Cyclization vs. elimination reactions of 5-Aryl-5-hydroxy 1,3-diones: One-pot synthesis of 2-Aryl-2,3-dihydro-4H-pyran-4-ones

Article abstract of DOI:10.1002/hlca.201000015

2-Aryl-2,3-dihydro-4H-pyran-4-ones were prepared in one step by cyclocondensation of 1,3-diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5-aryl-5-hydroxy 1,3-d

Full text of DOI:10.1002/hlca.201000015

Helvetica Chimica Acta – Vol. 93 (2010)
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Cyclization vs. Elimination Reactions of 5-Aryl-5-hydroxy 1,3-Diones:
One-Pot Synthesis of 2-Aryl-2,3-dihydro-4H-pyran-4-ones
by Rasheed Ahmad Kheraa), Rasheed Ahmada), Ihsan Ullaha), Obaid-Ur-Rahman Abida),
Olumide Fatunsina), Muhammad Sherc), Alexander Villingera), and Peter Langer*a)b)
a) Institut fꢀr Chemie, Universitꢁt Rostock, Albert-Einstein-Strasse 3a, D-18059 Rostock
(fax: þ 493814986412; e-mail: peter.langer@uni-rostock.de)
b) Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock, Albert-Einstein-Strasse 29a,
D-18059 Rostock
c) Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan
2-Aryl-2,3-dihydro-4H-pyran-4-ones were prepared in one step by cyclocondensation of 1,3-
diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very
important to avoid elimination reactions of the 5-aryl-5-hydroxy 1,3-diones formed as intermediates. The
TiCl4-mediated cyclization of
a 2-aryl-2,3-dihydro-4H-pyran-4-one with 1,3-silyloxybuta-1,3-diene
resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.
Introduction. – 2,3-Dihydro-4H-pyran-4-ones are present in a variety of natural
products, such as curcumin (Fig. 1), and are of considerable pharmacological relevance
[1]. 2,3-Dihydro-4H-pyran-4-ones have been prepared by hetero-Diels – Alder reaction
of aldehydes with Danishefskyꢂs diene [2] or related dienes [3][4]. A catalytic approach
to enantiomerically pure 2,3-dihydro-4H-pyran-4-ones has been reported [5]. It is
based on the condensation of 1,3-bis(silyloxy)buta-1,3-dienes1) with aldehydes. These
methods are limited by the fact that the synthesis of the (unstable) dienes requires two
to three steps and needs a special handling. In addition, they cannot be stored for a long
period of time, some of them not even at ꢀ 208. 2,3-Dihydro-4H-pyran-4-ones have
also been prepared by PdII-catalyzed oxidative cyclizations of b-hydroxy enones [7], by
reactions of b-ethoxy-a,b-unsaturated lactones [8], by (i-Pr)2NLi (LDA)-mediated
reactions of 3-methoxy 2-en-1-ones with aldehydes and subsequent acid-mediated
cyclization [9], and by reactions of lithiated dithianes with epoxides and subsequent
deprotection, oxidation, and cyclization [10].
Fig. 1. Structure of curcumin
1
)
For a review of 1,3-bis(trimethylsilyloxy) 1,3-dienes, see [6].
ꢃ 2010 Verlag Helvetica Chimica Acta AG, Zꢀrich

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Helvetica Chimica Acta – Vol. 93 (2010)
Results and Discussion. – The reaction of 1,3-dicarbonyl dianions with aldehydes
has been reported to give 5-hydroxy 1,3-dicarbonyl compounds, which undergo HCl/
MeOH-mediated dehydration or transformation into 2,3-dihydro-4H-pyran-4-ones
[11]2). The natural product stegobinone has been prepared by this methodology [13].
5-Hydroxy 1,3-diketones were transformed into 2-alkyl-2,3-dihydro-4H-pyran-4-ones
by using TsOH (CH2Cl2, 24 h, reflux, Dean – Stark trap, 3-ꢄ molecular sieves) [14].
However, this method is limited to the mentioned pyran-4-ones. Dehydration
(elimination of H2O) was observed in case of aromatic substrates. For example, the
reaction of TsOH with 6-hydroxy-6-phenylhexane-2,4-dione (A), prepared by
condensation of the dianion of acetylacetone (1a) with benzaldehyde (2a), gave 6-
phenylhex-5-ene-2,4-dione (B) rather than the desired pyran-4-one 3a (Scheme 1 and
Table) [14]. The facile formation of B is a result of the conjugation of the C¼C bond
with the aryl group. Denmark and Heemstra reported the TFA-mediated trans-
formation of A into 3a (0.001 equiv. of TFA in CH2Cl2, 08) [5]. Recently, we have
reported preliminary results related to the synthesis of 2-aryl-2,3-dihydro-4H-pyran-4-
ones [15]. Here, we report full details, a significant extension of the scope, and an
application of our methodology.
Scheme 1. Synthesis and Dehydration of A
a) 1. NaH, THF, 08, 15 min, 2. BuLi, 20 min, 08, 3. 2a, 15 min, 08. b) NH4Cl (sat.). c) TsOH, CH2Cl2, 24 h,
reflux, Dean – Stark trap, 3-ꢄ molecular sieves.
We have found that a variety of 2-aryl-2,3-dihydro-4H-pyran-4-ones can be
successfully prepared in good yields and in only one step by reaction of 1,3-diketone
dianions with aromatic aldehydes and subsequent aqueous workup using HCl (10%). 5-
hydroxy-5-phenylhexane-2,4-dione (A) was prepared by LDA-mediated condensation
of acetylacetone (1a) with PhCHO (2a) according to the procedure of Miller and co-
workers [14]. An aqueous solution of NH4Cl was used for the aqueous workup which
did not result in elimination or cyclization of A. The reaction of a MeNO2 solution of A
with catalytic amounts of FeCl3 · 6 H2O (10 mol-%) afforded the desired product in
high yield (Scheme 2 and Table). The same result was obtained by employment of HCl
(10%). Finally, we have developed a one-pot protocol: the reaction of the dianion
of acetylacetone (1a) (generated by means of 2.5 equiv. of LDA) with PhCHO (2a;
ꢀ 78 ! 208, 12 h), addition of HCl (10%) and, after 15 min, extraction of the mixture
with AcOEt afforded the desired pyran-4-one 3a in 87% yield (Scheme 2). The
formation of 3a (rather than B) can be explained by acid-mediated attack of the OH
group onto the CO group and subsequent elimination of H2O. While an elimination was
2
)
For a review of cyclization reactions of dianions, see [12].

Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 2. Synthesis of 3a – 3ac
1707
a) 1. (i-Pr)2NLi (LDA; 2.5 equiv), THF, 08, 1 h; 2. ꢀ 788, 1a, 1b, 1 h; 3. 2a – 2p, ꢀ 788 ! 208, 12 h.
b) addition of HCl (10%), 15 min, 208, then extraction (AcOEt).
Table. Synthesis of 3a – 3ac
Compound 1
Compound 2
Product 3
R
Ar
Yield [%]a)
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
b
b
b
b
b
b
b
b
b
b
b
a
b
c
d
e
f
g
h
i
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
87
65
70
76
69
76
89
90
64
73
70
67
69
57
60
86
87
82
78
62
66
71
79
72
61
73
68
67
83
2-ClꢀC6H4
3-ClꢀC6H4
4-ClꢀC6H4
3-BrꢀC6H4
3-MeꢀC6H4
4-MeꢀC6H4
4-EtꢀC6H4
4-MeOꢀC6H4
2,3-(MeO)2C6H4
2,4-(MeO)2C6H4
3-HOꢀC6H4
4-HOꢀC6H4
3-NO2ꢀC6H4
4-NO2ꢀC6H4
4-PhꢀC6H4
Furan-2-yl
j
k
l
m
n
o
p
q
r
a
b
d
e
g
i
k
m
n
o
p
Thiophen-2-yl
Ph
s
t
2-ClꢀC6H4
4-ClꢀC6H4
3-BrꢀC6H4
4-MeꢀC6H4
4-MeOꢀC6H4
2,4-(MeO)2C6H4
4-HOꢀC6H4
3-NO2ꢀC6H4
4-NO2ꢀC6H4
4-PhꢀC6H4
u
v
w
x
y
z
aa
ab
ac
Ph
Ph
a) Yields of isolated products.
observed with TsOH, a cyclization was induced by using an aqueous solution of HCl
(10%, 208). Therefore, the presence of water might play a role in the reaction. While
the reaction with TsOH was carried out under reflux conditions, the reaction with
CF3COOH (TFA), as reported by Denmark and Heemstra [5], was carried out at 08

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Helvetica Chimica Acta – Vol. 93 (2010)
(16 h). Therefore, the temperature seems to play an important role whether an
elimination or cyclization reaction occurs. The silica-gel chromatography of the
products may also play a role to induce a complete transformation of A into 3a.
