Rapid, one-pot conversion of aryl fluorides into phenols with 2-butyn-1-ol and potassium t-butoxide in DMSO

Article abstract of DOI:10.1081/SCC-120003637

Aryl fluorides react rapidly with 2-butyn-1-ol and potassium t-butoxide in DMSO under microwave irradiation to give propargylic ethers. These ethers isomerize in situ to the corresponding allenyl ethers, which hydrolyze on work-up to give phenols in good yield.

Full text of DOI:10.1081/SCC-120003637

This article was downloaded by: [University of California, San Francisco]
On: 26 September 2014, At: 06:40
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
RAPID, ONE-POT CONVERSION OF ARYL FLUORIDES
INTO PHENOLS WITH 2-BUTYN-1-OL AND POTASSIUM t-
BUTOXIDE IN DMSO
Jeremy I. Levin a & Mila T. Du a
a Wyeth-Ayerst Research , 401 N. Middletown Rd., Pearl River, NY, 10965, U.S.A.
Published online: 17 Aug 2006.
To cite this article: Jeremy I. Levin & Mila T. Du (2002) RAPID, ONE-POT CONVERSION OF ARYL FLUORIDES INTO PHENOLS
WITH 2-BUTYN-1-OL AND POTASSIUM t-BUTOXIDE IN DMSO, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:9, 1401-1406, DOI: 10.1081/SCC-120003637
To link to this article: http://dx.doi.org/10.1081/SCC-120003637
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 32(9), 1401–1406 (2002)
RAPID, ONE-POT CONVERSION OF
ARYL FLUORIDES INTO PHENOLS WITH
2-BUTYN-1-OL AND POTASSIUM
t-BUTOXIDE IN DMSO
*
Jeremy I. Levin and Mila T. Du
Wyeth-Ayerst Research, 401 N. Middletown Rd.,
Pearl River, NY 10965
ABSTRACT
Aryl fluorides react rapidly with 2-butyn-1-ol and potassium
t-butoxide in DMSO under microwave irradiation to give
propargylic ethers. These ethers isomerize in situ to the
corresponding allenyl ethers, which hydrolyze on work-up
to give phenols in good yield.
The conversion of an aryl fluoride into the corresponding phenol is a
useful synthetic transformation that is usually accomplished in two steps.
Among the most common methods is the displacement of the aryl fluoride
with an alkoxide, followed by the cleavage of the resulting aryl alkyl ether to
provide the desired phenol (Scheme 1).1
Procedures for the direct synthesis of phenols from aryl fluorides, that
do not require a separate deprotection step, are relatively few. These include
the use of sodium trimethylsilanoate,2 in which the trimethylsilyl group is
*Corresponding author.
1401
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1402
LEVIN AND DU
Scheme 1.
removed in situ by fluoride ion generated during the ipso substitution of the
aryl fluoride, as well as phase transfer catalyzed nucleophilic aromatic sub-
stitution by hydroxide ion.3 We now report that 2-butyn-1-ol can function
as a hydroxyl synthon by reacting in one pot with aryl fluorides via
consecutive SNAr displacement, in situ isomerization to the allenyl ether
and subsequent hydrolysis, to afford phenols rapidly and in good yield
(Scheme 2).
Scheme 2.
The displacement of aryl fluorides with propargylic alcohols and 3–5
equivalents of potassium carbonate in DMF is known.4 These rꢀeactions
require from 0.75to 31 h and temperatures ranging from 20–105 C. The
isomerization of propargylic ethers into allenyl ethers using a variety of
bases has also been reported.5,6 In addition, the deprotection of alkyl allenyl
ethers to the analogous alcohols using mercury salts, aqueous acid, or
catalytic OsO4 has been demonstrated.6 To our knowledge, the combination

CONVERSION OF ARYL FLUORIDES
1403
of these three reactions into a single convenient synthetic procedure has not
been shown.
The possibility of converting an aryl fluoride into a phenol was dis-
covered during the attempted preparation of butynyl ether 4a. Reaction of
fluoroaryl sulfonamide 3 with five equivalents of 2-butyn-1-ol and sodium
hydride in DMF at 80ꢀC did not provide the desired ether 4a, but instead
afforded the phenol carboxylic acid 4b in 85% yield.
Scheme 3.
In an effort to optimize reaction conditions we used a procedure
similar to one which had been shown to isomerize prop-2-ynyl ethers into
prop-1-ynyl ethers.5 Thus, when sulfonamide 1a was treated with
2-butyn-1-ol and potassium tert-butoxide in DMSO, under microwave
irradiation, phenol 2a was obtained in 85% yield after a mild acid work-
up. In contrast to results described by Moghaddam and Emami5 the
allenyl ether was never observed, even after a neutral aqueous work-up.
When the same reaction conditions were applied to the reaction of
propargyl alcohol with sulfonamide 1a, phenol 2a was obtained in slightly
lower yield (59%), and again no allenyl ether was isolated. When sodium
hydroxide was used as the nucleophile under the same reaction conditions,
only starting material was recovered. The application of this methodology
to a variety of ortho- and para-substituted aryl fluorides is shown in the
Table.
Examples 1c and 1h required an excess of potassium tert-butoxide,
relative to the 2-butyn-1-ol, for optimal yields. When equimolar amounts
of 2-butyn-1-ol and base were used for these examples, 5–15% of the
intermediate butynyl ethers (see Scheme 2) were obtained along with the
desired phenols. The 4-fluorobenzoate, 1g, also required an excess of
potassium tert-butoxide. In this case the main side product was 4-
fluorobenzoic acid. Under the same reaction conditions 4-fluorobenzoic
acid was unreactive. The poorest conversions were seen with 4-fluoro-

