Synthesis of 2,3-dihydrothiopyran-4-ones from 3-oxo-1-pentene-4-ynes

Article abstract of DOI:10.1007/s00706-006-0571-4

3-Oxo-1-pentene-4-ynes were converted with sodium sulfide or hydrogensulfide to give 2,6-disubstituted 2,3-dihydrothiopyran-4-one derivatives. The starting materials were prepared in two steps from terminal alkynes and α,β-unsaturated aldehydes.

Full text of DOI:10.1007/s00706-006-0571-4

Monatshefte fu¨r Chemie 138, 13–26 (2007)
DOI 10.1007/s00706-006-0571-4
Printed in The Netherlands
Synthesis of 2,3-Dihydrothiopyran-4-ones
from 3-Oxo-1-pentene-4-ynes
Anna Rosiak1;2, Ralf M. Mu¨ller2, and Jens Christoffers1;ꢀ
1
¨
Institut fu¨r Reine und Angewandte Chemie, Carl von Ossietzky-Universitat Oldenburg,
Oldenburg, Germany
2
¨
Institut fu¨r Organische Chemie, Universitat Stuttgart, Stuttgart, Germany
Received June 6, 2006; accepted (revised) July 4, 2006
Published online January 2, 2007 # Springer-Verlag 2007
Summary. 3-Oxo-1-pentene-4-ynes were converted with sodium sulfide or hydrogensulfide to give
2,6-disubstituted 2,3-dihydrothiopyran-4-one derivatives. The starting materials were prepared in two
steps from terminal alkynes and ꢀ,ꢁ-unsaturated aldehydes.
Keywords. Alkynes; Cyclizations; Enones; Heterocycles; Sulfur compounds.
Introduction
Successful drug development is dependent on the availability of heterocyclic build-
ing blocks with a specific substitution pattern. Of particular importance are com-
pounds comprising aromatic and heteroaromatic side chains with the need for a
broad variety of substituents. Moreover, in late stages of screening and optimiza-
tion a scalable access to the intermediates is desirable. In the course of a search
program with a background in medicinal chemistry we required 2,3-dihydro-
thiopyran-4-ones 2 with different aromatic substituents in the 2- and 6-positions
(Scheme 1). Heterocycles of this type are known [1] and have been applied in organ-
ic synthesis related to electronic applications [2]. They have so far been accessed
by oxidation of saturated tetrahydro-congeners 1 by halogenation-dehalogenation
sequences with various chlorinating [3] and fluorinating reagents [4]. However,
these oxidation reactions were reported to proceed without any significant regios-
electivity, thus, only symmetrically substituted compounds 2 with R ¼ R0 have been
reported in the literature so far. Therefore, we envisioned ring closure of enynones
3 with sulfide in order to access our target structures 2 with R ¼ R0. This concept was
successfully applied in the literature in order to prepare tetrahydrothiopyran-4-ones
1 from divinylketones [5]. 4H-Thiopyran-4-ones have been similarly accessed
ꢀ
Corresponding author. E-mail: jens.christoffers@uni-oldenburg.de

14
A. Rosiak et al.
Scheme 1
before from dialkynylketones [6], however, analogous cyclization of alkynylvi-
nylketones 3 has not been reported before.
Results and Discussion
Ring Closure with Sulfide
Model compound 3a with R ¼ R0 ¼ Ph was first tested in order to evaluate reaction
conditions for the ring closure by double thia-Michael reaction (Scheme 2). It
turned out that the result of these conjugate additions was highly dependent on
the solvent used. Two procedures have been identified to give satisfying results:
method A applied an excess of Na2S ꢁ 9H2O as source of the nucleophile and a
Scheme 2
Table 1. Ring closure by double conjugate additions; Method A: Na2S ꢁ 9H2O, THF=H2O; Method B:
NaSH ꢁ 1.2H2O, 2-ME
Starting material
R
R0
Method, t=h, T=ꢂC
Yield=%
3a
3b
3c
3d
3e
Ph
Ph
Ph
Ph
Ph
Ph
A, 72, 23
94 (2a)
96 (2b)
92 (2c)
84 (2d)
65 (2e)
43 (2e)
81 (2f)
60 (2g)
85 (2h)
34 (2i)
70 (2i)
36 (2j)
16 (2k)
8 (2l)
ꢃ
3,4-(MeO)2C6H3
B, 2, 50; 14, 23
B, 4, 40; 16, 23
B, 8, 40; 15, 23
A, 5, 55; 3, 23
B, 3, 55;
ꢃ
3-EtO-4-MeOC6H3
ꢃ
2-CF3C6H4
ꢃ
2,4-F2C6H3
3f
3g
3h
3i
2-thienyl
2-pyridyl
t-Bu
Ph
Ph
Ph
Ph
B, 18, 40
B, 2, 50
B, 16, 50
TMS, Ha
A, 10, 55; 10, 23
B, 3, 60
ꢃ
3j
3k
3l
3,4-(MeO)2C6H3
H
H
H
B, 2, 50; 14, 23
B, 3, 50; 2, 23
A, 3, 55
ꢃ
3-EtO-4-MeOC6H3
ꢃ
2,4-F2C6H3
a
The R ¼ TMS group in starting material 3i is lost under reaction conditions, R ¼ H in product 2i

Synthesis of 2,3-Dihydrothiopyran-4-ones
15
mixture of THF and water (1:1) as solvent. Full conversion is achieved after 72 h at
ambient temperature. Superior, however, is method B, which applied an excess of
NaSH-hydrate as reagent. The solvent is 2-methoxyethanol (2-ME) in this case full
conversion is achieved by stirring first for 4–16 h at 40–55ꢂC, and then for a few
hours at ambient temperature. After aqueous workup, the racemic products were
purified by column chromatography (SiO2). Results and reaction conditions for
different starting materials are summarized in Table 1.
The yields of derivatives with R0 ¼ Ph (2a–2i) range from satisfying (60% for 2g)
to excellent (96% for 2b). For R ¼ Ph (2a) and electron rich aromatics (2b and 2c)
yields are reaching 90%. Substrates with electron deficient phenyl residues (2d and
2e), electron rich (2f) and poor heteroaryl residues (2g) and aliphatic substituents
(2h) gave yields from 60 to 85%. The R ¼ TMS group in starting material 3i is lost
under reaction conditions, presumably due to the strong nucleophilicity of sulfide.
Product 2i is unsubstituted in the 6-position (R ¼ H). Yields for compounds 2j–2l
without a substituent in the 2-position are not satisfying at all (8–36%). This might
actually originate from the low stability of the respective starting materials 3j–3l,
which decompose under reaction as well as ambient conditions (see below).
Synthesis of 3-Oxopentenynes
Enynones 3 (Scheme 3) were prepared starting from a series of terminal alkynes
4 by deprotonating them with one equivalent of n-BuLi in THF and converting
them further with cinnamaldehyde 5a or acroleine 5b. After aqueous workup and
Scheme 3
Table 2. Preparation of enynones 3 from alkynes 1 in two steps
Yield alcohol
%
Yield ketone
%
Alkyne
Aldehyde
4a, R ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5a, R0 ¼ Ph
5b, R0 ¼ H
5b, R0 ¼ H
5b, R0 ¼ H
89 (6a)
90 (6b)
79 (6c)
78 (6d)
66 (6e)
51 (6f)
92 (6g)
85 (6h)
98 (6i)
71 (6j)
67 (6k)
71 (6l)
96 (3a)
84 (3b)
99 (3c)
99 (3d)
99 (3e)
99 (3f)
75 (3g)
99 (3h)
97 (3i)
77 (3j)
62 (3k)
99 (3l)
ꢃ
4b, R ¼ 3,4-(MeO)2C6H3
ꢃ
4c, R ¼ 3-EtO-4-MeOC6H3
ꢃ
4d, R ¼ 2-CF3C6H4
ꢃ
4e, R ¼ 2,4-F2C6H3
4f, R ¼ 2-thienyl
4g, R ¼ 2-pyridyl
4h, R ¼ t-Bu
4i, R ¼ TMS
ꢃ
4b, R ¼ 3,4-(MeO)2C6H3
ꢃ
4c, R ¼ 3-EtO-4-MeOC6H3
ꢃ
4e, R ¼ 2,4-F2C6H3