The reaction of the dianions of acetylacetone (1a) and benzoylacetone (1b) with
aldehydes 2a – 2r afforded the 2-aryl-2,3-dihydro-4H-pyran-4-ones 3a – 3ac in very
good yields (Scheme 2 and Table). The structures of all products were established by
spectroscopic methods. The structures of 3p and 3v were additionally confirmed by X-
ray crystal structure analysis (Figs. 2 and 3)3).
In conclusion, a variety of 2-aryl-2,3-dihydro-4H-pyran-4-ones were prepared in
one step by cyclocondensation of 1,3-diketone dianions with aldehydes and subsequent
workup using HCl (10%).
Fig. 2. ORTEP Plot of 3p (50% probability level)
Fig. 3. ORTEP Plot of 3v (50%
probability level)
3
)
CCDC-769126 and 769127 contain all crystallographic details of this publication and is available
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following
address: Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB21EZ; fax:
(þ44)1223-336-033; or deposit@ccdc.cam.ac.uk.

Helvetica Chimica Acta – Vol. 93 (2010)
1709
Experimental Part
General Comments. All solvents were dried by standard methods, and all reactions were carried out
under an inert atmosphere. Prep.-scale chromatography: silica gel (SiO2, 60 – 200 mesh; Merck). M.p.:
Microheating table HMK 67/1825 Kuestner (Bꢀchi apparatus); uncorrected. IR Spectra: Nicolet 380
FT-IR spectrameter; in cmꢀ1. 1H- and 13C-NMR spectra: Bruker AVANCE 300 III and Bruker AVANCE
250 II spectrometer. EI-MS and ESI-MS: Finnigan MAT 95-XP instrument; in m/z.
General Procedure for the Synthesis of 2,3-Dihydro-4H-pyran-4-ones 3a – 3ac. A THF soln. of LDA
(12.5 mmol) was prepared by addition of BuLi (5 ml, 12.5 mmol; 2.5m soln. in hexanes) to a THF soln.
(15 ml) of (i-Pr)2NH (1.26 g, 12.5 mmol) at 08. After stiring for 1 h, the soln. was cooled to ꢀ 788, and
pentane-2,4-dione (0.50 g, 5.0 mmol) was added. After stirring for 1 h at ꢀ 788, aldehyde (5.0 mmol) was
added, and the soln. was allowed to warm to 208 within 24 h. HCl (10%, 15 ml) was added, and the
mixture was allowed to stand for 15 min. AcOEt (25 ml) was added. The org. and aq. layers were
separated, and the latter was extracted with AcOEt (3 ꢁ 50 ml). The combined org. layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by
chromatography (SiO2; heptane/AcOEt 2 :1) to give 3a – 3ac.
2,3-Dihydro-6-methyl-2-phenyl-4H-pyran-4-one (3a). With a THF soln. of LDA (12.5 mmol), 1a
(0.50 g, 5.0 mmol), and 2a (0.53 g, 5.0 mmol) in THF (15 ml): 3a (0.82 g, 87%). Colorless crystalline solid.
M.p. 45 – 488. IR (KBr): 3062w, 3033w, 2962w, 2918w, 1661s, 1603s, 1392s, 1327s, 1237m, 1179m, 1023m,
999s, 950m, 808m, 755s, 696s. 1H-NMR (300 MHz, CDCl3): 1.98 (s, Me); 2.51 (dd, J ¼ 3.3, 16.8, 1 H, CH2);
2.76 (dd, J ¼ 14.0, 1 H, CH2); 5.31 (dd, J ¼ 3.6, 14.0, CH); 5.36 (s, 1 olefin. H); 7.28 – 7.33 (m, 5 arom. H).
13C-NMR (62 MHz, CDCl3): 21.1 (Me); 42.4 (CH2); 80.8 (CH); 105.2 (olefin. CH); 126.1, 128.8, 133.0
(arom. CH); 138.1 (arom. C); 174.3 (olefin. C); 192.3 (CO). GC/EI-MS (70 eV): 188 (2, Mþ), 170 (8),
155 (6), 145 (36), 104 (100), 91 (2), 78 (16), 77 (12). HR-ESI-TOF-MS: 189.0908 ([M þ H]þ, C12H13O2þ ;
calc. 189.0910). Anal. calc. for C12H13O2: C 76.57, H 6.43; found: C 76.43, H 6.40.
2-(2-Chlorophenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3b). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2b (0.70 g, 5.0 mmol) in THF (15 ml): 3b (0.72 g, 65%).
Colorless viscous oil. IR (KBr): 3411w, 3066w, 2918w, 1706w, 1604s, 1575s, 1471m, 1437m, 1398m, 1358m,
1287m, 1232m, 1032s, 752s. 1H-NMR (300 MHz, CDCl3): 2.07 (s, Me); 2.58 (dd, J ¼ 13.7, 1 H, CH2); 2.71
(dd, J ¼ 4.0, 16.8, 1 H, CH2); 5.44 (s, 1 olefin. H); 5.76 (dd, J ¼ 4.0, 13.7, CH); 7.28 (t, J ¼ 7.4, 1 arom. H);
7.32 (d, J ¼ 8.6, 1 arom. H); 7.36 (t, J ¼ 7.5, 1 arom. H); 7.59 (d, J ¼ 7.5, 1 arom. H). 13C-NMR (75 MHz,
CDCl3): 21.0 (Me); 41.1 (CH2); 77.7 (CH); 105.3 (olefin. CH); 127.2, 127.3, 127.6, 127.8 (arom. CH); 131.7,
136.1 (arom. C); 174.2 (olefin. C); 191.7 (CO). GC/EI-MS (70 eV): 222 (3, Mþ), 187 (20), 181 (10), 179
(26), 140 (33), 139 (11), 138 (100), 103 (38), 102 (10), 77 (13). HR-EI-MS: 222.0442 (Mþ, C12H11ClO2þ ;
calc. 222.0442).
2-(3-Chlorophenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3c). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2c (0.70 g, 5.0 mmol) in THF (15 ml): 3c (0.78 g, 70%). Solid.
M.p. 54 – 558. IR (KBr): 3399w, 3066w, 2958w, 2921w, 2853w, 1714w, 1663s, 1607s, 1573m, 1431m, 1391s,
1
1325s, 1237m, 1159m, 1064m, 1002m, 879m, 783m, 690m, 582m. H-NMR (300 MHz, CDCl3): 2.02 (s,
Me); 2.52 (dd, J ¼ 3.5, 16.8, 1 H, CH2); 2.74 (dd, J ¼ 13.9, 1 H, CH2); 5.28 (dd, J ¼ 3.6, 13.9, CH); 5.37 (s, 1
olefin. H); 7.27 (t, J ¼ 6.7, 1 arom. H); 7.29 (d, J ¼ 8.7, 1 arom. H); 7.32 (d, J ¼ 8.4, 1 arom. H); 7. 35 (s, 1
arom. H). 13C-NMR (62 MHz, CDCl3): 21.0 (Me); 42.3 (CH2); 79.9 (CH); 105.4 (olefin. CH); 124.1,
126.3, 128.9, 130.1 (arom. CH); 134.7, 140.2 (arom. C); 174.0 (olefin. C); 191.7 (CO). GC/EI-MS (70 eV):
222 (7, Mþ), 204 (10), 179 (24), 140 (32), 139 (10), 138 (100), 103 (33), 77 (13). HR-EI-MS: 222.0439
(Mþ, C12H11ClOþ2 ; calc. 222.0442).
