2H-pyran-2-ones from trichoderma viride and trichoderma asperellum

Article abstract of DOI:10.1002/ejoc.201300049

Volatiles emitted by the soil fungi Trichoderma viride 272 and Trichoderma asperellum 328 were collected by using the closed loop stripping analysis (CLSA) headspace technique, and the obtained extracts were analysed by GC/MS. Several alkyl- and alkenyl-2H-pyran-2-ones, including known compounds 6-pentyl-2H-pyran-2-one and (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and the new derivatives (E)-6-(pent-2-en-1-yl)-2H-pyran-2-one, 6-propyl-2H-pyran-2-one, and 6-heptyl-2H-pyran-2-one were found. The alkenyl derivative (E)-6-(hept-1-en-1- yl)-2H-pyran-2-one, previously tentatively identified from a marine Botrytis by MS analysis, was also detected. All alkenyl pyrones were synthesised by using a reported Stille coupling followed by lactonisation, whereas the alkylated pyrones were obtained through a reported synthetic approach by radical bromination of 5-alkylpent-2-en-5-olides and dehydrobromination. Because the yields in both cases were not satisfactory and fell a long way short of the yields reported for similar compounds, all compounds were synthesised again using a gold-catalysed coupling of terminal alkynes with propiolic acid recently developed by Schreiber and co-workers, giving high yields in all cases. A comparison of the synthetic methods is given. Copyright

Full text of DOI:10.1002/ejoc.201300049

FULL PAPER
DOI: 10.1002/ejoc.201300049
2H-Pyran-2-ones from Trichoderma viride and Trichoderma asperellum
[a]
[a]
[a]
Susanne M. Wickel, Christian A. Citron, and Jeroen S. Dickschat*
Keywords: Natural products / Synthetic methods / Structure elucidation / Analytical methods
Volatiles emitted by the soil fungi Trichoderma viride 272 and
Trichoderma asperellum 328 were collected by using the
closed loop stripping analysis (CLSA) headspace technique,
and the obtained extracts were analysed by GC/MS. Several
detected. All alkenyl pyrones were synthesised by using a
reported Stille coupling followed by lactonisation, whereas
the alkylated pyrones were obtained through a reported syn-
thetic approach by radical bromination of 5-alkylpent-2-en-
alkyl- and alkenyl-2H-pyran-2-ones, including known com- 5-olides and dehydrobromination. Because the yields in both
pounds 6-pentyl-2H-pyran-2-one and (E)-6-(pent-1-en-1-yl)-
H-pyran-2-one, and the new derivatives (E)-6-(pent-2-en-1-
yl)-2H-pyran-2-one, 6-propyl-2H-pyran-2-one, and 6-heptyl-
cases were not satisfactory and fell a long way short of the
yields reported for similar compounds, all compounds were
synthesised again using a gold-catalysed coupling of ter-
2
2H-pyran-2-one were found. The alkenyl derivative (E)-6- minal alkynes with propiolic acid recently developed by
(
hept-1-en-1-yl)-2H-pyran-2-one, previously tentatively
Schreiber and co-workers, giving high yields in all cases. A
comparison of the synthetic methods is given.
identified from a marine Botrytis by MS analysis, was also
Introduction
Fungi of the genus Trichoderma occur on cellulose mate-
rial, in soil, and root or foliar systems of plants. They are
known to promote plant growth and development and are
used in agriculture as biocontrol agents, taking advantage
of their activity against phytopathogenic microorga-
[
1,2]
nisms.
The fungi exhibit cytotoxicity towards plant
pathogens either by the excretion of hydrolytic cell-wall de-
grading enzymes such as chitinases[3] or release of a wide
[
4]
range of secondary metabolites with antibiotic properties,
exemplified by the structures of the cytotoxic compounds
trichodermamides A (1a) and B (1b) from Trichoderma vir-
[
5]
ens (Scheme 1). The heptaketide harziphilone (2) also ex-
hibits cytotoxic activity and was isolated from Trichoderma
[
6]
Scheme 1. A selection of secondary metabolites from Trichoderma.
harzianum, whereas the terpenoid T-2 toxine (3) from
Trichoderma lignorum is a representative of the large family
of trichothecenes. Upon intoxication, these compounds cently described from Trichoderma atroviride.[10] Pyrones
cause symptoms such as nausea, bloody vomiting, and diar- are also known from Trichoderma, with 6-pentyl-2H-pyran-
[7]
[
8]
rhea, similar to acute radiation symptoms.
2-one (6) as the first described representative of this class
Although these and other examples[ demonstrate that (Scheme 2), followed by the isolation of (E)-6-(pent-1-en-
4]
[11]
the diverse secondary metabolism of Trichoderma has been
intensively explored, little is known about volatiles from
Trichoderma and fungi in general. Early investigations re-
sulted in the identification of the spirocyclic sesquiterpenes
tricho-acorenol (4) and acorenone (5) in Trichoderma konin-
gii.[ A complex pattern of volatile compounds including
9]
alcohols, ketones, lactones, terpenes, and pyrones was re-
[
a] TU Braunschweig, Institut für Organische Chemie,
Hagenring 30, 38106 Braunschweig, Germany
Fax: +49-531-391-5272
E-mail: j.dickschat@tu-bs.de
Homepage: http://www.oc.tu-bs.de/dickschat/startseite_de.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300049.
Scheme 2. 6-Pentyl-2H-pyran-2-one and related compounds from
Trichoderma.
2906
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2906–2913

2H-Pyran-2-ones from Trichoderma viride and asperellum
1
-yl)-2H-pyran-2-one (7).[12,13] Further known derivatives identified from its mass spectrum (Figure 2, a) and direct
from Trichoderma include the saturated variants massoia- comparison to a commercially available standard. Further-
[4]
lactone (8) and δ-decanolactone (9), and the oxygenated more, trace amounts of the terpenoid geranyl acetone (16),
compound 6-(4-oxopent-1-yl)-2H-pyran-2-one (viridepy- the sesquiterpenes (E)-β-farnesene, trans-α-bergamotene,
[
14]
ronone, 10). All these lactones possess inhibitory activity (E)-nerolidol, and zingiberenol, the phenylpropanoid 3,4-
against plant pathogenic fungi such as Aspergillus, dimethoxystyrene (15), and the typical fungal compounds
[
13–15]
Botrytris, Rhizoctonia, Sclerotinia, and Pyrenochaeta,
oct-1-en-3-ol and octan-3-one were found. Two trace com-
or bacteria such as Staphylococcus aureus.[ Interestingly, pounds with similar mass spectra to that of 6 were present.
15]
7
is also a known component of the pheromone blend from The first compound exhibited a molecular ion of m/z 138
[16]
the red fire ant Solenopsis invicta.