16
A. Rosiak et al.
chromatographic purification the racemic allylic alcohols 6 were obtained, which
were subsequently oxidized with an excess (10–30 eq.) of MnO2 at 23ꢂC in CH2Cl2.
The progress of this reaction was followed by TLC. After full conversion was
achieved (5–30 min), manganese containing materials were simply removed by
filtration to yield the double Michael acceptors 3, which were in most cases ana-
lytically pure without further purification. Yields for both steps are generally very
good, in some cases even quantitative (Table 2). Alcohols 6a–6i and ketones 3a–3i
originating from cinnamaldehyde 5a (R0 ¼ Ph) are exclusively obtained with the
C–C double bond in E-configuration. Whereas vinylketones 3a–3i with R0 ¼ Ph
show reasonable stability, their congeners 3j–3k deriving from acroleine (R0 ¼ H)
tend to decompose within an hour at ambient conditions and can not even be stored
at lower temperatures and must therefore be further converted directly after filtration.
Experimental
General Methods
Procedures using n-BuLi were performed in flame dried glassware and with absolute THF under
an atmosphere of nitrogen. Acroleine (5a) was freshly distilled prior to use. MnO2 (activated) was
used as received from Fluka. n-BuLi (c ¼ 1.6 or 2.0 M in pentane), NaSH ꢁ 1.2H2O (72% NaSH,
M ¼ 77.68 g molꢃ1), and alkynes 4a, 4d, 4e, 4g, 4h, 4i were purchased from the Aldrich Chemical
Company. Alkynes 4b [7] and 4f [8] were prepared from the corresponding aryl aldehydes according to
literature procedures. Alkyne 4c was prepared from 3-ethoxy-4-methoxybenzaldehyde (Aldrich) by
adopting the procedure reported for 4b [7]. Column chromatography was carried out using Merck SiO2
60 with hexanes (PE, bp 40–60ꢂC) and ethyl acetate (EA) as eluents. 1H NMR spectra were recorded
on a Bruker ARX 500 (500 MHz), Bruker ARX 300 (300MHz), or a Bruker AC 250 (250 MHz).
13C NMR spectra were recorded on a Bruker ARX 500 (125MHz), a Bruker ARX 300 (75 MHz), or a
Bruker AC 250 (62 MHz). Multiplicities were determined with DEPT experiments. Melting points
were measured on a Bu¨chi 510. Elemental analyses were carried out with a Analytik Jena Vario EL
and their results agreed favourably with calculated values.
General Procedure for the Synthesis of Alcohols 6
A solution if n-BuLi (1 eq.) was dropwise added under an atmosphere of N2 and at ꢃ78ꢂC to a solution
of arylacetylene 4 (1 eq.) in abs. THF (ca. 2 dm3 molꢃ1) and the resulting mixture was stirred for
90min at ꢃ78ꢂC. Then aldehyde 5 (1.1–1.5 eq.) was added and stirring at ꢃ78ꢂC continued for
90min. Saturated, aqueous NH4Cl solution (ca. 5 dm3 molꢃ1) was added, and the aqueous phase was
extracted once with CH2Cl2 (ca. 5 dm3 molꢃ1). The combined organic layers were dried (MgSO4) and
after filtration evaporated. The residue was chromatographed on SiO2 (PE=EA) to give alcohols 6.
(E)-3-Hydroxy-1,5-diphenyl-4-penten-1-yne (6a, C17H14O)
Alkyne 4a (1.00 g, 9.79 mmol), n-BuLi (7.35 cm3, 11.8 mmol, c ¼ 1.6 M), and aldehyde 5a (3.70 cm3,
29.4mmol) were converted according to the general procedure to yield the title compound 6a (2.04 g,
1
89%) after chromatography (PE=EA¼ 5=1, Rf ¼ 0.26) as a colorless solid, mp 65–67ꢂC. H NMR
(500 MHz, CDCl3): ꢂ ¼ 2.13 (d, J ¼ 4.8 Hz, 1H), 5.29 (s, 1H), 6.38 (dd, J ¼ 15.8, 6.1 Hz, 1H), 6.84
(d, J ¼ 15.7Hz, 1H), 7.25–7.49 (m, 10H) ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 63.37 (CH),
86.38 (C), 87.96 (C), 122.35 (C), 126.78 (2CH), 128.01 (CH), 128.05 (CH), 128.27 (2CH), 128.55
(3CH), 131.71 (2CH), 131.95 (CH), 136.06 (C) ppm; IR (ATR): ꢃꢀ¼ 3394 (m), 3024 (m), 2232 (m),
1597 (m), 1489 (s), 1443 (m), 1398 (m), 1232 (m), 1092 (m), 1070 (m), 1028 (m), 1013 (s), 996 (s),
965 (s), 914 (m), 753 (s), 728 (m), 687 (s) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 234 (73) [Mþ], 215 (47),
204 (42), 157 (14), 129 (100), 115 (38), 104 (47), 102 (78), 91 (56), 77 (54).

Synthesis of 2,3-Dihydrothiopyran-4-ones
17
(E)-1-(3,4-Dimethoxyphenyl)-3-hydroxy-5-phenyl-4-penten-1-yne (6b, C19H18O3)
Alkyne 4b (1.00 g, 6.17 mmol), n-BuLi (3.1cm3, 6.2mmol, c ¼ 2.0 M), and aldehyde 5a (1.2cm3,
9.2 mmol) were converted according to the general procedure to yield the title compound 6b (1.64 g,
1
90%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.26) as a yellow oil. H NMR (250 MHz, CDCl3):
ꢂ ¼ 2.58 (br, s, 1H), 3.85 (s, 3H), 3.87 (s, 3H), 5.27 (d, J ¼ 5.6 Hz, 1H), 6.38 (dd, J ¼ 15.8, 6.0 Hz, 1H),
6.78 (d, J ¼ 8.3 Hz, 1H), 6.80 (d, J ¼ 15.9 Hz, 1H), 6.98 (d, J ¼ 1.8 Hz, 1H), 7.07 (dd, J ¼ 8.3, 1.8Hz,
1H), 7.25–7.44 (m, 5H) ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 55.87 (OCH3), 55.88 (OCH3),
63.47 (CH), 86.38 (C), 86.59 (C), 110.94 (CH), 114.43 (CH), 114.55 (C), 125.08 (CH), 126.80 (2CH),
128.08 (CH), 128.32 (CH), 128.61 (2CH), 131.78 (CH), 136.15 (C), 148.57 (C), 149.67 (C) ppm; IR
(ATR): ꢃꢀ¼ 1513 (s), 1265 (m), 1243 (m), 1023 (m) cmꢃ1; HR-MS (EI, 70eV): m=z (%) ¼ 294.1255
(100) [Mþ], calcd 294.1256 (for C19H18O3).
(E)-1-(3-Ethoxy-4-methoxyphenyl)-3-hydroxy-5-phenyl-4-penten-1-yne (6c, C20H20O3)
Alkyne 4c (500mg, 2.84 mmol), n-BuLi (1.5cm3, 3.0 mmol, c ¼ 2.0 M), and aldehyde 5a (420mg,
3.18mmol) were converted according to the general procedure to yield the title compound 6c
(688 mg, 79%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.29) as a light yellow oil. 1H NMR
(500 MHz, CDCl3): ꢂ ¼ 1.45 (t, J ¼ 7.0 Hz, 3H), 2.35 (br, s, 1H), 3.87 (s, 3H), 4.07 (q, J ¼ 7.0 Hz,
2H), 5.27 (dd, J ¼ 5.7, 0.9Hz, 1H), 6.38 (dd, J ¼ 15.8, 6.0 Hz, 1H), 6.79 (d, J ¼ 8.2 Hz, 1H), 6.80 (br, d,
J ¼ 16 Hz, 1H), 6.97 (d, J ¼ 1.8 Hz, 1H), 7.06 (dd, J ¼ 8.3, 1.8 Hz, 1H), 7.24–7.28 (m, 1H), 7.30–7.34
(m, 2H), 7.40–7.43 (m, 2H) ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 14.72 (CH3), 55.91 (OCH3),
63.51 (CH), 64.34 (OCH2), 86.39 (C), 86.54 (C), 111.18 (CH), 114.45 (C), 115.74 (CH), 125.02
(CH), 126.81 (2CH), 128.09 (CH), 128.31 (CH), 128.61 (2CH), 131.83 (CH), 136.15 (C), 147.91
(C), 149.98 (C) ppm; IR (ATR): ꢃꢀ¼ 1598 (m), 1577 (m), 1510 (s), 1441 (m), 1416 (m), 1395 (m),
1319 (m), 1290 (m), 1261 (s), 1240 (s), 1198 (m), 1174 (m), 1136 (m), 1025 (s), 966 (m), 809 (m),
752 (m), 696 (m) cmꢃ1; HR-MS (EI, 70eV): m=z (%) ¼ 308.1413 (100) [Mþ], calcd 308.1412
(for C20H20O3).
(E)-3-Hydroxy-5-phenyl-1-(2-trifluoromethylphenyl)-4-penten-1-yne (6d, C18H13F3O)
Alkyne 4d (500 mg, 2.94mmol), n-BuLi (1.55 cm3, 3.1 mmol, c ¼ 2.0 M), and aldehyde 5a (430mg,
3.25mmol) were converted according to the general procedure to yield the title compound 6d (690 mg,
1
78%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.49) as a light yellow crystals, mp 79–80ꢂC. H
NMR (250 MHz, CDCl3): ꢂ ¼ 2.15 (d, J ¼ 3.4 Hz, 1H), 5.30 (br, s, 1H), 6.39 (dd, J ¼ 15.8, 5.7Hz, 1H),
6.90 (dd, J ¼ 15.8, 0.9Hz, 1H), 7.23–7.36 (m, 3H), 7.38–7.54 (m, 4H), 7.60–7.70 (m, 2H) ppm;
13C{1H} NMR (125 MHz, CDCl3): ꢂ ¼ 63.43 (s, CH), 82.52 (s, C), 93.43 (s, C), 120.67 (q, 3J ¼ 2.2 Hz,
1
3
C), 123.52 (q, J ¼ 273.5 Hz, C), 125.88 (q, J ¼ 5.1 Hz, CH), 126.88 (s, 2CH), 127.35 (s, CH),
128.19 (s, CH), 128.41 (s, CH), 128.64 (s, 2CH), 131.46 (s, CH), 131.66 (q, 2J ¼ 30.6 Hz, C) 132.51
(s, CH), 134.16 (s, CH), 136.08 (s, C) ppm; IR (ATR): ꢃꢀ¼ 3272 (br, m), 1489 (m), 1449 (m), 1315
(s), 1265 (m), 1160 (s), 1107 (s), 1052 (m), 1010 (m), 965 (s), 906 (m) cmꢃ1; MS (EI, 70 eV): m=z
(%) ¼ 302 (15) [Mþ], 274 (7), 233 (100), 215 (12), 197 (26), 170 (26), 151 (10), 115 (9), 104 (18),
91 (15), 77 (9).
(E)-1-(2,4-Difluorophenyl)-3-hydroxy-5-phenyl-4-penten-1-yne (6e, C17H12F2O)
Alkyne 4e (500 mg, 3.62 mmol), n-BuLi (1.8 cm3, 3.6 mmol, c ¼ 2.0 M), and aldehyde 5a (530 mg,
4.02 mmol) were converted according to the general procedure to yield the title compound 6e
(642 mg, 66%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.50) as light yellow crystals, mp 64–66ꢂC.
1H NMR (250 MHz, CDCl3): ꢂ ¼ 2.82 (br, s, 1H), 5.29 (d, J ¼ 5.6 Hz, 1H), 6.36 (dd, J ¼ 15.8, 6.0Hz,
1H), 6.81 (t, J ¼ 8.2Hz, 1H), 6.83 (d, J ¼ 15.6Hz, 1H), 6.84 (d, J ¼ 1.9 Hz, 1H), 7.21–7.45 (m, 6H)
ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 63.41 (s, CH), 78.88 (s, C), 93.03 (s, C), 104.31 (t,
2J ¼ 25.8 Hz, CH), 107.40 (dd, 2J ¼ 15.9 Hz, 4J ¼ 4.0 Hz, C), 111.63 (dd, 2J ¼ 21.9 Hz, 4J ¼ 3.8 Hz,
CH), 126.91 (s, 2CH), 127.62 (s, CH), 128.23 (s, CH), 128.67 (s, 2CH), 132.37 (s, CH), 134.53

