Angewandte
Chemie
DOI: 10.1002/anie.201411066
Perfluoroalkylation
À
Heterogeneous Platinum-Catalyzed C H Perfluoroalkylation of
Arenes and Heteroarenes**
Lin He, Kishore Natte, Jabor Rabeah, Christoph Taeschler, Helfried Neumann,
Angelika Brꢀckner, and Matthias Beller*
Abstract: Fluorinated organic compounds are gaining increas-
ing interest for life science applications. The replacement of
hydrogen in arenes or heteroarenes by a perfluoroalkyl group
has a profound influence on the physical and biological
properties of such building blocks. Here, an operationally
was described by the group of Hartwig and involved a one-pot
iridium-catalyzed borylation of arenes/copper-reagent-medi-
ated perfluoroalkylation sequence.[11] In addition, a straight-
forward transformation was developed by Kamigata and co-
workers, whereby a wide range of arenes and heteroarenes
can be perfluoroalkylated with RfSO2Cl in the presence of
[RuCl2(PPh3)3].[12] Moreover in 2011, an interesting [Pd2dba3]/
binap-catalyzed reaction for the coupling between RfI and
aromatic compounds was reported by Sanford and co-work-
ers.[13] However, potential drawbacks of all these procedures
are the inherent problems associated with homogeneous
catalysis because of difficulties in separating and reusing
metals and ligands.
À
simple protocol for the direct C H perfluoroalkylation of
(hetero)arenes with RfI or RfBr has been developed, using
a robust supported platinum catalyst. The ready availability of
the starting materials, the excellent substrate tolerance, and the
reusability of the catalyst make this method attractive for the
synthesis of a variety of perfluoroalkyl-substituted aromatic
compounds. Preliminary mechanistic studies revealed the
formation of radicals to be crucial in the reaction system.
An ideal protocol would make use of stable and easily
À
O
rganofluorine chemistry plays a vital role for the advance-
recyclable catalysts for the direct C H perfluoroalkylation of
ment of medicinal, agricultural, and material sciences.[1] The
unique behavior of fluorinated compounds is attributed to the
high electronegativity of fluorine (4.0), combined with its size,
which is close to that of hydrogen.[2] Hence, perfluoroalkyl
groups, regarded as a gathering of fluorine atoms, determine
the electronic and steric properties of a given molecule in
a distinctive manner.[3,4] In the past decades, a number of
approaches based on thermal,[5] electrophilic,[6] and photo-
chemical[7] reactions have been reported. Despite impressive
achievements, practical issues (harsh reaction conditions),
experimental simplicity, and/or the requirement of unwanted
stoichiometric reagents[8] (e.g. perfluoro-copper species) are
persistent, thus stimulating progress in this area.
aromatic compounds. In this respect, heterogeneous catalysis
is the preferred choice. Unfortunately, to date, only rare
examples of such reactions in the presence of heterogeneous
catalysts (performed above 1508C) with very limited sub-
strate scope have been reported.[14] Thus, the search for
alternative materials for this transformation remains a chal-
lenging but rewarding task.
Herein, we present a general and versatile heterogeneous
platinum-catalyzed system for the coupling of various arenes
and heteroarenes with either easily available RfI or RfBr
(Scheme 1). The good performance of the present catalytic
system allowed us also to extend this methodology to the
perfluoroalkylation of caffeine as a representative example of
nucleobases.
Initially, the catalytic performance for the perfluoroalky-
lation of benzene with C10F21I was assessed by using several
metal-based catalysts. To our delight, in the presence of
For example, transition-metal catalysis has emerged as
a powerful tool for perfluoroalkylation reactions. Several
reports have demonstrated copper- or palladium-catalyzed
reactions for the preparation of perfluoroalkyl (including
trifluoromethyl) arenes from aryl halides.[9] In contrast,
analogous methods to prepare these compounds from
arenes, which are particularly desirable starting materials,
are notably lacking.[10] Recently, an elegant indirect strategy
[*] Dr. L. He, Dr. K. Natte, Dr. J. Rabeah, Dr. H. Neumann,
Prof. Dr. A. Brꢀckner, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse an der Universitꢁt Rostock e.V.
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
Dr. C. Taeschler
Lonza Ltd
Rottenstrasse 6, 3930 Visp (Switzerland)
[**] This research was funded Lonza Ltd. We thank Dr. C. Fischer, S.
Buchholz, and S. Schareina for technical and analytical support.
Supporting information for this article is available on the WWW
Scheme 1. Transition-metal-catalyzed perfluoroalkylation of arenes and
heteroarenes. binap=2,2’-bis(diphenylphosphanyl)-1,1’-binaphthyl.
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!