A new approach to 4,6-disubstituted-3,4-dihydropyran-2-ones by Domino Michael addition-cyclization reaction under PTC conditions

Article abstract of DOI:10.1016/j.tet.2014.09.022

Domino Michael addition-cyclization reactions of α,β-unsaturated carbonyl compounds with activated 1,3-dithiane-2-carbothioate esters under solid-liquid phase transfer catalysis conditions provide 4,6-disubstituted-3,4-dihydropyran-2-one-3,3-dithioacetals

Full text of DOI:10.1016/j.tet.2014.09.022

Tetrahedron 70 (2014) 8744e8749
Contents lists available at ScienceDirect
Tetrahedron
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A new approach to 4,6-disubstituted-3,4-dihydropyran-2-ones by
Domino Michael addition-cyclization reaction under PTC conditions
,
b
a
Nicoletta Gaggero a , Domenico C.M. Albanese , Donatella Nava
*
a
ꢀ
Dipartimento di Scienze Farmaceutiche (DISFARM), Sezione di Chimica Generale e Organica “Alessandro Marchesini” Universita degli Studi di Milano,
via Venezian 21, 20133 Milano, Italy
b
ꢀ
Dipartimento di Chimica, Universita degli Studi di Milano, via Golgi 19, 20133 Milano, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 July 2014
Received in revised form 27 August 2014
Accepted 8 September 2014
Available online 18 September 2014
Domino Michael addition-cyclization reactions of a,b-unsaturated carbonyl compounds with activated
1,3-dithiane-2-carbothioate esters under solid-liquid phase transfer catalysis conditions provide 4,6-
disubstituted-3,4-dihydropyran-2-one-3,3-dithioacetals in good chemical yield. Desulfurization pro-
ceeds chemoselectively under mild conditions affording 3,4-dihydropyran-2-ones in high yields.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Phase transfer catalysis
3,4-Dihydropyran-2-ones
1,3-Dithiane-2-carbothioate esters
Domino reactions
Thio-Michael addition
Organocatalysis
1. Introduction
generate suitable enolates for intra- and inter-molecular Michael
addition-lactonization processes directly from carboxylic acids.8
3,4-Dihydropyran-2-ones are versatile synthetic intermediates
in organic chemistry, widely employed in the synthesis of g-lac-
tones, substituted benzenoids and pyridines.1 Moreover, they
constitute the key functionalized subunit of isocoumarins, a family
of naturally occurring compounds, which show a broad spectrum of
interesting pharmacological activities.2
The Michael addition of enolates bearing good leaving groups to
a,b-unsaturated carbonyl compounds, followed by intramolecular
cyclization is one of the most straightforward, efficient and simple
methods for constructing the 3,4-dihydropyran-2-one skeleton and
is well precedented in the literature (Scheme 1, path a). For example,
Mukaiyama reported the use of silyl enolates derived from phenyl
esters in the presence of catalytic achiral quaternary ammonium
phenoxides3 and cinchonidine-derived chiral ones.4 Kobayashi
employed silyl enolates from thioesters with excess of mercuric
trifluoroacetate.5 Katritzky developed lithiated acylbenzotriazoles
as nucleophiles.6 More recently, 1,4-conjugate additions promoted
by catalytic N-heterocyclic carbenes were also reported.7 An alter-
native strategy exploited catalytic amounts of chiral isothioureas to
Scheme 1. Retrosynthesis of 4,6-disubstituted-3,4-dihydro pyran-2-ones.
Although these methods provide good yields of the expected
products, some of them suffer from limitations related to the use of
toxic or expensive compounds, or troublesome synthetic steps.
Therefore a practical method to carry out such transformations
would be desirable.
We envisioned the possibility of synthesizing enol lactones 4 by
a Michael addition-cyclization sequence utilizing activated thio-
ester enolates, generated in situ from 1,3-dithiane-2-carbothioate
* Corresponding author. Tel.: þ39 02 50314470; fax: þ 39 02 50314476; e-mail
address: nicoletta.gaggero@unimi.it (N. Gaggero).
http://dx.doi.org/10.1016/j.tet.2014.09.022
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

N. Gaggero et al. / Tetrahedron 70 (2014) 8744e8749
8745
Table 2
1,2, and chalcones 3 under phase transfer catalysis (PTC) conditions
(Scheme 2).
Synthesis of dihydropyran-2-ones 4aema
R2
R3
Yield (%)
3a,4a
3a,4ab
3b,4b
3c,4c
3d,4d
3e,4e
3f,4f
3g,4g
3h,4h
3i,4i
Ph
Ph
Ph
Ph
Ph
Ph
p-Cl-C6H4
Me
Ph
Ph
77
69
77
80
5
75
76
62
36
75
74
72
70
76
p-Cl-C6H4
p-OMe-C6H4
p-NO2-C6H4
p-F-C6H4
Ph
Scheme 2. Synthesis of 3,4-dihydropyran-2-ones under SL-PTC conditions.
The choice of nucleophiles 1 and 2 bearing 1,3-dithiane moiety
originated from abundant evidence regarding the marked stabi-
lizing effect of two sulfur atoms on an adjacent carbanion.9 Al-
though the commercially available ethyl 1,3-dithiane 2-carboxylate
could be deprotonated under PTC conditions thus establishing the
feasibility of the procedure, only the corresponding Michael adduct
could be isolated by reaction with chalcone 3a.10 The change from
an oxyester to a thioester is known to reduce the pKa value of the
Ph
Me
Ph
Ph
p-Br-C6H4
Ph
o-Cl-C6H4
3-methylthienyl
2-methylfuryl
3j,4j
3k,4k
3l,4l
p-OMe-C6H4
Ph
Ph
Ph
3m,4m
a
Reaction conditions: 1 (1 mmol), KOH (1 equiv), TEBA (0.1 equiv), 3 (1.1 equiv),
a
-proton thus facilitating the addition reaction.11
Most remarkably, the thioester group behaves as an excellent
CH3CN, rt, 5 h.
b
Thioester 2 was used and reacted for 24 h.
leaving group in the second step of the process allowing the
sequential cyclization of the Michael adduct to the desired
3,4-dihydropyran-2-ones 4.
The 1,3-dithiane group can be removed by many reported pro-
cedures.12 In our reaction scheme, we converted the enol lactones
4 intothecorresponding4,6-disubstituted-3,4-dihydropyran-2-ones
by nickel promoted reductive cleavage of the CeS bonds (Table 3).