18
A. Rosiak et al.
(dd, 3J ¼ 9.7 Hz, 3J ¼ 2.6 Hz, CH), 136.05 (s, C), 162.91 (dd, 1J ¼ 252 Hz, 3J ¼ 11.3 Hz, C), 163.19
1
3
(dd, J ¼ 266 Hz, J ¼ 10.9 Hz, C) ppm; IR (ATR): ꢃꢀ¼ 1502 (m), 1424 (m), 1267 (m), 1217 (m),
1140 (m), 1101 (m), 1007 (m), 964 (m), 852 (m), 819 (m), 754 (m) cmꢃ1; MS (EI, 70 eV): m=z
(%) ¼ 270 (100) [Mþ], 251 (46), 220 (30), 193 (8), 165 (76), 151 (19), 138 (48), 127 (52), 104
(55), 91 (43), 77 (30).
(E)-3-Hydroxy-5-phenyl-1-(2-thienyl)-4-penten-1-yne (6f, C15H12OS)
Alkyne 4f (345 mg, 3.19 mmol), n-BuLi (1.6cm3, 3.2 mmol, c ¼ 2.0 M), and aldehyde 5a (422 mg,
3.19mmol) were converted according to the general procedure to yield the title compound 6f (390 mg,
1
51%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.45) as a light yellow crystals, mp 77–79ꢂC. H
NMR (500 MHz, CDCl3): ꢂ ¼ 2.28 (d, J ¼ 6.2 Hz, 1H), 5.27 (dd, J ¼ 6.2 Hz, J ¼ 0.9 Hz, 1H), 6.35 (dd,
J ¼ 15.8, 6.1Hz, 1H), 6.79 (d, J ¼ 15.8Hz, 1H), 6.97 (dd, J ¼ 5.1, 3.8 Hz, 1H), 7.24–7.27 (m, 3H),
7.31–7.33 (m, 2H), 7.40–7.42 (m, 2H) ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 63.56 (CH), 79.76
(C), 91.73 (C), 122.23 (C), 126.84 (2CH), 126.99 (CH), 127.56 (CH), 127.65 (CH), 128.17 (CH),
128.62 (2CH), 132.18 (CH), 132.53 (CH), 135.99 (C) ppm; IR (ATR): ꢃꢀ¼ 1447 (m), 1270 (m), 1187
(m), 1069 (m), 1002 (s), 962 (s), 835 (m), 752 (s), 690 (s) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 240 (100)
[M+], 211 (79), 197 (17), 178 (43), 156 (19), 135 (72), 108 (83), 97 (32).
(E)-3-Hydroxy-5-phenyl-1-(2-pyridyl)-4-penten-1-yne (6g, C16H13NO)
Alkyne 4g (500 mg, 4.85mmol), n-BuLi (2.4cm3, 4.8mmol, c ¼ 2.0 M), and aldehyde 5a (645mg,
4.86mmol) were converted according to the general procedure to yield the title compound 6g (1.05 g,
92%) after chromatography (PE=EA ¼ 1=1, Rf ¼ 0.25) as a brown oil, which is crystallizing within a
1
few hours, mp 81–84ꢂC. H NMR (500MHz, CDCl3): ꢂ ¼ 4.30 (br, s, 1H), 5.38 (dd, J ¼ 6.0, 1.3Hz,
1H), 6.40 (dd, J ¼ 15.8, 6.0 Hz, 1H), 6.84 (dd, J ¼ 15.8, 0.8 Hz, 1H), 7.20–7.35 (m, 4H), 7.36–7.48 (m,
3H), 7.64 (dt, J ¼ 1.8, 7.8 Hz, 1H), 8.56 (ddd, J ¼ 4.9, 1.7Hz, 0.9 Hz, 1H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): ꢂ ¼ 62.92 (CH), 84.88 (C), 89.17 (C), 123.18 (CH), 126.84 (2CH), 127.34 (CH),
127.84 (CH), 128.01 (CH), 128.57 (2CH), 131.98 (CH), 136.22 (C), 136.44 (CH), 142.66 (C), 149.73
(CH) ppm; IR (ATR): ꢃꢀ¼ 3186 (br, m), 3057 (m), 1585 (s), 1563 (m), 1494 (m), 1465 (s), 1448 (m),
1429 (s), 1269 (m), 1027 (m), 966 (m), 778 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 235 (8) [Mþ], 217
(11), 207 (100), 130 (34), 103 (32), 78 (26).
(E)-6,6-Dimethyl-3-hydroxy-1-phenyl-1-hepten-4-yne (6h, C15H18O)
Alkyne 4h (0.950 g, 11.6mmol), n-BuLi (5.8cm3, 11.6mmol, c ¼ 2.0 M), and aldehyde 5a (1.55 g,
11.7mmol) were converted according to the general procedure to yield the title compound 6h (2.11 g,
85%) after chromatography (PE=EA¼ 5=1, Rf ¼ 0.31) as a light yellow solid, mp 50–51ꢂC. 1H NMR
(500 MHz, CDCl3): ꢂ ¼ 1.26 (s, 9H), 2.00 (d, J ¼ 5.7 Hz, 1H), 5.03 (td, J ¼ 5.3, 0.8Hz, 1H), 6.29 (dd,
J ¼ 15.8, 5.8Hz, 1H), 6.74 (dd, J ¼ 15.8, 1.0 Hz, 1H), 7.24–7.41 (m, 5H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): ꢂ ¼ 27.46 (C), 30.94 (3CH3), 63.08 (CH), 77.57 (C), 95.61 (C), 126.77 (2CH),
127.96 (CH), 128.57 (2CH), 128.92 (CH), 131.41 (CH), 136.28 (C) ppm; IR (ATR): ꢃꢀ¼ 3349 (br, m),
2969 (m), 1492 (m), 1449 (m), 1400 (br, m), 1363 (m), 1260 (m), 1204 (m), 1046 (s), 962 (vs), 867
(m), 751 (s), 693 (s) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 214 (61) [Mþ], 199 (97), 165 (24), 157 (39),
141 (15), 128 (27), 109 (54), 104 (100), 91 (66), 81 (32), 77 (39).
(E)-3-Hydroxy-1-phenyl-6-trimethylsilyl-1-penten-4-yne (6i, C14H18OSi)
Alkyne 4i (1.09 g, 10.0 mmol), n-BuLi (5.1cm3, 10.2mmol, c ¼ 2.0 M), and aldehyde 5a (1.35 g,
10.2mmol) were converted according to the general procedure to yield the title compound 6i
1
(2.25 g, 98%) after chromatography (PE=EA¼ 5=1, Rf ¼ 0.41) as a yellow oil. H NMR (500 MHz,
CDCl3): ꢂ ¼ 0.25 (s, 9H), 2.15 (d, J ¼ 4.5Hz, 1H), 5.08 (br, t, J ¼ 4.4 Hz, 1H), 6.32 (dd, J ¼ 15.8,
5.9 Hz, 1H), 6.81 (d, J ¼ 15.8Hz, 1H), 7.29–7.32 (m, 1H), 7.35–7.38 (m, 2H), 7.44–7.45 (m, 2H) ppm;
13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 0.00 (3CH3, TMS), 63.51 (CH), 91.51 (C), 104.37 (C), 126.97
(2CH), 128.01 (CH), 128.27 (CH), 128.76 (2CH), 132.22 (CH), 136.23 (C) ppm; IR (ATR): ꢃꢀ¼ 3294