2-(4-Chlorophenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3d). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2d (0.70 g, 5.0 mmol) in THF (15 ml): 3d (0.84 g, 76%).
Colorless crystalline solid. M.p. 81 – 828. IR (KBr): 3037w, 2965w, 2808w, 2889w, 1714w, 1600s, 1489m,
1392m, 1245m, 1087m, 1001m, 822s, 652m, 547m. 1H-NMR (300 MHz, CDCl3): 2.09 (s, Me); 2.59 (dd, J ¼
3.7, 16.7, 1 H, CH2); 2.77 (dd, J ¼ 14.0, 1 H, CH2); 5.37 (dd, J ¼ 3.8, 14.0, CH); 5.45 (s, 1 olefin. H); 7.33 –
7.37 (m, 2 arom. H); 7.39 – 7.42 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 21.0 (Me); 42.3 (CH2); 80.0
(CH); 105.3 (olefin. CH); 127.5, 129.0 (arom. CH); 134.6, 137.7 (arom. C); 174.0 (olefin. C); 191.8 (CO).

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Helvetica Chimica Acta – Vol. 93 (2010)
GC/EI-MS (70 eV): 222 (3, Mþ), 204 (11), 179 (24), 140 (33), 139 (10), 138 (100), 103 (23), 77 (10). HR-
EI-MS: 222.0443 (Mþ, C12H11ClOþ2 ; calc. 222.0442).
2-(3-Bromophenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3e). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2e (0.92 g, 5.0 mmol) in THF (15 ml): 3e (0.92 g, 69%).
Colorless crystalline solid. M.p. 59 – 608. IR (KBr): 3073w, 2968w, 2879w, 1655s, 1604s, 1472m, 1428m,
1388s, 1323s, 1256s, 1002s, 881m, 866m, 854m, 778s, 694s, 681s, 621m. 1H-NMR (300 MHz, CDCl3): 2.01 (s,
Me); 2.51 (dd, J ¼ 4.0, 16.7, 1 H, CH2); 2.67 (dd, J ¼ 14.0, 1 H, CH2); 5.30 (dd, J ¼ 3.5, 14.0, CH); 5.37 (s, 1
olefin. H); 7.21 (t, J ¼ 6.2, 1 arom. H); 7.22 (d, J ¼ 6.7, 1 arom. H); 7.43 (d, J ¼ 6.7, 1 arom. H); 7.51 (s, 1
arom. H). 13C-NMR (62 MHz, CDCl3): 21.0 (Me); 42.3 (CH2); 79.9 (CH); 105.4 (olefin. CH); 122 (arom.
C); 124.6, 129.2, 130.3, 131.8 (arom. CH); 140.4 (arom. C); 174.0 (olefin. C); 191.6 (CO). GC/EI-MS
(70 eV): 266 (7, Mþ), 250 (11), 248 (11), 184 (98), 182 (100), 144 (30). HR-ESI-MS: 265.9935 (Mþ,
C12H1179BrOþ2 ; calc. 265.9937), 267.9917 (Mþ, C12H1181BrO2þ ; calc. 267.9917).
2,3-Dihydro-6-methyl-2-(3-methylphenyl)-4H-pyran-4-one (3f). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2f (0.60 g, 5 mmol) in THF (15 ml): 3f (0.77 g, 76%). Colorless
oil. IR (KBr): 3317w, 3028w, 2918w, 2734w, 2610w, 1664s, 1604s, 1490w, 1435w, 1359m, 1256m, 1183m,
1095w, 1025m, 951m, 886m, 808m, 759m, 699m, 660w, 618w, 551w. 1H-NMR (300 MHz, CDCl3): 2.08 (s,
Me); 2.38 (s, Me of Ar), 2.53 (dd, J ¼ 3.5, 16.8, 1 H, CH2); 2.78 (dd, J ¼ 14.1, 1 H, CH2); 5.33 (dd, J ¼ 3.5,
14.1, CH); 5.42 (s, 1 olefin. H); 7.17 (d, J ¼ 7.8, 1 arom. H); 7.20 (d, J ¼ 7.2, 1 arom. H); 7.22 (s, 1 arom. H);
7.29 (t, J ¼ 7.5, 1 arom. H). 13C-NMR (75 MHz, CDCl3): 21.1 (Me); 21.4 (Me of Ar); 42.3 (CH2); 80.9
(CH); 105.1 (olefin. CH); 123.2, 126.9, 128.7, 129.5 (arom. CH); 138.1, 138.5 (arom. C); 174.2 (olefin. C);
192.2 (CO). GC/EI-MS (70 eV): 202 (3, Mþ), 184 (14), 160 (15), 159 (41), 119 (10), 118 (100), 117 (60),
115 (17), 91 (17). HR-EI-MS: 202.0989 (Mþ, C13H14Oþ2 ; calc. 202.0988). Anal. calc. for C13H14O2: C 77.20,
H 6.98; found: C 77.01, H 6.794.
2,3-Dihydro-6-methyl-2-(4-methylphenyl)-4H-pyran-4-one (3g). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2g (0.60 g, 5 mmol) in THF (15 ml): 3g (0.90 g, 89%). Colorless
crystalline solid. M.p. 44 – 458. IR (KBr): 3278w, 2998w, 2920w, 2865w, 1661s, 1600s, 1513m, 1339m,
1244m, 1183m, 1019s, 811m, 539s. 1H-NMR (300 MHz, CDCl3): 1.98 (s, Me); 2.29 (s, Me of Ar); 2.48 (dd,
J ¼ 3.5, 16.7, 1 H, CH2); 2.73 (dd, J ¼ 14.1, 1 H, CH2); 5.26 (dd, J ¼ 3.4, 14.1, CH); 5.34 (s, 1 olefin. H);
7.12 – 7.16 (m, 2 arom. H); 7.19 – 7.24 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 21.1 (Me); 21.2 (Me of
Ar); 42.2 (CH2); 80.8 (CH); 105.1 (olefin. CH); 126.2, 129.4 (arom. CH); 137.2, 138.8 (arom. C); 174.4
(olefin. C); 192.5 (CO). EI-MS (70 eV): 202 (2, Mþ), 184 (11), 160 (22), 159 (30), 119 (10), 118 (100),
117 (60), 115 (16), 91 (17). HR-EI-MS: 202.0989 (Mþ, C13H14O2þ ; calc. 202.0988). Anal. calc. for
C13H14O2: C 77.20, H 6.98; found: C 77.21, H 6.95.
2-(4-Ethylphenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3h). With
a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2h (0.67 g, 5.0 mmol) in THF (15 ml): 3h (0.97 g, 90%).
Colorless crystalline solid. M.p. 72 – 738. IR (KBr): 3308w, 3058w, 2963w, 2933w, 2871w, 2608w, 1806w,
1714w, 1658s, 1602s, 1546m, 1435m, 1390s, 1326m, 1230m, 1178m, 998s, 815m, 791m, 659m, 539m.
1H-NMR (300 MHz, CDCl3): 1.27 (t, J ¼ 7.5, MeCH2); 2.08 (s, Me); 2.54 (dd, J ¼ 3.5, 16.8, 1 H, CH2); 2.69
(q, J ¼ 7.5, MeCH2); 2.84 (dd, J ¼ 14.1, 1 H, CH2); 5.26 (dd, J ¼ 3.5, 14.1, CH); 5.45 (s, 1 olefin. H); 7.26 –
7.28 (m, 2 arom. H); 7.34 – 7.36 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 15.5 (MeCH2); 21.5 (Me);
28.6 (MeCH2); 42.2 (CH2); 80.8 (CH); 105.1 (olefin. CH); 126.3, 128.3 (arom. CH); 135.4, 145.1 (arom.