Table 3
Desulfurization of enol lactones
Table 1
Methoda
R2
R3
Yield (%)
88
Optimization of the reaction conditionsa
4a,5a
4b,5b
4c,5c
4e,5e
4f,5f
4g,5g
4i,5i
4j,5j
A
B
B
B
B
B
B
B
B
B
B
Ph
Ph
Ph
Ph
p-Cl-C6H4
Me
Ph
Ph
Entry
1d
2
3
4
5
6
7
8
Base (eq)
Thioester
Conditionsb
Yield (%)c
p-Cl-C6H4 72
p-OMe-C6H4
p-F-C6H4
Ph
Ph
p-Br-C6H4
Ph
o-Cl-C6H4
3-methylthienyl
5-methylfuryl
KOH (1.1)
KOH (1)
KOH (1)
KOH (1)
KOH (1)
KOH (2)
KOH (0.1)
t-BuOK (1)
KOH (1)
K2CO3 (1)
K2CO3 (1)
K2CO3 (2)
KOH (1)
KOH (1)
KOH (1)
KOH (1)
K2CO3 (1)
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
5, DCM, rt
5, DCM, rt
74
75
76
76
d
70
65
76
58
77
70
69
72
73
24, DCM, rt
5, CH3CN, rt
24, CH3CN, reflux
24, DCM, rt
24, DCM, rt
24, THF, reflux
5, DCM, rt
24, DCM, rt
24, DCM, rt
24, DCM, rt
5, DCM, rt
d
p-OMe-C6H4
10
d
4k,5k
4l,5l
4m,5m
Ph
Ph
Ph
9e
10
11f
12
13g
14h
15i
16
17
30
78
55
d
a
Method A: Ni-Raney, EtOH, rt, overnight. Method B: NiCl2$6H2O, NaBH4, DMF,
0
ꢀC, 15 min.
85
83
77
69
d
5, DCM, rt
5, DCM, rt
24, DCM, rt
24, DCM, rt
air-stable solids and could be stored on the bench for several
months without special precautions.
The addition of 1,3-dithiane-2-carbothioate 1 to trans-chal-
cone 3a was chosen as a model reaction in order to find the best
reaction conditions. When the reaction was carried out with solid
KOH (1.1 equiv) in the presence of 10% of Bu4NþHSO4e, 9,11-
diphenyl-8-oxa-1,4-dithiaspiro[5.5]undec-9-en-7-one (4a) was
obtained in 74% chemical yield along with unreacted starting
materials (Table 1, entry 1). Similar results were obtained with
benzyltriethylammonium chloride (TEBA, Table 1, entry 2) that
was preferred to Bu4NþHSO4e in all subsequent experiments due
to its lower atomic mass (ensuring higher atomic efficiency).
Moreover, an additional amount of base was required to neu-
tralize the acidic hydrogensulfate anion in reactions carried out
with Bu4NþHSOe4 .
a
Performed on a 0.2 mmol scale at 0.4 M in dichloromethane (DMC) at rt with 1
(1 equiv), 3a (1 equiv), base (1 equiv), TEBA (0.1 equiv).
b
Reaction time (h), solvent and temperature, respectively.
Isolated yield after chromatography.
Bu4NHSO4 (0.1 equiv) was used instead of TEBA.
Without TEBA.
TEBA (0.05 equiv).
Thioester 1 (1.5 equiv).
3a (1.5 equiv).
3a (1.1 equiv).
c
d
e
f
g
h
i
2. Results and discussion
S-2,2,2-Trifluoroethyl-1,3-dithiane-2-carbothioate 1 was pre-
pared from 1,3-dithiane-2-carboxylic acid13 and 2,2,2-trifluoro
ethanethiol by means of HOBt and EDC$HCl.14 S-Phenyl-1,3-
dithio-2-carbothioate 2 was synthesized via 1,3-dithiane-2-acid
chloride15 by reaction with thiophenol in the presence of triethyl-
amine. Both thioesters 1 and 2 were isolated in high yields, were
Similar yields were obtained upon increasing the reaction time
to one day (Table 1, entry 3). This result can possibly be due to
partial hydrolysis of thioester 1. The same yield was obtained when
replacing dichloromethane with acetonitrile (Table 1, entry 4). On
the other hand, when the reaction was performed at reflux in
acetonitrile for one day or excess of KOH was used, only 3a was

8746
N. Gaggero et al. / Tetrahedron 70 (2014) 8744e8749
recovered along with unknown materials (Table 1, entries 5, 6). A
low amount of the expected 4a was generated by using a catalytic
amount of base (Table 1, entry 7), whereas the reaction did not
proceed without base. A complex reaction mixture was obtained
when t-BuOK was used under homogeneous conditions in THF, at
reflux (Table 1, entry 8).
examined, with the exception of 3h, only the starting ketones were
recovered along with enol lactones 4.
The 1,3-dithiane moiety of enol lactones 4 could be easily re-
moved by reductive desulfurization as demonstrated by the clean
conversion of 4a into 1,6-diphenyl-3,4-dihydropyran-2-one (5a) by
treatment with Raney-Ni in absolute ethanol at room temperature
(Table 3).
The desulfurization has also been carried out with the nickel
boride protocol, which enables faster reactions.19 When NaBH4 was
added in small portions to a solution of enol lactones 4 in DMF in
the presence of NiCl2 at 0 ꢀC, complete conversion to 5 was ob-
served after 15 min only. Desulfurized ring opening products were
isolated when the same reaction has been carried out in the pres-
ence of alcohols as reaction media. Following this procedure
3,4-dihydropyran-2-ones 5b,c,eeg,iem have been generated in
58e77% yields from the corresponding enol lactones 4.
The enol lactone 4a was recovered in 30% yield in the absence of
the phase transfer catalyst (Table 1, entry 9). This observation
supports the idea that the reaction proceeds through a PTC mech-
anism even though a certain amount of background reaction also
occurs.16 The potassium salt is formed through deprotonation of
1,3-dithiane-2-carbothioate 1 by solid KOH at the solideliquid
phase boundary. The latter is converted into the more reactive and
more soluble quaternary ammonium salt by cation exchange with
the PT catalyst.17 The reaction also occurred if solid, anhydrous
potassium carbonate was used with thioester 1 as nucleophile,
affording the desired product in slightly better yield as compared
with KOH for the same reaction time (Table 1, entry 10). The re-
action rate gradually increased with the amount of catalyst as ex-
pected in the case of a PTC process. In fact, when the reaction was
carried out in the presence of 0.05 equiv of TEBA enol lactone 4a
was generated in 55% yield after 24 h (Table 1, entry 11). Also in the
case of K2CO3, excess of base proved unfruitful probably due to the
competitive nucleophile hydrolysis (Table 1, entry 12).
In order to increase the reaction yield a series of experiments
were carried out by using exceeding amounts of 3a or thioester 1.
When 1.5 equiv of thioester 1 or chalcone 3a were used the yield of
enol lactone 4a was increased to 85 and 83%, respectively (Table 1,
entries 13,14). The enol lactone 4a was generated in 77% yield by
using 1.1 equiv of 3a (Table 1, entry 15). Similar yields of enol lac-
tone 4a could also be obtained by using the cheaper S-phenyl-1,3-
dithiane-2-carbothioate (2) as the nucleophile, although in a longer
reaction time (Table 1, entry 16). However, no conversion was ob-
served using K2CO3 as the base instead of KOH (Table 1, entry 17).
The lower reactivity of thioester 2 can likely be ascribed to a re-
duced leaving group ability of the thiophenolate anion with respect
to the trifluoroethylthiolate. Therefore, the more reactive thioester
1 was used in the following experiments.
3. Conclusion
In conclusion a new domino process was disclosed for the
synthesis of functionalized dihydropyranones 4,5aem. The re-
actions were carried out with simple, bench-stable starting mate-
rials under mild conditions and using inexpensive bases. PTC
methodology allowed reduced reaction times, ensuring an easy and
economic procedure suitable for scale-up.