(Figure 2, b), whereas the second volatile was characterised
Here we report on the volatiles released by two strains of by a molecular ion at m/z 194 (Figure 2, c). Due to the
Trichoderma viride and Trichoderma asperellum. The head- mass differences of minus and plus 28 atomic mass units
space extracts were mainly composed of pyrones. In ad- compared with 6, the unknown volatiles were suggested to
dition to a few known compounds, several new derivatives
were identified and their structures were unambiguously as-
signed by comparison to synthetic standards.
Results and Discussion
The volatiles emitted by two strains of Trichoderma were
trapped on charcoal by using the closed loop stripping
analysis (CLSA) technique,[ and the obtained extracts
were analysed by GC/MS. The results of these analyses are
summarised in Table S1 of the Supporting Information.
Representative gas chromatograms are illustrated in Fig-
ure 1, and the identified compounds are shown in
Scheme 3. The main component 6 of T. viride was readily
17]
Figure 1. Total ion chromatograms of the headspace extracts ob-
tained from (a) T. viride, and (b) T. asperellum. Peaks marked by
ϫ indicate unidentified compounds or compounds originating
from the medium.
Figure 2. EI mass spectra of (a) 6-pentyl-2H-pyran-2-one (6), (b)
6
-propyl-2H-pyran-2-one (11), (c) 6-heptyl-2H-pyran-2-one (12),
(
d) (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one (7), (e) (E)-6-(hept-1-en-
Scheme 3. Volatiles identified in the headspace extracts from
Trichoderma.
1-yl)-2H-pyran-2-one (13), and (f) tentatively identified (E)-6-
(pent-2-en-1-yl)-2H-pyran-2-one (14).
Eur. J. Org. Chem. 2013, 2906–2913
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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S. M. Wickel, C. A. Citron, J. S. Dickschat
FULL PAPER
be the two carbon truncated and elongated homologues 6- was demonstrated in the identification of some previously
propyl-2H-pyran-2-one (11) and 6-heptyl-2H-pyran-2-one unknown 2H-pyran-2-one derivatives including 11–14. The
(
12), respectively. A synthesis of reference compounds was aromatic compound 3,4-dimethoxystyrene (15) was de-
[
19]
carried out as described below, which established their scribed previously from liverworts
identity.
and is a constituent
but has never been identified from a
[
20]
of roasted coffee,
Another trace compound from T. viride eluted slightly fungus.
later (I = 1533) than the main compound 6 (I = 1464) and
Usually for the identification of natural products large
showed a molecular ion of m/z 164 in its mass spectrum volumes of cultures are extracted, followed by laborious pu-
(Figure 2, d). This compound was assumed to be an unsatu- rification steps using chromatographic methods. During
rated analogue of 6. Due to its increased retention index such procedures trace compounds are frequently over-
compared with 6, the structure of (E)-6-(pent-1-en-1-yl)- looked, especially in the case of volatiles, because they are
2H-pyran-2-one (7) was suggested, in agreement with other easily lost during concentration steps. Application of the
examples for which extended π systems result in increased CLSA headspace method and analysis of the obtained
GC retention times.[ The previous identification of this headspace extracts avoids fractioning and, consequently,
compound from Trichoderma lent further support to this the danger of losing trace compounds is eliminated. How-
18]
[
12,13]
idea.
Another volatile with a similar mass spectrum ever, unambiguous structural assignment is often only pos-
and a molecular ion of m/z 192 (Figure 2, e) was assumed sible by comparison to reference compounds that can be
to be the previously unreported (E)-6-(hept-1-en-1-yl)-2H- obtained by synthesis.
pyran-2-one (13). A synthesis of 7 and 13 was carried out as
Known synthetic approaches to 6-pentyl-2H-pyran-2-
described below, which confirmed the suggested structures. one include a formylation of 3-heptanone to the corre-
The same analytical method used for the identification sponding hydroxy methylene ketone, followed by Knoeven-
of volatiles from T. viride was also applied for T. asperellum. agel condensation with malonic acid to the keto acid. Treat-
The gas chromatogram of a representative headspace ex- ment with acetic anhydride yields 6-pentyl-2H-pyran-2-
[
21]
tract from a T. asperellum agar plate culture obtained after one. For the synthesis of 6-alkyl-2H-pyran-2-ones 6, 11,
four days of growth is shown in Figure 1 (b). The main and 12, a route was developed using a radical bromination
component emitted by T. asperellum was readily identified of 5-alkylpent-2-en-5-olides followed by dehydrobromin-
as 7 by comparison to the synthetic standard. Further pyr- ation as key steps (Scheme 4, a). These reactions have been
one derivatives were represented by two compounds with described for a successful synthesis of the 2H-pyran-2-one
saturated side chains, 11 and 6. Geranylacetone (16) was
also found in large amounts, in addition to traces of 15.
Furthermore, an unknown compound was present in the
headspace extract with a mass spectrum showing a molecu-
lar ion at m/z 164 and a base peak at m/z 95 (Figure 2, f)
that was also seen in the mass spectrum of 6. This com-
pound was suggested to be an analogue of 6 with an unsat-
urated side chain and an isomer of the main compound 7
with a different double bond position in the side chain. An
attempt to synthesise (E)-6-(pent-2-en-1-yl)-2H-pyran-2-
one (14) failed (see below), because this compound was
highly sensitive towards isomerisation to 7. However, imme-
diate GC analysis of the crude reaction product after
workup showed the presence of two compounds, one of
which was the main product 7, accompanied by traces of
14. Comparison of the mass spectrum and retention index
to those of the natural product confirmed the identity of
the two compounds, but because we were not able to obtain
NMR spectroscopic data from the minor synthetic product,
the structure assignment of the volatile as (E)-6-(pent-2-en-
1-yl)-2H-pyran-2-one (14) remains tentative.
Analysis of the volatiles released by T. viride and T. as-
perellum resulted in the identification of a pattern of several
alkylated and alkenylated 2H-pyran-2-ones with different
lengths of the side chains and positions of olefinic double
bonds. Compounds 6 and 7 were detected in both head-
space extracts, with 6 being the main volatile from T. viride,
and T. asperellum mainly producing 7. These compounds
have been described previously from other Trichoderma
strains. The high potential of the CLSA headspace method Scheme 4. Synthesis of 6-alkyl-2H-pyran-2-ones.
2908
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2906–2913

2H-Pyran-2-ones from Trichoderma viride and asperellum
system from pent-2-en-5-olide (R = H).[22] Aldehydes 17a–
c were transformed into homoallyl alcohols 18a–c with allyl
[23]
benzoate, diethylzinc, and [Pd(PPh ) ].
Treatment with
3
4
acryloyl chloride in triethylamine gave acrylate esters 19a–
c, which were converted into the α,β-unsaturated lactones
2
0a, massoialactone (8), and 20c by subsequent ring closing
[
24]
metathesis using the second-generation Grubbs’ catalyst.
