TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3585–3587
Mild conversion of electron deficient aryl fluorides to phenols
using 2-(methylsulfonyl)ethanol
John F. Rogers and Daniel M. Green*
Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Received 10 January 2002; revised 11 March 2002; accepted 19 March 2002
Abstract—Useful yields are achieved in the synthesis of phenols from aryl fluorides via a mild one-pot procedure using
commercially available 2-(methylsulfonyl)ethanol. Examples and representative yields are shown. © 2002 Elsevier Science Ltd. All
rights reserved.
Phenols are widespread as intermediates and targets in
synthetic organic chemistry. Unfortunately direct synthe-
sis of the phenol moiety is limited. Most synthetic routes
utilize ether based protecting groups, which are later
unmasked to the phenol.1 Alternatively, anilines can be
diazotized and then hydrolyzed to yield phenols, how-
ever, this chemistry requires drastic oxidative and ther-
mal conditions.2 Other rearrangements and oxygen
insertions have been reported in the literature but are too
narrow in scope to have much synthetic utility.3
We now wish to report a mild, one-pot procedure for
converting electron deficient aryl fluorides to phenols at
room temperature by way of a nucleophilic aromatic
substitution reaction. This reaction requires only com-
mercially available 2-(methylsulfonyl)ethanol and
sodium hydride. We have found that aryl fluorides
containing a variety of common ortho and para electron
withdrawing functional groups can produce high yields
of products after purification by simple silica gel chro-
matography.6 The yields correspond well to the degree
of electron withdrawing character of the ring, and the
amount of steric hindrance seen by the approaching
nucleophile.
Due to their wide commercial availability and/or their
easy preparation, aryl halides are ideal starting materials
for phenol synthesis using nucleophilic aromatic substi-
tution. Traditionally, this involved the reaction of aryl
halides with alkoxides under strongly basic conditions
and with prolonged heating. Recently, Hartwig and
Buchwald have reported the intermolecular conversion
of aryl bromides and chlorides to phenols via a silyl or
tert-butyl ether which is easily cleaved.4,5 This involves
the use of nickel or palladium catalysts and expensive
phosphine reagents. Additionally the reactions were run
at elevated temperatures for several hours.
In an extension of our work to generate functionalized
4-ether derivatives of methyl 3-(morpholino-4-sulfonyl)
benzoate from aromatic fluoride 1 via a nucleophilic
aromatic displacement mechanism, we reacted 2-
(methylsulfonyl)ethanol with 1 and sodium hydride in
DMF. This reaction failed to provide the desired
product but instead gave phenol 3 in good yield (see
Fig. 1).
Figure 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
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