Phosphazene bases for the preparation of biaryl thioethers from aryl iodides and arenethiols

Article abstract of DOI:10.1016/S0040-4039(99)02269-8

In the presence of phosphazene P₂-Et base as well as 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU) the coupling of aryl iodides with arenethiois only requires catalytic amounts of CuBr. Under these conditions the reaction can be performed in refluxing toluene to give biaryl thioethers in excellent yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02269-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1283–1286
Phosphazene bases for the preparation of biaryl thioethers from
aryl iodides and arenethiols
Claudio Palomo,∗ Mikel Oiarbide, Rosa López and Enrique Gómez-Bengoa
Dpto. de Química Orgánica, Facultad de Química, Universidad del País Vasco, Apartado: 1072, 20080-San Sebastián, Spain
Received 27 October 1999; accepted 7 December 1999
Abstract
In the presence of phosphazene P2-Et base as well as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) the coupling of
aryl iodides with arenethiols only requires catalytic amounts of CuBr. Under these conditions the reaction can be
performed in refluxing toluene to give biaryl thioethers in excellent yields. © 2000 Elsevier Science Ltd. All rights
reserved.
The reaction of aryl halides with sodium or potassium arenethiolates, promoted by copper additives,
results in the formation of diaryl sulfides.1 This reaction, which is analogous to the Ullmann biaryl ether
synthesis,1,2 frequently requires temperatures up to 200–300°C, long reaction times and strong polar and
often toxic solvents such as quinoline, hexamethylphosphoric triamide, and N,N-dimethylacetamide.3 In
addition to these requirements, the main problem associated with this reaction is the formation of isomer-
ic diaryl compounds via substitution through an elimination–addition mechanism.4 As a consequence,
most investigations on this subject have dealt with the use of stoichiometric amounts of copper additives
to facilitate the coupling reaction.1,2 However, under these conditions the reductive homocoupling of
the aryl halide component5 which, for instance, occurs easily when hindered nucleophiles are involved,
constitutes another inherent problem of this reaction. Despite considerable success to date,6 these
efforts have identified the same solution to these problems, namely, the preactivation of the aryl halide
component through, for instance, the use of transition metals,7,8 or by placing an electron withdrawing
substituent ortho or para to the leaving group.9
Scheme 1.
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02269-8
tetl 16197

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Table 1
The Ullmann type biaryl thioether synthesis promoted by P2-Et base in combination with CuBra
Recently, we have reported a procedure for the Ullmann biaryl ether synthesis10 that combines the
concept of the ‘naked anion’ phenomenon11 with the use of Schwesinger’s phosphazene bases.12 Now
we have found that these bases,13 Scheme 1, in combination with a catalytic amount of Cu(I) salts, are
extremely effective in promoting reactions of aryl halides with a variety of thiophenols. As shown in Table
1, the method is suitable for electron neutral (entries 1–6), electron rich (entries 7, 8) and electron poor
(entry 9) aryl iodides with a variety of thiophenols. Aryl chlorides, on the other hand, did not react under
these conditions with thiophenols to form biaryl thioethers. Accordingly, p-chloroiodobenzene (entry
9) reacted chemoselectively to afford 3i. By the same token, it was possible to perform chemoselective

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couplings between chlorothiophenols and aryl iodides (entries 1, 5, and 7) without any self-condensation.
Aryl bromides, with the exception of those bearing electron withdrawing groups (entries 10, 11), did
not react with thiophenols to give the expected products. This method is particularly suitable for aryl
iodides and ortho-substituted thiophenols. For example, 2,6-dichlorothiophenol (entry 5) provided the
corresponding biaryl thioether in good yield, and even the o-isopropylthiophenol (entry 8) coupled with
p-methoxyiodobenzene to give the desired biaryl thioether in 60% yield.
We have systematically employed the P2-Et base, but P1-But base was also effective. Most notably,
in the presence of any of these bases and a catalytic amount of CuBr, the reaction can be carried out
in toluene as solvent thus avoiding the use of high-boiling or water soluble solvents.14 Other common
15
bases, such as triethylamine, N,N-dimethylaminopyridine, diisopropylethylamine, and Cs2CO3 failed
to produce the coupling product. However, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)16 afforded similar
results to those attained with P2-Et base, albeit with somewhat longer reaction times. On the other hand,
copper salts such as CuCl, CuI and Cu(OTf)2–benzene, were also effective, but in their absence no
coupling products were formed.
Next, we have evaluated the reaction selectivity when both a phenol and a thiophenol group are
present simultaneously under the conditions employed. In this respect, we knew, from the results in our
previous report,10 that the P4-But-assisted coupling of aryl iodides with phenols requires stoichiometric
amounts of CuBr. Therefore, we predicted a higher reactivity for thiophenols as compared to phenols.
Indeed, in experiments carried out with a catalytic amount of CuBr, the expected biarylthioethers were
formed in a completely chemoselective manner in isolated yields of 63% and 65% (entries 12 and 13).
The same selectivity level and improved yields (81% and 95%) were observed for the latter reactions
when stoichiometric CuBr was employed. In a similar way, the coupling of hydroxybenzenethiol with
p-methyliodobenzene (entry 14) led to the corresponding biaryl thioether exclusively.
From the examples in Table 1, it also seems that the reaction conditions used are compatible with
various functional groups. Nevertheless, neither the amino nor the amido functionalities were inert under
these reaction conditions. For example, whereas the reaction of 4a with p-methylbenzenethiol, Scheme
2, hardly proceeded to give 5a, 4b and 4c led to 5b and 5c in 50% and 52% yields, respectively.17
Although moderate yields are attained, it should be noted that, once again, other common bases, i.e.
triethylamine, tributylamine and diisopropylethylamine, were completely ineffective in promoting this
coupling reaction.
Scheme 2.
In summary, the present work shows a new application of the Schwesinger phosphazene bases for an
efficient Cu(I) catalyzed conversion of aryl iodides to biarylthioethers.

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Acknowledgements
This work was financially supported by Universidad del País Vasco (Project 170.215-EB 172/97). A
grant to R.L. from Gobierno Vasco is also acknowledged.
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