This procedure is the first involving 1,3-dithiane-2-carboxy
thioesters, a class of versatile reagents, which promise access to
a much wider array of compounds.
4. Experimental section
4.1. General remarks
€
Melting points were determined with a BUCHI 535 and are
corrected. Infrared (IR) spectra were recorded with a PerkineElmer
1725 X FTIR spectrometer. NMR spectra were recorded on a Bruker
AC 300 operating at 300.13 MHz for 1H NMR, 75.3 MHz for 13C NMR
and 282 MHz for 19F NMR. Chemical shifts were reported using
CHCl3 (7.24 ppm for 1H NMR and 77.0 for 13C NMR) and CFCl3
(0 ppm for 19F NMR) as standards. APT experiments were used in
the assignment of carbon spectra. Some aromatic CH perfectly
overlap therefore not all carbons are visible in the 13C NMR. Column
chromatography on silica gel (230e400 mesh) was performed by
the flash technique. For thin-layer chromatography (TLC), silica gel
plates Merck 60F254 were used and compounds were visualized by
irradiation with UV light.
The reaction scope was investigated by using thioester 1,
a chalcone:nucleophile ratio of 1.1:1, and replacing DCM with
CH3CN. For this purpose
a series of 1,3-alkyl,aryl and 1,3-
diarylpropenones 3aem were reacted with 1 in CH3CN at room
temperature in the presence of a stoichiometric amount of solid
KOH and 0.1 equiv of TEBA (Table 2).
The reaction is compatible with various substituents on the
ortho or para position of the aromatic rings.
However, the strong electron-withdrawing nitro group on the
para position of R3 has a detrimental effect on yield. It is interesting
to note that no Michael adduct was ever isolated when 3d was used
as the acceptor. 1-Phenyl-2-buten-1-one (3h) provided the corre-
sponding enol lactone 4h in 36% chemical yield along with 20% of
the Michael adduct.18 This result can be explained on the basis of
Scheme 1. In fact, when R3¼Ar, the conjugate addition step is
supported by the phenyl group and enolate moiety of A rapidly
attacks the thioester group (LG¼SCH2CF3) giving rise to enol lac-
tone B (path a). On the other hand, when R3¼CH3, the coniugate
addition is slower and the restoration of the carbonyl form in the
Michael adduct C via acid/base equilibrium (Scheme 1, path b)
competes with the cyclization step.
4.2. Synthesis of S-2,2,2-trifluoroethyl 1,3-dithiane-2-carbo
thioate (1)
To a solution of dithiane carboxylic acid13 (821 mg, 5.00 mmol)
in dry dichloromethane (25 mL) was added HOBt (709 mg,
5.25 mmol) at 0 ꢀC, and the resulting solution was stirred for 10 min
at the same temperature. EDC$HCl (1.01 g, 5.25 mmol) was added at
0
ꢀC and the mixture was stirred for 30 min at the same temper-
ature. Finally, 2,2,2-trifluoroethanethiol (638 mg, 5.50 mmol) was
added at 0 ꢀC, and the mixture was allowed to warm to room
temperature. After being stirred overnight, the reaction mixture
was diluted with dichloromethane (10 mL) and water (30 mL) was
added. The aqueous layer was extracted with dichloromethane
(2ꢁ15 mL) and the organic phases were washed with water
(2ꢁ10 mL) and brine (10 mL), dried over MgSO4, and evaporated in
vacuo to give the title compound 1 (1.25 g, 95%) as a white solid, mp
56e57 ꢀC.
Chemical yields are not affected when the chloro or methoxy
substituent are present in the para position of R2.
When 4-phenyl-3-buten-2-one (3g) was used as substrate no
Michael product was observed, but the chemical yield was de-
creased in comparison with the series of chalcones. Heteroaromatic
chalcones 3l,m, bearing substituted thiophene or furan rings gave
good yields of the corresponding enol lactones 4l,m. In all the cases
dH (300 MHz, CDCl3) 4.25 (s, 1H), 3.62 (q, J¼9.8 Hz, 2H),
3.24e3.16 (m, 2H), 2.68e2.60 (m, 2H), 2.20e1.96 (m, 2H); dC

N. Gaggero et al. / Tetrahedron 70 (2014) 8744e8749
8747
(75 MHz, CDCl3) 192.7 (C), 124.0 (q, J¼272.0 Hz), 49.5 (CH), 31.8
(q, J¼33.8 Hz, CH2), 26.4 (2 CH2), 24.7 (CH2); dF (282 MHz, CDCl3)d
67.2; nmax (KBr) 2998, 2970, 2934, 2907, 1698, 1686, 1400, 1307,
1270, 1237, 1131, 1081, 1009, 992, 910, 764 cmꢂ1; C7H9F3OS3
(262.34): calcd. C, 32.05, H, 3.46; found C, 32.14, H, 3.47.
(CH), 53.7 (C), 49.3 (CH), 28.0 (CH2), 27.5 (CH2), 23.7 (CH2). nmax
(KBr) 3080, 3030, 2926, 2840, 1737, 1671, 1595, 1492, 1310, 1159,
1106, 1046, 1008, 962, 819, 759, 700 cm-1 C20H17ClO2S2 (388.93):
calcd. C 61.76, H 4.41; found C 61.61, H, 4.40.
4.4.3. 11-(4-Methoxyphenyl)-9-phenyl-8-oxa-1,5-dithiaspiro[5.5]
undec-9-en-7-one (4c). Rf (EtOAc/hexane 1:4) 0.32, (308 mg, 80%),
white solid, mp 176e177 ꢀC. dH (300 MHz, CDCl3) 7.69e7.65
(m, 2H), 7.42e7.33 (m, 3H), 7.18e7.13 (m, 2H), 6.86e6.82 (m, 2H),
5.92 (d, J¼6.4 Hz, 1H), 3.89 (d, J¼6.4 Hz, 1H), 3.77 (s, 3H), 3.65e3.55
(m, 1H), 3.07 (ddd, J¼14.8, 12.9, 2.2 Hz, 1H), 2.74e2.58 (m, 2H),
2.18e2.04 (m, 1H), 1.80 (qt, J¼13.3, 3.1 Hz, 1H). dC (75 MHz, CDCl3)
164.9 (C), 159.8 (C), 148.9 (C), 131.7 (C), 129.9 (CH), 129.3 (CH), 128.6
(CH), 127.6 (C), 124.8 (CH), 114.1 (CH), 101.8 (CH), 55.2 (CH3), 51.5
(C), 49.8 (CH), 28.6 (CH2), 27.9 (CH2), 24.4 (CH2). nmax (KBr) 3098,
3041, 3010, 2962, 2919, 2833, 1745, 1670, 1604, 1581, 1508, 1495,
1448, 1438, 1303, 1261, 1236, 1177, 1152, 1102, 1029, 951, 771,
748 cmꢂ1 C21H20O3S2 (384.51): calcd. C, 65.60, H, 5.24; found C,
65.70, H, 5.22.