Subsequent radical bromination with N-bromosuccinimide
(
(
NBS)/ azobisisobutyronitrile (AIBN) in chlorobenzene
120 °C) gave complex mixtures containing two diastereo-
isomeric bromination products and the desired 6-alkyl-2H-
pyran-2-ones. Treatment with triethylamine resulted in con-
version of the bromo derivatives into the respective 6-alkyl-
2H-pyran-2-ones 6, 11, and 12, which were subsequently
isolated by repeated column chromatography.
After the syntheses of the 6-alkyl-2H-pyran-2-ones
through the bromination-dehydrobromination methodol-
ogy had been performed in our laboratory, Schreiber and
co-workers published a gold-catalysed coupling reaction of
terminal alkynes with propiolic acids to pyrones.[ Because
the yields obtained with the bromination–dehydrobromina-
tion approach were unsatisfactory and much lower than re-
ported for the stem system (reported yield 70%), the syn-
thesis of 11, 6, and 12 was repeated by using gold-catalysed
coupling of propiolic acid with 1-pentyne, 1-heptyne, and
25]
1
6
-nonyne, respectively (Scheme 4, b), resulting in yields of
1–88%, in agreement with published data (65% for 6).
A synthetic route to (E)-6-(pent-1-en-1-yl)-2H-pyran-2-
ones was developed by Rocca et al. that starts with conden-
sation of (E)-but-2-enoyl chloride and trichloroacetyl chlor-
ide in triethylamine to yield 6-trichloromethyl-2H-pyran-2-
one. The trichloromethyl group is subsequently converted
into the corresponding carboxylic acid, then into the acid
chloride and Rosenmund reduction to the aldehyde; a final
Wittig reaction yields 7.[ Another method for the prepa-
ration of (E)-6-(alk-1-en-1-yl)-2H-pyran-2-ones reported by
Scheme 5. Synthesis of (E)-6-(alken-1-yl)-2H-pyran-2-ones.
16]
Conclusions
[
26]
Thibonet et al.
proceeds through Stille reaction of tri-
butylstannyl 4-(tributylstannyl)but-3-enoate (27), which is
In summary, the volatiles emitted by the soil fungi T.
readily available from homopropargyl alcohol (23) by Jones viride and T. asperellum were collected using the CLSA
oxidation to but-3-ynoic acid (24) and radical stannylation, technique. GC/MS analyses showed a pattern of structur-
with an acid chloride (26) and subsequent lactonisation ally related 2H-pyran-2-ones released by both fungi. The
(Scheme 5, a). This method was successfully applied in the principle components of T. viride, 6, and of T. asperellum,
synthesis of 7 and 13, albeit in much lower than the re- 7, have previously been reported from other strains of the
ported yield of 52% for 7, whereas the synthesis of 14 Trichoderma genus. In addition to these known compounds,
proved to be difficult due to the rapid isomerisation of the three novel 2H-pyran-2-ones 11–13 were detected. Struc-
product to 7. However, as discussed above, GC/MS analysis tural proposals were based on their mass spectra and cor-
of the crude product gave mass spectroscopic data of the roborated by the synthesis of reference materials. For the
desired compound that served in the tentative identification synthesis of the 6-alkyl-2H-pyran-2-ones, a method involv-
of 14 in the headspace extract from T. asperellum.
ing radical bromination of α,β-unsaturated δ-lactones and
Because the syntheses of 7 and 13 were performed using subsequent elimination of hydrogen bromide was devel-
highly toxic tin compounds and the obtained yields were oped, whereas the 6-alkenyl-2H-pyran-2-ones were pre-
low, another route to these compounds using Schreiber’s pared by a reported Stille coupling and lactonisation ap-
efficient gold-catalysed method[
25]
was developed proach.
[26]
However, the best method for the synthesis of
(
Scheme 5, b). Compound 29 was obtained by gold-cata- these compounds proved to be the gold-catalysed coupling
[
25]
lysed coupling of propargyl bromide (28) with 22 and sub- of propiolic acid with terminal alkynes.
Future experi-
sequently converted with P(OEt) into diethyl phosphonate ments in our laboratory will include the analysis of further
3
30. A Horner–Wadsworth–Emmons reaction with butyral- fungal strains for the production of novel volatile com-
dehyde or hexanal yielded 7 and 13 in acceptable yields. pounds.
Eur. J. Org. Chem. 2013, 2906–2913
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2909

S. M. Wickel, C. A. Citron, J. S. Dickschat
FULL PAPER
(
m, 1 H, CH
H, CH
2
), 2.14 (dtt, 2JH,H = 13.9, 3JH,H = 7.9, 4JH,H = 1.1 Hz,
Experimental Section
1
2
), 1.87 (br. s, 1 H, OH), 1.52–1.30 (m, 4 H, 2ϫ CH
2
), 0.94
) ppm. C NMR (100 MHz, CDCl ): δ
), 70.4 (CH), 41.9 (CH ), 39.0 (CH ),
) ppm. MS (EI, 70 eV): m/z (%) = 114 (1)
M ], 96 (1), 73 (53), 69 (4), 55 (100).
Strains, Media, and Growth Conditions: Trichoderma viride 272 and
Trichoderma asperellum 328 were obtained from Gabriele König
3
13
(
=
1
t, JH,H = 7.0 Hz, 3 H, CH
134.9 (CH), 118.0 (CH
8.8 (CH ), 14.1 (CH
3
3
2
2
2
(
University of Bonn, Germany) and cultured in BM medium (bio-
2
3
–1
malt, 20 gL ). Mycelia were maintained at 28 °C and 200 rpm in
liquid medium. After 5 d of growth, agar plates containing BM
agar were inoculated with three pieces of mycelium and incubated
at 28 °C for 3 d prior to headspace analysis.
+
[
Non-1-en-4-ol (18b): Yield 1.41 g (9.9 mmol, 99%). R
ane/ethyl acetate, 4:1). GC (BPX5): I = 1070. UV/Vis (CH
λ
3
f
= 0.53 (hex-
Cl ):
2
2
–
1
–1
max (ε, Lmol cm ) = 230 (213) nm. IR (ATR): ν˜ = 3351 (w, br),
077 (w), 2958 (w), 2930 (s), 2862 (w), 1714 (w), 1641 (w), 1463
w), 1438 (w), 1379 (w), 1271 (w), 1124 (w), 1025 (w), 996 (w), 969
Sampling of Volatiles: The volatile organic compounds released by
the agar plate cultures were collected by using the CLSA headspace
(
(
(
(
[
12]
technique.