C); 174.3 (olefin. C); 192.5 (CO). EI-MS (70 eV): 216 (2, Mþ), 198 (13), 174 (29), 173 (30), 133 (10), 132
(77), 118 (10), 117 (100), 115 (18), 91 (14). HR-EI-MS: 216.1145 (Mþ, C14H16O2þ ; calc. 216.1145).
2,3-Dihydro-2-(4-methoxyphenyl)-6-methyl-4H-pyran-4-one (3i). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2i (0.68 g, 5.0 mmol) in THF (15 ml): 3i (0.70 g, 64%). Colorless
solid. M.p. 64 – 658. IR (KBr): 2998w, 2934w, 2836w, 1712m, 1608s, 1511s, 1461m, 1396m, 1242s, 1173s,
1149s, 1028s, 1006m, 957m, 930m, 869m, 828s, 818s, 798m, 658m, 545m. 1H-NMR (300 MHz, CDCl3): 1.98
(s, Me); 2.47 (dd, J ¼ 3.4, 16.8, 1 H, CH2); 2.74 (dd, J ¼ 14.1, 1 H, CH2); 3.75 (s, MeO); 5.25 (dd, J ¼ 3.4,
14.1, CH); 5.34 (s, CH); 6.85 – 6.88 (m, 2 arom. H); 7.25 – 7.28 (m, 2 arom. H). 13C-NMR (75 MHz,
CDCl3): 21.1 (Me); 42.1 (CH2); 55.3 (MeO); 80.6 (CH); 105.1 (olefin. CH); 114.1, 127.8 (arom. CH);
130.1, 160.0 (arom. C); 174.4 (olefin. C); 192.6 (CO). GC/EI-MS (70 eV): 218 (7, Mþ), 200 (8), 175 (13),
160 (22), 134 (100), 119 (21), 91 (14), 77 (5). HR-EI-MS: 218.0938 (Mþ, C13H14O3þ ; calc. 218.0938).

Helvetica Chimica Acta – Vol. 93 (2010)
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2-(2,3-Dimethoxyphenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3j). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2j (0.83 g, 5.0 mmol) in THF (15 ml): 3j (0.91 g, 73%). Solid.
M.p. 86 – 878. IR (KBr): 2962w, 2937w, 2835w, 1721w, 1664w, 1602m, 1586m, 1478m, 1429m, 1395m,
1302m, 1273m, 1219m, 1082m, 999s, 927m, 856m, 785m, 747m, 629m, 558m. 1H-NMR (300 MHz, CDCl3):
1.99 (s, Me); 2.49 (dd, J ¼ 3.5, 16.8, 1 H, CH2); 2.66 (dd, J ¼ 14.3, 1 H, CH2); 3.79 (s, MeO); 3.81 (s, MeO);
5.45 (s, 1 olefin. H); 5.65 (dd, J ¼ 3.5, 14.3, CH); 6.77 (d, J ¼ 7.7, 1 arom. H); 7.01 (t, J ¼ 7.4, 1 arom. H); 7.8
(d, J ¼ 7.8, 1 arom. H). 13C-NMR (62 MHz, CDCl3): 21.1 (Me); 41.7 (CH2); 55.8, 60.0 (2 MeO); 76.1
(CH); 105.0 (olefin. CH); 111.6, 118.3, 124.3 (arom. CH); 132.0, 146.2, 152.3 (arom. C); 174.5 (olefin. C);
192.7 (CO). EI-MS (70 eV): 248 (Mþ, 37), 230 (19), 217 (30), 206 (47), 205 (51), 175 (21), 174 (20), 164
(78), 150 (10), 149 (100), 121 (75), 91 (29), 78 (20), 77 (21). HR-ESI-TOF-MS: 249.1118 ([M þ H]þ,
C14H16Oþ4 ; calc. 249.1121). Anal. calc. for C14H16O4: C 67.73, H 6.50; found: C 67.70, H 7.19.
2-(2,4-Dimethoxyphenyl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3k). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2k (0.83 g, 5.0 mmol) in THF (15 ml): 3k (0.86 g, 70%). Solid.
M.p. 108 – 1108. IR (KBr): 3073w, 2971w, 2837w, 1655s, 1603s, 1583s, 1508m, 1461m, 1439m, 1158s, 1031m,
1
1020m, 991s, 827s, 804s, 547m. H-NMR (300 MHz, CDCl3): 1.99 (s, Me); 2.49 (dd, J ¼ 3.7, 16.7, 1 H,
CH2); 2.56 (dd, J ¼ 14.0, 1 H, CH2); 3.73 (s, MeO); 3.75 (s, MeO); 5.33 (s, 1 olefin. H); 5.61 (dd, J ¼ 3.7,
14.0, CH); 6.41 (s, 1 arom. H); 6.46 (d, J ¼ 8.4, 1 arom. H); 7.30 (d, J ¼ 8.4, 1 arom. H). 13C-NMR
(75 MHz, CDCl3): 21.1 (Me); 41.4 (CH2); 55.3, 55.4 (2 MeO); 75.9 (CH); 98.4 (arom. CH); 104.9 (olefin.
CH); 105.3 (arom. CH); 119.2 (arom. C); 127.4 (arom. CH); 157.3, 161.0 (arom. C); 174.8 (olefin. C);
193.3 (CO). GC/EI-MS (70 eV): 248 (27, Mþ), 205 (21), 164 (100), 149 (83), 121 (45), 91 (13), 77 (12).
HR-EI-MS: 248.1041 (Mþ, C14H16O4þ ; calc. 248.1043). Anal. calc. for C14H16O4: C 67.73, H 6.50; found: C
67.64, H 6.57.
2,3-Dihydro-2-(3-hydroxyphenyl)-6-methyl-4H-pyran-4-one (3l). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2l (0.61 g, 5.0 mmol) in THF (15 ml): 3l (0.68 g, 67%). Solid.
M.p. 140 – 1428. IR (KBr): 3052m, 2957m, 2829w, 2600w, 1633m, 1596m, 1580s, 1574s, 1484m, 1397m,
1360m, 1220s, 1175m, 1025m, 1004m, 939m, 786m, 697m, 529m. 1H-NMR (300 MHz, (D6)DMSO): 2.10
(s, Me); 2.55 (dd, J ¼ 3.7, 16.9, 1 H, CH2); 2.81 (dd, J ¼ 13.8, 1 H, CH2); 5.40 (dd, J ¼ 3.6, 13.8, CH); 5.46
(s, 1 olefin. H); 6.78 (t, J ¼ 7.4, 1 arom. H); 6.89 (d, J ¼ 7.8, 1 arom. H); 6.91 (d, J ¼ 7.3, 1 arom. H); 7.24 (s,
1 arom. H); 9.46 (br. s, OH). 13C-NMR (75 MHz, (D6)DMSO): 21.1 (Me); 42.9 (CH2); 82.1 (CH); 105.3
(olefin. CH); 114.1, 116.6, 118.3, 130.8 (arom. CH); 141.2, 158.9 (arom. C); 177.5 (olefin. C); 195.4 (CO).
GC/EI-MS (70 eV): 204 (12, Mþ), 186 (13), 161 (24), 120 (100), 91 (21). HR-EI-MS: 204.0784
(C12H12Oþ3 ; calc. 204.0781).
2,3-Dihydro-2-(4-hydroxyphenyl)-6-methyl-4H-pyran-4-one (3m). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2m (0.61 g, 5.0 mmol) in THF (15 ml): 3m (0.70 g, 69%).
Colorless crystalline solid. M.p. 160 – 1618. IR (KBr): 3151w, 3069w, 2974w, 2900w, 1630m, 1615m, 1576m,
1515m, 1463m, 1393m, 1251m, 1234s, 1224m, 1188m, 1066m, 1017m, 997m, 818s, 792m, 744m, 666m.
