Preparation of some heterocyclic enones and ynones by isomerisation of the propargylic alcohols

Article abstract of DOI:10.3184/030823409X464467

The propargylic alcohols were synthesised by treatment of aldehydes with substituted acetylenes. The conversion of propargylic alcohols to propynones and propenones takes place with pyridine hydrochloride in methanol at room temperature. In presence of pyridinium triflate and p-toluenesulfonate the propynone was the only product isolated in the isomerisation of alcohol. The silylated propenone undergoes with cyclopentadiene a Diels-Alder cycloaddition to give ketone whose skeleton is related to that of quinine.

Full text of DOI:10.3184/030823409X464467

JOURNAL OF CHEMICAL RESEARCH 2009
JULY, 459-464
RESEARCH PAPER 459
Preparation of some heterocyclic enones and ynones by isomerisation of
the propargylic alcohols
Ramazan Erenler*a,b, Masaharu UnoC, Thirumani Venkateshwar Gouda and
Jean-Fran~ois Biellmanna
alnstitute of Chemistry, Academia Sinica, Nankang 115, Taipei, Taiwan
bDepartment of Chemistry, Faculty of Art and Science, Gaziosmanpasa University 60240 Tokat, Turkey
cGakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588, Japan
The propargylic alcohols were synthesised by treatment of aldehydes with substituted acetylenes. The conversion
of propargylic alcohols to propynones and propenones takes place with pyridine hydrochloride in methanol at room
temperature. In presence of pyridinium triflate and p-toluenesulfonate
the propynone was the only product isolated
in the isomerisation of alcohol. The silylated propenone undergoes with cyclopentadiene a Diels-Alder cycloaddition
to give ketone whose skeleton is related to that of quinine.
Keywords: isomerisation, propargylic alcohol, enone; ynone, heterocyclic
Thepyridinering plays a keyrole in severalbiologicalprocesses.1,2
The quinoline ring system is an important target in synthetic
chemistry. It is found in a large number of natural products,
many of which have important biological activities.3-7 In
addition, they are used as dyestuffs and photographic sensitisers.8
In a preliminary communication we reported the facile
isomerisation of heterocyclic propargylic alcohols to
propenones and propynones in the presence of pyridine
hydrochloride.9 We had shown that this isomerisation occurs
when the propargylic hydrogen is activated at C-2 and C-4 in
case of pyridine and that the ethylenic protons originated from
protons of the solvent. An enolic allene was postulated as an
intermediate and its protonation gives a (Z) enone subsequently
isomerised to the (E) form. Related isomerisations have been
reported on different systems under various conditions.10-20
We now report more examples of this isomerisation and the
results obtained with two other pyridinium salts as catalysts
and the Diels-Alder reaction of one of these enones whose
chemistry has not been explored.
We tried with the quinoline alcohol other pyridinium
salts: trifluoromethanesulfonate, p-toluensulfonate, and
compared the results with those obtained with pyridinium
hydrochloride. (Table 2). The ynone 6 was the only product
isolated in the presence of pyridinium triflate and pyridinium
toluenesulfonate. Enone 7 was found only in the presence
of pyridinium hydrochloride. The presence of air seemed
to increase the yield of the ynone, but the ynone was also
obtained under argon (Table 2). In addition to the ynone and
enone, coloured and polar material was obtained.
Concerning the mechanism of the conversion of the
propargylic alcohols, the protonation of the nitrogen is
an essential step. So the first step is the protonation at the
nitrogen to give the pyridinium or quinolinium cation.
Now the hydrogen at the alpha position is activated and is
abstracted by a base to give the anhydro base 8. This base 8
Results and discussions
We prepared in good yields the proparglic alcohols 3 from
aldehydes 1 and substituted acetylenes 2. These alcohols 3
except 3a, 3m and 3n are not too stable and their isomerisation
was carried out without delay. Table I shows the results
of the preparation of the propargylic alcohols 3 and their
isomerisation with pyridine hydrochloride catalyst to ynones
4 and enones 5. The structure of enone 5d was elucidated by
X-ray diffraction (Fig. I).
Fig. 1 ORTEPstructure of 5d.
Table 1 Preparation of propargylic alcohols (3) and their conversion to ynones (4) and enones (5)with pyridinium hydrochloride
Compound
3°
4 (ynone)
Yield/Yo
5 (enone)
Yield/Yo
R1
R2
Yield/Yo
Phenyl
100
83
82
90
96
79
83
80
74
88
97
a
b
C
d
e
f
g
h
i
Me3Si
Me3Si
Me
Phenyl
t-Butyl
Me3Si
Me
t-Butyl
Phenyl
Me3Si
Me3Si
H
4-Pyridyl
26
52
49
55
75
4-Pyridyl
15
4-Pyridyl
10
12
4-Pyridyl
4-Quinolyl
4-Quinolyl
4-Quinolyl
4-Quinolyl
2-Pyridyl
see Table 2
30
26
24
36
37 (E)-18(Z)
21
k
m
n
42
3-PyridyI21,22
3-PyridyI21,22
Stable
Stable
"Except for 3n prepared from 3m by removal of the trimethylsilyl group by TBAF.
* Correspondent.E-mail:reren1er@gop.edu.tr

460 JOURNAL OF CHEMICAL RESEARCH 2009
a
+
o~ ~I
H C = = C --R 2
1
2
4
5
3
Scheme
1
Reagents and conditions:
salts
(a) n-BuLi, THF, -78°C (b) C5H6NCI, MeOH.
Table
2
Conversion
of 3f using various pyridinium
and later the appearance of the (Z) enone is observed and its
transformation to the (E) enone and both hydrogens at the
ethylenic positions are exchanged with a deuteron as shown
by IH NMR and mass spectrometry. A related intramolecular
dismutation reaction has been observed in the reaction of
vinylmagnesium bromide with isonicotinaldehyde.28
-a TMS
!'"
HO
MeOH
The isomerisation of y-hydroxy-a,13-alkynoates 11 to
y-oxo-a,13-alkenoates with the organic base (DABCO) or
sodium bicarbonate in DMSO-water has been studied.29
The base removes the propargylic proton giving rise to a
cumulene 12 which is protonated by the conjugated acid to an
allenol 13 which in tum is protonated by an external proton.