Synthesis of 2,3-Dihydrothiopyran-4-ones
19
(br, m), 2958 (m), 1448 (m), 1416 (br, m), 1250 (s), 1091 (m), 1068 (m), 1025 (s), 965 (s), 905 (m),
841 (vs) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 230 (38) [Mþ], 197 (23), 139 (18), 125 (26), 105 (23), 104
(43), 91 (21).
1-(3,4-Dimethoxyphenyl)-3-hydroxy-4-penten-1-yne (6j, C13H14O3)
Alkyne 4b (1.00 g, 6.17 mmol), n-BuLi (3.1cm3, 6.2mmol, c ¼ 2.0 M), and aldehyde 5b (520mg,
9.26mmol) were converted according to the general procedure to yield the title compound 6j
1
(950 mg, 71%) after chromatography (PE=EA¼ 2:1, Rf ¼ 0.29) as a yellow oil. H NMR (250 MHz,
CDCl3): ꢂ ¼ 2.54 (br, s, 1H), 3.86 (s, 3H), 3.87 (s, 3H), 5.10 (d, J ¼ 5.4 Hz, 1H), 5.26 (dt, J ¼ 10.1,
1.3 Hz, 1H), 5.52 (dt, J ¼ 17.0, 1.3 Hz, 1H), 6.06 (ddd, J ¼ 17.0, 10.1, 5.4 Hz, 1H), 6.78 (d, J ¼ 8.3 Hz,
1H), 6.94 (d, J ¼ 1.8 Hz, 1H), 7.05 (dd, J ¼ 8.3, 1.8Hz, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3):
ꢂ ¼ 55.87 (2OCH3), 63.65 (CH), 86.24 (C), 86.36 (C), 110.92 (CH), 114.39 (CH), 114.54 (C), 116.39
(CH2), 125.04 (CH), 137.13 (CH), 148.53 (C), 149.62 (C) ppm; IR (ATR): ꢃꢀ¼ 1514 (m), 1266 (m),
1243 (m), 1023 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 218 (100) [Mþ], 203 (21), 159 (12), 138 (14),
115 (15), 91 (10).
1-(3-Ethoxy-4-methoxyphenyl)-3-hydroxy-4-penten-1-yne (6k, C14H16O3)
Alkyne 4k (870 mg, 4.94 mmol), n-BuLi (3.0cm3, 6.0 mmol, c ¼ 2.0 M), and aldehyde 5b (350mg,
6.24mmol) were converted according to the general procedure to yield the title compound 6k (770 mg,
1
67%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.36) as a colorless solid, mp 53–55ꢂC. H NMR
(500 MHz, CDCl3): ꢂ ¼ 1.45 (t, J ¼ 7.1 Hz, 3H), 2.28 (br, s, 1H), 3.87 (s, 3H), 4.07 (q, J ¼ 7.0 Hz, 2H),
5.09 (br, s, 1H), 5.26 (d, J ¼ 10.1 Hz, 1H), 5.52 (dd, J ¼ 17.0, 0.8 Hz, 1H), 6.06 (ddd, J ¼ 17.0,
10.1, 5.6 Hz, 1H), 6.79 (d, J ¼ 8.3Hz, 1H), 6.95 (br, s, 1H), 7.03 (dd, J ¼ 8.2, 0.9 Hz, 1H) ppm;
13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 14.72 (CH3), 55.92 (OCH3), 63.70 (CH), 64.36 (CH2),
86.20 (C), 86.39 (C), 111.20 (CH), 114.49 (C), 115.79 (CH), 116.40 (CH2), 125.00 (CH), 137.15
(CH), 147.91 (C), 149.98 (C) ppm; IR (ATR): ꢃꢀ¼ 3293 (br, m), 2929 (m), 1598 (m), 1510 (s), 1439
(m), 1416 (m), 1393 (m), 1260 (m), 1241 (s), 1199 (m), 1174 (m), 1135 (s), 1021 (br, s), 935 (m), 894
(m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 232 (100) [Mþ], 203 (13), 189 (16), 175 (13), 161 (13), 133
(17), 124 (9), 115 (24).
1-(2,4-Difluorophenyl)-3-hydroxy-4-penten-1-yne (6l, C11H8F2O)
Alkyne 4l (800mg, 5.79mmol), n-BuLi (2.9cm3, 5.8 mmol, c ¼ 2.0 M), and aldehyde 5b (360 mg,
6.42mmol) were converted according to the general procedure to yield the title compound 6l (798 mg,
1
71%) after chromatography (PE=EA¼ 2=1, Rf ¼ 0.47) as a colorless solid, mp 30–32ꢂC. H NMR
(250 MHz, CDCl3): ꢂ ¼ 2.11 (br, s, 1H), 5.13 (d, J ¼ 5.2 Hz, 1H), 5.29 (dt, J ¼ 10.1, 1.1Hz, 1H), 5.57
(dt, J ¼ 17.0, 1.2 Hz, 1H), 6.07 (ddd, J ¼ 17.0, 10.2, 5.3 Hz, 1H), 6.80–6.89 (m, 2H), 7.37–7.47 (m,
1H) ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 63.66 (s, CH), 78.85 (s, C), 93.05 (s, C), 104.29
(t,2J ¼ 24.9Hz, CH), 111.59 (dd, 2J ¼ 21.9Hz, 4J ¼ 3.7 Hz, CH), 116.99 (s, CH2), 134.46 (dd,
3
3J ¼ 9.9 Hz, J ¼ 2.5Hz, CH), 136.46 (s, CH) ppm; resonances for carbon atoms C-10, C-20, and
C-40 are not observed due to poor signal-to-noise ratio; IR (ATR): ꢃꢀ¼ 3317 (br, m,), 1587 (m),
1500 (s), 1420 (m), 1289 (m), 1262 (s), 1217 (m), 1142 (m), 1095 (m), 1012 (br, m,), 962 (m), 932
(m), 847 (s), 810 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 194 (69) [Mþ], 175 (16), 165 (100), 151 (64),
138 (32), 119 (54), 114 (60), 99 (15), 80 (22).
General Procedure for the Synthesis of Ketones 3
MnO2 (up to 30 eq.) was added portionwise to a solution of alcohol 6 (1 eq.) in CH2Cl2 (10 dm3 molꢃ1
)
at ambient temperature, until almost quantitative conversion was achieved (5–60min). The progress of
the reaction was monitored by TLC. If no starting material was left, the product started to decompose.
The reaction mixture was filtered with vacuum through SiO2 to separate MnO2, the residue was washed
several times with EA. The filtrate was concentrated under vacuum to give ketones 3 in analytically
pure form in most cases. If necessary, the products 3 can be purified by chromatography on SiO2

20
A. Rosiak et al.
(PE=EA). Compounds with R0 ¼ H are not stable, not even at low temperatures, and must be converted
further directly after filtration and evaporation of the solvent.
(E)-1,5-Diphenyl-3-oxo-4-penten-1-yne (3a, C17H12O)
Alcohol 6a (1.00 g, 4.27mmol) and MnO2 (4.30 g, 49.5mmol) were converted according to the general
procedure to yield ketone 3a (952 mg, 96% without chromatography) as a yellow solid, mp 70–72ꢂC.
1
Rf (SiO2, PE=EA¼ 5=1)¼ 0.39; H NMR (500 MHz, CDCl3): ꢂ ¼ 6.88 (d, J ¼ 16.1 Hz, 1H), 7.41–
7.50 (m, 6H), 7.59–7.67 (m, 4H), 7.92 (d, J ¼ 16.1Hz, 1H) ppm; 13C{1H} NMR (125MHz, CDCl3):
ꢂ ¼ 86.67 (C), 91.56 (C), 120.28 (C), 128.61 (CH), 128.70 (2CH), 128.72 (2CH), 129.12 (2CH),
130.64 (CH), 131.18 (CH), 132.97 (2CH), 134.14 (C), 148.28 (CH), 178.22 (C¼O) ppm; IR (ATR):
ꢃꢀ¼ 3061 (m), 2212 (s), 2160 (m), 1626 (s), 1608 (s), 1595 (s), 1571 (s), 1488 (m), 1444 (m), 1311 (m),
1288 (m), 1173 (s), 971 (s), 873 (s), 757 (s), 689 (s), 672 (s), 579 (m) cmꢃ1; MS (EI, 70 eV): m=z
(%) ¼ 232 (55) [Mþ], 231 (100), 204 (22), 203 (41), 129 (40), 102 (30), 77 (14).
(E)-1-(3,4-Dimethoxyphenyl)-3-oxo-5-phenyl-4-penten-1-yne (3b, C19H16O3)
Alcohol 6b (500mg, 1.70mmol) and MnO2 (3.20 g, 36.8mmol) were converted according to the
general procedure to yield ketone 3b (415mg, 84% after chromatography) as a yellow solid, mp
87–88ꢂC. Rf (SiO2, PE=EA¼ 2=1) ¼ 0.38; 1H NMR (250MHz, CDCl3): ꢂ ¼ 3.92 (s, 3H), 3.94 (s, 3H),
6.88 (d, J ¼ 16.3Hz, 1H), 6.89 (d, J ¼ 8.5 Hz, 1H), 7.14 (d, J ¼ 1.9 Hz, 1H), 7.31 (dd, J ¼ 8.3, 1.9Hz,
1H), 7.42–7.47 (m, 3H), 7.59–7.63 (m, 2H), 7.89 (d, J ¼ 16.1Hz, 1H) ppm; 13C{1H} NMR (62 MHz,
CDCl3): ꢂ ¼ 56.04 (OCH3), 56.08 (OCH3), 86.39 (C), 92.67 (C), 111.09 (CH), 112.03 (C), 115.33
(CH), 127.28 (CH), 128.56 (2CH), 128.66 (CH), 129.08 (2CH), 131.09 (CH), 134.16 (C), 147.73 (CH),
148.87 (C), 151.57 (C), 178.18 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 2184 (m), 1737 (br, w), 1612 (m), 1589
(m), 1511 (m), 1457 (m), 1438 (m), 1228 (m), 1132 (m), 1017 (m) cmꢃ1; MS (EI, 70 eV): m=z
(%) ¼ 292 (100) [Mþ], 261 (13), 189 (17), 162 (24).
(E)-1-(3-Ethoxy-4-methoxyphenyl)-3-oxo-5-phenyl-4-penten-1-yne (3c, C20H18O3)
Alcohol 6c (500mg, 1.62 mmol) and MnO2 (3.2g, 37mmol) were converted according to the general
procedure to yield ketone 3c (495mg, 99% without chromatography) as a yellow solid, mp 75–76ꢂC.
1
Rf (SiO2, PE=EA¼ 2=1)¼ 0.35; H NMR (500 MHz, CDCl3): ꢂ ¼ 1.49 (t, J ¼ 7.0Hz, 3H), 3.93 (s,
3H), 4.13 (q, J ¼ 7.0 Hz, 2H), 6.87 (d, J ¼ 16.1Hz, 1H), 6.89 (d, J ¼ 8.4Hz, 1H), 7.13 (d, J ¼ 1.8 Hz,
1H), 7.29 (dd, J ¼ 8.3, 1.8 Hz, 1H), 7.42–7.46 (m, 3H), 7.59–7.63 (m, 2H), 7.89 (d, J ¼ 16.0 Hz, 1H)
ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 14.70 (CH3), 56.03 (OCH3), 64.55 (OCH2), 86.34 (C),
92.84 (C), 111.31 (CH), 111.96 (C), 116.61 (CH), 127.18 (CH), 128.60 (CH), 128.66 (2CH), 129.08
(2CH), 131.06 (CH), 134.20 (C), 147.67 (CH), 148.22 (C), 151.88 (C), 178.19 (C¼O) ppm; IR (ATR):
ꢃꢀ¼ 2181 (vs), 1627 (s), 1591 (s), 1509 (vs), 1475 (m), 1441 (m), 1418 (m), 1308 (m), 1246 (vs), 1202
(m), 1181 (m), 1154 (m), 1132 (s), 1096 (s), 1041 (m), 1020 (s), 973 (m), 857 (m), 807 (m), 760 (s),
698 (m), 675 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 306 (100) [Mþ], 235 (10), 176 (13), 148 (10).
(E)-3-Oxo-5-phenyl-1-(2-trifluoromethylphenyl)-4-penten-1-yne (3d, C18H11F3O)
Alcohol 6d (300mg, 0.99 mmol) and MnO2 (870 mg, 10.0mmol) were converted according to the
general procedure to yield ketone 3d (294mg, 99% without chromatography) as a yellow solid, mp
52–53ꢂC. Rf (SiO2, PE=EA¼ 2=1)¼ 0.55; 1H NMR (500 MHz, CDCl3): ꢂ ¼ 6.86 (d, J ¼ 16.2 Hz, 1H),
7.42–7.46 (m, 3H), 7.56–7.63 (m, 4H), 7.77 (d, J ¼ 7.3 Hz, 1H), 7.83 (d, J ¼ 7.2Hz, 1H), 8.03 (d,
J ¼ 16.1Hz, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): ꢂ ¼ 86.04 (s, C), 90.65 (s, C), 118.52 (q,
3J ¼ 1.8 Hz, C), 123.40 (q, 1J ¼ 273.5 Hz, CF3), 126.22 (q, 3J ¼ 5.2 Hz, CH), 128.49 (s, CH), 128.80 (s,
2
2CH), 129.14 (s, 2CH), 130.39 (s, CH), 131.36 (s, CH), 131.88 (s, CH), 132.43 (q, J ¼ 30.9 Hz, C),
134.11 (s, C), 135.78 (s, CH), 149.85 (s, CH), 178.00 (s, C¼O) ppm; IR (ATR): ꢃꢀ¼ 2213 (m), 1616
(s), 1595 (s), 1574 (m), 1487 (m), 1447 (m), 1318 (s), 1261 (s), 1154 (s), 1107 (s), 1054 (m), 969 (s),
758 (vs), 690 (m), 653 (m) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 300 (56) [Mþ], 299 (67), 272 (18), 251
(47), 231 (100), 203 (25), 197 (18), 169 (28), 102 (14), 77 (10).