1H-NMR (300 MHz, (D6)DMSO): 1.96 (s, Me); 2.37 (dd, J ¼ 3.5, 16.9, 1 H, CH2); 2.77 (dd, J ¼ 14.1, 1 H,
CH2); 5.25 (dd, J ¼ 3.5, 14.1, CH); 5.32 (s, 1 olefin. H); 6.68 – 6.73 (m, 2 arom. H); 7.15 – 7.20 (m, 2 arom.
H); 9.52 (br. s, OH). 13C-NMR (75 MHz, (D6)DMSO): 21.1 (Me); 42.7 (CH2); 82.3 (CH); 105.1 (olefin.
CH); 116.3, 129.1 (arom. CH); 130.4, 159.2 (arom. C); 177.8 (olefin. C); 195.9 (CO). GC/EI-MS (70 eV):
204 (51, Mþ), 186 (43), 171 (28), 161 (79), 147 (100), 119 (29), 91 (21), 77 (8). HR-EI-MS: 204.0782 (Mþ,
C12H12Oþ3 ; calc. 204.0781).
2,3-Dihydro-6-methyl-2-(3-nitrophenyl)-4H-pyran-4-one (3n). With
a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2n (0.75 g, 5.0 mmol) in THF (15 ml): 3n (0.66 g, 57%). Solid.
M.p. 108 – 1098. IR (KBr): 3089w, 2915w, 1721m, 1611m, 1524s, 1479m, 1413m, 1346s, 1308m, 1231m,
1055m, 928m, 804m, 735s, 684m. 1H-NMR (300 MHz, CDCl3): 2.05 (s, Me); 2.59 (dd, J ¼ 4.0, 16.6, 1 H,
CH2); 2.71 (dd, J ¼ 13.6, 1 H, CH2); 5.40 (s, CH); 5.44 (dd, J ¼ 4.0, 13.6, CH); 7.55 (t, J ¼ 7.9, 1 arom. H);
7.67 (d, J ¼ 7.7, 1 arom. H); 8.18 (d, J ¼ 8.1, 1 arom. H); 8.26 (s, 1 arom. H). 13C-NMR (75 MHz, CDCl3):
21.0 (Me); 42.3 (CH2); 79.3 (CH); 105.6 (olefin. CH); 121.1, 123.6, 129.9, 131.9 (arom. CH); 140.4, 148.5
(arom. C); 173.7 (olefin. C); 190.9 (CO). EI-MS (70 eV): 233 (6, Mþ), 176 (11), 174 (6), 152 (25), 150
(22), 100 (58), 91 (8), 85 (100), 105 (21), 100 (58), 77 (29), 43 (68). HR-EI-MS: 233.0679 (Mþ,
C12H11NOþ4 ; calc. 233.0683).

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2,3-Dihydro-6-methyl-2-(4-nitrophenyl)-4H-pyran-4-one (3o). With
a
THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2o (0.75 g, 5.0 mmol) in THF (15 ml): 3o (0.70 g, 60%).
Colorless crystalline solid. M.p. 128 – 1308. IR (KBr): 3074w, 2905w, 2847w, 1721m, 1651s, 1598s, 1512s,
1494m, 1436m, 1396m, 1342s, 1330s, 1296m, 1234m, 1184m, 1161m, 1104m, 1071m, 1030m, 1009m, 950m,
899m, 850s, 833s, 747m, 697m, 682m, 648m. 1H-NMR (300 MHz, CDCl3): 2.05 (s, Me); 2.58 (dd, J ¼ 4.4,
16.7, 1 H, CH2); 2.67 (dd, J ¼ 13.1, 1 H, CH2); 5.62 (s, 1 olefin. H); 5.45 (dd, J ¼ 4.5, 13.1, CH); 7.51 – 7.54
(m, 2 arom. H); 8.20 – 8.23 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 21.0 (Me); 42.3 (CH2); 79.4
(CH); 105.7 (olefin. CH); 124.1, 126.7 (arom. CH); 145.2, 148.0 (arom. C); 173.7 (olefin. C); 190.9 (CO).
GC/EI-MS (70 eV): 233 (10, Mþ), 200 (11), 191 (23), 174 (15), 149 (100), 119 (41), 103 (32), 102 (14), 91
(28), 77 (42), 69 (10), 51 (11), 43 (19). HR-EI-MS: 233.0678 (Mþ, C12H11NO4þ ; calc. 233.0683).
2-(1,1’-Biphenyl-4-yl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3p). With a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2p (0.91 g, 5.0 mmol) in THF (15 ml): 3p (1.13 g, 86%).
Colorless crystalline solid. M.p. 76 – 778. IR (KBr): 3056w, 3027w, 2990w, 2836w, 1712w, 1660m, 1601s,
1485m, 1432m, 1394m, 1331m, 1235m, 1000s, 951m, 899m, 872m, 763m, 730m, 701s, 657m. 1H-NMR
(300 MHz, CDCl3): 2.01 (s, Me); 2.55 (dd, J ¼ 3.0, 16.8, 1 H, CH2); 2.78 (dd, J ¼ 14.1, 1 H, CH2); 5.36 (dd,
J ¼ 3.4, 14.1, CH); 5.45 (s, 1 olefin. H); 7.26 – 7.57 (m, 9 arom. H). 13C-NMR (62 MHz, CDCl3): 21.1 (Me);
42.2 (CH2); 80.6 (CH); 105.2 (olefin. CH); 126.6, 127.1, 127.4, 127.6, 128.8 (arom. CH); 137.0, 140.4, 141.8
(arom. C); 174.3 (olefin. C); 192.3 (CO). EI-MS (70 eV): 264 (6, Mþ), 222 (18), 221 (19), 180 (100), 165
(10), 152 (9). HR-EI-MS: 264.1144 (Mþ, C18H16O2þ ; calc. 264.1145).
2-(Furan-2-yl)-2,3-dihydro-6-methyl-4H-pyran-4-one (3q). With a THF soln. of LDA (12.5 mmol),
1a (0.50 g, 5.0 mmol), and 2q (0.48 g, 5.0 mmol) in THF (15 ml): 3q (0.77 g, 87%). Colorless crystalline
solid. M.p. 57 – 588. IR (KBr): 3076w, 2962w, 2917w, 1660s, 1603s, 1434m, 1390s, 1315s, 1235s, 1196m,
1167m, 1155m, 1034m, 992s, 944m, 850m, 810m, 701s, 630m, 595m. 1H-NMR 300 MHz, CDCl3): 1.96 (s,
Me); 2.56 (dd, J ¼ 3.8, 16.3, 1 H, CH2); 2.92 (dd, J ¼ 13.0, 1 H, CH2); 5.36 (dd, J ¼ 3.8, 13.0, CH); 5.33 (s,
CH); 6.33 (t, J ¼ 3.3, 1 furyl H); 6.37 (d, J ¼ 3.2, 1 furyl H); 7.40 (d, J ¼ 1.7, 1 furyl H). 13C-NMR (62 MHz,
CDCl3): 21.0 (Me); 38.5 (CH2); 73.3, 105.2 (CH); 109.4, 110.5, 143.4 (furyl CH); 150.3 (furyl C); 173.6
(olefin. C); 191.5 (CO). GC/EI-MS (70 eV): 178 (14, Mþ), 160 (5), 94 (100), 66 (17), 65 (12), 39 (11).
HR-EI-MS: 178.0623 (Mþ, C10H10O3þ ; calc. 178.0625).