The protonation occurs to give first the (Z) isomer 14 later
isomerised to the (E) isomer 15. The propargylic proton is
transferred to the vinylic position with little exchange and
the other proton originates from solvent. In the propargylic
alcohol, the ester group provides the acidity so that the proton
can be removed. In the propargylic alcohols in Table I, the
protonation at the nitrogen lowers the pKa of the proton so
that it can be removed by a base.
The easy preparation of heterocyclic enone induced us to
try the Diels-Alder reaction with cyclopentadiene to prepare
a cyclic system related to quinine. The Diels-Alder adduct
16 with cyclopentadiene was obtained at 120°C (neat) in a
yield of25%.
In boron trifluoride etherate at -78 °C in toluene,
no adduct was isolated. So, we turned to lithium chloride
as a catalyst and obtained in THF at 25°C the adduct 16 in a
yield of 50%.30 The endo cycloaddition product is obtained
as expected.31,32This has been ascertained by the structure
determination by X-ray diffraction (Fig. 2).
Atmosphere
Additive
6
7
Air
Ar
Air
Ar
Ar
Air
Ar
36%
32%
67%
49%
33%
40%
40%
CI
50%
may be protonated at several positions: I, 2 and 3. At position
I to give back the pyridinium salt, resulting in the exchange of
this hydrogen. With the protonation at position 2, the terminal
carbon of the triple bond, the pyridinium allenol 9 is obtained.
The deprotonation of the nitrogen and the ketonisation of the
allenol gives at first the (Z) isomer of ketone later isomerised
to the (E) isomer. The kinetic product of the protonation of the
allenol 9 to (Z) isomer of ketone is documented in the cases
where allenols are intermediates.23-27The protonation at C-3
(position 3) gives iminium salt 10 which could be involved in
the oxidation of the alcohol to the ynones. We have not tried to
isolate the reduced products resulting from this dismutation. If
we follow the reaction by NMR using Me02H, the exchange
of the alpha hydrogen of propargylic alcohol is observed
R
H
R
R
-
H
H
~
H+-l
~
(E)
5
--
2
--
h
N+
----
8
k
(Z) 5
R
~3
10

JOURNAL OF CHEMICAL RESEARCH 2009 461
H-OR
HO
HO
(
)
)
Ph
Ph
13
12
o
p~C 02M e-
15
14
o
~MS
Conditions
5f
These enones and ynones not previously prepared should open
a new strategy for the synthesis of some complex heterocyclic
systems such as alkaloids. They also could be the precursors
of synthetically and pharmaceutically
valuable compounds.
Fig.2
ORTEP structure of 16.
Experimental
General procedures
8.36 (d, J = 5.9 Hz, 2H). l3C NMR (100 MHz, CDCI3): 834.8,62.5,
78.8,82.8,121.6,149.0,151.1.
Ca1cd for C9H9NO: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.40; H,
Commercial reagents were purchased from standard chemical
suppliers and purified if needed. Solvents were purified and dried
by passing through activated aluminum oxide under argon pressure.
Flash column chromatography was carried out on Silica Gel 60 (230-
400 mesh, E. Merck). TLC was performed on pre-coated glass plates
of Silica Gel 60 F254 (0.25 mm, E. Merck); detection was done by
spraying with a solution of Ce(NH4h(N03)6, (NH4)6M07024, and
H2S04 in water or ninhydrin and acetic acid solution in n-butanol and
subsequent heating on a hot plate. Melting points were determined
with a Biichi B-540 apparatus and are uncorrected. IH and l3C NMR
spectra were recorded with Bruker AV400 and 500 MHz instruments.
Chemical shifts are in ppm from TMS as internal standard, generated
from the CDCI3. IR spectra were taken with a Perkin-Elmer Paragon
1000 FT-IR spectrometer. Elemental analysis was done with a Perkin-
Elmer 2400CHN instrument. Mass spectra were obtained with a FAB
JMS-700 double focusing mass spectrometer (JEOL, Tokyo, Japan).
MS (FAB+): mlz 148 (M + W). Anal.
6.12; N, 9.47%.
4-(1-Hydroxy-3-phenyl-2-propynyl)pyridine
(3d): Phenylacety1ene
(1.04 g) in THF (10 mL) was treated as for 3b with n-BuLi (7.0 mL)
and 4-pyridinecarboxaldehyde (1.0 g) in THF (5 mL) was added. The
product (1.75 g, 90%) was a liquid. UV (CH2CI2): Am" (e) 242 (5100),
309 (1300). IR (CH2CI2): 1042, 1243, 1376, 1461, 1733,2869,2926,
2960, 3583. IH NMR (500 MHz, CDCI3): 8 3.95 (brs, lH), 5.68 (s,
lH), 7.27 (m, 3H), 7.40 (m, 2H), 7.53 (d, J= 6.0 Hz, 2H), 8.55 (d,
J=6.0Hz2H).
13CNMR(125 MHz, CDCI3): 863.2, 86.7, 87.9,121.4,
121.6,128.2,128.6,131.7,146.2,149.4.
MS (FAB+):m/z201 [M+H]+.
Anal. Ca1cd for CI4HllNO (209.2): C, 80.36; H, 5.30; N, 6.69. Found:
C, 80.20; H, 5.34; N, 6.74%.
