic
oxidation using RuCl3, Pd/C, activated carbon, and Fe(ClO4)3 in ace-
tic acid has thus been developed.3 Additionally, Tung reported a
photocatalytic aromatization of 1,4-DHP by platinum(II) terpyridyl
complexes with the release of H2.4 Liu and co-workers also reveal
an aerobic aromatization catalyzed by N-hydroxyphthalimide
(NHPI).5 More recently, Liu and Li et al. established a mild aerobic
oxidation of 1,4-DHPs using 9-phenyl-10-methylacridinium as a
reusable organocatalyst.6 Although these elegant methods have
been established, some limitations still confine their further appli-
cations, such as low catalytic efficiency, inconvenient preparation
of catalyst, limited scope, and harsh reaction condition. Therefore,
the development of more convenient, efficient, and general cata-
lytic oxidation remains a challenging task in this hot area.
Recently, we reported, for the first time, the catalytic radical
cation initiated CÀH functionalization of glycine derivatives with
styrenes to forge quinoline skeletons in both inter- and intramolec-
ularly ways (Fig. 1A).7 This method represented
a catalytic
approach to sp3 C–H bond oxidation, avoiding use of excess
quantities of the oxidants. In this reaction, tris(4-bromophe-
nyl)aminium hexachloroantimonate (TBPA+Å) is the crucial catalyst
to activate molecular oxygen participating in aerobic oxidation of
sp3 C–H bond. Inspired by this work, we questioned whether this
catalytic system could also be applied to the aromatization of
1,4-DHPs (Fig. 1B). Herein, we wish to report a new method for
the catalytic aromatization of 1,4-DHPs using radical cation salt
as a catalyst.
At the outset, the aromatization of 1a was chosen as the model
reaction to screen the best reaction conditions (Table 1). In the
presence of 1 mol % of TBPA+Å under air atmosphere, the desired
aromatization product 2a was isolated in 25% yield (entry 1). High-
er catalyst loading increased the yields, and when 5 mol % of the
catalyst added, the pyridine product was obtained in nearly quan-
titative yield (entry 3). If TBPA+Å was increased to 10 or 15 mol %,
the reaction become faster, but the yield decreased about 10%,
probably due to over oxidation. We also performed the model reac-
tion in oxygen atmosphere, and lower isolated yield was obtained,
probably due to further oxidation. Next, solvent screen was
conducted (entries 7–10). The results show that acetonitrile was
the best solvent, and other nonpolar solvent gave lower yields of
the desired product. In the absence of TBPA+Å and oxygen
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