Synthesis of 2,3-Dihydrothiopyran-4-ones
21
(E)-1-(2,4-Difluorophenyl)-3-oxo-5-phenyl-4-penten-1-yne (3e, C17H10F2O)
Alcohol 6e (450mg, 1.66 mmol) and MnO2 (2.9g, 33mmol) were converted according to the general
procedure to yield ketone 3e (440 mg, 99% without chromatography) as a yellow solid, mp 110–
1
112ꢂC. Rf (SiO2, PE=EA¼ 2=1)¼ 0.55; H NMR (250MHz, CDCl3): ꢂ ¼ 6.86 (d, J ¼ 16.1 Hz, 1H),
6.91–6.99 (m, 2H), 7.43–7.47 (m, 3H), 7.59–7.67 (m, 3H), 7.99 (d, J ¼ 16.1Hz, 1H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): ꢂ ¼ 83.74 (s, C), 90.95 (t, 3J ¼ 2.4 Hz, C), 104.81 (dd, 2J ¼ 25.1 Hz,
2
4
2
4
2J ¼ 24.5Hz, CH), 105.58 (dd, J ¼ 15.9Hz, J ¼ 4.0 Hz, C), 112.35 (dd, J ¼ 22.5Hz, J ¼ 5.9 Hz,
CH), 128.34 (s, CH), 128.80 (s, 2CH), 129.12 (s, 2CH), 131.33 (s, CH), 134.03 (s, C), 135.84 (dd,
3J ¼ 10.0Hz, 3J ¼ 1.7Hz, CH), 149.33 (s, CH), 164.35 (d, 1J ¼ 256.7 Hz, C), 164.45 (d, 1J ¼ 256.7Hz,
C), 177.91 (s, C¼O) ppm; IR (ATR): ꢃꢀ¼ 2215 (m), 1632 (m), 1604 (m), 1496 (m), 1317 (m), 1267
(m), 1224 (m), 1174 (m), 1093 (m), 973 (m), 963 (m), 847 (m), 756 (m) cmꢃ1; MS (EI, 70eV): m=z
(%) ¼ 267 (100) [Mþ ꢃ H], 249 (55), 239 (59), 220 (17), 165 (45), 137 (14), 102 (33), 77 (21).
(E)-3-Oxo-5-phenyl-1-(2-thienyl)-4-penten-1-yne (3f, C15H10OS)
Alcohol 6f (100 mg, 0.42 mmol) and MnO2 (360mg, 4.14mmol) were converted according to the
general procedure to yield ketone 3f (99 mg, 99% without chromatography) as a yellow oil, which
solidified after a few hours at 23ꢂC, mp 69–72ꢂC. Rf (SiO2, PE=EA ¼ 2=1)¼ 0.49; 1H NMR
(250 MHz, CDCl3): ꢂ ¼ 6.85 (d, J ¼ 16.1Hz, 1H), 7.10 (dd, J ¼ 5.1, 3.7 Hz, 1H), 7.40–7.47 (m,
3H), 7.50 (dd, J ¼ 5.1, 1.1Hz, 1H), 7.54 (dd, J ¼ 3.6, 1.1 Hz, 1H), 7.57–7.63 (m, 2H), 7.85 (d,
J ¼ 16.1Hz, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 85.46 (C), 91.39 (C), 120.01 (C),
127.77 (CH), 128.26 (CH), 128.73 (2CH), 129.12 (2CH), 131.22 (CH), 131.38 (CH), 134.07 (C),
136.43 (CH), 148.03 (CH), 177.66 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 2189 (vs), 1623 (vs), 1595 (s), 1449
(m), 1272 (m), 1222 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 238 (100) [Mþ], 209 (34), 165 (17), 134
(28), 107 (23), 77 (17).
(E)-3-Oxo-5-phenyl-1-(2-pyridyl)-4-penten-1-yne (3g, C16H11NO)
Alcohol 6g (400 mg, 1.70 mmol) and MnO2 (3.00 g, 34.5mmol) were converted according to the
general procedure to yield ketone 3g (298mg, 75% after chromatography) as a brown oil, which
solidified after a few hours at 23ꢂC, mp 55–58ꢂC. Rf (SiO2, PE=EA ¼ 1=1)¼ 0.41; 1H NMR
(250 MHz, CDCl3): ꢂ ¼ 6.89 (d, J ¼ 16.1Hz, 1H), 7.35–7.45 (m, 4H), 7.60–7.68 (m, 3H), 7.76 (dt,
J ¼ 7.7, 1.7 Hz, 1H), 8.00 (d, J ¼ 16.1Hz, 1H), 8.70 (dt, J ¼ 4.7, 1.0 Hz, 1H) ppm; 13C{1H} NMR
(62 MHz, CDCl3): ꢂ ¼ 84.64 (C), 88.99 (C), 124.59 (CH), 128.21 (CH), 128.85 (3CH), 129.10 (2CH),
131.35 (CH), 133.97 (C), 136.47 (CH), 141.12 (C), 149.28 (CH), 150.54 (CH), 177.84 (C¼ O) ppm;
IR (ATR): ꢃꢀ¼ 2220 (m), 1627 (vs), 1577 (s), 1516 (s), 1460 (s), 1447 (m), 1426 (m), 1279 (s), 1183
(s), 1112 (m), 1083 (m), 972 (s), 867 (m), 778 (s), 761 (s), 697 (s), 676 (m) cmꢃ1; MS (EI, 70eV): m=z
(%) ¼ 233 (59) [Mþ], 232 (92), 205 (41), 204 (100), 130 (21), 103 (12), 102 (19), 78 (19).
(E)-6,6-Dimethyl-3-oxo-1-phenyl-1-hepten-4-yne (3h, C15H16O)
Alcohol 6h (400 mg, 1.87 mmol) and MnO2 (2.2g, 25mmol) were converted according to the general
procedure to yield ketone 3h (392 mg, 99% without chromatography) as colorless crystals, mp 30–
31ꢂC. Rf (SiO2, PE=EA¼ 5=1) ¼ 0.42, 1H NMR (500 MHz, CDCl3): ꢂ ¼ 1.37 (s, 9H), 6.77 (d,
J ¼ 16.0Hz, 1H), 7.41–7.43 (m, 3H), 7.55–7.57 (m, 2H), 7.77 (d, J ¼ 16.0Hz, 1H) ppm; 13C{1H}
NMR (125MHz, CDCl3): ꢂ ¼ 27.92 (C), 30.22 (3CH3), 77.76 (C), 102.36 (C), 128.59 (2CH), 128.69
(CH), 129.03 (2CH), 130.98 (CH), 134.14 (C), 147.97 (CH), 178.74 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 2968
(m), 2196 (br, m), 1620 (vs), 1449 (s), 1360 (m), 1275 (s), 1224 (s), 1197 (s), 976 (s), 950 (m), 878 (m)
cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 212 (100) [Mþ], 197 (80), 182 (20), 169 (44), 153 (24), 141 (29),
131 (27), 115 (16), 103 (29), 77 (23).
(E)-3-Oxo-1-phenyl-6-trimethylsilyl-1-penten-4-yne (3i, C14H16OSi)
Alcohol 6i (500mg, 2.17mmol) and MnO2 (2.5g, 29mmol) were converted according to the gen-
eral procedure to yield ketone 3i (480mg, 97% without chromatography) as yellow oil. Rf (SiO2,