4-(1-Hydroxy-4,4-dimethyl-2-pentynyl)pyridine (3e): 3, 3-Dimethyl-
I-butyne (0.46 g) in THF (10 mL) was treated as for 3b with n-BuLi
(3.5 mL, 1.6 M in hexane) and 4-pyridinecarboxaldehyde (0.50 g) in
THF (3.0 mL) was added. The product 3e (0.85 g, 96%) was a solid,
m.p. 85-88°C. UV (CHCI3): Amax (e) 257 (2000). IR (CH2CI2): 1068,
I-Phenyl-3-trimethylsilanyl-prop-2-yn-l-ol
to the literature and its physical data were in agreement with those
published.2'
(3a): Prepared according
1404, 1599,2232,2333,2363,2970,3060,3596,3685
em-I. IH NMR
4-(1-Hydroxy-3-trimethylsilanyl-2-propynyl) pyridine (3b): To
solution of (trimethylsilyl) acetylene (1.7 mL) in THF (20 mL) at
-78°C was added a solution ofn-BuLi (7 mL, 1.6 M in hexane). The
reaction mixture was allowed to warm to -10°C, then a solution of
4-pyridinecarboxaldehyde (1.0 g) in THF (3 mL) was added. After
I h stirring, saturated NH4CI solution in water was added and the
organic layer was washed with brine (2 x 30 mL), extracted with
CH2CI2 and dried over MgS04 and concentrated in vacuo. Product
3b is a colourless solid (1.6 g, 83%), m.p. 94-95°C. (lit. m.p. 83-
a
(500 MHz, CDCI3): 81.20 (s, 9H), 3.50 (brs, lH), 5.42 (s, lH), 7.44 (d,
J=4.7Hz, 2H), 8.50 (d,J=4.7 Hz, 2H). 13CNMR(125 MHz,CDCI3):
827.4,30.7,62.8,77.6,95.9,121.4,149.3,151.0.
MS (FAW): mlz 190
[M + H]+. Anal. Ca1cd for C12HISNO(189.3): C, 76.16; H, 7.99; N,
7.40. Found: C, 76.11; H, 8.03; N, 7.47%.
4-(1-Hydroxy-3-trimethylsilanyl-2-propynyl)quinoline (3f):Trimethyl-
silylacetylene (0.39 g) in THF (10 mL) was treated as for 3b with n-
BuLi (2.5 mL, 1.6 M, in hexane) and 4-quinolinecarboxaldehyde
(0.5 g) in THF (2 mL) was added. The product 3f was
a solid
85oC).24 IH NMR (400 MHz, CDCI3): 80.17 (s, 9H), 4.60 (brs, lH),
(0.64 g, 78%). m.p. 95-96°C; UV (CH2CI2):Amax (e) 234 (13900), 281
(4800M-I cm-I).IR(CH2Cl2): 1510, 1573, 1607, 1636, 1654, 1686, 1717,
1734,1750,1774,1801,1830, 1884, 1963, 2174, 2305,2339,2360cm-l.
IH NMR (400 MHz, CDCI3): 80.15 (s, 9H), 4.80 (brs, lH), 6.10 (s,
lH), 7.55 (dd, J= 7.6 Hz, J= 15.6 Hz, lH), 7.65 (dd, J= 7.6 Hz,
J= 15.6 Hz, lH), 7.69 (d, J= 4.4 Hz, lH), 8.10 (d, J= 8.4 Hz, lH),
8.25 (d,J= 8.4 Hz, lH), 8.72 (d, J= 4.4 Hz, lH). 13CNMR (100 MHz,
CDCI3): 8 -{l.4, 61.3, 92.4, 104.1, 118.2, 124.1, 125.6, 126.7, 129.3,
5.48 (s, lH), 7.49 (d, J= 6.0 Hz 2H), 8.53 (d, J= 6.0 Hz 2H). l3C
NMR (100 MHz, CDCI3): 8 -1U8, 63.2, 92.0, 104.2, 121.5, 149.4,
150.3. MS (EI): m/z 205 [Mj+.
4-(1-Hydroxy-2-butynyl) pyridine (3c): To a solution of propyne
(1.12 g) in THF (10 mL), was added a solution ofn-BuLi (7.0 mL,
1.6 M in hexane) as for 3b. A solution of 4-pyridinecarboxaldehyde
(1.0 g) in THF (5 mL) was added. The product 3c was isolated as for
3b, and as a liquid (1.12 g, 82%). UV (CH2CI2):Am" (e) 255 (3540 M-I
em-I). IR (CH2CI2): 1230, 1414, 1564, 1602, 1716,2232,2874,2959,
3018,3026,3061 em-I. IH NMR (400 MHz, CDCI3): 8 1.76 (s, 3H),
5.37 (d, J = 1.6 Hz, lH), 6.30 (brs, lH), 7.41 (d J = 5.9 Hz, 2H),
129.4,146.1,147.7,149.8.
MS (FAB+): mle (%): 256 [M + H]+ (100),
180(5), 154 (6), 130 (10). Anal. Ca1cd for CIsH17NOSi: C, 70.54; H,
6.71; N 5.48. Found: C, 70.50; H, 6.69; N, 5.52%.

462 JOURNAL OF CHEMICAL RESEARCH 2009
4-(1-Hydroxy-2-butynyl)quinoline (3g): Propyne (0.38 g) in THF
(10mL) was treated as for3b withn-BuLi (2.5 mL, 1.6M in hexane),
and 4-quino1inecarboxa1dehyde (0.50 g) in THF (2 mL). The product
3g was a solid (0.52 g, 83%); m.p. 130°C. UV (MeOH): Am" (e)
210 (13400), 222 (13000), 283 (4400). IR (CH2C12):556, 648, 698,
1035, 1049, 1109, 1379, 1414, 1432, 1453, 1475,2808,2878,2900,
7.05 (d,J= 18.8Hz, lH), 7.25 (d,J= 18.8Hz, lH), 7.60 (dd,J= 6.0 Hz,
J = 2.0 Hz, 2H), 8.70 (dd, J = 6.0 Hz, J = 2.0 Hz, 2H). l3C NMR
(100 MHz, CDC13): 8 -1.8,121.8,137.4,143.9,
150.7, 152.7, 189.9.
MS (EI): 205 [Mj+. Anal. Calcd for CllH,sNOSi (205.3): C, 64.34;
7.36; N, 6.82. Found: C, 64.30; H, 7.34; N, 6.85%.
2978,2992,3056,3092,3184,3432,3567
cm-'. 'H NMR (400 MHz,
Reaction of 4-(1-hydroxy-2-butynyl) pyridine (3c) with pyridinium
hydrochloride
4-(1-Hydroxy-2-butyny1) pyridine 3c (0.18 g) in MeOH (8 mL),
pyridinium hydrochloride (7 mg) yielded the two products separated
by column chromatography (silica gel, CHC1iHexane, 2/1).