In a closed apparatus containing the agar plates, a
–1 1
w), 911 (s), 857 (w), 788 (w), 733 (w), 640 (w) cm . H NMR
400 MHz, CDCl , TMS): δ = 5.89–5.78 (m, 1 H, CH), 5.17–5.14
m, 1 H, CH ), 5.13–5.11 (m, 1 H, CH ), 3.68–3.62 (m, 1 H, CH),
.34–2.28 (m, 1 H, CH ), 2.19–2.09 (m, 1 H, CH ), 1.58 (br. s, 1
H, OH), 1.49–1.26 (m, 8 H, 4ϫ CH
circulating air stream was passed through a charcoal filter (Chrom-
tech GmbH, Idstein, Germany, Precision Charcoal Filter, 5 mg) for
3
2
2
24 h. The adsorbed volatiles were eluted with 30 μL of analytically
2
2
2
pure dichloromethane. The obtained extracts were analysed by GC/
MS and stored at –80 °C.
3
2
), 0.89 (t, JH,H = 6.8 Hz, 3
) ppm. C NMR (100 MHz, CDCl ): δ = 134.9 (CH), 118.0
), 70.7 (CH), 41.9 (CH ), 37.3 (CH ), 31.9 (CH ), 25.3 (CH ),
2.6 (CH ), 14.0 (CH ) ppm. MS (EI, 70 eV): m/z (%) = 101 (19)
M – vinyl], 83 (56), 71 (7), 55 (87), 41 (100).
13
H, CH
CH
2
3
3
(
2
2
2
2
2
GC/MS: GC/MS analyses were carried out with an Agilent 7890A
gas chromatograph fitted with a HP-5 fused silica capillary column
2
3
+
[
(30 m, 0.25 mm i. d., 0.25 μm film) connected to an Agilent 5975C
inert mass selective detector. Conditions were as follows, inlet pres-
Undec-1-en-4-ol (18c): Yield 1.62 g (9.5 mmol, 95%). R
f
= 0.53
–1
sure: 77.1 kPa, He 23.3 mLmin ; injection volume: 2 μL; transfer
line: 300 °C; electron energy: 70 eV. The GC was programmed as
follows: 5 min at 50 °C, 5 °C min–1 to 320 °C, and operated in split-
(
(
hexane/ethyl acetate, 5:1). GC (BPX5): I = 1278. UV/Vis
–1
–1
CH
2 2
Cl ): λmax (ε, Lmol cm ) = 230 (122) nm. IR (ATR): ν˜ =
3349 (w, br), 3077 (w), 2956 (w), 2925 (vs), 2855 (vs), 1641 (w), 1464
–
1
less mode (60 s valve time). The carrier gas was He at 1 mL . Re-
–1 1
(
w), 1126 (w), 1043 (w), 994 (w), 912 (vs), 722 (w), 641 (w) cm . H
NMR (400 MHz, CDCl , TMS): δ = 5.89–5.78 (m, 1 H, CH), 5.17–
.14 (m, 1 H, CH ), 5.12–5.11 (m, 1 H, CH ), 3.66–3.61 (m, 1 H,
CH), 2.34–2.27 (m, 1 H, CH ), 2.18–2.10 (m, 1 H, CH ), 1.64 (br.
s, 1 H, OH), 1.50–1.24 (m, 12 H, 6ϫ CH ), 0.88 (t, JH,H = 6.8 Hz,
) ppm. C NMR (100 MHz, CDCl ): δ = 134.9 (CH),
118.0 (CH ), 70.7 (CH), 41.9 (CH ), 36.8 (CH ), 31.8 (CH ), 29.6
(CH ), 29.3 (CH ), 25.7 (CH ), 22.6 (CH ), 14.1 (CH ) ppm. MS
tention indices I were determined from a homologous series of n-
alkanes (C –C32). Identification of compounds was performed by
8
comparison of mass spectra to library spectra, of retention indices
to tabulated data from the literature, and by direct comparison to
synthetic standards.
3
5
2
2
2
2
3
2
13
3
H, CH
3
3
General Synthetic Methods: Chemicals were purchased from Acros
Organics (Thermo Fisher Scientific Schwerte, Germany) or Sigma
Aldrich GmbH (Steinheim, Germany) and used without further
purification. Solvents were purified by distillation and dried ac-
cording to standard methods. Reactions were performed in flame-
dried glassware under nitrogen atmosphere. Thin-layer chromatog-
raphy was carried out using 0.2 mm precoated plastic sheets Poly-
gram Sil G/UV254 (Machery–Nagel). Column chromatography was
performed with Merck silica gel 60 (70–200 mesh) and the same
2
2
2
2
2
2
2
2
3
+
(EI, 70 eV): m/z (%) = 170 (1) [M ], 129 (17), 111 (19), 83 (6), 69
(100), 55 (39), 41 (54).
Preparation of Homoallyl Acrylates: To an ice-cold solution of
homoallyl alcohol 18a–c (5.00 mmol) in anhydrous CH
2
Cl
2
(
50 mL) and triethylamine (40 mmol, 4.0 g) was added dropwise
[20]
acryloyl chloride (32 mmol, 2.88 g).
The reaction mixture was
stirred overnight and warmed to room temperature. The excess of
acryloyl chloride was quenched by the addition of satd. NaHCO
solution. The resulting mixture was extracted three times with
Et O. The combined organic layers were dried (MgSO ) and con-
solvent mixtures used for the determination of R
H and C NMR spectra were determined with a Bruker AMX400
f
values in TLC.
3
1
13
spectrometer (chemical shifts are given in ppm, and J values are
given in Hz). UV spectra were obtained with a Varian Cary 100
Bio spectrometer and IR spectra were recorded with a Bruker Ten-
sor 27 ATR spectrometer.
2
4
centrated under reduced pressure and the crude product was puri-
fied by column chromatography on silica gel to yield the esters 24
as colourless liquids.
Preparation of Homoallyl Alcohols: To a solution of [Pd(PPh
0.58 g, 0.5 mmol) in anhydrous THF (30 mL) was added allyl ben-
zoate (1.94 g, 12 mmol), aldehyde 17a–c (10 mmol), and diethylzinc
3 4
) ]
Hept-1-en-4-yl Acrylate (19a): Yield 571 mg (3.40 mmol, 68%). R
0.37 (pentane/diethyl ether, 20:1). GC (BPX5): I = 1088. UV/Vis
f
(
=
–1
–1
(CH
2
Cl
2
): λmax (ε, Lmol cm ) = 228 (242) nm. IR (ATR): ν˜ =
1 m in hexane, 24 mmol, 24 mL).[ The resulting pale-yellow solu-
19]
(
3080 (w), 2961 (w), 2937 (w), 2875 (w), 1722 (vs), 1640 (w), 1405
tion was stirred at room temp. for 4 h. The reaction mixture was
diluted with ethyl acetate, washed with 2 n HCl, and aqueous
(
9
s), 1295 (s), 1270 (s), 1190 (vs), 1128 (w), 1046 (s), 985 (s), 964 (s),
–1 1
15 (s), 809 (s), 674 (w) cm . H NMR (400 MHz, CDCl
3
, TMS):
NaHCO
3
. The organic layer was dried (MgSO
4
) and concentrated.