22
A. Rosiak et al.
PE=EA¼ 5=1)¼ 0.46; 1H NMR (250MHz, CDCl3): ꢂ ¼ 0.30 (s, 9H), 6.78 (d, J ¼ 16.1Hz, 1H), 7.40–
7.47 (m, 3H), 7.53–7.59 (m, 2H), 7.84 (d, J ¼ 16.1Hz, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3):
ꢂ ¼ ꢃ0.65 (3CH3), 98.72 (C), 100.57 (C), 128.19 (CH), 128.69 (2CH), 129.05 (2CH), 131.21 (CH),
133.98 (C), 148.90 (CH), 177.99 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1626 (vs), 1598 (m), 1449 (m), 1236 (s),
1196 (s), 1122 (m), 976 (m), 869 (s), 845 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 228 (100) [Mþ], 213
(43), 198 (12), 185 (42), 103 (13).
1-(3,4-Dimethoxyphenyl)-3-oxo-4-penten-1-yne (3j, C13H12O3)
Alcohol 6j (300 mg, 1.38 mmol) and MnO2 (2.40 g, 27.6mmol) were converted according to the
general procedure to yield ketone 3j (230 mg, 77% after chromatography) as a yellow oil. Rf (SiO2,
PE=EA¼ 2=1)¼ 0.40. 1H NMR (250 MHz, CDCl3): ꢂ ¼ 3.90 (s, 3H), 3.93 (s, 3H), 6.22 (dd, J ¼ 10.0,
1.2 Hz, 1H), 6.48 (dd, J ¼ 17.4, 10.0Hz, 1H), 6.66 (dd, J ¼ 17.4, 1.2 Hz, 1H), 6.87 (d, J ¼ 8.3 Hz, 1H),
7.09 (d, J ¼ 1.9 Hz, 1H), 7.26 (dd, J ¼ 8.3, 1.9 Hz, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3):
ꢂ ¼ 56.01 (OCH3), 56.03 (OCH3), 85.56 (C), 93.25 (C), 111.09 (CH), 111.75 (C), 115.32 (CH),
127.43 (CH), 133.04 (CH2), 138.02 (CH), 148.85 (C), 151.68 (C), 178.79 (C¼O) ppm; IR (ATR):
ꢃꢀ¼ 2181 (s), 1735 (m), 1637 (s), 1593 (s), 1510 (s), 1461 (m), 1398 (m), 1248 (s), 1136 (m), 995 (m)
cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 216 (100) [Mþ], 189 (86), 173 (10), 145 (11).
1-(3-Ethoxy-4-methoxyphenyl)-3-oxo-4-penten-1-yne (3k, C14H14O3)
Alcohol 6k (480 mg, 2.07 mmol) and MnO2 (5.4g, 62mmol) were converted according to the general
procedure to yield ketone 3k (295mg, 62% after chromatography) as a yellow solid, mp 86–87ꢂC. Rf
(SiO2, PE=EA¼ 2=1) ¼ 0.42; 1H NMR (500 MHz, CDCl3): ꢂ ¼ 1.48 (t, J ¼ 7.1 Hz, 3H), 3.91 (s, 3H),
4.10 (q, J ¼ 7.1 Hz, 2H), 6.20 (dd, J ¼ 10.1, 0.8 Hz, 1H), 6.48 (dd, J ¼ 17.5, 10.4 Hz, 1H), 6.64 (dd,
J ¼ 16.7, 0.8 Hz, 1H), 6.87 (d, J ¼ 8.3 Hz, 1H), 7.08 (d, J ¼ 1.8Hz, 1H), 7.24 (dd, J ¼ 8.4, 1.8 Hz, 1H)
ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 14.67 (CH3), 56.02 (OCH3), 64.54 (OCH2), 85.54 (C),
93.42 (C), 111.33 (CH), 111.69 (C), 116.64 (CH), 127.32 (CH), 132.92 (CH2), 138.05 (CH),
148.21 (C), 152.00 (C), 178.78 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 2981 (m), 2186 (vs), 1636 (s), 1592
(s), 1575 (m), 1515 (vs), 1480 (m), 1397 (m), 1311 (m), 1251 (vs), 1165 (m), 1137 (s), 1018 (m),
1005 (m), 974 (m), 962 (m), 771 (m) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 230 (100) [Mþ], 203 (19),
175 (75), 159 (20), 131 (15).
1-(2,4-Difluorophenyl)-3-oxo-4-penten-1-yne (3l, C11H6F2O)
Alcohol 6l (400 mg, 2.06mmol) and MnO2 (2.7g, 31mmol) were converted according to the general
procedure to yield ketone 3l (394mg, 99% without chromatography) as a yellow solid, mp 29–31ꢂC.
Rf (SiO2, PE=EA¼ 2=1)¼ 0.56; 1H NMR (500MHz, CDCl3): ꢂ ¼ 6.28 (dd, J ¼ 10.2, 0.8 Hz, 1H), 6.48
(dd, J ¼ 17.3, 10.2 Hz, 1H) 6.72 (dd, J ¼ 17.3, 0.8 Hz, 1H), 6.88–6.98 (m, 2H), 7.55–7.64 (m, 1H)
2
ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 77.24 (s, C), 84.18 (s, C), 104.79 (dd, J ¼ 26.7 Hz,
2
4
2
4
2J ¼ 24.1Hz, CH), 105.29 (dd, J ¼ 19.3Hz, J ¼ 4.5 Hz, C), 112.32 (dd, J ¼ 22.2Hz, J ¼ 3.9 Hz,
CH), 134.25 (s, CH2), 135.87 (dd, 3J ¼ 10.2Hz, 3J ¼ 1.9 Hz, CH), 137.82 (s, CH), 164.43 (d,
1J ¼ 261.4 Hz, C), 164.56 (d, J ¼ 255.9Hz, C), 178.43 (s, C ¼ O) ppm; IR (ATR): ꢃꢀ¼ 2965 (m),
1
2203 (m), 1667 (s), 1607 (s), 1501 (s), 1427 (m), 1267 (m), 1223 (m), 1143 (s), 1094 (m), 966 (m), 848
(m) cm ꢃ1; MS (EI, 70 eV): m=z (%) ¼ 192 (45) [Mþ], 165 (100), 137 (14).
2,3-Dihydro-2,6-diphenylthiopyran-4-one (2a, C17H14OS)
Method A: A mixture of ketone 3a (470 mg, 2.02mmol), Na2S ꢁ 9H2O (972 mg, 4.05mmol), THF
(9cm3), and H2O (9cm3) was stirred for 72h at 23ꢂC. CH2Cl2 (25 cm3) was added, and the mixture
was further stirred for 17h. The organic layer was separated. The aqueous phase was neutralized with
saturated NH4Cl solution (40 cm3) and then extracted with CH2Cl2 (3ꢄ40cm3). The combined organic
layers were washed with brine (50 cm3) and dried (MgSO4). After filtration, the solvent was stripped
off and the residue purified by chromatography (SiO2, PE=EA¼ 5=1, Rf ¼ 0.44) to yield the title
1
compound 2a (507 mg, 94%) as a yellow oil. H NMR (500MHz, CDCl3): ꢂ ¼ 2.99 (dd, J ¼ 16.4,

