Angewandte
Communications
Chemie
Heterocycles
Tris(pentafluorophenyl)borane-Catalyzed Acceptorless
Dehydrogenation of N-Heterocycles
Masahiro Kojima and Motomu Kanai*
Abstract: Catalytic acceptorless dehydrogenation is an envi-
ronmentally benign way to desaturate organic compounds.
This process is traditionally accomplished with transition-
metal-based catalysts. Herein, a borane-catalyzed, metal-free
acceptorless dehydrogenation of saturated N-heterocycles is
disclosed. Tris(pentafluorophenyl)borane was identified as
a versatile catalyst, which afforded several synthetically
important N-heteroarenes in up to quantitative yield. Specif-
ically, the present metal-free catalytic system exhibited
a uniquely high tolerance toward sulfur functionalities, and
demonstrated superior reactivity in the synthesis of benzothia-
zoles compared to conventional metal-catalyzed systems. This
protocol can thus be regarded as the first example of metal-free
acceptorless dehydrogenation in synthetic organic chemistry.
^
Nitrogen-containing heteroarenes are a commonly encoun-
Scheme 1. Dehydrogenation methods for the synthesis of N-hetero-
arenes.
tered structural motif in pharmaceuticals, natural products,
and synthetic materials. Therefore, the development of
efficient methods for the synthesis of this compound class is
a central research area in synthetic organic chemistry. One
method to access these heteroarenes is the dehydrogenation
of the corresponding saturated N-heterocycles using a stoi-
chiometric oxidant (Scheme 1a).[1] Conversely, catalytic
acceptorless dehydrogenations are more atom efficient[2]
since no external reagent is required, and in addition,
valuable molecular hydrogen is expelled during the desatura-
tion.[3] Synthetically, the most relevant reaction conditions
have been accomplished with ruthenium-[4] or iridium-based[5]
homogeneous transition-metal catalysts (Scheme 1b). Fujita,
Yamaguchi, et al. have made primary contributions to this
field, and reported the catalytic dehydrogenation of 1,2,3,4-
tetrahydroquinoline and other cyclic amines using homoge-
neous iridium catalysts.[5a,c] Xiao and co-workers were able to
achieve acceptorless dehydrogenations under milder reaction
conditions by using cyclometalated iridium complexes, and
also disclosed the unique characteristics of using trifluoro-
ethanol as a solvent.[5b,g] Crabtree and co-workers used
homogeneous iridium/N-heterocyclic carbenes and chelated
iridium catalysts for the dehydrogenation of 1,2,3,4-tetrahy-
droquinaldine.[5e] Recently, Jones reported related dehydro-
genation reactions based on homogeneous iron[5d] and
cobalt[5f] catalysts. These precedents prompted us to explore
a new class of acceptorless dehydrogenations, which may be
suitable for the synthesis of N-heterocycles with high func-
tional-group tolerance and environmental friendliness.
In an attempt to develop a versatile acceptorless dehy-
drogenation for the synthesis of N-heteroarenes, we focused
our attention on Lewis-acidic borane catalysts in the context
of frustrated Lewis pairs (FLPs).[6] Borane catalysts play
a fundamental role in FLP-mediated hydrogenations,[7] but
their use in catalytic dehydrogenations of organic compounds
has remained unexplored.[8] We hypothesized that hydride
abstraction from amines by tris(pentafluorophenyl)borane to
generate borohydride species,[9] and subsequent hydrogen gas
evolution through protonolysis of the borohydride, would
allow the development of a novel catalytic acceptorless
dehydrogenation process. Indeed, catalytic hydride abstrac-
tion from an amine and cyclohexadienyl silanes by the
electrophilic borane was previously described in transfer
hydrogenation[9b] and transfer hydrosilylation,[9f,g,h] respec-
tively. In addition, the modest coordination ability of the
nitrogen lone pair in various N-heteroarenes, together with
appropriate sterics on the Lewis acid catalyst, should provide
high catalytic turnover numbers. Considering the uniquely
high chemoselectivity of borane catalysis and the fact that
these systems do not require expensive or toxic metals,
borane-catalyzed dehydrogenations should constitute
a highly valuable method for the synthesis of N-heteroarenes
(Scheme 1c).
[*] M. Kojima, Prof. Dr. M. Kanai
Graduate School of Pharmaceutical Sciences, The University of Tokyo
Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
E-mail: kanai@mol.f.u-tokyo.ac.jp
Prof. Dr. M. Kanai
Japan Science and Technology Agency, ERATO
Kanai Life Science Catalysis Project
Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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