DMSO-d6): 8 1.75 (s, 3H), 5.95 (brs, lH), 6.35 (d, J= 4.4 Hz, lH),
7.60 (t,J= 5.7 Hz, J= 12.2 Hz, lH), 7.63 (d, J= 3.4 Hz, lH), 7.72 (t,
J=5.7Hz,J= 12.2Hz, lH), 8.01 (d,J=6.6Hz, lH), 8.24 (d,J= 6.6 Hz,
lH), 8.84 (d, J = 3.4 Hz, lH). l3C NMR (100 MHz, DMSO-d6):
83.6,60.3,80.1,82.9,
118.4, 124.9, 125.4, 126.9, 129.7 (2C), 147.6,
I-Pyridin-4-yl-but-2-yn-l-one
(4c): Yellow liquid (27 mg, 15%),
148.1, 150.8. MS (EI): m/e (%): 197 [Mj+ (100), 182 (77), 130 (50),
129 (20). Anal. Calcd for Cl3HllNO (197.2): C, 79.16; H, 5.62; N
7.10. Found: C, 79.27; H, 5.80; N 6.99%.
UV (CH2C12): Am" (e) 247 (9050 M-' cm-'). IR (CH2C12): 1206,
1223, 1271, 1467, 1710, 2398, 2872, 2886, 2928, 2958, 3016,
3024 cm-'. 'H NMR (400 MHz, CDC13): 8 2.17 (s, 3H), 7.68 (d,
J= 5.8 Hz, 2H), 8.81 (d, J= 5.8 Hz). l3C NMR (100 MHz, CDC13):
4-(1-Hydroxy-4,4-dimethyl-2-pentynyl)quinoline(3h): 3,3-Dimethy1-
1-butyne (0.31 g) in THF (8 mL) was treated as for 3b with n-BuLi
(2.4 mL, 1.6 M in hexane), and 4-quino1inecarboxa1dehyde (0.5 g)
in THF (3 mL) was added. The product was liquid (0.61 g, 80%).
UV (CH2C12):Am,,(e) 283 (4900). IR (CH2C12):3428 cm-'. 'H NMR
(500 MHz, CDC13): 8 1.18 (s, 9H), 4.20 (brs, lH), 6.08 (s, lH), 7.55
(dd, J= 1.1 Hz, J= 8.2 Hz, lH), 7.67 (m, 2H), 8.10 (d, J= 8.4 Hz,
lH), 8.26 (d, J= 8.4 Hz, lH), 8.79 (d, J= 4.4 Hz, lH). l3C NMR
(125 MHz, CDC13):827.5,30.7,61.3,77.5,96.7,118.0,124.1,125.7,
829.7,78.6,94.7,122.1,142.4,150.8,177.0.
MS (EI): m/z 145 [Mj+.
HRMS Calcd for C9H9NO: 145.1580. Found: 145.1577.
(E)-1-Pyridin-4-yl-but-2-en-l-one
(Sc): Yellow liquid (88 mg,
49%), UV (CH2C12): Am" (e) 249 (9300 M-' cm-'). IR (CH2C12):
1228,1296, 1336, 1441, 1555, 1595, 1625, 1676,3018,3024 cm-'.
'H NMR (400 MHz, CDC13):82.04 (dd,J= 1.6 Hz,J= 6.9 Hz, 3H),
6.81 (dq, J = 1.6 Hz, J = 3.2 Hz, J = 15.4 Hz, lH), 7.07-7.16 (m,
lH), 7. 69 (d, J= 5.8 Hz, 2H), 8.80 (d, J= 5.8 Hz, 2H). l3C NMR
(100 MHz, CDC13): 8 18.8, 121.7, 127.2, 144.3, 147.7, 150.7, 190.1.
MS (EI): m/z 147 [Mj+. HRMS Calcd for C9H9NO: 147.1739. Found:
147.1735.
126.6,129.2,129.6,146.5,148.0,150.0.
MS (FAB+):m/z240[M +H]+.
Anal. Calcd for C'6H17NO: C, 80.30; H, 7.16; N, 5.85. Found: C,
80.19; H, 7.22; N, 5.91%.
4-(1-Hydroxy- 3-phenyl- 2-propynyl)quinoline (3i): Pheny1acety1ene
(0.39 g) in THF (8 mL) was treated as for 3b with n-BuLi (2.39 mL,
1.6 M in hexane) and 4-quinolinecarboxa1dehyde (0.50 g) in THF
(3 mL) was added. The product 3j (0.610 g, 74%) was a liquid. UV
(CH2C12): Am" (e) 225 (24000). IR (acetone): 3618 cm-'. 'H NMR
(500 MHz, MeOD): 84.85 (brs, lH), 6.33 (s, lH), 7.30 (m, 3H), 7.39
(m, 2H), 7.67 (ddd,J= 0.9 Hz,J= 8.1 Hz, lH), 7.78 (ddd,J= 0.9 Hz,
J= 8.1 Hz, lH), 7.86 (d,J=4.5 Hz, lH), 8.07 (d,J= 8.4 Hz, lH), 8.43
(d, J = 8.4 Hz, lH), 8.88 (d, J = 4.5 Hz, lH). l3C NMR (125 MHz,
MeOD): 860.7,86.3,87.8,117.9,122.2,124.2,125.6,126.6,128.1,
Reaction of 4-(1-hydroxy-3-phenyl-2-propynyl) pyridine (3d) with
pyridinium hydrochloride
3-Pheny1-1-(pyridine-4-y1) prop-2-yn-1-01 (3d) (0.20 g) in MeOH
(5 mL), pyridinium hydrochloride (5.5 mg) yielded two products
separated by column chromatography (silica gel, hexane/EtOAc, 1/1).
