Mild and solvent-free alkynylation of ketones on the KF/alumina

Article abstract of DOI:10.1081/SCC-200054195

The solvent-free alkynylation of various ketones on the surface of KF/alumina under mild conditions is described. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200054195

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Mild and Solvent‐Free Alkynylation of
Ketones on the KF/Alumina
Ali Sharifi a , Mojtaba Mirzaei a & M. Reza Naimi‐Jamal a
a Chemistry & Chemical Engineering Research Center of Iran , Tehran, Iran
Published online: 16 Aug 2006.
To cite this article: Ali Sharifi , Mojtaba Mirzaei & M. Reza Naimi‐Jamal (2005) Mild and Solvent‐Free
Alkynylation of Ketones on the KF/Alumina, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:8, 1039-1044, DOI: 10.1081/SCC-200054195
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Synthetic Communicationsw, 35: 1039–1044, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054195
Mild and Solvent-Free Alkynylation of
Ketones on the KF/Alumina
Ali Sharifi, Mojtaba Mirzaei, and M. Reza Naimi-Jamal
Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran
Abstract: The solvent-free alkynylation of various ketones on the surface of
KF/alumina under mild conditions is described.
Keywords: Alkynes, alkynylation, ketones, KF/alumina, solvent-free
INTRODUCTION
Carbon–carbon bond formations are among the most important reactions in
organic synthesis.[1] One significant example is alkynylation of carbonyl
compounds for the preparation of propargylic alcohols. The traditional
approach to these reactions involves the addition of alkynylide anions to
carbonyl compounds. This process requires the conversion of alkynes to
corresponding alkynylide anions using 1 equiv. of a strong air-sensitive
base such as Grignard reagent,[2] alkyl lithium,[3] or sodium amide[4] in an
anhydrous solvent. Adding the carbonyl compound gradually to this mixture
prevents the competitive aldol reaction. More recent methods, making use
of catalytic amounts of bases such as t-BuOK,[5] cesium hydroxide,[6] zinc
alkynylides,[7] and quaternary ammonium hydroxide[8] are more favorable.
However, these reactions suffer from the lack of generality and require the
use of a solvent. Replacement of the organic solvents with ionic liquids,[9]
Received in Poland October 25, 2004
Address correspondence to Ali Sharifi, Chemistry & Chemical Engineering
Research Center of Iran, P.O. Box 14335-186, Tehran, Iran. Tel.: þ98-21-8036144;
Fax: þ98-21-8037185; E-mail: sharifi@ccerci.ac.ir; M. Reza Naimi-Jamal, Institut
¨
fu¨r Reine und Angew. Chemie, Universitat Oldenburg, Oldenburg, Postfach 2503,
D-26111 Oldenburg, Germany (current address). E-mail: naimi@uni.oldenburg.de

1040
A. Sharifi, M. Mirzaei, and M. R. Naimi-Jamal
supercritical CO2,[10] water,[11] or an adsorbent[12] seems to be more economi-
cal and ecological, and is garnering special interest. Recently, Miyamoto et al.
have reported that the addition of ethynylbenzene to ketones using potassium
t-butoxide or potassium hydroxide proceeds efficiently in the absence of a
solvent.[13] However, the generality of this method has yet to be investigated
for aliphatic acetylenes.
Earlier studies have revealed that potassium fluoride (KF), either alone or
in the form of an adsorbed reagent, can be employed as a mild, effective, and
nonnucleophilic base in organic reactions. In 1979, Yamawaki and Ando
introduced KF/alumina as a useful, versatile reagent in alkylation
reactions.[14] So far, the usefulness of this reagent has been widely investi-
gated in many C–O, C–N, and C–C bond formation reactions.[15] With our
continuing interest in developing practical, solvent-free reactions in
mind,[16] we decided to investigate this reagent. We now report the reaction
of terminal alkynes with ketones at room temperature using KF/alumina.
RESULTS AND DISCUSSION
This reaction of terminal alkynes with ketones proceeds on the surface
of KF/alumina without solvent in up to 95% yield (Scheme 1). The results
are summarized in Table 1. The solvent-free reaction appears to be more
efficient than the solution phase reaction. For example, phenyl acetylene 1a
reacts with cyclohexanone 2h on the surface of KF/alumina at room temp-
erature to give 95% yield of the corresponding alcohol (Table 1, entry 8),
whereas for the same substrates in DMSO using KOtBu as a base, 83%
yield has been reported.[13] The reaction of less acidic acetylenes fails
when employing these conditions. For example, addition of 1-hexyne and
Scheme 1.