4.3. Synthesis of S-phenyl 1,3-dithiane-2-carbothioate (2)
To a stirred solution of dithiane carboxylic acid (0.492 g,
3.00 mmol) in dry dichloromethane (25 mL) under nitrogen at-
mosphere was added 1 drop of dimethylformamide and thionyl
chloride (0.405 g, 3.40 mmol) dropwise. The solution was stirred for
15 min at room temperature, then the solvent was evaporated
affording the crude acid chloride as a red-orange solid. The latter
was dissolved in dry toluene (9 mL) and slowly added (20 min) to
a toluene solution (6 mL) of thiophenol (0.330 g, 3.00 mmol) and
triethylamine (0.304 g, 3.00 mmol) at room temperature, with
stirring. Precipitation of triethylammonium hydrogen chloride
made the reaction mixture turn to a turbid suspension. After
30 min of additional stirring the reaction mixture was filtered,
washed with saturated aq sodium hydrogen carbonate solution
(2ꢁ15 mL) and water (10 mL). The organic phase was dried over
anhydrous MgSO4, filtered and evaporated in vacuo to give the title
compound (0.70 g, 95%) as a pale yellow solid that was recrystal-
lized from diethyl ether yielding the desired thioester (0.63 g, 86%)
as a white crystalline solid, mp 118e119 ꢀC.
4.4.4. 11-(4-Fluorophenyl)-9-phenyl-8-oxa-1,5-dithiaspiro[5.5] un-
dec-9-en-7-one (4e). Rf (EtOAc/hexane 1:4) 0.35, (279 mg, 75%),
white solid, mp 180e181 ꢀC. dH (300 MHz, CDCl3) 7.72e7.69 (m,
2H), 7.45e7.39 (m, 3H), 7.28e7.22 (m, 2H), 7.06e7.00 (m, 2H), 5.93
(d, J¼6.4 Hz, 1H), 3.97 (d, J¼6.4 Hz, 1H), 3.62 (dt, J¼13.5, 2.8 Hz, 1H),
3.11 (ddd, J¼14.8,12.9, 2.3 Hz,1H), 2.86e2.50 (m, 2H), 2.16e2.21 (m,
1H), 1.85e1.80 (m, 1H). dC (75 MHz, CDCl3) 164.7 (C), 161.2 (C), 149.3
(C), 131.5 (C), 131.4 (C), 130.6 (d, J¼8.3 Hz, CH), 129.5 (CH), 128.6
(CH), 124.9 (CH), 115.7 (CH, d, J¼21.5 Hz), 101.3 (CH), 51.2 (C), 49.8
(CH), 28.6 (CH2) 28.0 (CH2), 24.3 (CH2), 19F NMR (282 MHz, CDCl3):
dH (300 MHz, CDCl3) 7.49e7.46 (m, 5H), 4.34 (s, 1H), 3.40e3.31
(m, 2H), 2.67e2.60 (m, 2H), 2.19e2.04 (m, 2H); dC (75 MHz, CDCl3)
192.6 (C), 129.7 (CH), 129.3 (CH), 127.5 (C), 46.9 (CH), 26.3 (2 CH2),
24.8 (CH2); nmax (KBr) 3043, 2988, 2817, 1682, 1417, 1266, 985, 777,
750, 712, 687 cmꢂ1; C11H12OS3 (256.41): calcd C, 51.53; H, 4.52;
found C 51.65, H 4.53.
d
¼ꢂ114.0 (s, 1 F). nmax (KBr) 3085, 3020, 2946, 2852, 1740, 1675,
1560, 1495, 1330, 1165, 1120, 1023, 950, 819, 720 cm-1 C20H17FO2S2
(372.48): calcd. C, 64.49; H, 4.60; found C 64.40, H 4.62.
4.4. General procedure for the Michael addition-cyclization
domino reaction
4.4.5. 9-(4-Chlorophenyl)-11-phenyl-8-oxa-1,5-dithiaspiro[5.5] un-
dec-9-en-7-one (4f). Rf (EtOAc/hexane 1:4) 0.30, (296 mg, 76%),
white solid, mp 183e184 ꢀC. dH (300 MHz, CDCl3) 7.66e7.61 (m,
2H), 7.41e7.32 (m, 5H), 7.28e7.23 (m, 2H), 5.94 (d, J¼6.4 Hz, 1H),
3.97 (d, J¼6.4 Hz,1H), 3.62 (dt, J¼13.5, 2.8 Hz, 1H), 3.10 (ddd, J¼14.8,
12.9, 2.2 Hz, 1H), 2.78e2.61 (m, 2H), 2.20e2.15 (m, 1H), 1.90e1.76
(m, 1H). dC (75 MHz, CDCl3) 164.5 (C), 148.2 (C), 135.6 (C), 135.3 (C),
130.1 (C), 128.8 (CH), 126.2 (CH), 102.0 (CH), 51.0 (C), 50.6 (CH), 28.6
(CH2), 27.9 (CH2), 24.3 (CH2). nmax (KBr) 3078, 3032, 2916, 2850,
1740, 1668, 1596, 1492, 1310, 1149, 1101, 1036, 1010, 952, 819, 759,
699 cme1. C20H17ClO2S2 (388.93): calcd. C, 61.76, H, 4.41; found C
61.64, H, 4.42.
Well-crushed KOH (56.0 mg, 1.00 mmol) was added under vig-
orous stirring at room temperature to a solution of thioester 1
(262 mg, 1.00 mmol), chalcone 3 (1.10 mmol) and TEBA (22.8 mg,
0.10 mmol) in acetonitrile (4 mL). After 5 h the reaction mixture
was concentrated and directly purified by flash chromatography
(hexane/EtOAc mixture 8:2 to 15:1) to afford dihydropyranones
4aem. The eluant, yield and physical, spectroscopic data of 4aem
are as follows.
4.4.1. 9,11-Diphenyl-8-oxa-1,5-dithiaspiro[5.5]undec-9-en-7-one
(4a). Rf (EtOAc/hexane 1:4) 0.34, (273 mg, 77%), white solid, mp
198e199 ꢀC. dH (300 MHz, CDCl3) 7.73e7.69 (m, 2H), 7.62e7.21
(m, 8H), 5.96 (d, J¼6.4 Hz, 1H), 3.98 (d, J¼6.4 Hz, 1H), 3.63
(dt, J¼13.5, 2.7 Hz,1H), 3.10 (dd, J¼19.9, 7.4 Hz,1H), 2.70 (dd, J¼14.2,
3.2 Hz, 2H), 2.21e2.16 (m, 1H), 1.90e1.75 (m, 1H). dC (75 MHz,
CDCl3) 164.1 (C), 148.5 (C), 135.2 (C), 130.9 (C), 128.7 (CH), 128.2
(CH), 128.0 (CH), 127.9 (CH), 124.1 (CH), 100.8 (CH), 50.5 (C), 49.9
(CH), 27.9 (CH2), 27.3 (CH2), 23.7 (CH2). nmax (KBr) 3107, 3086, 3061,
3031, 2981, 2936, 2903, 2876, 1726, 1602, 1584, 1453, 1368, 1258,
1157, 1096, 1018, 867, 752, 700 cmꢂ1. C20H18O2S2 (354.49): calcd. C
67.76, H 5.12; found C 67.50, H 5.14.