I-Pyridin-4-yl-3-phenyl-prop-2-yn-l-one
(4d): (20 mg, 10%), UV
(CH2C12):Am" (e) 233 (9300),301 (7200). IR (CH2C12): 1264, 1421,
1551, 1604, 1650, 1961 cm-'. 'H NMR (400 MHz, CDC13): 87.41
(m, 2H), 7.48 (m, lH), 7.66 (m, 2H), 7.96 (d, J= 5.8 Hz, 2H), 8.83
(d,J= 5.8 Hz, 2H). '3C NMR (100 MHz, CDC13):8 86.2,95.2,119.3,
122.1,128.8,131.4, 133.3, 142.5, 150.6, 176.7. MS (FAB+): m/z 208
[M + H]+. Anal. Calcd for C'4H9NO (207.2): C, 81.14; H, 4.38; N,
6.76. Found: C, 81.02; H, 4.42; N, 6.69%.
128.3,128.4,129.4,131.1,147.6,
149.8.MS(FAB+):m/z260
[M +H]+.
Anal. Calcd for C'8Hl3NO: C, 83.37; H, 5.05; N, 5.40.Found: C,
83.41; H, 5.11; N, 5.31%.
2-(1-Hydroxy-3-trimethylsilanyl-2-propynyl)
pyridine
(3k):
The same experiment was carried out as above except that 2-
pyridinecarboxa1dehyde was added. The product 3k was isolated as
oil in a yield of 88% (1.69 g). UV (CH2C12):Am" (e) 260 (6060). IR
(E)-1-Pyridin-4-yl-3-phenyl-prop-2-en-l-one
(Sd) (0.11 g, 55%).
m.p. 75-76°C. UV (CH2C12):Am" (e) 235 (14800), 308 (14600). IR
(CH2C12): 1149, 1261, 1416, 1541, 2291, 2397, 2516, 2675, 2980,
3046, 3682, 3755 cm-'. 'H NMR (500 MHz, CDC13): 8 7.39 (d,
J = 15.7 Hz, lH), 7.43 (m, 3H), 7.63 (m, 2H), 7.76 (d, J = 5.4 Hz,
2H), 7.81 (d, J= 15.7 Hz, lH), 8.82 (d, J= 5.4 Hz, 2H). l3C NMR
(125 MHz, CDC13):8121.2, 121.5, 128.6, 129.1, 131.2, 134.3, 144.4,
146.8, 150.7, 189.8. MS (FAB+): m/z 210 [M + H]+. Anal. Calcd for
C'4HllNO (209.2): C, 80.36; H, 5.30; N, 6.69. Found: C, 80.40; H,
5.29; N, 6.72%.
(CH2C12):894,1262,1421,1590,2302,2405,2678,2981,3062
cm-'.
'H NMR (400 MHz, CDC13): 80.13 (s, 9H), 4.40 (brs, lH), 5.48 (s,
lH), 7.22 (m, lH), 7.51 (m, lH), 7.70 (m, lH), 8.49 (m, lH). l3C
NMR (100 MHz, CDC13): 8 -0.15, 64.0, 90.5, 104.5, 120.9, 123.3,
137.2, 148.1, 153.7. MS (FAB+): m/z 206 [M + Hj+. Anal. Calcd for
CllH,sNOSi (205.3): C, 64.34; H, 7.36; N, 6.82. Found: C, 64.29; H,
7.39; N, 6.89%.
General procedure for the reaction of propargylic alcohol (3) with
pyridinium hydrochloride
Reaction of 4-(1-hydroxy-4, 4-dimethyl-2-pentynyl) pyridine (3e)
with pyridinium hydrochloride
To a solution ofpropargylic alcoho13 (1 mmo1) in MeOH (4 mL) was
added pyridinium hydrocWoride (0.04 mmo1) at r.t. After stirring for
6 h, water (5 mL) was added, extraction with CH2C12(2 x 10 mL)
was performed. The organic layer was dried over MgS04 and
concentrated under vacuum to yield the products 4b-i and Sb-i
which were separated by column chromatography.
4-(1-Hydroxy-4, 4-dimethyl-2-pentyny1) pyridine (3e) (0.57 g) in
MeOH (10 mL) pyridinium hydrocWoride (17 mg) yielded after
column chromatography (silica gel, hexane/EtOAc, 9/1) two products.
I-Pyridin-4-yl-4,4-dimethyl-pent-2-yn-l-one
12%). UV (CHC13): Am" (e) 239 (13500). IR (CH2C12): 1062, 1209,
1257,1324,1365,1407,1457,1560,1652,2212,2975 cm-'. 'HNMR
(4e): (68 mg, liquid,
(500 MHz, CDC13): 8 1.35 (s, 9H), 7.84 (d, J= 5.2 Hz, 2H), 8.78 (d,
J = 5.2 Hz, 2H). l3C (125 MHz, CDC13): 8 28.1, 30.0, 77.6, 106.1,
121.9, 142.5, 150.7, 177.1. MS (FAB+): m/z 188 [M + H]+. Anal.
Calcd for C12Hl3NO (189.3): C, 76.98; H, 7.00; N, 7.48. Found: C,
76.94; H, 7.03; N, 7.51%.
Reaction of 4-(1-hydroxy-3-trimethylsilanyl-2-propynyl)
(3b) with pyridinium hydrochloride
4-(1-Hydroxy-3-trimethy1si1anyl-2-propyny1) pyridine 3b (0.20 g) in
MeOH (4.0 mL), pyridinium hydrocWoride (5.6 mg). yielded the two
products separated by column chromatography (silica gel, hexane/
EtOAc, 4/1).
pyridine
(E)-1-Pyridin-4-yl-4,-4-dimethyl-pent-2-en-l-one
75%). UV (CHC13): Am" (e) 235 (11300). IR (CH2C12); 1220, 1300,
1334,1610,1652, 1671,2206,2297,2859,2959,3044 cm-'. 'H NMR
(Se): (0.43 g,
I-Pyridin-4-yl-3-trimethylsilanyl-prop-2yn-l-one
(4b):
Yellow
liquid (0.52 g, 26%). UV (CH2C12):Am" (e) 237 (6610). IR (CH2C12):
1408, 1558, 1650, 1737, 1943, 2154, 2856, 2909, 2927, 2963, 3052,
3055 cm-'. 'H NMR (400 MHz, CDC13): 80.30 (s, 9H), 7.87 (dd,
J = 6.0 Hz, J = 3.0 Hz, 2 H), 8.81 (dd, J = 6.0 Hz, J = 3.0 Hz, 2H). l3C
NMR (100 MHz, CDC13): 8 -0.7, 100.1, 103.2, 122.1, 142.1, 150.9,
176.7. MS (FAB+):204 [M +H]+.Anal. Calcd forCllHl3NOSi (203.3):
C, 64.98; H, 6.44; N, 6.89. Found: C, 64.95; H, 6.41; N, 6.85%.