Synthesis of 2,3-Dihydrothiopyran-4-ones
23
3.1 Hz, 1H), 3.15 (dd, J ¼ 16.4, 14.1Hz, 1H), 4.77 (dd, J ¼ 14.1, 3.1 Hz, 1H), 6.58 (s, 1H), 7.35–7.49
(m, 8H), 7.64–7.66 (m, 2H) ppm; 13C{1H} NMR (125 MHz, CDCl3): ꢂ ¼ 44.31 (CH2), 46.72 (CH),
120.70 (CH), 127.18 (2CH), 127.59 (2CH), 128.62 (CH), 128.89 (2CH), 129.07 (2CH), 131.13 (CH),
136.93 (C), 137.85 (C), 160.37 (C), 195.00 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1646 (vs), 1550 (s), 1318 (m),
1297 (m), 1266 (s), 856 (m), 762 (m), 725 (m), 695 (s), 633 (m) cmꢃ1; HR-MS (EI, 70eV): m=z
(%) ¼ 266.0765 (81) [Mþ], calcd 266.0759 (for C17H14OS).
General Procedure for the Ring Closure with NaSH (Method B)
A mixture of ketone 3 (1 eq.), NaSHꢁ 1.2H2O (3–5 eq.), and 2-ME (ca. 10dm3 molꢃ1) was stirred for
the time and at the temperature specified in Table 1. Saturated aqueous NH4Cl solution (ca. 10 dm3
molꢃ1) was added and the mixture was extracted with EA (3ꢄ15dm3 molꢃ1). The combined organic
phases were dried (MgSO4), filtered, and evaporated. The residue was chromatographed (SiO2,
PE=EA) to give dihydrothiopyranones 2.
6-(3,4-Dimethoxyphenyl)-2,3-dihydro-2-phenylthiopyran-4-one (2b, C19H18O3S)
Ketone 3b (150 mg, 0.51 mmol), NaSHꢁ 1.2H2O (260 mg, 3.35mmol), and 2-ME (15 cm3) were con-
verted for 2 h at 50ꢂC and for 14h at 23ꢂC according to the general procedure (method B) to give
dihydrothiopyranone 2b (160 mg, 96%) after chromatography (SiO2, PE=EA¼ 2=1, Rf ¼ 0.22) as a
brown solid, mp 89–92ꢂC. 1H NMR (250 MHz, CDCl3): ꢂ ¼ 2.98 (dd, J ¼ 16.5, 3.4Hz, 1H), 3.15 (dd,
J ¼ 16.5, 13.8 Hz, 1H), 3.91 (s, 3H), 3.93 (s, 3H), 4.75 (dd, J ¼ 13.8, 3.4Hz, 1H), 6.57 (s, 1H), 6.89 (d,
J ¼ 8.5 Hz, 1H), 7.16 (d, J ¼ 2.2 Hz, 1H), 7.32 (dd, J ¼ 8.4, 2.2 Hz, 1H), 7.35–7.48 (m, 5H) ppm;
13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 44.49 (CH2), 46.54 (CH), 55.99 (OCH3), 56.04 (OCH3), 109.86
(CH), 110.96 (CH), 119.32 (CH), 120.61 (CH), 127.68 (2CH), 128.66 (CH), 129.08 (2CH), 129.34 (C),
137.87 (C), 149.09 (C), 151.78 (C), 160.24 (C), 195.17 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1644 (s), 1594 (m),
1546 (m), 1507 (s), 1458 (m), 1411 (m), 1257 (s), 1144 (s), 1022 (s) cmꢃ1; MS (EI, 70eV): m=z
(%) ¼ 326 (100) [Mþ], 298 (10), 222 (28), 193 (48).
6-(3-Ethoxy-4-methoxyphenyl)-2,3-dihydro-2-phenylthiopyran-4-one (2c, C20H20O3S)
Ketone 3c (390 mg, 1.27 mmol), NaSHꢁ 1.2H2O (390 mg, 5.02 mmol), and 2-ME (25 cm3) were con-
verted for 4 h at 40ꢂC and for 16h at 23ꢂC according to the general procedure (method B) to give
dihydrothiopyranone 2c (399 mg, 92%) after chromatography (SiO2, PE=EA ¼ 2=1, Rf ¼ 0.34) as a
1
yellow solid, mp 100–101ꢂC. H NMR (500MHz, CDCl3): ꢂ ¼ 1.48 (t, J ¼ 6.9 Hz, 3H), 2.98 (dd,
J ¼ 16.5, 3.1 Hz, 1H), 3.14 (dd, J ¼ 16.1, 14.3Hz, 1H), 3.91 (s, 3H), 4.13 (q, J ¼ 6.9Hz, 2H), 4.73 (dd,
J ¼ 14.0, 3.0 Hz, 1H), 6.55 (s, 1H), 6.89 (d, J ¼ 8.6 Hz, 1H), 7.17 (d, J ¼ 2.2Hz, 1H), 7.30 (dd, J ¼ 8.4,
2.1 Hz, 1H), 7.36–7.46 (m, 5H) ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 14.71 (CH3), 44.51
(CH2), 46.52 (CH), 56.06 (OCH3), 64.50 (OCH2), 111.17 (2CH), 119.24 (CH), 120.50 (CH),
127.66 (2CH), 128.62 (CH), 129.07 (2CH), 129.26 (C), 137.92 (C), 148.41 (C), 152.07 (C), 160.27
(C), 195.15 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1639 (s), 1590 (m), 1546 (m), 1498 (m), 1260 (br, m), 1143
(m), 1021 (m), 871 (m), 797 (m), 719 (m), 695 (vs) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 340 (100) [Mþ],
312 (12), 236 (30), 208 (41), 165 (21).
2,3-Dihydro-2-phenyl-6-(2-trifluoromethylphenyl)thiopyran-4-one (2d, C18H13F3OS)
Ketone 3d (160 mg, 0.53 mmol), NaSHꢁ 1.2H2O (220 mg, 2.83mmol), and 2-ME (10 cm3) were con-
verted for 8 h at 40ꢂC and for 15h at 23ꢂC according to the general procedure (method B) to give
dihydrothiopyranone 2d (149 mg, 84%) after chromatography (SiO2, PE=EA¼ 2=1, Rf ¼ 0.55) as a
light brown oil. 1H NMR (500MHz, CDCl3): ꢂ ¼ 2.99 (dd, J ¼ 16.4, 3.1 Hz, 1H), 3.17 (dd, J ¼ 16.4,
14.2Hz, 1H) 4.83 (dd, J ¼ 14.2, 3.0Hz, 1H), 6.25 (s, 1H), 7.33–7.46 (m, 6H), 7.51 (t, J ¼ 7.7, 1H),
7.57 (t, J ¼ 7.3Hz, 1H), 7.72 (d, J ¼ 7.7, 1H) ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 43.93 (s,
1
3
3
CH2), 47.98 (s, CH), 123.66 (q, J ¼ 274.1 Hz, C), 124.80 (q, J ¼ 1.6 Hz, C), 126.72 (q, J ¼ 5.3 Hz,
2
CH), 127.55 (s, 2CH), 127.91 (q, J ¼ 30.9 Hz, C), 128.71 (s, CH), 129.09 (s, 2CH), 129.51 (s, CH),
130.26 (s, CH), 131.72 (s, CH), 135.85 (s, C), 137.51 (s, C), 157.96 (s, CH), 194.07 (s, C¼O) ppm; IR

24
A. Rosiak et al.
(ATR): ꢃꢀ¼ 1655 (s), 1565 (m), 1311 (s), 1287 (m), 1262 (m), 1167 (m), 1125 (s), 1107 (s), 1060 (m),
1033 (m), 764 (m) cmꢃ1; MS (CI, CH4): m=z (%) ¼ 335 (100) [M þ Hþ], 306 (5), 257 (5), 230 (31),
211 (9), 202 (30), 176 (8), 131 (8), 104 (9).
6-(2,4-Difluorophenyl)-2,3-dihydro-2-phenylthiopyran-4-one (2e, C17H12F2OS)
Method A: A mixture of ketone 3e (100 mg, 0.37mmol), Na2S ꢁ 9 H2O (180mg, 0.74mmol), THF
(3cm3), H2O (3 cm3), and AcOH (0.5cm3) was stirred for 5 h at 55ꢂC and for 3 h at 23ꢂC. Water
(10 cm3) was added and the mixture was extracted with EA (2ꢄ15cm3). The combined organic layers
were dried (MgSO4), filtered, and evaporated. The residue was chromatographed (SiO2, PE=EA¼ 2=1,
Rf ¼ 0.56) to give dihydrothiopyranone 2e (74 mg, 65%) as a brown oil. 1H NMR (500 MHz, CDCl3):
ꢂ ¼ 2.99 (dd, J ¼ 16.4, 3.3 Hz, 1H), 3.18 (dd, J ¼ 16.4, 13.9 Hz, 1H), 4.78 (dd, J ¼ 13.9, 3.3Hz, 1H),
6.48 (d, J ¼ 1.6 Hz, 1H), 6.86–6.97 (m, 2H), 7.33–7.45 (m, 5H), 7.51–7.60 (m, 1H) ppm; 13C{1H}
NMR (125MHz, CDCl3): ꢂ ¼ 44.01 (s, CH2), 47.14 (s, CH), 105.07 (t, 2J ¼ 26.0Hz, CH), 111.90 (dd,
2J ¼ 21.6Hz, 4J ¼ 4.1 Hz, CH), 121.42 (dd, 3J ¼ 13.4Hz, 3J ¼ 4.9 Hz, C), 124.56 (d, 4J ¼ 5.1 Hz, CH),
127.58 (s, 2CH), 128.75 (s, CH), 129.12 (s, 2CH), 131.21 (dd, 3J ¼ 9.9 Hz, 3J ¼ 3.4 Hz, CH), 137.46 (s,
3
1
3
1
C), 153.01 (d, J ¼ 1.9 Hz, C), 159.75 (dd, J ¼ 256 Hz, J ¼ 12.4Hz, C), 163.92 (dd, J ¼ 254 Hz,
3J ¼ 12.0Hz, C), 194.65 (s, C¼O) ppm; IR (ATR): ꢃꢀ¼ 1650 (vs), 1608 (s), 1558 (m), 1496 (s), 1425
(m), 1264 (br, s), 1143 (s), 1100 (s), 975 (m), 850 (m), 733 (m), 698 (m) cmꢃ1; MS (EI, 70eV): m=z
(%) ¼ 302 (84) [Mþ], 274 (13), 225 (5), 198 (51), 170 (100), 126 (9), 104 (32).
2,3-Dihydro-2-phenyl-5-(2-thienyl)thiopyran-4-one (2f, C15H12OS2)
Ketone 3f (50 mg, 0.21mmol), NaSHꢁ 1.2H2O (91 mg, 1.17mmol), and 2-ME (3cm3) were converted
for 18h at 40ꢂC according to the general procedure (method B) to give dihydrothiopyranone 2f (45 mg,
81%) after chromatography (SiO2, PE=EA¼ 2=1, Rf ¼ 0.44) as a brown solid, mp 68–69ꢂC. 1H NMR
(250 MHz, CDCl3): ꢂ ¼ 2.99 (dd, J ¼ 16.6, 3.4 Hz, 1H), 3.15 (dd, J ¼ 16.6, 13.4Hz, 1H), 4.76 (dd,
J ¼ 13.5, 3.4 Hz, 1H), 6.62 (s, 1H), 7.10 (dd, J ¼ 5.1, 3.8 Hz, 1H), 7.35–7.45 (m, 5H), 7.48 (dd, J ¼ 5.1,
1.1 Hz, 1H), 7.52 (dd, J ¼ 3.8, 1.1 Hz, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 44.73 (CH2),
46.68 (CH), 118.51 (CH), 127.67 (2CH), 128.36 (CH), 128.41 (CH), 128.73 (CH), 129.13 (2CH),
129.81 (CH), 137.56 (C), 140.13 (C), 152.15 (C), 194.78 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1637 (s), 1544
(s), 1495 (m), 1415 (m), 1354 (m), 1285 (m), 1259 (br, m), 1142 (m), 1049 (m), 823 (m), 696 (s) cmꢃ1
;
MS (CI, CH4): m=z (%) ¼ 273 (100) [Mþ Hþ], 244 (7), 168 (22), 140 (26).
2,3-Dihydro-2-phenyl-6-(2-pyridyl)thiopyran-4-one (2g, C16H13NOS)
Ketone 3g (200 mg, 0.86mmol), NaSH ꢁ 1.2H2O (372mg, 4.79mmol), and 2-ME (20 cm3) were con-
verted for 2 h at 50ꢂC according to the general procedure (method B) to give dihydrothiopyranone 2g
(139 mg, 60%) after chromatography (SiO2, PE=EA=NHEt2 ¼ 2=1=0.02, Rf ¼ 0.27) as a light yellow
1
solid, mp 98–100ꢂC. H NMR (250MHz, CDCl3): ꢂ ¼ 3.00 (dd, J ¼ 16.4, 3.5 Hz, 1H), 3.17 (dd,
J ¼ 16.4, 13.9Hz, 1H), 4.72 (dd, J ¼ 13.9, 3.5 Hz, 1H), 6.98 (s, 1H), 7.28–7.48 (m, 6H), 7.70–7.81
(m, 2H), 8.65–8.68 (m, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): ꢂ ¼ 44.19 (CH2), 46.24 (CH),
120.71 (CH), 121.17 (CH), 125.13 (CH), 127.68 (2CH), 128.59 (CH), 129.02 (2CH), 137.00 (CH),
137.94 (C), 149.64 (CH), 153.48 (C), 158.99 (C), 195.56 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1636 (vs), 1581
(w), 1548 (m), 1454 (s), 1436 (m), 1404 (m), 1316 (m), 1266 (m), 1251 (s), 1139 (m), 1089 (m), 992
(m), 860 (m), 783 (vs), 726 (s), 698 (s), 616 (m) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 267 (26) [Mþ], 163
(38), 135 (20), 104 (14), 88 (100).
6-tert-Butyl-2,3-dihydro-2-phenylthiopyran-4-one (2h, C15H18OS)
Ketone 3h (100 mg, 0.47 mmol), NaSHꢁ 1.2H2O (200mg, 2.57mmol), and 2-ME (6cm3) were con-
verted for 16h at 50ꢂC according to the general procedure (method B) to give dihydrothiopyranone 2h
(98 mg, 85%) after chromatography (SiO2, PE=EA¼ 5=1, Rf ¼ 0.30) as an offensive smelling, light
yellow solid, mp 62–63ꢂC. 1H NMR (500MHz, CDCl3): ꢂ ¼ 1.26 (s, 9H), 2.86 (dd, J ¼ 16.3, 3.2Hz,
1H), 3.00 (dd, J ¼ 16.4, 14.5Hz, 1H), 4.53 (dd, J ¼ 14.4, 3.2Hz, 1H), 6.28 (s, 1H), 7.34–7.41 (m, 5H)