3
2
δ = 6.39 (dd, JH,H = 17.3, JH,H = 1.6 Hz, 1 H, CH
2
), 6.39 (dd,
), 6.11 (dd, JH,H = 17.3,
0.3 Hz, 1 H, CH), 5.80 (dd, JH,H = 10.4, JH,H = 1.6 Hz, 1 H,
Column chromatography on silica gel yielded the homoallyl
alcohols 18 as colourless oils.
3
2
3
J
H,H = 17.3, JH,H = 1.6 Hz, 1 H, CH
2
3
2
1
3
Hept-1-en-4-ol (18a): Yield 0.57 g (5.0 mmol, 50%). R
f
= 0.43 (hex-
Cl
ε, Lmol–1 cm ) = 231 (125) nm. IR (ATR): ν˜ = 3353 (br), 3077
w), 2959 (w), 2931 (w), 2873 (w), 1641 (w), 1463 (w), 1226 (w), H, CH
CH
(m, 3 H, CH, CH
1.44–1.25 (m, 2 H, CH
2
), 5.76 (ddt, JH,H = 17.1, 10.1, 7.1 Hz, 1 H, CH), 5.12–4.97
), 2.35 (m, 2 H, CH ), 1.62–1.50 (m, 2 H, CH ),
), 0.91 (t, JH,H = 7.3, JC,H = 124.9 Hz, 3
) ppm. C NMR (100 MHz, CDCl ): δ = 165.9 (C), 133.7
(CH), 130.3 (CH ), 128.9 (CH), 117.6 (CH ), 73.3 (CH), 38.6
68 (w), 844 (w), 744 (w), 640 (w) cm . H NMR (400 MHz, (CH ), 35.7 (CH ), 18.5 (CH ), 13.9 (CH ) ppm. MS (EI, 70 eV):
, TMS): δ = 5.88–5.78 (m, 1 H, CH), 5.16–5.14 (m, 1 H, m/z (%) = 127 (22) [M – allyl], 96 (4), 81 (5), 67 (4), 55 (100), 41
), 5.13–5.11 (m, 1 H, CH ), 3.69–3.63 (m, 1 H, CH), 2.34–2.27 (19).
ane/ethyl acetate, 4:1). GC (BPX5): I = 873. UV/Vis (CH
2
2
): λmax
2
2
2
–1
3
1
(
(
2
1
3
3
3
1
8
122 (w), 1084 (w), 1066 (w), 1015 (w), 995 (s), 957 (w), 911 (s),
2
2
–1
1
2
2
2
3
+
CDCl
CH
3
2
2
2910
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2906–2913

2H-Pyran-2-ones from Trichoderma viride and asperellum
Non-1-en-4-yl Acrylate (19b): Yield 592 mg (3.02 mmol, 60%). R
f
1.6 Hz, 1 H, CH), 4.47–4.38 (m, 1 H, CH), 2.42–2.25 (m, 2 H, 2ϫ
CH ), 1.86–1.74 (m, 1 H, CH ), 1.70–1.37 (m, 3 H, 2ϫ CH ), 1.37–
1.29 (m, 4 H, 2ϫ CH
), 0.90 (t, 3JH,H = 6.8, JC,H = 124.7 Hz, 3
) ppm. C NMR (100 MHz, CDCl ): δ = 164.6 (C), 145.0
(CH), 121.3 (CH), 78.0 (CH), 34.8 (CH ), 31.5 (CH ), 29.3 (CH ),
24.4 (CH ), 22.4 (CH ), 13.9 (CH ) ppm. MS (EI, 70 eV): m/z (%)
H,H = 1.6, = 168 (1) [M ], 150 (1), 139 (2), 122 (3), 108 (7), 97 (100), 68 (78),
), 6.11 (dd, JH,H = 10.3, 17.3 Hz, 1 H, 55 (9), 41 (50).
=
0.59 (hexane/ethyl acetate, 10:1). GC (BPX5): I = 1262. UV/Vis
2
2
2
): λmax (ε, Lmol–1 cm ) = 228 (397) nm. IR (ATR): ν˜ =
–1
1
(CH
2
Cl
2
2
1
3
3079 (w), 2956 (w), 2931 (w), 2861 (w), 1722 (vs), 1640 (s), 1620 H, CH
3
3
(
(
w), 1464 (w), 1405 (s), 1295 (s), 1270 (s), 1190 (vs), 1128 (w), 1046
2
2
2
–
1
s), 985 (s), 965 (s), 916 (s), 809 (s), 728 (w), 650 (w), 552 (w) cm .
2
2
3
1
2
+
3
H NMR (400 MHz, CDCl , TMS): δ = 6.39 (dd, J
3JH,H = 17.3 Hz, 1 H, CH
3
2
2
3
CH), 5.80 (dd, JH,H = 1.6, JH,H = 10.3 Hz, 1 H, CH
H,H = 17.1, 10.1, 7.0 Hz, 1 H, CH), 5.10–5.03 (m, 2 H, CH
.00 (quint, JH,H = 6.1 Hz, 1 H, CH), 2.38–2.32 (m, 2 H, CH
2
), 5.76 (ddt,
6
-Heptyl-5,6-dihydro-2H-pyran-2-one
(20c):
Yield
361 mg
3
J
2
),
),
(
(
(
(
(
1.84 mmol, 92%). R
BPX5): I = 1729. UV/Vis (CH Cl ): λmax (ε, Lmol cm ) = 229
2 2
1203) nm. IR (ATR): ν˜ = 3358 (w, br), 3077 (w), 2958 (w), 2930
s), 1641 (w), 1464 (w), 1437 (w), 1124 (w), 1124 (w), 1025 (w), 995
f
= 0.35 (hexane/ethyl acetate, 3:1). GC
3
5
2
–
1
–1
1
.64–1.53 (m, 2 H, CH ), 1.38–1.23 (m, 6 H, 3ϫ CH
2
2
), 0.88 (t,
) ppm. C NMR (100 MHz, CDCl ): δ
165.9 (C), 133.7 (CH), 130.3 (CH ), 128.9 (CH), 117.6 (CH ),
3.6 (CH), 38.6 (CH ), 33.5 (CH ), 31.6 (CH ), 24.9 (CH ), 22.5
CH ), 14.0 (CH ) ppm. MS (EI, 70 eV): m/z (%) = 155 (58) [M
allyl], 124 (12), 96 (9), 83 (56), 73 (10), 67 (30), 55 (100), 41 (96).