(400 MHz, CDC13): 8 1.05 (s, 9H), 6.59 (d, J = 15.8 Hz, lH), 7.01
(d, J = 15.8 Hz, lH), 7.57 (d, J = 5.7 Hz, 2H), 8.68 (d, J = 5.7 Hz,
2H). l3C NMR (100 MHz, CDC13):8 28.5, 34.3,120.4,121.5,114.5,
150.5, 161.7, 190.6. MS (FAB+): m/z 190 [M + H]+' Anal. Calcd for
C12H,sNO (189.3): C, 76.16; H, 7.99; N, 7.40. Found: C, 76.13; H,
8.06; N, 7.35%.
(E)-1-Quinolin-4-yl-3-trimethylsilanyl-prop-2-en-l-one
(Sf): 4-(1-
(E)-1-Pyridin-4-yl-3-trimethylsilanyl-prop-2-en-l-one
(Sb):
Hydroxy-3-trimethy1si1anyl-2-propyny1) quinoline (3f) (0.42 g) in
MeOH (8 mL) pyridinium hydrocWoride (9.5 mg, For the
p-to1uenesu1fonate and the triflate pyridinium salts the same molar
amount was used), yielded after column chromatography (hexane/
(0.105 g, 52%). UV (CH2C12): Am" (e) 195 (2900), 231 (4500),
277(2300).IR (CH2C12): 1409, 1557, 1652,2294,2316,2351,2854,
2863,2923,2954,3055 cm-'. 'HNMR( 400 MHz, CDC13):80.11(s, 9H),

JOURNAL OF CHEMICAL RESEARCH 2009 463
EtOAc 4/1) one product 5f (0.231 g, 55%), as a yellow liquid. UV
(CH2Cl2): Am" (E) 232 (11200), 317 (2450 M-' cm-'). IR (CH2C12):
1463,1509,1579,1603, 1658, 1726,2332,2862,2932,3374,361Ocm-'.
'H NMR (400 MHz, CDC13): 80.14 (s, 9H), 6.95 (d, J= 15.3 Hz,
lH), 7.09 (d, J = 15.3 Hz, lH), 7.39 (d, J = 3.4 Hz, lH), 7.58 (t,
l-Quinolin-4-yl-3-phenyl-prop-2yn-l-one
(4i): (0.17 g, 24%). UV
(CH2C12): Am" (E) 230 (25200), 309 (13200). IR (CH2C12): 1605,
2354,3679 cm-'. 'H NMR (400 MHz, CDC13): 87.43-7.47 (m, 2H),
7.50 (m, lH), 7.69-7.74 (m, 3H), 7.78-7.83 (m, lH), 8.21 (d, J= 8.5
Hz, lH), 8.25 (d, J= 4.4 Hz, lH), 8.98 (d, J= 8.5 Hz, lH), 9.15 (d,
J= 4.4 Hz, lH). BC NMR (100 MHz, CDC13): 888.2,93.8,119.7,
J=5.6Hz,J=
12.2 Hz, lH), 7.74(t,J=5.6Hz,J=
12.2 Hz, lH),
124.1,125.7,128.9,129.2,130.2,131.4,133.3,139.7,
179.1. MS (FAB+). m/z 258 [M + Hj+. Anal. Calcd for C'8HllNO: C,
84.03; H, 4.31; N, 5.44. Found: C, 84.11; H, 4.23; N, 5.49%.
(E)-1-Quinolin-4-yl-3-phenyl-prop-2-en-l-one
UV (CH2C12): Am" (E) 230 (21300), 305 (17200). IR (CH2C12): 1599,
2156,2191 cm-'. 'H NMR (500 MHz, CDC13):8 7.18 (d,J= 16.1 Hz,
lH), 7.35-7.40 (m, 3H), 7.47-7.53 (m, 4H), 7.57 (t, J = 7.8 Hz,
J = 15.2 Hz, lH), 7.74 (t, J = 7.8 Hz, J = 15.2 Hz, lH), 8.07 (d,
J = 8.4 Hz, lH), 8.17 (d, J = 8.4 Hz, lH), 9.01 (d, J = 4.1 Hz, lH).
BC NMR (125 MHz, CDC13): 8 119.2, 124.5, 126.2, 127.8, 129.1,
149.4, 150.1,
8.01 (d, J= 7.0 Hz, lH), 8.15 (d, J= 7.0 Hz, lH), 8.98 (d, J= 3.4 Hz,
lH). BC NMR (100 MHz, CDC13): 8 -1.9, 119.4, 125.3, 127.7,
129.9 (2C), 141.7, 143.9, 148.7, 149.5, 154.0, 155.4, 194.6. MS (EI):
m/e (%): 255 [M]+(50), 240 (100), 183 (10),156 (15),128 (20). Anal.
Calcd for C'sH17NOSi (255.4): C, 70.54; H, 6.71; N, 5.48. Found: C,
70.51; H, 6.74; N, 5.50%.
(5i): (0.15 g, 21%).
Reaction of 4-(1-hydroxy-2-butynyl) quinoline (3g) with pyridinum
hydrochloride
4-(1-Hydroxy-2-butyny1) quinoline (3g) (0.22 g) in MeOH (10 mI.),
pyridinium hydrochloride (6.4 mg) yielded after column chromato-
graphy (silica gel, hexane/EtOAc, 4/1) two products.
129.5,129.9,130.0,131.3,133.9,144.6,148.0,148.7,
MS (FAB+): m/z 260 [M + H]+. Anal. Calcd for C'8HBNO: C, 83.37;
H, 5.05; N, 5.40. Found: C, 83.31; H, 5.07; N, 5.49%.
(E)-1-Pyridin-2-yl-3-trimethylsilanyl-prop-2-en-l-one (5k): Obtained
149.6, 194.7.
l-Quinolin-4-yl-but-2-yn-l-one
(4g): Colourless liquid (65 mg,
30%). UV (MeOH): Am" (E) 230 (8700), 248 (8600), 329 (2500).