4.4.6. 9-Methyl-11-phenyl-8-oxa-1,5-dithiaspiro[5.5]undec-9-en-7-
one (4g). Rf (EtOAc/hexane 1:9) 0.34, (181 mg, 62%), white solid,
mp 179e181 ꢀC. dH (300 MHz, CDCl3) 7.32e7.27 (m, 3H), 7.18e7.15
(m, 2H), 5.15 (dd, J¼6.2, 1.1 Hz, 1H), 3.70 (d, J¼6.2 Hz, 1H), 3.56 (dt,
J¼13.5, 2.8 Hz, 1H), 3.04 (ddd, J¼14.8, 12.8, 2.3 Hz, 1H), 2.75e2.68
(m, 2H), 2.17e2.09 (m, 1H), 1.98 (s, 3H), 1.86e1.70 (m, 1H). dC
(75 MHz, CDCl3) 164.7 (C), 148.1 (C), 135.9 (C), 128.2 (CH), 128.1 (C),
127.9 (C), 101.5 (CH), 50.5 (C), 49.8 (CH), 28.1 (CH2), 27.4 (CH2), 23.9
(CH2), 17.8 (CH3). nmax (KBr) 3077, 3048, 3027, 2948, 2917, 2851,
1742, 1425, 1300, 1278, 1147, 1095, 986, 922, 764, 701 cm-1
C15H16O2S2 (292.42): calcd. C, 61.61; H, 5.52; found C 61.57, H 5.54.
4.4.2. 11-(4-Chlorophenyl)-9-phenyl-8-oxa-1,5-dithiaspiro[5.5] un-
dec-9-en-7-one (4b). Rf (EtOAc/hexane 1:4) 0.37, (300 mg, 77%),
white solid, mp 172e173 ꢀC. dH (300 MHz, CDCl3) 7.68-7.64 (m, 2H),
7.38e7.30 (m, 3H), 7.29e7.26 (m, 2H), 7.18e7.16 (m, 2H), 5.88 (d,
J¼6.3 Hz, 1H), 3.93 (d, J¼6.3 Hz, 1H), 3.58e3.53 (m, 1H), 3.13e3.05
(m, 1H), 2.74e2.61 (m, 2H), 2.17e2.13 (m, 1H), 1.82e1.77 (m, 1H). dC
(75 MHz, CDCl3) 165.0 (C), 149.0 (C), 133.8 (C), 132.9 (CH), 130.9 (C),
129.7 (CH), 129.0 (CH), 128.4 (CH), 128.1 (CH), 124.4 (CH), 100.5
4.4.7. 11-(4-Bromophenyl)-9-phenyl-8-oxa-1,5-dithiaspiro[5.5] un-
dec-9-en-7-one (4i). Rf (EtOAc/hexane 1:4) 0.4, (325 mg, 75%),
white solid, mp 175e176 ꢀC. dH (300 MHz, CDCl3) 7.71e7.68 (m, 2H),
7.48e7.40 (m, 5H), 7.16e7.13 (m, 2H), 5.91 (d, J¼6.3 Hz, 1H), 3.95 (d,
J¼6.3 Hz, 1H), 3.61 (dt, J¼13.4, 2.8 Hz, 1H), 3.14 (dd, J¼12.8, 2.3 Hz,
1H), 3.09 (dd, J¼12.8, 2.3 Hz, 1H), 2.78e2.62 (m, 2H), 2.20e2.13 (m,
1H), 1.89e1.74 (m, 1H). dC (75 MHz, CDCl3) 164.0 (C), 149.0 (C), 134.4

8748
N. Gaggero et al. / Tetrahedron 70 (2014) 8744e8749
(C), 134.4 (CH), 131.3 (CH), 130.0 (CH), 129.0 (CH), 128.1 (CH), 124.4
(CH), 122.2 (C), 100.4 (CH), 50.3 (C), 49.4 (CH), 28.0 (CH2), 27.4
(CH2), 23.7 (CH2). nmax (KBr) 3078, 3047, 3027, 2950, 2920, 2850,
1740, 1420, 1305, 1280, 1150, 1093, 985, 920, 764 cm-1 C20H17BrO2S2
(433.38): calcd. C, 55.43; H, 3.95; found C 55.50, H 3.96.
then was filtered through a Celite pad and washed with absolute
ethanol. The organic solution was dried over MgSO4 and concen-
trated in vacuum to afford a crude residue that was purified by flash
column chromatography (Et2O/hexane 1:8) to give the title com-
pound (220 mg, 88% yield) whose physical and spectroscopic data
are identical to those reported.20
4.4.8. 9-(4-Methoxyphenyl)-11-phenyl-8-oxa-1,5-dithiaspiro[5.5]
undec-9-en-7-one (4j). Rf (EtOAc/hexane 1:4) 0.30, (285 mg, 74%),
white solid, mp 179e180 ꢀC. dH (300 MHz, CDCl3) 7.60e7.55 (m,
2H), 7.45e7.20 (m, 3H), 7.10e7.02 (m, 2H), 6.89e6.79 (m, 2H), 5.90
(d, J¼6.4 Hz, 1H), 3.95 (d, J¼6.4 Hz, 1H), 3.70 (s, 3H), 3.65e3.55 (m,
1H), 3.05 (ddd, J¼14.8, 12.9, 2.2 Hz, 1H), 2.78e2.54 (m, 2H),
2.18e2.04 (m, 1H), 1.85 (m, 1H). dC (75 MHz, CDCl3) 164.5 (C), 159.2
(C), 149.0 (C), 131.3 (C), 129.9 (CH), 129.4 (CH), 128.3 (CH), 127.9 (C),
125 (CH), 114.8 (CH), 101.9 (CH), 55.3 (CH3), 51.3 (C), 50.0 (CH), 28.6
(CH2), 27.9 (CH2), 24.4 (CH2). nmax (KBr) 3098, 3040, 2982, 2833,
1750, 1604, 1581, 1510, 1490, 1438, 1303,1261, 1177, 1152, 1100, 1040,
850, 771, 748 cmꢂ1 C21H20O3S2 (384.51): calcd. C, 65.60, H, 5.24;
found C, 65.68, H, 5.24.
4.5.2. Method Bdgeneral procedure. A solution of 4 (0.50 mmol) in
THF (2 mL) was added to a stirred solution of NiCl2$6H2O (1.90 g,
8.00 mmol) in DMF (2 mL). After cooling at 0 ꢀC, NaBH4 (605 mg,
16.0 mmol) was added in portions. The reaction mixture was stirred
at 0 ꢀC for 15 min, then was filtered through a Celite pad and
washed with AcOEt. The organic solution was dried over MgSO4
and concentrated in vacuum to afford a crude residue that was
purified by flash column chromatography to give desulfurized
dihydropyranones 5bem. Eluant, yield and physical, spectroscopic
data of 5bem are as follows.