2,3-Dihydro-6-methyl-2-(thiophen-2-yl)-4H-pyran-4-one (3r). With
a THF soln. of LDA
(12.5 mmol), 1a (0.50 g, 5.0 mmol), and 2r (0.56 g, 5.0 mmol) in THF (15 ml): 3r (0.80 g, 82%). Redish
viscous oil. IR (KBr): 3139w, 3127w, 3078w, 2914w, 1657m, 1604s, 1503m, 1439m, 1387s, 1322s, 1183s,
1147s, 1000s, 900m, 864m, 841m, 820m, 741s, 683m, 597m. 1H-NMR (300 MHz, CDCl3): 2.07 (s, Me); 2.77
(dd, J ¼ 4.0, 16.7, 1 H, CH2); 2.93 (dd, J ¼ 12.6, 1 H, CH2); 5.44 (s, CH); 5.64 (dd, J ¼ 4.0, 12.6, CH); 7.04
(d, J ¼ 3.5, 1 thienyl H); 7.12 (t, J ¼ 3.5, 1 thienyl H); 7.39 (d, J ¼ 5.0, 1 thienyl H). 13C-NMR (75 MHz,
CDCl3): 21.1, (Me); 42.1 (CH2); 76.2 (CH); 105.4 (CH); 126.1, 126.6, 126.9 (thienyl CH); 140.8 (thienyl
C); 173.7 (olefin. C); 191.5 (CO). EI-MS (70 eV): 194 (7, Mþ), 176 (16), 161 (10), 151 (12), 110 (100),
109 (13). HR-EI-MS: 194.0399 (Mþ, C10H10O2Sþ; calc. 194.0396).
2,3-Dihydro-2,6-diphenyl-4H-pyran-4-one (3s). With a THF soln. of LDA (12.5 mmol), 1b (0.81 g,
5.0 mmol), and 2a (0.53 g, 5.0 mmol) in THF (15 ml): 3s (0.97 g, 78%). Colorless crystalline solid. M.p.
93 – 948. IR (KBr): 3292w, 3064w, 3029w, 2896w, 1710s, 1650s, 1592m, 1570m, 1490m, 1382m, 1315m,
1
1245m, 1178m, 1046m, 937m, 854m, 762s, 692s, 664m, 614m, 569m. H-NMR (300 MHz, (D6)DMSO):
2.69 (dd, J ¼ 3.4, 16.6, 1 H, CH2); 3.02 (dd, J ¼ 13.6, 1 H, CH2); 5.75 (dd, J ¼ 3.4, 13.6, CH); 6.21 (s, 1
olefin. H); 7.40 – 7.88 (m, 10 arom. H). 13C-NMR (75 MHz, (D6)DMSO): 41.8 (CH2); 80.1 (CH); 101.9
(olefin. CH); 126.4, 126.5, 128.54, 128.59, 128.8, 131.7 (arom. CH); 132.2, 138.5 (arom. C); 168.7 (olefin.
C); 192.0 (CO). EI-MS (70 eV): 250 (6, Mþ), 232 (11), 145 (25), 144 (17), 105 (40), 104 (100), 103 (18),
78 (16), 77 (23). HR-EI-MS: 250.0991 (C17H14Oþ2 ; calc. 250.0988). Anal. calc. for C17H14O2: C 81.58, H
5.64; found: C 81.56, H 5.72.
2-(2-Chlorophenyl)-2,3-dihydro-6-phenyl-4H-pyran-4-one (3t). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2b (0.70 g, 5.0 mmol) in THF (15 ml): 3t (0.88 g, 62%).
Colorless crystalline solid. M.p. 96 – 988. IR (KBr): 3282w, 3063w, 3035w, 2968w, 2916w, 1651s, 1595s,
1570m, 1450m, 1378s, 1327s, 1293m, 1233m, 1131m, 1071m, 993m, 941m, 856m, 805m, 772m, 754s, 685s,
669s, 616m, 567m, 540m. 1H-NMR (300 MHz, (D6)DMSO): 2.68 (dd, J ¼ 3.3, 16.7, 1 H, CH2); 3.07 (dd,
J ¼ 14.0, 1 H, CH2); 5.95 (dd, J ¼ 3.2, 14.0, CH), 6.25 (s, 1 olefin. H); 7.47 – 7.89 (m, 9 arom. H). 13C-NMR

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(62 MHz, (D6)DMSO): 40.2 (CH2); 77.2 (CH); 101.9 (olefin. CH); 126.4, 127.7, 128.1, 128.8, 129.7, 130.4,
131.8 (arom. CH); 131.9, 132.0, 135.3 (arom. C); 168.8 (olefin. C); 191.6 (CO). GC/EI-MS (70 eV): 284
(9, Mþ), 249 (22), 179 (10), 178 (10), 140 (34), 139 (10), 138 (100), 105 (48), 103 (35), 102 (11), 77 (29).
HR-EI-MS: 284.0599 (C17H13ClOþ2 ; calc. 284.0599). Anal. calc. C17H13ClO2: C 71.71, H 4.60; found: C
71.74, H 4.62.
2-(4-Chlorophenyl)-2,3-dihydro-6-phenyl-4H-pyran-4-one (3u). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2d (0.70 g, 5.0 mmol) in THF (15 ml): 3u (0.94 g, 82%).
Colorless crystalline solid. M.p. 90 – 928. IR (KBr): 3281w, 3089w, 3058w, 2965w, 2895w, 1651s, 1595s,
1568s, 1492s, 1449m, 1376m, 1328m, 1293m, 1215m, 1160m, 1089m, 993m, 855m, 835m, 804m, 768s, 681s,
664s, 615m, 566m, 540m. 1H-NMR (300 MHz, (D6)DMSO): 2.72 (dd, J ¼ 3.4, 16.6, 1 H, CH2); 3.05 (dd,
J ¼ 13.6, 1 H, CH2); 5.78 (dd, J ¼ 3.4, 13.6, CH); 6.21 (s, 1 olefin. H); 7.35 – 7.56 (m, 5 arom. H); 7.62 – 7.65
(m, 2 arom. H); 7.84 – 7.88 (m, 2 arom. H). 13C-NMR (62 MHz, (D6)DMSO): 41.6 (CH2); 79.3 (CH);
101.9 (olefin. CH); 126.4, 128.4, 128.5, 128.8, 131.7 (arom. CH); 132.1, 133.1, 137.5 (arom. C); 168.6
(olefin. C); 191.8 (CO). GC/EI-MS (70 eV): 284 (6, Mþ), 179 (13), 178 (10), 140 (32), 139 (10), 138
(100), 105 (44), 103 (25), 102 (10), 77 (24). HR-ESI-TOF-MS: 284.0603 (C17H13ClOþ2 ; 284.0599). Anal.
calc. C17H13ClO2: C 71.71, H 4.60; found: C 71.65, H 4.95.
2-(3-Bromophenyl)-2,3-dihydro-6-phenyl-4H-pyran-4-one (3v). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2e (0.92 g, 5.0 mmol) in THF (15 ml): 3v (1.16 g, 72%).
Colorless crystalline solid. M.p. 103 – 1048. IR (KBr): 3291w, 3057w, 2976w, 2910w, 1722w, 1651s, 1593s,
1567m, 1492m, 1448m, 1366m, 1292m, 1241m, 1174m, 1073m, 991m, 946m, 880m, 830m, 783m, 767s, 684s,
1
661m, 612m, 586m. H-NMR (300 MHz, (D6)DMSO): 2.70 (dd, J ¼ 3.4, 16.7, 1 H, CH2); 3.04 (dd, J ¼
13.7, 1 H, CH2); 5.80 (dd, J ¼ 3.3, 13.7, CH); 6.21 (s, 1 olefin. H); 7.41 – 7.64 (m, 6 arom. H), 7.81 – 7.88
(m, 3 arom. H). 13C-NMR (62 MHz, (D6)DMSO): 41.2 (CH2); 79.3 (CH); 102.0 (olefin. CH); 121.8
(arom. C); 125.6, 126.4, 128.8, 129.3, 130.8, 131.4, 131.7 (arom. CH); 132.1, 141.2 (arom. C); 168.6 (olefin.
C); 191.8 (CO). GC/EI-MS (70 eV): 328 (5, Mþ), 312 (13), 310 (12), 224 (12), 222 (11), 184 (85), 183
(10), 182 (88), 144 (14), 106 (10), 105 (100), 103 (46), 102 (21), 77 (55), 51 (13). HR-MS: 328.0089 (Mþ,
C17H1379BrO2þ ; calc. 328.0093), 330.0073 (Mþ, C17H1381BrOþ2 ; calc. 330.0073). Anal. calc. for C17H13BrO2:
C 62.03, H 3.98; found: C 62.01, H 3.97.
