A novel method for the synthesis of aryl sulfones

Article abstract of DOI:10.1016/S0040-4039(01)00164-2

New sulfones were produced from aryl trifluoromethyl sulfones and Grignard reagents in good to high yields. The advantage of this transformation over a previous method by which sulfones were prepared from sulfonyl fluorides and organometallic reagents is discussed.

Full text of DOI:10.1016/S0040-4039(01)00164-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2281–2283
A novel method for the synthesis of aryl sulfones
Ruo W. Steensma,* Sharen Galabi,† Jayaram R. Tagat and Stuart W. McCombie
Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Received 5 January 2001; revised 19 January 2001; accepted 22 January 2001
Abstract—New sulfones were produced from aryl trifluoromethyl sulfones and Grignard reagents in good to high yields. The
advantage of this transformation over a previous method by which sulfones were prepared from sulfonyl fluorides and
organometallic reagents is discussed. © 2001 Published by Elsevier Science Ltd.
Sulfones, by virtue of their diverse chemistry, are valu-
able intermediates in organic transformations.1 Most
uses of sulfones involve sulfonylcarbanions, which react
with a wide range of electrophiles to produce new
sulfones that may be further transformed to olefins by
(1)
reduction, elimination or cyclization by a sulfur dioxide
Trifluoromethylsulfonylbenzene6 when treated with var-
extrusion process. Vinyl sulfones are excellent acceptors
ious Grignard reagents 2, either at room temperature or
in conjugate addition reactions and participate in
at reflux in tetrahydrofuran (THF), afforded sulfones 3
cycloaddition processes. In addition, alkyl- or aryl-sul-
in good yields. Examples are shown in Table 1. In most
fonyl groups can act as leaving groups under promo-
cases, the reaction was completed in about 1 hour at
tion by transition metals or Lewis acids.
room temperature. An aqueous ammonium chloride
quench, followed by extractive work-up, afforded sul-
fones 3 and, in many cases, no further purification was
needed.
Although sulfones are commonly obtained by oxidation
of the corresponding sulfides,1c,2–5 preparative methods
that involve the direct formation of the CꢀSO2 bond
are also valuable. These methods include nucleophilic
In general, primary saturated and allylic Grignards
displacements by a sulfinic acid salt,1e,2,4 Friedel–Crafts
(entries a–d) were quite suitable for this reaction. The
reactions of sulfonyl halides with activated aromatic
compounds,6 and reactions of sulfonyl fluorides with
organolithium species or Grignard reagents.7–10
Although the latter process is useful for the synthesis of
diaryl sulfones, when an aliphatic organometallic spe-
cies bearing an alpha proton is treated with a sulfonyl
fluoride, 1,1-disulfones tend to arise through further
deprotonation and sulfonylation of the initial
product.7,10 In fact, this can be the dominant process,
even with Grignard reagents. In this paper, we present
an alternative to sulfonyl fluorides that overcomes this
limitation.
yields from these reactions ranged from 56 to 83%.
Secondary Grignards (entries e and f) also reacted
satisfactorily, although elevated temperature was
needed in the case of isopropyl magnesium chloride.
tert-Butyl magnesium chloride did not react with tri-
fluoromethylsulfonylbenzene even after reflux in THF
overnight. Treatment of trifluoromethylsulfonylbenzene
with aryl Grignards (entries g and h) also produced the
corresponding diaryl sulfones in good yields. With vinyl
magnesium bromide, consumption of trifluoromethyl-
sulfonylbenzene without formation of the desired sul-
fone was observed at various temperatures. para-
Substituted phenyl trifluoromethyl sulfones (entries i–k)
were also suitable for this reaction.
The general process is shown in Eq. (1) in which an aryl
trifluoromethyl sulfone (aryl triflone) reacts with a
Grignard reagent to produce a new sulfone.
No 1,1-disulfones were observed from the reactions of
triflones with aliphatic Grignard species bearing alpha
protons. Although products 3 were undoubtedly metal-
lated under the reaction conditions,7,10 the resulting
* Corresponding author. Tel.: (908)740-5769; fax: (908)740-7441;
e-mail: ruo.steensma@spcorp.com
Summer intern from Rutgers University, New Brunswick, NJ, USA.
†
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00164-2

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R. W. Steensma et al. / Tetrahedron Letters 42 (2001) 2281–2283
Table 1.
Experimental procedure: To a solution of triflone 1 (1 mmol) in anhydrous THF (2 mL) was added Grignard reagent 2 (5 mmol) in THF or
diethyl ether at 0°C and the mixture stirred at the temperature and for the time specified in Table 1. The reaction was quenched with ice-cold
saturated ammonium chloride and the resulting aqueous mixture extracted with ethyl acetate (3×). The organic portions were combined, washed
with saturated sodium bicarbonate and brine, dried over sodium sulfate, filtered, and concentrated to give sulfone 3. Silica gel column
chromatography was applied, when needed.
species were not sulfonylated by aryl triflone, in con-
trast to their facile sulfonylation by aryl sulfonyl
fluoride.
References
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In addition, trifluoromethylsulfonylbenzene also
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yield. The reaction was conducted at −78°C for 30
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In summary, we have presented a new and effective
procedure for the preparation of aryl–alkyl and diaryl
sulfones. This method should serve as a useful addi-
tion to the existing methods for the synthesis of sul-
fones.

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