4.5.3. 4-(4-Chlorophenyl)-6-phenyl-3,4-dihydro-2H-pyran-2-one
(5b). Rf (AcOEt/hexane 1:12) 0.33, (103 mg, 72%); dH (300 MHz,
CDCl3) 7.71e7.66 (m, 2H), 7.46e7.31 (m, 5H), 7.28e7.21 (m, 2H),
5.94 (d, J¼4.4 Hz, 1H), 4.16e3.94 (m, 1H), 3.04 (dd, J¼15.8, 6.8 Hz,
1H), 2.79 (dd, J¼15.8, 8.2 Hz, 1H). dC (75.2 MHz, CDCl3) 167.3 (C),
149.9 (C), 141.3 (C), 135.2 (C), 130.7 (C), 129.2 (CH), 128.8 (CH), 127.7
(CH), 127.0 (CH), 126.0 (CH), 104.7 (CH), 37.3 (CH), 36.8 (CH2). nmax
(thin film) 2927, 2858, 1735, 1684, 1587, 1460, 1380, 1072, 1021, 761,
701. C17H13ClO2 (284.74): calcd. C 71.71, H 4.60; found C 71.60, H
4.61.
4.4.9. 11-(2-Chlorophenyl)-9-phenyl-8-oxa-1,5-dithiaspiro[5.5] un-
dec-9-en-7-one (4k). Rf (EtOAc/hexane 1:4) 0.37, (280 mg, 72%),
white solid, mp 205e206 ꢀC. dH (300 MHz, CDCl3) 7.68-7.65 (m, 2H),
7.40e7.37 (m, 4H), 7.22e7.21 (m, 3H), 5.89 (d, J¼6.6 Hz, 1H), 4.76 (d,
J¼6.6 Hz, 1H), 3.58e3.53 (dt, J¼13.4, 2.8 Hz, 1H), 3.08e3.03 (m, 1H),
2.76e2.60 (m, 2H), 2.19e2.13 (m, 1H), 1.90e1.85 (m, 1H). dC
(75 MHz, CDCl3) 164.7 (C), 149.5 (C), 134.4 (C), 131.5 (C), 129.8 (CH),
129.4 (CH), 129.0 (CH), 128.6 (CH), 127.6 (CH), 124.9 (CH), 100.8
(CH), 50.9 (C), 45.5 (CH), 28.5 (CH2), 27.8 (CH2), 24.1 (CH2). nmax
(KBr) 3080, 3030, 2926, 2840, 1737, 1671, 1595, 1492, 1310, 1159,
1106, 1046, 1008, 962, 819, 759, 700 cm-1 C20H17ClO2S2 (388.9):
calcd. C 61.76, H 4.41; found C 61.70, H, 4.42.
4.5.4. 4-(4-Methoxyphenyl)-6-phenyl-3,4-dihydro-2H-pyran-2-one-
(5c). Rf (AcOEt/hexane 1:12) 0.33, (98 mg, 70%); dH (300 MHz,
CDCl3) 7.71e7.68 (m, 2H), 7.42e7.40 (m, 3H), 7.21e7.18 (m, 2H),
6.92e6.87 (m, 2H), 5.96 (d, J¼4.5 Hz,1H), 3.94e3.87 (m,1H), 3.80 (s,
3H), 3.02 (dd, J¼15.7, 6.7 Hz, 1H), 2.79 (dd, J¼15.7, 8.2 Hz, 1H). dC
(75.2 MHz, CDCl3) 167.8 (C) 159.0 (C), 150.6 (C), 133.5 (C), 132.3 (C),
128.9 (CH),128.8 (CH),128.5 (CH),124.7 (CH),114.5 (CH),104.6 (CH),
55.3 (CH3), 37.1 (CH2), 36.5 (CH). vmax (thin film) 2955, 2840, 1770,
1615, 1515, 1250, 1180, 1020, 832, 763, 690 cm-1; C18H16O3 (280.32):
calcd. C 77.12, H 5.75; found C 77.25, H 5.74.
4.4.10. 11-(3-Methylthiophen-2-yl)-9-phenyl-8-oxa-1,5-dithiaspiro
[5.5] undec-9-en-7-one (4l). Rf (EtOAc/hexane 1:4) 0.38, (262 mg,
70%), white solid, mp 205e206 ꢀC. dH (300 MHz, CDCl3) 7.68e7.66
(m, 2H), 7.40e7.38 (m, 3H), 7.18 (d, J¼5.1 Hz, 1H), 6.79 (d, J¼5.1 Hz,
1H), 5.93 (d, J¼6.3 Hz, 1H), 4.36 (d, J¼6.3 Hz, 1H), 3.66 (dt, J¼13.5,
2.7 Hz, 1H), 3.71e3.61 (m, 1H), 2.75e2.60 (m, 2H), 2.33 (s, 3H),
2.21e2.15 (m, 1H), 1.86e1.81 (m, 1H). dC (75 MHz, CDCl3) 164.5 (C),
149.0 (C), 137.1 (C), 133.2 (C), 131.6 (C), 129.8 (CH), 129.4 (CH), 128.5
(CH), 125.0 (CH), 124.7 (CH), 101.8 (CH), 52.4 (C), 43.4 (CH), 28.5
(CH2), 28.0 (CH2), 24.3 (CH2), 14.7 (CH3). nmax (KBr) 3081, 3039,
4.5.5. 4-(4-Fluorophenyl)-6-phenyl-3,4-dihydro-2H-pyran-2-one-
(5e). Rf (AcOEt/hexane 1:12) 0.33, (87 mg, 65%); dH (300 MHz,
CDCl3) 7.67e7.65 (m, 2H), 7.39e7.38 (m, 3H), 7.25e7.20 (m, 2H),
7.04 (t, J¼8.6 Hz, 2H), 5.92 (d, J¼4.4 Hz, 1H), 3.99e3.93 (m, 1H), 3.02
(dd, J¼15.8, 6.8 Hz, 1H), 2.76 (dd, J¼15.8, 8.1 Hz, 1H). dC (75.2 MHz,
CDCl3, 13C decoupled) 163.8, 153.2, 133.2, 129.4, 128.6, 128.0, 125.7,
124.7, 116.0 (d, J¼21.3 Hz, CF), 115.9, 103.8, 37.0, 36.6. dF (282 MHz,
CDCl3)d115.3. vmax (thin film) 2930, 1770, 1598, 1480, 1213, 1148,
1050,1030, 768, 696 cm1; C17H13FO2 (268.28): calcd. C 77.12, H 5.75;
found C 77.25, H 5.74.
2924, 2855,1750,1670,1598,1495,1290,1160,1121,1030,1020, 958,
ꢂ1
821, 759 cm
C H18O2S3 (374.54): calcd. C 60.93, H 4.84; found C
19
61.01, H, 4.83.