2,3-Dihydro-2-(4-methylphenyl)-6-phenyl-4H-pyran-4-one (3w). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2g (0.60 g, 5.0 mmol) in THF (15 ml): 3w (1.04 g, 79%).
Colorless crystalline solid. M.p. 72 – 738. IR (KBr): 3065w, 2918w, 1713w, 1648s, 1590s, 1566s, 1489m,
1411m, 1377s, 1329s, 1248m, 1047m, 936, 828m, 809s, 771s, 687s, 558m. 1H-NMR (300 MHz, CDCl3): 2.2
(s, Me); 2.67 (dd, J ¼ 4.0, 16.5, 1 H, CH2); 2.88 (dd, J ¼ 13.3, 1 H, CH2); 5.57 (dd, J ¼ 3.9, 13.4, CH); 6.04
(s, 1 olefin. H); 7.20 – 7.41 (m, 9 arom. H). 13C-NMR (62 MHz, CDCl3): 21.2 (Me); 42.9 (CH2); 81.0 (CH);
102.3 (olefin. CH); 126.2, 126.6, 127.6, 129.7, 131.7 (arom. CH); 132.6, 135.2, 138.8 (arom. C); 170.4
(olefin. C); 193.2 (C). EI-MS (70 eV): 264 (4, Mþ), 246 (13), 159 (34), 158 (13), 118 (100), 117 (51), 91
(16), 77 (15). HR-EI-MS: 264.1144 (C18H16Oþ2 ; calc. 264.1145).
2,3-Dihydro-2-(4-methoxyphenyl)-6-phenyl-4H-pyran-4-one (3x). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2i (0.68 g, 5.0 mmol) in THF (15 ml): 3x (1.0 g, 72%). Colorless
crystalline solid. M.p. 94 – 958. IR (KBr): 3271w, 3082w, 3014w, 2933w, 2837w, 1712w, 1650m, 1588m,
1507s, 1494m, 1453m, 1375m, 1325m, 1288m, 1209m, 1158m, 1124m, 1029s, 954m, 835m, 733s, 695s, 674m,
1
617m, 573m, 527m. H-NMR (300 MHz, (D6)DMSO): 2.61 (dd, J ¼ 3.3, 16.7, 1 H, CH2); 3.05 (dd, J ¼
13.7, 1 H, CH2); 3.79 (s, MeO); 5.68 (dd, J ¼ 3.3, 13.7, CH); 6.18 (s, 1 olefin. H); 7.00 – 7.03 (m, 2 arom.
H), 7.46 – 7.55 (m, 5 arom. H); 7.81 – 7.85 (m, 2 arom. H). 13C-NMR (62 MHz, (D6)DMSO): 41.6 (CH2);
55.1 (Me); 80.0 (CH); 101.7 (olefin. CH); 113.9, 126.3, 128.2, 128.7 (arom. CH); 130.3 (arom. C); 131.6
(arom. CH); 132.3, 159.4 (arom. C); 168.8 (olefin. C); 192.3 (CO). GC/EI-MS (70 eV): 280 (4, Mþ), 262
(13) 175 (30), 134 (100), 119 (20), 105 (15), 91 (16), 77 (14). HR-EI-MS: 280.1097 (C18H16Oþ3 ; calc.
280.1094). Anal. calc. for C18H16O3: C 77.12, H 5.75; found: C 77.27, H 5.70.
2,3-Dihydro-2-(2,4-dimethoxyphenyl)-6-phenyl-4H-pyran-4-one (3y). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2k (0.83 g, 5.0 mmol) in THF (15 ml): 3y (0.96 g, 73%). Colorless
crystalline solid. M.p. 101 – 1028. IR (KBr): 3271w, 3082w, 2966w, 2933w, 2837w, 1650m, 1613m, 1566m,
1453m, 1375m, 1288m, 1209m, 1158m, 1029m, 954m, 835m, 773s, 695s. 1H-NMR (300 MHz, (D6)DMSO):
2.67 (dd, J ¼ 4.0, 16.8, 1 H, CH2); 2.78 (dd, J ¼ 13.5, 1 H, CH2); 3.77 (s, 2 Me); 5.80 (dd, J ¼ 4.0, 13.5, CH);

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Helvetica Chimica Acta – Vol. 93 (2010)
6.03 (s, 1 olefin. H); 6.45 (s, 1 arom. H); 6.50 (d, J ¼ 8.4, 1 arom. H); 7.34 – 7.42 (m, 4 arom. H); 7.71 (d, J ¼
8.1, 1 arom. H). 13C-NMR (75 MHz, (D6)DMSO): 41.9 (CH2); 55.4 (2 MeO); 76.2 (CH); 98.5 (arom.
CH); 102.1 (arom. CH); 104.4 (olefin. CH); 117.4, 124.7 (arom. C); 126.6, 127.4, 128.6, 131.5 (arom. CH);
155.5, 159.1 (arom. C); 168.9 (olefin. C); 192.0 (CO). EI-MS (70 eV): 310 (20, Mþ), 205 (67), 165 (13.4),
164 (100), 149 (73), 121 (39.1), 105 (24.8), 91 (11), 77 (20). HR-MS: 311.1275 ([M þ H]þ, C19H19O4þ ;
calc. 311.1278).
2,3-Dihydro-2-(4-hydroxyphenyl)-6-phenyl-4H-pyran-4-one (3z). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2m (0.61 g, 5 mmol) in THF (15 ml): 3z (0.97 g, 73%). Colorless
crystalline solid. M.p. 181 – 1828. IR (KBr): 3075m, 2963m, 2818m, 2753w, 2691w, 2613w, 1614m, 1565m,
1490m, 1367m, 1298w, 1236m, 1171m, 1072m, 991m, 934m, 865m, 821s, 770s, 687s, 639m, 583m. 1H-NMR
(300 MHz, (D6)DMSO): 2.57 (dd, J ¼ 3.3, 16.6, 1 H, CH2); 3.01 (dd, J ¼ 13.8, 1 H, CH2); 5.60 (dd, J ¼ 3.3,
13.8, CH); 6.15 (s, 1 olefin. H); 6.81 – 6.84 (m, 2 arom. H); 7.38 – 7.51 (m, 5 arom. H); 7.79 – 7.82 (m, 2
arom. H); 9.61 (br. s, OH).13C-NMR (75 MHz, (D6)DMSO): 41.6 (CH2); 80.2 (CH); 101.7 (olefin. CH);
115.9 (arom. CH); 125.7 (arom. C); 126.3 (arom. CH); 127.0 (arom. C); 128.3 (arom. CH); 128.6 (arom.
C); 128.7 (arom. CH); 130.2 (arom. C); 131.6 (arom. CH); 132.3, 157.7 (arom. C); 168.9 (olefin. C); 192.4
(CO). GC/EI-MS (70 eV): 266 (21, Mþ), 248 (53), 161 (88), 160 (35), 147 (31), 121 (31), 120 (100), 119
(32), 106 (20), 105 (76), 91 (55), 84 (10), 77 (37), 69 (20), 51 (10), 44 (19), 43 (11). HR-EI-MS:
266.093631 (Mþ, C17H14O3þ ; calc. 266.0938). Anal. calc. for C17H14O3: C 77.12, H 5.75; found: C 75.93, H
6.40.
2,3-Dihydro-2-(3-nitrophenyl)-6-phenyl-4H-pyran-4-one (3aa). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2n (0.75 g, 5.0 mmol) in THF (15 ml): 3aa (1.0 g, 68%).