3
13
J
H,H = 6.7 Hz, 3 H, CH
3
3
=
7
(
2
2
–
1 1
3
w), 911 (s), 731 (w), 639 (w) cm . H NMR (400 MHz, CDCl ,
2
2
2
2
3
TMS): δ = 6.89 (ddd, JH,H = 9.7, 5.4, 3.2 Hz, 1 H, CH), 6.01 (ddd,
+
2
3
–
3
4
J
H,H = 9.7, JH,H = 2.2, 1.4 Hz, 1 H, CH), 4.42 (m, 1 H, CH),
.40–2.26 (m, 2 H, CH ), 1.84–1.74 (m, 1 H, CH ), 1.71–1.60 (m,
1 H, CH ), 1.55–1.36 (m, 2 H, CH ), 1.36–1.28 (m, 8 H, 4ϫ CH ),
) ppm. C NMR
): δ = 164.5 (C), 145.0 (CH), 121.3 (CH), 78.0
), 31.7 (CH ), 29.3 (CH ), 29.2 (CH ), 29.0 (CH ),
), 22.5 (CH ), 14.0 (CH ) ppm. MS (EI, 70 eV): m/z (%)
H,H = 1.5, = 196 (1) [M ], 168 (1), 150 (2), 136 (4), 125 (2), 111 (3), 97 (100),
), 6.10 (dd, JH,H = 10.4, 17.3 Hz, 1 H, 86 (4), 81 (5), 68 (67), 55 (11).
2
2
2
Undec-1-en-4-yl Acrylate (19c): Yield 730 mg (3.26 mmol, 65%). R
0.59 (hexane/ethyl acetate, 10:1). GC (BPX5): I = 1458. UV/Vis
f
2
3
2
2
1
13
=
0.88 (t, JH,H = 6.7, JC,H = 124.5 Hz, 3 H, CH
(100 MHz, CDCl
927 (s), 2857 (w), 1723 (s), 1640 (s), 1463 (w), 1405 (s), 1295 (w), (CH), 34.8 (CH
3
–1
(CH
2
Cl
2
): λmax (ε, Lmol–1 cm ) = 228 (437) nm. IR (ATR): ν˜ =
3
2
2
2
2
2
2
–
1
1
269 (s), 1191 (vs), 1046 (s), 984 (s), 964 (s), 915 (s), 808 (s) cm . 24.7 (CH
2
2
3
1
2
+
3
H NMR (400 MHz, CDCl , TMS): δ = 6.38 (dd, J
3JH,H = 17.3 Hz, 1 H, CH
3
2
2
3
CH), 5.80 (dd, JH,H = 1.5, JH,H = 10.4 Hz, 1 H, CH
2
), 5.76 (ddt,
Preparation of 6-Alkyl-2H-pyran-2-ones: To a solution of the re-
spective 5,6-dihydro-2H-pyran-2-one 20a, 8, or 20c (1.0 mmol) in
chlorobenzene (5 mL), was added NBS (196 mg, 1.1 mmol) and a
catalytic amount of AIBN (1 mg). The resulting mixture was
heated to 120 °C for 8 h. After cooling to room temperature, the
precipitated solids were filtered off and washed with CHCl
combined organic portions were washed with saturated aqueous
NaSO solution and brine, dried (MgSO ), and concentrated under
reduced pressure. Purification by column chromatography on silica
gel gave an inseparable mixture of the respective 6-alkyl-2H-pyran-
2-one and two diastereomeric 5-bromo-6-alkyl-5,6-dihydro-2H-
pyran-2-ones. This mixture was heated to reflux in triethylamine
(5 mL) for 4 d. The precipitate was removed by filtration and
washed with petane. The filtrate was diluted with pentane, washed
with 2 n HCl to remove triethylamine, and extracted three times
3
J
H,H = 17.2, 10.1, 7.0 Hz, 1 H, CH), 5.10–5.03 (m, 2 H, CH
.00 (quint, JH,H = 6.2 Hz, 1 H, CH), 2.37–2.32 (m, 2 H, CH
2
),
),
3
5
2
1
.63–1.56 (m, 2 H, CH ), 1.43–1.19 (m, 10 H, 5ϫ CH
2
2
), 0.87 (t,
) ppm. C NMR (100 MHz, CDCl ): δ
165.9 (C), 133.7 (CH), 130.3 (CH ), 128.9 (CH), 117.6 (CH ),
3.6 (CH), 38.6 (CH ), 33.6 (CH ), 31.8 (CH ), 29.4 (CH ), 29.1
CH ), 25.3 (CH ), 22.6 (CH ), 14.0 (CH ) ppm. MS (EI, 70 eV):
m/z (%) = 183 (5) [M – allyl], 152 (3), 111 (39), 96 (3), 81 (5), 67
11), 55 (100), 41 (34).
3
13
J
H,H = 6.8 Hz, 3 H, CH
3
3
=
7
(
2
2
3
. The
2
2
2
2
2
2
2
3
+
3
4
(
Preparation of 5,6-Dihydro-2H-pyran-2-ones: Acrylates 19a–c
2.00 mmol) were dissolved in toluene (40 mL). Grubbs’ second-
(
generation catalyst (20 mg, 0.02 mmol) was added and the reaction
mixture was heated to reflux for 1.5 h. After cooling to room tem-
perature the solvent was removed under reduced pressure. Purifica-
tion of the residue by column chromatography on silica gel yielded
the 5,6-dihydro-2H-pyran-2-ones as colourless oils.
4
with pentane. The combined organic layers were dried (MgSO )
and concentrated under reduced pressure. Purification of the resi-
due by column chromatography on silica gel yielded the desired 6-
alkyl-2H-pyran-2-ones as pale-yellow liquids. Due to the volatility
of the products, the use of solvents with low boiling points (pent-
ane, diethyl ether) during the workup procedure and chromato-
graphic purification is strongly recommended.
6
-Propyl-5,6-dihydro-2H-pyran-2-one
1.82 mmol, 91%). R = 0.20 (hexane/ethyl acetate, 3:1). GC
BPX5): I = 1302. UV/Vis (CH
1514) nm. IR (ATR): ν˜ = 2960 (w), 2935 (w), 2875 (w), 1714 (vs),
(20a):
Yield
255 mg
(
(
(
f
Cl
2
): λmax (ε, Lmol–1 cm ) = 228
–1
2
1
466 (w), 1385 (s), 1243 (vs), 1159 (w), 1114 (s), 1069 (s), 1027 (s),
60 (w), 920 (w), 813 (vs), 744 (s), 662 (w), 575 (w), 553 (w) cm .