1404
LEVIN AND DU
Table.
Equivalents
2-Butyn-1-ol
Equivalents
KOtBu
Yield
(%)
Reactant
Product
2
2
1
2
2
2
2
2
2
2
85
78
72
90
73
2
2
2
4
26
41
2
4
78
benzaldehyde (1f), as expected, and 4-fluorobenzotrifluoride. The latter gave
no appreciable amount of the desired phenol under a variety of
conditions. Finally, it should be noted that the yield for the conversion of
1,4-difluoroanthracene-9,10-dione 1h into 1,4-dihydroxyanthracene-9,10-

CONVERSION OF ARYL FLUORIDES
1405
dione (2h) is equivalent to the yield obtained from the Krapcho procedure2 on
the same substrate using sodium trimethylsilanoate.
GENERAL EXPERIMENTAL PROCEDURE
All reactions were carried out in glass vials using a CEM Corporation
Mars 5commercial microwave at a maximum of 648 Watts.
A mixture of aryl fluoride (0.4 mmol), 2-butyn-1-ol (0.8 mmol) and
potassium tert-butoxide (0.8 mmol) in 0.4 ml of DMSO was subjected to
microwave irradiation according to the following program. The reaction
mixtures were heated to 125ꢀC in 1 min from room temperature and then
held at 125ꢀC for 2 min. The reaction was then cooled to room temperature
and diluted with water and then acidified to pH 3–4. The resulting mixture
was extracted with ethyl acetate and the combined organics were washed
with water and brine, dried over magnesium sulfate, filtered and concen-
trated in vacuo. The residue was purified by preparative TLC or column
chromatography on silica gel to provide the pure phenol.
2a: White solid, m.p. 90–92ꢀC; H NMR (300 MHz, CDCl3) d 1.1 (t,
1
6H, J ¼ 7.0 Hz), 3.2 (q, 4H), 5.7 (br, OH), 6.9 (d, 2H, J ¼ 8.7 Hz), 7.7 (d, 2H,
J ¼ 8.7 Hz); Electrospray MS: 228 (M-H)À. Anal. calcd for C10H15NO3S: C,
52.38; H, 6.59; N, 6.11. Found: C, 52.41; H, 6.46; N, 6.03.
2b: Pale orange solid; m.p. 112–114ꢀC (lit. 113–115ꢀC); 1H NMR
(300 MHz, CDCl3) d 5.5 (br, OH), 6.9 (d, 2H, J ¼ 9 Hz), 8.2 (d, 2H,
J ¼ 9 Hz); Electrospray MS: 138 (M-H)À.
2c: Yellow solid; m.p. 45–46ꢀC (lit. 44–45ꢀC); H NMR (300 MHz,
1
CDCl3) d 7.0 (m, 1H), 7.2 (d, 1H, J ¼ 9.7 Hz), 7.6 (m, 1H), 8.1 (d, 1H,
J ¼ 8.5Hz), 10.6 (s, OH); Electrospray MS: 138 (M-H) À.
2d: White solid; m.p. 112–113ꢀC (lit. 110–113ꢀC); 1H NMR (300 MHz,
CDCl3) d 5.4 (s, OH), 6.9 (d, 2H, J ¼ 8.8 Hz), 7.6 (d, 2H, J ¼ 8.8 Hz);
Electrospray MS: 118 (M-H)À.
2e: Beige solid; m.p. 93–95ꢀC (lit. 92–95ꢀC); 1H NMR (300 MHz,
CDCl3) d 5.7 (br, OH), 7.0 (m, 2H), 7.5 (m, 2H); Electrospray MS: 118 (M-
H)À.
2f: Pale yellow solid; m.p. 114–115ꢀC (lit. 117–119ꢀC); 1H NMR
(300 MHz, CDCl3) d 5.7 (br, OH), 7.0 (d, 2H, J ¼ 8.6 Hz), 7.8 (d, 2H,
J ¼ 8.6 Hz), 9.9 (s, 1H); Electrospray MS: 121 (M-H)À.
2g: White solid; m.p. 212–214ꢀC (lit. 215–217ꢀC); 1H NMR (300 MHz,
CDCl3) d 6.8 (d, 2H, J ¼ 8.7 Hz), 7.9 (d, 2H, J ¼ 8.7 Hz); Electrospray MS:
137 (M-H)À.
2h: Red–orange solid; m.p. 192–194ꢀC (lit. 198–199ꢀC); 1H NMR
(300 MHz, CDCl3) d 7.3 (s, 2H), 7.9 (m, 2H), 8.4 (m, 2H), 12.9 (s, 2OH);

1406
LEVIN AND DU
EI MS: 240 (Mþ). Anal. calcd for C14H8O4: C, 70.00; H, 3.36. Found: C,
69.42; H, 3.24.
REFERENCES
1. (a) Preston, P.N.; Winick, T.J. Chem. Soc. Perkin Trans. I 1983,
1439–1441; (b) Showalter, H.D.H.; Johnson, J.L.; Hoftiezer, J.M. J.
Heterocyclic Chem. 1986, 23(5), 1491–1501.
2. Krapcho, A.P.; Waterhouse, D. Synth. Commun. 1998, 28(18),
3415–3422.
3. Feldman, D.; Segal-Lew, D.; Rabinovitz, M. J. Org. Chem. 1991, 56(26),
7350–7354.
4. Raeppel, S.; Raeppel, F.; Suffert, J. Synlett 1998, 794–796.
5. Moghaddam, F.M.; Emami, R. Synth. Commun. 1997, 27(23),
4073–4077.
6. Mereyala, H.B.; Gurrala, S.R.; Mohan, S.K. Tetrahedron 1999, 55(37),
11331–11342.
Received in the USA May 14, 2001