Colorless crystalline solid. M.p. 104 – 1058. IR (KBr): 3107w, 3088w, 3068w, 2930w, 2894w, 1613s, 1573s,
1519m, 1494m, 1458m, 1393m, 1345s, 1285m, 1237m, 1185m, 1147m, 1060m, 1019m, 898m, 874m, 818m,
1
764s, 684s, 616m, 541m. H-NMR (300 MHz, (D6)DMSO): 2.77 (dd, J ¼ 3.4, 16.5, 1 H, CH2); 3.07 (dd,
J ¼ 13.8, 1 H, CH2); 5.93 (dd, J ¼ 3.4, 13.7, CH); 6.24 (s, 1 olefin. H); 7.46 – 8.28 (m, 8 arom. H), 8.46 (s, 1
arom. H). 13C-NMR (62 MHz, (D6)DMSO): 41.7 (CH2); 79.0 (CH); 102.1 (olefin. CH); 121.2, 123.3,
126.4, 128.8, 130.2, 131.7, 133.0 (arom. CH); 140.7, 147.8 (arom. C); 168.5 (olefin. C); 191.5 (CO). GC/EI-
MS (70 eV): 295 (2, Mþ), 162 (34), 161 (27), 151 (37), 150 (34), 147 (28), 120 (11), 105 (100), 104 (7), 78
(12), 77 (85), 76 (10), 69 (47), 51 (37), 50 (13), 43 (18). HR-EI-MS: 295.0840 (C17H13NOþ4 ; calc.
295.0839).
2,3-Dihydro-2-(4-nitrophenyl)-6-phenyl-4H-pyran-4-one (3ab). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2o (0.75 g, 5.0 mmol) in THF (15 ml): 3ab (0.98 g, 67%). Solid.
M.p. 118 – 1198. IR (KBr): 3108w, 3089w, 3068w, 2931w, 2895w, 1611s, 1573s, 1519m, 1495m, 1457m,
1394m, 1346s, 1286m, 1238m, 1185m, 1147m, 1060m, 1019m, 898m, 874m, 818m, 764s, 684s, 616m, 541m.
1H-NMR (300 MHz, (D6)DMSO): 2.73 (dd, J ¼ 4.2, 16.8, 1 H, CH2); 2.82 (dd, J ¼ 13.2, 1 H, CH2); 5.64
(dd, J ¼ 4.1, 13.2, CH); 6.09 (s, 1 olefin. H); 7.37 – 8.27 (m, 9 arom. H). 13C-NMR (75 MHz, (D6)DMSO):
42.9 (CH2); 79.7 (CH); 102.6 (olefin. CH); 124.2, 126.6, 126.8, 128.8, 132.1 (arom. CH); 135.4, 145.2
(arom. C); 169.8 (olefin. C); 191.4 (CO). GC/EI-MS (70 eV): 295 (48, Mþ), 294 (14), 176 (19), 173 (26),
144 (14), 115 (14), 106 (12), 105 (100), 102 (15), 77 (36), 69 (22), 51 (11). HR-EI-MS: 295.0842
(C17H13NOþ4 ; calc. 295.0839).
2-(1,1’-Biphenyl-4-yl)-2,3-dihydro-6-phenyl-4H-pyran-4-one (3ac). With a THF soln. of LDA
(12.5 mmol), 1b (0.81 g, 5.0 mmol), and 2p (0.91 g, 5.0 mmol) in THF (15 ml): 3ac was isolated as a
colorless crystalline solid (1.35 g, 83%). M.p. 110 – 1118. IR (KBr): 3368w, 3029w, 2964w, 1650s, 1593s,
1568s, 1487m, 1448m, 1378m, 1365m, 1229m, 1046m, 930m, 839m, 760s, 728s, 689s, 665m, 621m, 614m,
579m. 1H-NMR (300 MHz, CDCl3): 2.71 (dd, J ¼ 3.8, 16.7, CH); 2.89 (dd, J ¼ 13.2, 1 H, CH2); 5.56 (dd,
J ¼ 3.7, 13.2, CH); 6.08 (s, 1 olefin. H); 7.26 – 7.50 (m, 14 arom. C). 13C-NMR (75 MHz, CDCl3): 42.9
(CH2); 80.8 (CH); 102.3 (olefin. CH); 126.7, 127.1, 127.3, 127.6, 128.7, 128.8, 131.8, 132.5 (arom. CH);
127.0, 137.1, 140.4, 141.8 (arom. C); 170.3 (olefin. C); 192.8 (CO). GC/EI-MS (70 eV): 326 (5, Mþ), 308
(9), 221 (27), 180 (100), 165 (10), 105 (29), 91 (2), 77 (9). HR-EI-MS: 326.1300 (Mþ, C23H18O2þ ; calc.
326.1301). Anal. calc. for C23H18O2 C 84.64, H 5.56; found: C 84.63, H 5.54.
Financial support from the State of Pakistan (HEC scholarship for R. A. and I. U. and the DAAD
scholarships for R. A. K., I. U., and O. U. R.) is gratefully acknowledged.

Helvetica Chimica Acta – Vol. 93 (2010)
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REFERENCES
[1] S. J. Danishefsky, W. H. Pearson, B. E. Segmuller, J. Am. Chem. Soc. 1985, 107, 1280; S. J.
Danishefsky, M. P. DeNinno, Angew. Chem., Int. Ed. 1987, 26, 15; S. J. Danishefsky, M. T. Bilodeau,
Angew. Chem., Int. Ed. 1996, 35, 1380; S. J. Danishefsky, H. G. Selnick, R. E. Zelle, M. P. DeNinno, J.
Am. Chem. Soc. 1988, 110, 4368; J. D. Rainier, S. P. Allwein, J. M. Cox, Org. Lett. 2000, 2, 231; J. M.
Cox, J. D. Rainier, Org. Lett. 2001, 3, 2919; Y. Yamashita, S. Saito, H. Ishitani, S. Kobayashi, J. Am.
Chem. Soc. 2003, 125, 3793; D. R. Williams, R. W. Heidebrecht Jr., J. Am. Chem. Soc. 2003, 125,
1843; F. Kiuchi, Y. Goto, N. Sugimoto, N. Akao, K. Kondo, Y. Tsuda, Chem. Pharm. Bull. 1993, 41,
1640.
[2] K. A. Jørgensen, Angew. Chem., Int. Ed. 2000, 39, 3558; K. A. Jørgensen, Eur. J. Org. Chem. 2004,
2093.
´
[3] J. Barluenga, F. Aznar, M. Fernandez, Tetrahedron Lett. 1995, 36, 6551; P. A. Evans, J. D. Nelson, J.
Org. Chem. 1996, 61, 7600; P. A. Evans, J. D. Nelson, T. Manangan, Synlett 1997, 968; Y. Huang, V. H.
Rawal, J. Am. Chem. Soc. 2002, 124, 9662.
[4] G. Casiraghi, F. Zanardi, G. Appendino, G. Rassu, Chem. Rev. 2000, 100, 1929; A. Soriente, M. De
Rosa, R. Villano, A. Scettri, Curr. Org. Chem. 2004, 8, 993; S. E. Denmark, J. R. Heemstra Jr., G. L.
Beutner, Angew. Chem., Int. Ed. 2005, 44, 4682; M. Kalesse, Topics Curr. Chem. 2005, 244, 43.
[5] S. E. Denmark, J. R. Heemstra Jr., J. Org. Chem. 2007, 72, 5668.
[6] P. Langer, Synthesis 2002, 441.
[7] M. Reiter, S. Ropp, V. Gouverneur, Org. Lett. 2004, 6, 91.
[8] J. D. Winkler, K. Oh, Org. Lett. 2005, 7, 2421.
[9] B. Gao, Z. Yua, Z. Fua, X. Fenga, Tetrahedron Lett. 2006, 47, 1537.
[10] H. Wang, B. J. Shuhler, M. Xiang, J. Org. Chem. 2007, 72, 4280.
[11] R. J. Light, C. R. Hauser, J. Org. Chem. 1961, 26, 1716.
[12] P. Langer, W. Freiberg, Chem. Rev. 2004, 104, 4125.
[13] J. M. Ansell, A. Hassner, W. E. Burkholder, Tetrahedron Lett. 1979, 2497.
[14] J. R. Peterson, T. J. Winter, C. P. Miller, Synth. Commun. 1988, 18, 949.
[15] R. Ahmad, R. A. Khera, A. Villinger, P. Langer, Tetrahedron Lett. 2009, 50, 3020.
Received January 12, 2010