IR (CH2C12): 725, 895, 1262, 1418, 1633, 2300, 2689, 2989, 3058,
3419,3945 cm-'. 'H NMR (400 MHz, CDC13):8 2.20 (s, 3H), 7.71 (t,
J= 7.1 Hz, J= 15.4 Hz, lH), 7.79 (t, J= 7.1 Hz, J= 15.4 Hz, lH),
8.16 (d, J= 4.0 Hz, lH), 8.19 (d, J= 8.4 Hz, lH), 8.93 (d, J= 8.4 Hz,
lH), 9.12 (d, J= 4 Hz, lH). 13C NMR (100 MHz, CDC13): 829.8,
80.4,93.4, 124.1, 124.3, 125.7, 129.1, 130.0 (2C), 139.6, 149.3, 149.9,
179.2. MS (EI): m/z 195 [M]+. Anal. Calcd for CBH9NO (195.2): C,
79.98; H, 4.65; N, 7.17. Found: C, 79.95; H, 4.68; N, 7.15%.
from 2-(1-hydroxy-3-trimetby1si1anyl-2-propyny1)pyridine
3k with
pyridinium hydrochloride as above in a yield of 42%. 'H NMR
(400 MHz, CDC13):8 0.12 (s, 9H), 7.37 (ddd, J= 1.0 Hz, J= 4.7 Hz,
lH), 7.44 (d, J = 18.9 Hz, lH), 7.83 (ddd, J = 2.0 Hz, 7.8 Hz,
lH), 8.01 (d, J = 18.9 Hz, lH), 8.10 (d, J = 7.8 Hz, lH), 8.70 (d,
J=4.7 Hz, lH). '3CNMR (100 MHz, CDC13):8-1.76, 123.2, 126.7,
136.4, 136.9, 148.8, 150.2, 154.0, 188.4. IR (CH2C12): 1316, 1600,
1666, 2326, 2359, 2955, 3479 cm-'. UV (CH2C12): Am" (E) 257
(11850). MS (FAB+): m/z 206 [M + Hj+. Anal. Calcd for CllH,sNOSi
(205.3): C, 64.34; H, 7.36; N, 6.82. Found: C, 64.37; H, 7.31;
N,6.90%.
(E)-1-Quinolin-4-yl-but-2-en-l-one
(5g): Orange liquid (79 mg,
36%). UV (CHC13): Am" (E) 243 (9700), 306 (2800), 317(2900). IR
(CH2C12): 1264, 1282, 1456, 1503, 1539, 1621, 1653, 1683, 1716,
1732, 1771, 1843, 2401, 2851, 2925 cm-'. 'H NMR (400 MHz,
CDC13): 8 2.0 (dd, J = 1.1 Hz, J = 6.8 Hz, 3H), 6.62 (dd, J = 1.1 Hz,
J= 15.7 Hz, lH), 6.82 (septet, lH), 7.41 (d, J= 3.6 Hz, lH), 7.59 (t,
J= 7.3 Hz, J= 15.3 Hz, lH), 7.77 (t, J= 7.3 Hz, J= 15.3 Hz, lH),
8.02 (d,J= 8.5 Hz, lH), 8.18 (d, J= 8.5 Hz, lH), 9.0 (d, J= 3.6 Hz,
lH). BC NMR (100 MHz, CDC13): 830.2, 119.2, 124.7, 125.4 (2C),
127.8, 129.9, 130.1, 132.4, 144.8, 148.8, 149.6, 195.0. MS (EI): m/z
197 [Mj+. Anal. Calcd for CBHllNO (197.2): C, 79.16; H, 5.62; N,
7.10. Found: C, 79.18; H, 5.59; N, 7.7%.
Reaction of 4-(1-hydroxy-3-trimethylsilanyl-2-propynyl)
(3b) with pyridinium hydrochloride in Me02 H
pyridine
To
a
solution of 4-(1-hydroxy-3-trimethy1si1anyl-2-propyny1)
pyridine (3b) (0.15 g) in d-Me02H (4.0 mI.) was added pyridine
hydrochloride (4.2 mg) at ct. After stirring for 6 h, water (5 mI.) was
added, extracted with CH2C12 (2 x 10 mI.), dried over MgS04 and
concentrated under vacuum to yield the product purified by column
chromatography (silica gel, hexane/EtOAc, 4/1). (E)-1-pyridin-4-
yl-3-trimethy1si1any1-prop-2-en-1-one 5b was obtained in a yield of
51%. 'HNMR (500 MHz, CDC13):80.17(s, 9H), 7.64 (dd,J=4.5 Hz,
J = 1.6 Hz, 2H), 8.76 (dd, J = 4.5 Hz J = 1.6 Hz, 2H). BC NMR
Reaction of 4-(1-hydroxy-4, 4-dimethyl-2-pentynyl) quinoline (3h)
with pyridinium hydrochloride
4-(1-Hydroxy-4, 4-dimethyl-2-pentyny1) quinoline (3h) (0.40 g) in
MeOH (10 mI.), pyridiniym hydrocWoride (9.6 mg) yielded after
column chromatography (silica, hexane/EtOAc, 9/1) three products.
(125 MHz, CDC13): 8 -1.9,121.7,137.2,143.7,
150.6, 152.4, 189.9.
MS (FAW): 208 [M + H]+. Anal. Calcd for CllHBD2NOSi (207.3):
C, 63.72; H, 8.26; N, 6.76. Found: C, 63.69; H, 8.24; N, 6.79%.