–
1
9
6-Propyl-2H-pyran-2-one (11): Yield 14 mg (0.10 mmol, 10%). R
f
1
H NMR (400 MHz, CDCl
.03 (ddd, JH,H = 9.7, JH,H = 2.3, 1.5 Hz, 1 H, CH), 4.47–4.40
3
, TMS): δ = 6.91–6.87 (m, 1 H, CH), = 0.21 (pentane/diethyl ether, 5:1). GC (HP-5): I = 1253. UV/Vis
3
4
–1
–1
6
2 2
(CH Cl ): λmax (ε, Lmol cm ) = 228 (1766), 300 (2855) nm. IR
(
1
3
m, 1 H, CH), 2.38–2.29 (m, 2 H, CH
2
), 1.85–1.76 (m, 1 H, CH
2
), (ATR): ν˜ = 3402 (w), 3088 (w), 2965 (w), 2877 (w), 1699 (vs), 1629
3
1
.67–1.40 (m, 3 H, 2ϫ CH
H, CH
) ppm. 13C NMR (100 MHz, CDCl
), 29.3 (CH
) ppm. MS (EI, 70 eV): m/z (%) = 140 (1) [M ], 122 (2),
12 (3), 97 (99), 68 (100), 55 (6), 41 (46).
2
), 0.96 (t, JH,H = 7.3, JC,H = 125.2 Hz,
): δ = 164.5 (C), 145.0
3
), 18.0 (CH ), (400 MHz, CDCl , TMS): δ = 7.26 (dd, JH,H = 9.3, 6.5 Hz, 1 H,
(s), 1554 (s), 1465 (w), 1381 (w), 1208 (w), 1173 (w), 1108 (w), 1085
–1
1
3
3
(w), 990 (w), 908 (w), 801 (s), 731, 554 (s) cm . H NMR
3
(CH), 121.4 (CH), 77.7 (CH), 36.8 (CH
2
2
2
+
3
4
1
1
3.7 (CH
3
CH), 6.16 (dd, JH,H = 9.2, JH,H = 0.5 Hz, 1 H, CH), 5.99 (dd,
J
3
4
3
H,H = 6.6, JH,H = 0.8 Hz, 1 H, CH), 2.47 (t, JH,H = 7.5 Hz, 2
H, CH
), 1.60 (sext, 3JH,H = 7.5 Hz, 2 H, CH ), 0.97 (t, 3JH,H
.6 Hz, 3 H, CH ) ppm. C NMR (100 MHz, CDCl ): δ = 166.5
C), 162.9 (C), 143.8 (CH), 113.1 (CH), 102.8 (CH), 35.7 (CH
0.2 (CH ), 13.4 (CH
M ], 110 (27), 95 (100), 81 (47), 39 (35).
2
2
=
6
8
-Pentyl-5,6-dihydro-2H-pyran-2-one (8): Yield 269 mg (1.60 mmol,
1
3
7
3
3
0%). R = 0.30 (hexane/ethyl acetate, 3:1). GC (BPX5): I = 1516.
f
(
2
),
2 2
Cl
): λmax (ε, Lmol–1 cm ) = 228 (1161), 355 (16) nm.
–1
UV/Vis (CH
IR (ATR): ν˜ = 2931 (s), 2868 (w), 1715 (vs), 1464 (w), 1385 (s),
1
7
2
[
2
3
) ppm. MS (EI, 70 eV): m/z (%) = 138 (38)
+
248 (vs), 1156 (w), 1118 (s), 1058 (s), 1037 (s), 954 (s), 813 (vs),
–1 1
29 (w), 662 (w), 552 (w) cm . H NMR (400 MHz, CDCl
3
, TMS): 6-Pentyl-2H-pyran-2-one (6): Yield 35 mg (0.21 mmol, 21%). R
f
=
3
4
δ = 6.92–6.86 (m, 1 H, CH), 6.01 (ddd, JH,H = 9.8, JH,H = 2.1, 0.22 (pentane/diethyl ether, 5:1). GC (HP-5): I = 1468. UV/Vis
Eur. J. Org. Chem. 2013, 2906–2913 © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org 2911

S. M. Wickel, C. A. Citron, J. S. Dickschat
FULL PAPER
): λmax (ε, Lmol–1 cm ) = 229 (1544), 299 (1620) nm. IR
–1
fluoride yielded the desired alkenyl pyrones 7 and 13 as yellow
(CH
2
Cl
2
(
(
9
ATR): ν˜ = 2957 (s), 2931 (s), 2871 (w), 1704 (vs), 1629 (s), 1554 liquids. The synthesis of 14 was unsuccessful due to the rapid
w), 1467 (w), 1406 (w), 1379 (w), 1209 (w), 1173 (w), 1092 (w), isomerisation of this compound to 13 under the reaction and/or
84 (w), 937 (w), 804 (w), 729 (w), 560 (w) cm . H NMR workup conditions. However, the reaction product contained traces
–1
1
3
(400 MHz, CDCl
3
, TMS): δ = 7.26 (dd, JH,H = 6.5, 9.4 Hz, 1 H,
of a compound tentatively identified as 14 in addition to the main
product 13.
3
4
CH), 6.15 (dd, JH,H = 9.3, JH,H = 0.6 Hz, 1 H, CH), 5.97 (dd,
3
4
3
1
J
H,H = 6.6, JH,H = 0.8 Hz, 1 H, CH), 2.48 (t, JH,H = 7.6, JC,H
(
E)-6-(Pent-1-en-1-yl)-2H-pyran-2-one (7): Yield 0.21 g (1.3 mmol,
2%). R = 0.18 (hexane/ethyl acetate, 5:1). GC (HP-5): I = 1533.
=
128.8 Hz, 2 H, CH ), 1.72–1.63 (m, 2 H, CH ), 1.36–1.24 (m, 4
2
2
1
f
3
13
H, 2ϫ CH
2
), 0.88 (t, JH,H = 6.7 Hz, 3 H, CH
100 MHz, CDCl ): δ = 166.8 (C), 162.9 (C), 143.7 (CH), 102.5
CH), 33.8 (CH ), 31.5 (CH ), 26.9 (CH ), 22.6 (CH ), 14.1
CH ) ppm. MS (EI, 70 eV): m/z (%) = 166 (34) [M ], 138 (8), 123
6), 110 (39), 95 (100), 81 (36), 67 (17), 53 (7), 39 (29).