4.4.11. 11-(5-Methylfuran-2-yl)-9-phenyl-8-oxa-1,5-dithiaspiro [5.5]
undec-9-en-7-one (4m). Rf (EtOAc/hexane 1:4) 0.32, (272 mg, 76%),
white solid, mp 130e131 ꢀC. dH (300 MHz, CDCl3) 7.68e7.66 (m,
2H), 7.41e7.35 (m, 3H), 6.18 (d, J¼3.1 Hz, 1H), 5.90e5.89 (m, 1H),
5.80 (d, J¼6.5, 1H), 3.98 (d, J¼6.5, 1H), 3.68 (dt, J¼13.4, 2.7 Hz),
3.12e3.04 (m, 1H), 2.74e2.64 (m, 2H), 2.23e2.16 (m, 4H), 1.90e1.76
(m, 1H). dC (75.2 MHz, CDCl3) 164.5 (C), 153.2 (C), 149.9 (C), 146.3
(C), 131.8 (C), 129.3 (CH), 128.5 (CH), 124.9 (CH), 110.7 (CH), 106.3
(CH), 98.4 (CH), 50.3 (C), 43.9 (CH), 28.6 (CH2), 28.0 (CH2), 24.5
(CH2), 13.7 (CH3). vmax (thin film) 2940, 1770, 1599, 1482, 1213, 1150,
1060, 1040, 770, 696 cm1; C19H18O3S2 (358.47): calcd. C 63.66, H
5.06; found C 63.59, H 5.06.
4.5.6. 6-(4-Chlorophenyl)-4-phenyl-3,4-dihydro-2H-pyran-2-one
(5f). Rf (AcOEt/hexane 1:12) 0.33, (108 mg, 76%); dH (300 MHz,
CDCl3) 7.61e7.58 (m, 2H), 7.41e7.24 (m, 7H), 5.93 (d, J¼4.2 Hz, 1H),
3.99e3.83 (m), 3.03 (dd, J¼15.9, 6.9 Hz,1H), 2.80 (dd, J¼15.9, 8.7 Hz,
1H). dC (75.2 MHz, CDCl3, 13C decoupled) 167.0, 141.5, 129.2, 128.9,
127.7, 127.0, 126.1, 104.8, 37.4, 36.7. vmax (thin film) 2925, 1774, 1598,
1479, 1214, 1148, 1050, 1025, 770, 695 cm-1; C17H13ClO2 (284.06):
calcd. C 71.71, H 4.60; found C 71.63, H 4.59.
4.5. Desulfurization of enol lactones 4
4.5.7. 4-Methyl-6-phenyl-3,4-dihydro-2H-pyran-2-one
(5g). Rf
(AcOEt/hexane 1:12) 0.33, (55 mg, 58%); dH (300 MHz, CDCl3)
7.35e7.17 (m, 5H), 5.14 (d, J¼3.9 Hz, 1H), 3.77e3.70 (m, 1H), 2.90
(dd, J¼15.8, 6.8 Hz, 1H), 2.66 (dd, J¼15.8, 8.3 Hz, 1H); dC (75.2 MHz,
CDCl3) 168.1 (C), 150.1 (C), 142.0 (C), 129.2 (CH), 129.0 (CH), 127.3
(CH), 104.2 (CH), 36.9 (CH), 36.8 (CH2), 18.8 (CH3). vmax (thin film)
4.5.1. Method A: 3,4-dihydro-4,6-diphenyl-2H-pyran-2-one (5a). To
a solution of 4a (354 mg, 1.00 mmol) in absolute ethanol (10 mL),
Raney-nickel (8 g, Aldrich-2800 50% slurry in water) was added.
The reaction mixture was stirred at room temperature for 24 h,

N. Gaggero et al. / Tetrahedron 70 (2014) 8744e8749
8749
2935, 1772, 1680, 1455, 1220, 1083, 765, 705 cm-1; C12H12O2
(188.22): calcd. C 76.57, H 6.43; found C 76.64, H 6.42.
5.94 (d, J¼4.8 Hz, 1H), 5.88 (d, J¼3.0 Hz, 1H), 4.00e3.94 (m, 1H),
3.02e2.89 (m, 2H), 2.26 (s, 3H). dC (75.2 MHz, CDCl3) 167.5 (C), 152.1
(C), 151.6 (CH), 150.9 (C), 132.2 (C), 129.3 (CH), 128.5 (CH), 106.4
(CH), 106.2 (CH), 101.6 (CH), 33.8 (CH2), 31.0 (CH), 13.5 (CH3). vmax
(thin film) 2940, 1775, 1600, 1482, 1213, 1155, 1070, 1030, 775,
700 cm1; C16H14O3 (254.28) calcd. C 75.57, H 5.55; found C 75.62, H,
5.55.
4.5.8. 4-(4-Bromophenyl)-6-phenyl-3,4-dihydro-2H-pyran-2-one
(5i). Rf (AcOEt/hexane 1:12) 0.33, (127 mg, 77%); dH (300 MHz,
CDCl3) 7.71e7.66 (m, 2H), 7.46e7.31 (m, 5H), 7.28e7.21 (m, 2H),
5.94 (d, J¼4.4 Hz, 1H), 4.16e3.94 (m, 1H), 3.04 (dd, J¼15.8, 6.8 Hz,
1H), 2.79 (dd, J¼15.8, 8.2 Hz, 1H). dC (75.2 MHz, CDCl3) 167.3 (C),
149.9 (C), 141.3 (C), 135.2 (C), 130.7 (C), 129.2 (CH), 128.8 (CH), 127.7
(CH), 127.0 (CH), 126.0 (CH), 104.7 (CH), 37.3 (CH), 36.8 (CH2). nmax
(thin film) 2927, 2858, 1705, 1684, 1487, 1460, 1410, 1021, 701.
Supplementary data
1H and 13C NMR spectra of 1,3-dithiane-2-carbothioates 1 and 2,
compounds 4aem,5bem. Supplementary data related to this ar-
ticle can be found at http://dx.doi.org/10.1016/j.tet.2014.09.022.
C
17H13BrO2 (329.19): calcd. C 62.03, H 3.98; found C 62.11, H 3.99.
4.5.9. 6-(4-methoxyphenyl)-4-phenyl-3,4-dihydro-2H-pyran-2-one
(5j). Rf (AcOEt/hexane 1:15) 0.33, (98 mg, 70%); dH (300 MHz,
CDCl3) 7.68 (d, J¼9.0 Hz, 2H), 7.42e7.25 (m, 5H), 6.92 (d, J¼9.0 Hz,
2H), 5.90 (d, J¼4.5 Hz, 1H), 3.94e3.85 (m, 1H), 3.80 (s, 3H), 3.02 (dd,
J¼15.7, 6.7 Hz, 1H), 2.79 (dd, J¼15.7, 8.2 Hz, 1H). dC (75.2 MHz,
CDCl3) 167.8 (C) 159.0 (C), 150.6 (C), 141.5 (), 129.9 (C), 127.3 (C),
127.0 (CH), 126.1 (CH), 124.4 (CH), 114.5 (CH), 104.6 (CH), 55.3 (CH3),
37.1 (CH2), 36.8 (CH). vmax (thin film) 2950, 2840, 1770, 1515, 1250,
1180, 1150, 1020, 832, 763, 690 cm-1; C18H16O3 (280.32): calcd. C
77.12, H 5.75; found C 77.20, H 5.76.
References and notes
1. (a) Rosenthal, D.; Grabowich, P.; Sabo, E. F.; Fried, J. J. Am. Chem. Soc. 1963, 85,
3971e3979; (b) Kume, T.; Iwasaki, H.; Yamamoto, Y.; Akiba, K. Tetrahedron Lett.
