Tetrahedron Letters
Synthesis of 6-carboxylated phenanthridines by oxidative
alkoxycarbonylation–cyclization of 2-isocyanobiphenyls
with carbazates
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Gao Wang, Shan-Yong Chen , Xiao-Qi Yu
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An iron-catalyzed synthesis of 6-carboxylated phenanthridines starting with readily prepared
isocyanides and carbazates was developed. Reactions occurred via addition of alkoxycarbonyl radicals
to the isocyanide group and subsequent intramolecular cyclization.
Received 6 June 2014
Revised 7 July 2014
Accepted 14 July 2014
Available online 31 July 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Carbazates
Phenanthridines
Alkoxycarbonylation/cyclization
Phenanthridines are biologically important compounds by its
widespread presence in natural products, drugs, or drug candi-
dates.1 Many phenanthridines show antibacterial, antitumoral,
and cytotoxic activities.2 They are also widely used in material
science due to their significant optoelectronic properties.3 There-
fore, it is highly desirable to develop novel methods for the synthe-
sis of diversified phenanthridines. Isocyanides are isoelectronic
with carbon monoxide, and thus isocyanides can also act as radical
acceptors to form imidoyl radicals, which can undergo bimolecular
addition or cyclization.4 A few studies have been focused on the
addition of radicals to 2-isocyanobiphenyls followed by intramo-
lecular cyclization to generate phenanthridines (Scheme 1). Radi-
cals were limited within trifluoromethyl,5 carbonyl,6 alkyl,7 and
photosensitizer-catalyzed and oxygen-oxidated hydrazines to
radical followed cyclization with 2-isocyanobiphenyls.12 It pro-
vided a general and practical method for the construction of 6-
substituted phenanthridines. But only one 6-carboxylated phenan-
thridine was mentioned with 56% yield after irradiation for 18 h.
Considering the importance of esters, we reported an iron-cata-
lyzed oxidative alkoxycarbonylation–cyclization of 2-isocyanobi-
phenyls with carbazates.13,14
Initially, we started to optimize reaction conditions by employ-
ing 2-isocyano-5-methylbiphenyl (1a) and methyl carbazate (2a)
as model substrates. Using TBHP (tert-butyl hydroperoxide
70 wt % in water) as oxidant and FeCl2ꢀ4H2O as catalyst, the desired
product 3a was isolated in 56% yield after stirring in ethyl acetate
(Table 1, entry 1). Without a catalyst, only a trace of the product
was observed. Based on our previous results that ligands can
coordinate with iron salt and influence the oxidation process of
phosphoryl8
.
On the other hand, carboxylic esters are valuable commodity
chemicals and useful synthetic building blocks.9 Using carbazates
as the precursors of alkoxycarbonyl radicals, Taniguchi and Tian
reported introducing alkoxycarbonyl groups to styrenes to obtain
carboxylic esters.10 Very recently, Du and our group reported the
iron-catalyzed arylalkoxycarbonylation of N-arylacrylamides with
carbazates independently, and various oxindole-3-acetates were
obtained in good yields.11 In 2014, Zhou reported a reaction about
HAS
+
R
NC
N
R
N
R
Reported: R=CF3, ArCO, alkyl, Ph2P(O) this work: R= CO2R'
Scheme 1. Reported synthesis of phenanthridine derivates and our design.
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Corresponding authors. Tel./fax: +86 28 85415886.
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.