Alkynylation of Ketones on KF/Alumina
1041
Table 1. Solvent-free alkynylation of ketones on the surface of KF/alumina
Entry
Alkyne
Ketone
Producta
Time/h (temp)
Yield (%)b
1
2
3
4
1a
1a
1a
1a
2a
2b
2c
2d
3a[8]
3b[13]
3c[8]
3d[8]
20 (rt)
20 (rt)
90
95
90
42
90
32
95
46
30
93
95
40
70
90
95
20
20 (rt)
15 (rt)
15 (608C)
17 (rt)
5
1a
2e
3e[13]
15 (608C)
17 (rt)
17 (rt)
6
7
1a
1a
2f
2g
3f[3a]
3g[20]
15 (608C)
17 (rt)
20 (rt)
8
9
1a
1a
2h
2i
3h[13]
3i[13]
40 (rt)
10
11
12
1b
1b
1b
2h
2b
2a
3j[19]
3k[19]
3l[19]
20 (608C)
20 (608C)
5 (rt)
17 (rt)
20 (rt)
70
c
13
14
15
16
1c
1d
1e
1f
2h
2h
2h
2h
3m
3n
3o
c
20 (rt)
20 (608C)
20 (608C)
92
90
3p
aMp and/or spectral data (IR, 1H-NMR and 13C-NMR) of known compounds (3a–l)
were compared with given references.
bIsolated yields.
cNo reaction occurred.
1-heptyne to the cyclohexanone does not occur after 20 h at room temperature
(Table 1, entries 13, 14).
The method is also suitable for functionalized acetylenes such as
propargyl ethers 1b and 1e–f. They react with ketones to give the correspond-
ing tertiary alcohols with moderate to high yields. These reactions are more
efficient at higher temperatures (Table 1, entries 10, 15, 16). Raising the
reaction temperature considerably affects the reaction rate and yield. For
example, the addition of phenyl acetylene 1a to the ketone 2g results in
30% and 93% yields of the product 3g, at room temperature and 608C, respect-
ively (Table 1, entry 7).
Using unsupported KF instead of KF/alumina dramatically decreases the
reaction yields. The reason for this change might be explained by the lower
basicity of unsupported KF compared with KF/alumina.[17] According to
Ando,[17b] the basicity of KF/alumina not only results from the presence of
active F2 (as in KF itself), but also from generated OH2 and Al–OH.

1042
A. Sharifi, M. Mirzaei, and M. R. Naimi-Jamal
In summary, we report here that KF/alumina is a very mild and efficient
catalyst to promote the addition of primary alkynes to ketones, in an environ-
mentally friendly reaction, without need of any reaction solvent and at room
temperature.
EXPERIMENTAL
Mps were determined on a hot stage or oil-bath apparatus without correction.
1H-NMR (80 MHz or 300 MHz) and 13C-NMR (75 MHz) spectra were
recorded on a Bruker 80 MHz or Bruker WP 300 MHz in CDCl3 using TMS
as internal standard. HRMS were obtained on a Finnigan MAT system
MAT 212.
Preparation of KF/Alumina[18]
Neutral alumina (60–80 mesh, 30 g) in water (150 ml) is added to a stirred
solution of potassium fluoride (20 g) in water (150 ml). After 30 min the
water is evaporated in a rotary evaporator at ꢀ608C. When most of the
water has been removed, the remaining mixture is heated to 140–1508C
and maintained at that temperature under vacuum (5 mmHg) for 6 h to give
50 g of KF/alumina reagent.
General Procedure for the Preparation of Tertiary Alcohols from
Alkynes and Ketones
Alkyne (1 mmol), ketone (1.2 mmol), and KF/alumina (1 g) were mixed in a
25-mL flask at room or mentioned temperature. The progress of reaction was
monitored by GC. After the given time, the reaction mixture was washed with
petrol and filtered, and the solvent was evaporated on the rotavapour. The
residue was purified with the bulb-to-bulb distillation technique or with a
short silica-gel column (eluent: light petroleum ether/ethyl acetate, 20:1).
3o. Colorless oil, IR (KBr, n, cm21): 3200–3500, 3020, 2932, 2856,
1
1256, 1215, 1130, 801. H-NMR (CDCl3): d ¼ 1.41–1.84 (m, 10H), 2.15
(s, 3H), 2.19 (s, 3H), 2.30 (s, 1H), 4.83 (s, 2H), 6.60–6.80 (m, 3Harom).
13C-NMR (CDCl3): d ¼ 15.85, 20.14, 22.88 (2C), 24.90, 39.47 (2C), 56.47,
58.50, 78.50, 91.34, 112.38, 126.63, 128.59, 130.63, 131.35, 154.93. MS
(EI): m/z ¼ 55 (46), 77 (38), 91 (40), 107 (42), 122 (100%), 136 (20), 160
(20), 258 (33) [Mþ]. HRMS (EI): m/z calcd. for C17H22O2: 258.1620;
found: 258.1620.
3p. Colorless oil, IR (KBr, n, cm21): 3200–3500, 3055, 2925, 2858,
1580, 1504, 1266, 1228, 1173, 1097, 1018, 791. 1H-NMR (CDCl3):

Alkynylation of Ketones on KF/Alumina
1043
d ¼ 1.43–1.75 (m, 10H), 2.10 (s, 1H), 4.86 (s, 2H), 6.80 (m, 1Harom), 7.30–
7.50 (m, 4Harom), 7.70–7.80 (m, 1Harom), 8.20–8.40 (m, 1Harom). 13C-NMR
(CDCl3): d ¼ 22.95 (2C), 24.90, 39.52 (2C), 56.20, 68.32, 78.91, 91.36,
105.75, 120.85, 121.91, 124.80, 125.09, 125.39, 126.22, 127.25, 134.12,
153.48. MS (EI): m/z ¼ 41 (38), 55 (35), 115 (28), 152 (88), 171 (62), 181
(100), 209 (53), 233 (42), 262 (22), 280 (93) [Mþ]. HRMS (EI): m/z calcd.
for C19H20O2: 280.1463; found: 280.1464.
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