1988, 29, 3825e3828; (c) Mandal, A. K.; Jawalkar, D. G. Tetrahedron Lett. 1986,
27, 99e100; (d) Mandal, A. K.; Jawalkar, D. G. J. Org. Chem. 1989, 54, 2364e2369;
(e) Robl, J. A. Tetrahedron Lett. 1990, 31, 3421e3424; (f) Yhang, S. H.; Rigg, D. J.
Synth. Commun. 1993, 23, 2355e2361; (g) Harrowven, D. C.; Hannam, J. C.
Tetrahedron 1999, 55, 9333e9340; (h) Zhang, F.-Y.; Corey, E. J. Org. Lett. 2000, 2,
1097e1100; (i) Candish, L.; Lupton, D. W. Org. Lett. 2010, 12, 4836e4839.
2. Pal, S.; Chatare, V.; Pal, M. Curr. Org. Chem. 2011, 15, 782e800.
3. (a) Tozawa, T.; Fujisawa, H.; Mukaiyama, T. Chem. Lett. 2004, 33, 1454e1455; (b)
Tozawa, T.; Yamane, Y.; Mukaiyama, T. Chem. Lett. 2005, 34, 514e515.
4. (a) Nagao, H.; Yamane, Y.; Mukaiyama, T. Chem. Lett. 2006, 35, 1398e1399; (b)
Tozawa, T.; Nagao, H.; Yamane, Y.; Mukaiyama, T. Chem.dAsian J. 2007, 2,
123e134.
4.5.10. 4-(2-Chlorophenyl)-6-phenyl-3,4-dihydro-2H-pyran-2-one
(5k). Rf (AcOEt/hexane 1:12) 0.33, (98 mg, 69%); dH (300 MHz,
CDCl3) 7.73e7.70 (m, 2H), 7.44e7.42 (m, 4H), 7.31e7.24 (m, 3H),
5.98 (d, J¼4.8 Hz, 1H), 4.49 (dd, J¼7.0, 4.9 Hz, 1H), 3.10 (dd, J¼15.9,
7.2 Hz, 1H), 2.86 (dd, J¼15.9, 6.9 Hz, 1H). dC (75.2 MHz, CDCl3) 179.7
(C), 167.3 (C), 156.6 (C), 138.3 (C), 130.1 (CH), 129.4 (CH), 128.9 (CH),
128.6 (CH), 128.0 (CH), 127.6 (CH), 124.8 (CH), 102.6 (CH), 34.9 (CH),
33.9 (CH2). nmax (thin film) 2930, 2860, 1740, 1685, 1592, 1465, 1384,
1075, 1024, 764, 705. C17H13ClO2 (284.74): calcd. C 71.71, H 4.60;
found C 71.62, H 4.59.
5. Kobayashi, S.; Moriwaki, M. Synlett 1997, 551e552.
6. Katritzky, A. R.; Denisko, O. V. J. Org. Chem. 2002, 67, 3104e3108.
7. Albanese, D. C. M.; Gaggero, N. Eur. J. Org. Chem. 2014, 5631e5640. http://dx.doi.
org/10.1002/ejoc.201402024 in press, and references therein.
8. Belmessieri, D.; Morrill, L. C.; Simal, C.; Slawin, A. M.; Smith, A. D. J. Am. Chem.
Soc. 2011, 133, 2714e2720.
9. (a) Bulman Page, P. C.; van Niel, M. B.; Prodger, J. C. Tetrahedron 1989, 45,
7643e7677; (b) Yus, M.; Najera, C.; Foube, F. Tetrahedron 2003, 59, 6147e6212.
10. Unpublished results.
11. Alonso, D. A.; Kitagaki, S.; Utsumi, N.; Barbas, C. F., III. Angew. Chem., Int. Ed.
ꢁ
2008, 47, 4588e4591.
4.5.11. 4-(3-Methylthiophen-2-yl)-6-phenyl-3,4-dihydro-2H-pyran-
2-one (5l). Rf (AcOEt/hexane 1:12) 0.33, (97 mg, 72%); dH (300 MHz,
CDCl3) 7.68e7.65 (m, 2H), 7.41e7.37 (m, 3H), 7.11 (d, J¼5.1 Hz, 1H),
6.84 (d, J¼5.1 Hz, 1H), 5.95 (d, J¼4.1 Hz, 1H), 4.33e4.27 (m, 1H), 3.03
(dd, J¼15.8, 6.5 Hz, 1H), 2.80 (dd, J¼15.8, 9.1 Hz, 1H), 2.24 (s, 3H). dC
(75.2 MHz, CDCl3) 167.0 (C), 150.7 (C), 137.9 (C), 133.3 (C), 132.0 (C),
130.5 (CH), 129.2 (CH), 128.4 (CH), 124.7 (CH), 122.5 (CH), 104.1
(CH), 36.4 (CH2), 30.8 (CH), 13.5 (CH3). vmax (thin film) 2940, 1770,
1599, 1482, 1213, 1150, 1060, 1040, 770, 696 cm1; C16H14O2S
(270.35): calcd. C 71.08, H 5.22; found C 71.15, H 5.21.
12. (a) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; Wiley-
Intersciences: New York, 1999, 329e344, pp 724e727; (b) Organosulfur
Chemistry. Synthetic Aspects; Page, P., Ed.; Academic: London, 1995; chapter 4.
13. Bates, G. S.; Ramaswamy, S. Can. J. Chem. 1980, 58, 716e720.
14. Utsumi, N.; Kitagaki, S.; Barbas, C. F., III. Org. Lett. 2008, 10, 3405e3408.
15. Aggarwal, V. K.; Esquivel-Zamora, B. N.; Evans, G. R.; Jones, E. J. Org. Chem. 1998,
63, 7306e7310.
16. (a) Albanese, D. “Phase Transfer Catalysis” Kirk-Othmer Encyclopedia of Chemical
Technology On-line Edition 2008; John Wiley & Sons: New York, 15 July 2008;
p 1993; (b) Albanese, D. Mini-reviews Org. Chem. 2006, 3, 195e217.
17. Albanese, D.; Landini, D.; Lupi, V.; Penso, M.; Scaletti, D. J. Mol. Cat. A: Chem.
2008, 288, 28e32.
18. The enol lactone 4h and the Michael adduct could not be separated by chro-
matography. However, the composition of this mixture could be determined by
1H NMR through integration of methyl doublets
19. (a) Back, T. G.; Baron, D. L.; Yang, K. J. Org. Chem. 1993, 58, 2407e2413; (b)
Zaman, S. S.; Sarmah, P.; Barua, N. C.; Sharma, R. P. Chem. Ind. 1989, 806e807.
20. Li, G.-Q.; Dai, L.-X.; You, S.-L. Org. Lett. 2009, 11, 1623e1625.
4.5.12. 4-(5-Methylfuran-2-yl)-6-phenyl-3,4-dihydro-2H-pyran-2-
one (5m). Rf (AcOEt/hexane 1:15) 0.33, (93 mg, 73%); dH (300 MHz,
CDCl3) 7.67e7.64 (m, 2H), 7.39e7.37 (m, 3H), 6.01 (d, J¼3.1 Hz, 1H),