Synthesis of 2,3-Dihydrothiopyran-4-ones
25
ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 29.71 (3CH3), 38.76 (C), 44.06 (CH2), 46.49 (CH),
119.04 (CH), 127.54 (2CH), 128.48 (CH), 128.97 (2CH), 138.19 (C), 174.43 (C), 195.81 (C¼O)
ppm; IR (ATR): ꢃꢀ¼ 2958 (br, m), 1639 (vs), 1550 (vs), 1496 (m), 1454 (m), 1404 (m), 1364 (m),
1315 (m), 1289 (s), 1269 (s), 1241 (s), 1201 (m), 1145 (m), 986 (m), 936 (m), 838 (m), 828 (m), 796
(s), 721 (s), 698 (vs), 618 (m) cmꢃ1; MS (EI, 70 eV): m=z (%) ¼ 246 (100) [Mþ], 142 (21), 127 (56),
104 (13), 100 (16).
2,3-Dihydro-2-phenylthiopyran-4-one (2i, C11H10OS)
Ketone 3i (108 mg, 0.47 mmol), NaSHꢁ 1.2H2O (227mg, 2.92mmol), and 2-ME (6cm3) were con-
verted for 3 h at 60ꢂC according to the general procedure (method B) to give dihydrothiopyranone 2i
(62 mg, 70%) after chromatography (SiO2, PE=EA¼ 5=1, Rf ¼ 0.24) as a light yellow solid, mp 49–
1
50ꢂC. H NMR (500MHz, CDCl3): ꢂ ¼ 2.92 (dd, J ¼ 16.3, 3.1 Hz, 1H), 3.11 (dd, J ¼ 16.3, 14.2 Hz,
1H), 4.69 (dd, J ¼ 14.2, 3.1Hz, 1H), 6.27 (d, J ¼ 10.2Hz, 1H), 7.32–7.42 (m, 5H), 7.49 (d,
J ¼ 10.3Hz, 1H) ppm; 13C{1H} NMR (125MHz, CDCl3): ꢂ ¼ 44.91 (CH2), 46.94 (CH), 123.48
(CH), 127.44 (2CH), 128.60 (CH), 129.03 (2CH), 137.80 (C), 146.26 (CH), 194.30 (C¼O) ppm; IR
(ATR): ꢃꢀ¼ 1651 (vs), 1547 (vs), 1489 (m), 1452 (m), 1400 (m), 1362 (m), 1350 (s), 1264 (s), 1250 (s),
1154 (m), 1134 (m), 1080 (m), 938 (m), 783 (s), 756 (s) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 190 (69)
[Mþ], 104 (100), 86 (10), 78 (12), 77 (10).
6-(3,4-Dimethoxyphenyl)-2,3-dihydrothiopyran-4-one (2j, C13H14O3S)
Ketone 3j (120mg, 0.56mmol), NaSHꢁ 1.2H2O (260 mg, 3.35 mmol), and 2-ME (20 cm3) were con-
verted for 2 h at 50ꢂC and for 14h at 23ꢂC according to the general procedure (method B) to give
dihydrothiopyranone 2j (50 mg, 36%) after chromatography (SiO2, PE=EA ¼ 2=1, Rf ¼ 0.19) as a light
1
yellow solid, mp 81–83ꢂC; H NMR (250MHz, CDCl3): ꢂ ¼ 2.74–2.79 (m, 2H), 3.26–3.31 (m, 2H),
3.92 (s, 3H), 3.93 (s, 3H), 6.47 (s, 1H), 6.89 (d, J ¼ 8.5 Hz, 1H), 7.14 (d, J ¼ 2.2 Hz, 1H), 7.29 (dd,
J ¼ 8.4, 2.2Hz, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 27.16 (CH2), 37.21 (CH2), 55.99
(OCH3), 56.05 (OCH3), 109.86 (CH), 110.91 (CH), 119.59 (CH), 120.62 (CH), 129.84 (C), 149.05 (C),
151.71 (C), 160.51 (C), 194.87 (C¼O) ppm; IR (ATR): ꢃꢀ¼ 1633 (s), 1591 (m), 1546 (m), 1513 (s),
1460 (m), 1335 (m), 1247 (s), 1168 (m), 1137 (s), 1016 (m), 805 (m) cmꢃ1; MS (EI, 70eV): m=z
(%) ¼ 250 (100) [Mþ], 222 (69), 194 (86), 179 (48).
6-(3-Ethoxy-4-methoxyphenyl)-2,3-dihydrothiopyran-4-one (2k, C14H16O3S)
Ketone 3k (200 mg, 0.87 mmol), NaSHꢁ 1.2H2O (490 mg, 6.31mmol), and 2-ME (20 cm3) were con-
verted for 3 h at 50ꢂC and for 2 h at 23ꢂC according to the general procedure (method B) to give
dihydrothiopyranone 2k (36 mg, 16%) after chromatography (SiO2, PE=EA¼ 2=1, Rf ¼ 0.18) as a light
1
yellow solid, mp 82–85ꢂC. H NMR (500 MHz, CDCl3): ꢂ ¼ 1.49 (t, J ¼ 7.0 Hz, 3H), 2.74–2.79 (m,
2H), 3.25–3.30 (m, 2H), 3.91 (s, 3H), 4.13 (q, J ¼ 7.0 Hz, 2H), 6.45 (s, 1H), 6.90 (d, J ¼ 8.4 Hz, 1H),
7.15 (d, J ¼ 2.2 Hz, 1H), 7.27 (dd, J ¼ 8.8, 2.1 Hz, 1H) ppm; 13C{1H} NMR (125MHz, CDCl3):
ꢂ ¼ 14.72 (CH3), 27.16 (CH2), 37.21 (CH2), 56.06 (OCH3), 64.50 (OCH2), 111.16 (CH), 111.24
(CH), 119.51 (CH), 120.52 (CH), 129.77 (C), 148.39 (C), 152.03 (C), 160.51 (C), 194.81 (C¼O)
ppm; IR (ATR): ꢃꢀ¼ 1636 (s), 1591 (m), 1540 (m), 1503 (s), 1441 (m), 1418 (m), 1394 (m), 1240 (s),
1139 (s), 1019 (s), 919 (m), 800 (m) cmꢃ1; MS (EI, 70eV): m=z (%) ¼ 264 (100) [Mþ], 236 (51), 208
(75), 193 (11), 180 (17), 164 (31); HR-MS (EI, 70eV): m=z (%) ¼ 264.0821 (100) [Mþ], calcd
264.0820 (for C14H16O3S).
6-(2,4-Difluorophenyl)-2,3-dihydrothiopyran-4-one (2l, C11H8F2OS)
Method A: A mixture of ketone 3l (100mg, 0.52mmol), Na2S ꢁ 9H2O (250mg, 1.04mmol), THF
(3cm3), H2O (3cm3), and AcOH (ca. 50mg) were stirred for 3 h at 55ꢂC. The mixture was then
washed with water (10 cm3). The aqueous phase was extracted with EA (2ꢄ20 cm3). The combined
organic layers were dried (MgSO4), filtered, and evaporated. The residue was chromatographed (SiO2,
1
PE=EA¼ 2=1, Rf ¼ 0.40) to yield the title compound 2l (10 mg, 8%) as a light yellow oil. H NMR

26
A. Rosiak et al.: Synthesis of 2,3-Dihydrothiopyran-4-ones
(500 MHz, CDCl3): ꢂ ¼ 2.75–2.84 (m, 2H), 3.28–3.36 (m, 2H), 6.38 (d, J ¼ 1.7 Hz, 1H), 8.83–7.00 (m,
2H), 7.48–7.60 (m, 1H) ppm; 13C{1H} NMR (62 MHz, CDCl3): ꢂ ¼ 27.79 (s, CH2), 36.73 (s, CH2),
105.03 (t, 2J ¼ 24.8Hz, CH), 111.75 (dd, 2J ¼ 21.5Hz, 4J ¼ 3.8 Hz, CH), 124.85 (d, 3J ¼ 4.5 Hz, CH),
3
3
131.25 (dd, J ¼ 9.9 Hz, J ¼ 3.5 Hz, CH), 194.14 (s, C¼O) ppm; resonances for carbon atoms C-6,
C-10, C-20, and C-40 are not observed due to poor signal-to-noise ratio; IR (ATR): ꢃꢀ¼ 2931 (m), 1646
(s), 1613 (s), 1593 (s), 1497 (s), 1182 (s), 1141 (s), 1097 (s), 976 (s) 848 (s) cmꢃ1; MS (EI, 70eV): m=z
(%) ¼ 226 (40) [Mþ], 198 (28), 170 (100), 138 (9), 126 (8).
Acknowledgement
We are grateful to the ALTANA Pharma AG, Konstanz, Germany for generous support of this work.
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