Endo- 2 -(qu i no Iin- 4-y 1-carbony I) -exo- 3-tr im et hy Is i lany 1-
bicyclo[2.2.1}hepte-5-ene (16): A solution of the si1y1ated enone 5f
(50 mg) and of cyclopentadiene (1 mI.) in 0.1 M LiC1 THF (1 mI.)
was left at 25°C for 12 h. The reaction medium was chromatographed
on a silica gel column (hexane-EtOAc, 9: 1). The product 16 was
isolated in a yield of 50%. Crystallised in MeOH:acetone (7: 3) as a
white solid, m.p. 87.4°C. UV (MeOH) Am,,: 205 nm (0.7758), 232
(0.2188). IR (MeOH): 1679,2974 em-I. 'HNMR(CDC13.400 MHz):
80.06 (s, 9H), 1.28-1.34 (m, 3H), 2.88 (s, lH), 3.07 (s, lH), 3.63 (q,
J= 3.6 Hz, lH), 5.63 (q, J= 3.2, 2.8 Hz, lH), 6.41 (q, J= 3.2, 2.8 Hz,
lH), 7.54 (d, J= 4.4 Hz, lH), 7.57 (m, lH), 7.59 (t, J= 6.8 Hz, lH),
7.75 (d, J= 8.4 Hz, lH), 8.15 (d, J= 8.4 Hz, lH), 9.0 (d, J= 4.4 Hz,
lH). BC NMR (CDC13 100 MHz): 8 -1.85,27.88,44.5,48.2,48.9,
54.2, 118.1, 125.1, 127.9, 128.6, 129.7, 130.0, 139.5, 141.1, 145.4,
148.4, 149.3, 204.2. MS (FABMS): m/z 322 [M + H]+; Exact mass
l-Quinolin-4-yl-4,
4-dimethyl-pent-2-yn-l-one
(4h): (0.103 g,
26%). UV (CH2C12): Am" (E) 250 (12100), 328 (6400). IR (CH2C12):
1508, 1652,2204,2974 cm-'. 'H NMR (500 MHz, CDC13):8 1.37 (s,
9H), 7.64 (ddd, J= 1.2 Hz, J= 6.8 Hz, lH), 7.74 (ddd, J= 1.2 Hz,
J= 6.8 Hz, lH), 8.07 (d, J= 4.4 Hz, lH), 8.15 (d, J= 8.1 Hz, lH),
8.88 (d, J = 8.1 Hz, lH), 9.08 (d, J = 4.4 Hz lH). BC NMR (125
MHz, CDC13): 828.1,29.9,79.5,
104.5, 123.9, 124.0, 125.5, 128.8,
129.8 (2C), 139.8, 149.2, 149.8, 179.3. MS (FAB+): m/z 238 [M +
H]+. Anal. Calcd for C'6H,sNO: C, 80.98; H, 6.37; N, 5.90. Found:
C, 80.85; H, 6.45; N, 6.01%.
(E)-1-Quinolin-4-yl-4, 4-dimethyl-pent-2-en-l-one (5h): (0.149 g,
37%). UV (CH2C12): Am" (E) 230 (13400), 307 (2940), 317 (2940).
IR (CH2C12): 1651, 2303, 2955, 3060 cm-'. 'H NMR (400 MHz,
CDC13):81.06 (s, 9H), 6.48 (d, J= 16.1 Hz, lH), 6.77 (d,J= 16.1 Hz,
lH), 7.38 (d, J= 4.3 Hz, lH) 7.55 (ddd, J= 1.1 Hz, J= 7.0 Hz, lH),
Calcd for C2oH240NS: 322.1627. Found: 322.1627.
7.71 (ddd,J= 1.1 Hz,J=7.0Hz,
lH), 8.01 (d,J= 8.5 Hz, lH), 8.14
(d, J= 8.5 Hz, lH), 8.96 (d, J= 4.3 Hz, lH). BC NMR (100 MHz,
CDC13):828.6,34.5,119.4,124.7,125.5,125.9,127.7,129.9,130.0,
144.7, 148.9, 149.7, 163.5, 195.6. MS (FAB+): m/z 240 [M + H]+.
Anal. Calcd for C'6H17NO: C, 80.30; H, 7.16; N, 5.85. Found: C,
80.41; H, 7.01; N, 6.05%.
Crystal structure determination
Diffraction measurements were made on an Enraf-Nonius CAD-4
diffratometer by use of graphite-monochromatised MoKa radiation
(A = 0.7107A). Unit cell parameters were obtained by least squares
fit to the automatically centred settings for 25 reflections. Intensity
data were collected by use of 0l-2fl scan mode. All intensity data
were collected for Lorentz polarisation and absorption (empirical '"
corrections). Crystallographic data (excluding structure factors) for
the structures of enone (5d) and oftbe Die1s-A1der adduct (16) have
been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication no CCDC 658185 for enone (5d) and
CCDC 658184 for D7A adduct (16). These data can be obtained free
(Z)-1-Quinolin-4-yl-4,
4-dimethyl-pent-2-en-l-one
(5h): (18%
evaluated from NMR spectrum) 'H NMR (400 MHz, CDC13):8 1.16
(s, 9H), 6.08 (d, J= 13.1 Hz, lH), 6.27 (d,J= 13.1 Hz, lH), 7.56-7.60
(m, 2H), 7.68 (ddd, J= 1.3 Hz, J= 6.9 Hz, lH), 8.10 (d, J= 8.4 Hz,
lH), 8.50 (d, J = 8.4 Hz, lH), 8.95 (d, J = 4.3 Hz, lH).
Reaction of 4-(1-hydroxy-3-phenyl-2-propynyl) quinoline (3i) with
pyridinium hydrochloride
of charge via www.ccdc.cam.ac.uk/dataJequest/cif
or by emailing
4-(1-Hydroxy-3-phenyl-2-propyny1) quinoline (3i) (0.70 g) in MeOH
(10 mI.), pyridinium hydrocWoride (16 mg) yielded after column
chromatography (silica gel, hexane/EtOAc, 9/1) two products.
dataJequest@ccdc.cam.ac.uk or by contacting The Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: + 44 1223 336033.

464 JOURNAL OF CHEMICAL RESEARCH 2009
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We are grateful to Professor Sunney I. Chan for his
encouragement. This work was supported by Academia Sinica.
We also thank the Scientific and Technological Research
Council of Turkey (TUBITAK) for financial support of the
visit of the senior author (J.P. Biellman) to the Gaziosmanpasa
University Tokat-Turkey.
Received 6 February 2009; accepted 30 April 2009
Paper 09/0436 doi: 10.3184/030823409X464467
Published online: 15 July 2009
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