Hydro-dediazoniation of diazonium salts using trichlorosilane: New cleavage conditions for the T1 traceless linker

Article abstract of DOI:10.1016/S0040-4039(00)00524-4

An efficient, selective cleavage of triazenes and in situ hydro- dediazoniation of the intermediately formed diazonium salts with trichlorosilane (HSiCl₃) in liquid as well on solid phase is reported. Starting from anilines, attachment to solid support and subsequent cleavage gives rise to the corresponding unsubstituted arenes. This cleavage reagent is compatible with various functionalities (esters, amides, nitro groups, halides, aliphatic double and triple bonds). (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00524-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3813–3816
Hydro-dediazoniation of diazonium salts using trichlorosilane:
1
new cleavage conditions for the T traceless linker
1
∗
Matthias Lormann, Stefan Dahmen and Stefan Bräse
RWTH Aachen, Institut für Organische Chemie, Professor-Pirlet-Straße 1, D-52074 Aachen, Germany
Received 19 January 2000; accepted 23 March 2000
Abstract
An efficient, selective cleavage of triazenes and in situ hydro-dediazoniation of the intermediately formed
diazonium salts with trichlorosilane (HSiCl3) in liquid as well on solid phase is reported. Starting from anilines,
attachment to solid support and subsequent cleavage gives rise to the corresponding unsubstituted arenes. This
cleavage reagent is compatible with various functionalities (esters, amides, nitro groups, halides, aliphatic double
and triple bonds). © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: deamination; diazo compounds; linker; solid-phase synthesis; triazenes.
2
The reduction of anilines to the corresponding unsubstituted arenes is a well-known process in organic
3
synthesis and has been widely used for the synthesis of various compounds. In general, an intermediate
diazonium salt is reduced using various reductants. Among the most successful examples are phosphinic
4
–6
7
acid derivatives, which have become the standard, and sodium borohydride. Various solvents such
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9
10
11
as methanol (with or without copper salts), ethanol, THF, or DMF are suitable hydrogen donors.
Some transition-metal catalysts or mediators (copper,12 iron,11 and rhodium salts) are also applicable.
However, most of the methods are not general and give only moderate yields especially for electron-rich
arenes. In particular, formation of haloarenes or phenol/phenolether as by-products has been observed.
Recently, we have demonstrated the use of triazenes as linker moieties in solid phase organic synthesis
to detach arenes in a traceless manner.13–15 The cleavage conditions used (THF, HCl, and ultrasound),
however, were not suitable for automation. In addition, we observed various amounts of polymeric by-
products due to ring opening of THF. Therefore, we looked for alternatives for this cleavage/reduction
protocol, which avoid the use of toxic materials, high-boiling reagents (bp >120°C) and complicated
work-up procedures. Although methanol or ethanol are in principle suitable reductants, we observed
various amounts of ether formation with less electron-poor arenes. Triethylsilane in dichloromethane is
a suitable reductant, however, in some cases, the formation of triethylsilylarenes was observed.16
∗
Corresponding author. Tel/fax: +(49) (0) 241/8888127; e-mail: braese@oc.rwth-aachen.de (S. Bräse)
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040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00524-4
tetl 16803

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814
Trichlorosilane is an economical, volatile reagent (bp 32°C) with selective reducing properties
1
7
18
(
e.g. phosphine oxides to phosphines, benzyl carbamate cleavage, and reductive enolization of α-
1
9
18
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20
chloroketones ), which does not attack ketones, triple bonds, and double bonds under metal-
free conditions and in the absence of radical initiators. Furthermore, the by-products after hydrolysis
(silicones) are readily removable. To best of our knowledge, the reduction of diazonium salts with this
reagent has not been reported before.
Therefore, the use of trichlorosilane in the reduction of diazonium salts 2 was examined. The latter
were readily prepared from the corresponding anilines (tBuONO, BF ·OEt , CH Cl ). Treatment of the
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2
2
2
crude salts 2 as a slurry with three equivalents of trichlorosilane in dichloromethane at room temperature,
addition of silica gel after 15 min to remove the excess of trichlorosilane, filtration, and evaporation of
the solvent gave rise to the arenes 3 in excellent yields.
Subsequently, the cleavage and reduction of a triazene in liquid phase was examined. The reaction
of the triazene 4c (Scheme 1) [mixture of 3-cyclohex-1-enyl and 4-cyclohex-1-enyl (ca. 70:30)] with
trichlorosilane in dichloromethane proceeds cleanly to give the required hydrocarbons 3c in excellent
purity (>95%) and the corresponding amines as the hydrochloride salts, which were removed by filtration.
Scheme 1.
1
3,14,21
The execution of the solid phase synthesis was accomplished using the T linker.
Starting from
1
2
2
benzylaminomethyl polystyrene (1–2% cross-linked with DVB, 100–200 mesh), the required diverse
arylresins 5 were prepared from substituted anilines in good yields. Modifications of the triazenes
Heck reaction1
3,21,23
(entries 3, 6, 7, 11) and acylation (entry 8)] were carried out to install various
[
functionalities. The cleavage of the resin in the presence of trichlorosilane was conducted as above.
Filtration and evaporation afforded the products 3 in 70 to 95% yield and over 90% purity without any
further purification (NMR-, GC, and GC–MS spectroscopy).24

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815
General procedure for the traceless cleavage of the T linker: A suspension of the resin (200 mg) in
1
dichloromethane was treated with 4 equiv. of trichlorosilane (Caution: corrosive and low boiling material)
and the mixture was stirred at 40°C (external) for 15 min or at room temperature for 60 min. After being
cooled to room temperature, silica gel (100 mg) was added, the mixture was filtered and the solvent was
removed (Table 1).
Table 1
Cleavage and reduction conducted with trichlorosilane
The compatibility with functional groups is in the expected range (Scheme 1). Alkenes, alkynes, tert-
butyl and other esters, nitro groups, and halides are tolerated. Both electron withdrawing and electron-
donor substituents can be present in the target molecule.
In conclusion, a novel technique for the hydro-dediazoniation of diazonium salts was developed, giving
rise to products in high yield and purity. The method was also successfully applied in the traceless
cleavage of the T triazene linker.
1
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (BR 1750/1) and the Fonds der
Chemischen Industrie (Liebig stipend to St. B.). The companies Bayer AG, BASF AG, Grünenthal
GmbH, and Calbiochem-Novabiochem AG have to be acknowledged for donations of chemicals. We
thank Prof. Dr. D. Enders for the support of our work, K. Hennig for technical assistance and C. Dinter
for some GC–MS measurements.

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