3
) ppm. C NMR
1
3
H NMR (400 MHz, CDCl
3
3
, TMS): δ = 7.29 (dd,
J
H,H = 6.8,
(
(
(
(
3
9
(
(
.4 Hz, 1 H, CH), 6.70 (dt, JH,H = 7.2, 15.6 Hz, 1 H, CH), 6.17
2
2
2
2
3
2
d, JH,H = 9.3 Hz, 1 H, CH), 6.03–5.97 (m, 2 H, 2ϫ CH ), 2.20
+
3
3
4
3
2
dq, JH,H = 7.3, JH,H = 1.5 Hz, 2 H, CH ), 1.50 (sext, JH,H =
), 0.94 (t, 3
1
7
.3 Hz, 2 H, CH
2
J
H,H = 7.4,
): δ = 162.0 (C), 159.7 (C),
), 21.8
JC,H = 125.2 Hz, 3 H,
1
3
6
-Heptyl-α-pyrone (12): Yield 52 mg (0.27 mmol, 27%). R
f
= 0.25
3 3
CH ) ppm. C NMR (100 MHz, CDCl
(
143.8 (CH), 139.6 (CH), 113.6 (CH), 103.0 (CH), 34.8 (CH
(
(CH ), 13.6 (CH ) ppm. MS (EI, 70 eV): m/z (%) = 164 (92) [M ],
(
ATR): ν˜ = 2955 (w), 2926 (s), 2856 (s), 1727 (vs), 1634 (s), 1557 136 (13), 122 (83), 109 (45), 107 (97), 94 (100), 79 (44), 77 (43), 66
(s), 1463 (s), 1378 (w), 1356 (w), 1256 (w), 1211 (w), 1211 (w), 1084
(8), 55 (21), 50 (7), 39 (55).
(
pentane/diethyl ether, 5:1). GC (HP-5): I = 1677. UV/Vis
2
CH
2
Cl
2
): λmax (ε, Lmol–1 cm ) = 228 (2364), 300 (5170) nm. IR
–1
2
3
+
–1 1
s), 979 (w), 857 (w), 797 (s), 549 (w) cm . H NMR (400 MHz,
(
E)-6-(Hept-1-en-1-yl)-2H-pyran-2-one
(13):
Yield
0.232 g
3
3
CDCl , TMS): δ = 7.26 (dd, JH,H = 9.3, 6.4 Hz, 1 H, CH), 6.15
(
1.2 mmol, 12%). R = 0.24 (hexane/ethyl acetate, 8:1). GC (HP-5):
f
3
4
3
(
dd, JH,H = 9.3, JH,H = 0.8 Hz, 1 H, CH), 5.97 (dd, JH,H = 6.6,
–1
–1
I = 1744. UV/Vis (CH
25 (4210) nm. IR (ATR): ν˜ = 3434 (w), 2957 (w), 2928 (s), 2858
w), 1726 (vs), 1648 (s), 1537 (s), 1461 (w), 1095 (s), 974 (w), 908
2 2
Cl ): λmax (ε, Lmol cm ) = 231 (5531),
4
3
J
2
H,H = 0.8 Hz, 1 H, CH), 2.48 (t, JH,H = 7.6 Hz, 2 H, CH ), 1.70–
3
(
(
3
1
6
.62 (m, 2 H, CH
.8 Hz, 3 H, CH
2
), 1.38–1.20 (m, 8 H, 4ϫ CH
2
), 0.88 (t, JH,H
): δ = 166.8
),
), 14.0
) ppm. MS (EI, 70 eV): m/z (%) = 194 (16) [M ], 165 (5), 149
5), 137 (5), 123 (21), 110 (32), 95 (100), 82 (50), 68 (18), 53 (19),
1 (41).
=
) ppm. 13C NMR (100 MHz, CDCl
–1 1
3
3
w), 878 (w), 796 (s), 728 (w), 549 (w) cm . H NMR (400 MHz,
(
3
(
(
C), 162.9 (C), 143.7 (CH), 113.0 (CH), 102.6 (CH), 33.8 (CH
1.6 (CH ), 28.89 (CH ), 28.87 (CH ), 26.8 (CH ), 22.5 (CH
CH
2
3
3
CDCl , TMS): δ = 7.29 (dd, JH,H = 9.3, 6.7 Hz, 1 H, CH), 6.71
(
3
3
2
2
2
2
2
dt, JH,H = 15.6, 7.2 Hz, 1 H, CH), 6.17 (d, JH,H = 9.3 Hz, 1 H,
+
3
4
3
CH), 5.99 (dt, JH,H = 15.6,
JH,H = 1.5 Hz, 1 H, CH), 5.97 (d,
3
4
3
J
H,H = 6.3 Hz, 1 H, CH), 2.22 (dt, JH,H = 1.4, JH,H = 7.3 Hz, 2
H, CH ), 1.51–1.42 (m, 2 H, CH ), 1.37–1.25 (m, 4 H, 2ϫ CH ),
.92–0.87 (t, 3JH,H = 7.0 Hz, 3 H, CH
) ppm. C NMR (100 MHz,
CDCl ): δ = 162.0 (C), 159.7 (C), 143.8 (CH), 139.9 (CH), 121.5
4
2
2
2
13
0
3
Preparation of 6-Alkyl-2H-pyran-2-ones and 6-(Bromomethyl)-2H-
pyran-2-one by Gold Catalysis:[
25]
In a sealed tube, propiolic acid
3
(
2
[
6
CH), 113.6 (CH), 103.0 (CH), 32.7 (CH
2.4 (CH ), 13.9 (CH ) ppm. MS (EI, 70 eV): m/z (%) = 192 (31)
M ], 164 (2), 147 (4), 135 (8), 122 (50), 107 (35), 94 (100), 77 (57),
6 (10), 39 (75).
2 2 2
), 31.3 (CH ), 28.3 (CH ),
(
5
95 mg, 1.36 mmol), the respective alkyne 21a–c or 28 (6.8 mmol,
equiv.) and [(PPh )AuCl] (0.068 mmol, 0.05 equiv.) were dissolved
in CH Cl (6 mL). After addition of AgOTf (0.068 mmol,
.05 equiv.), the tube was immediately sealed and heated to 50 °C
2
3
3
+
2
2
0
for 8–12 h. The reaction was then stopped and the solvent was
evaporated. Column chromatography of the residue on silica gel
yielded the pure 2H-pyran-2-ones. Spectroscopic data of 6, 11, and
(
E)-6-(Pent-2-en-1-yl)-2H-pyran-2-one (14): Yield Ͻ1% determined
by GC analysis. GC (HP-5): I = 1468. MS (EI, 70 eV): m/z (%) =
1
6
+
64 (36) [M ], 149 (1), 136 (5), 107 (17), 95 (100), 79 (8), 77 (11),
7 (3), 39 (26).
12 were the same as noted above.
6
-(Bromomethyl)-2H-pyran-2-one (29): Yield 105 mg (0.56 mmol,
Diethyl [(2-Oxo-2H-pyran-6-yl)methyl]phosphonate (30): Com-
pound 29 (357 mg, 1.9 mmol, 1 equiv.) and triethyl phosphite
(316 mg, 1.9 mmol, 1 equiv.) were mixed and heated to 160 °C for
3 h. After cooling to room temperature, the product was purified
by column chromatography on silica gel (CH Cl /MeOH, 10:1) to
f
41%). R = 0.21 (pentane/diethyl ether, 1:2). GC (BPX5): I = 1437.
): λmax (ε, Lmol–1 cm ) = 300 (6788) nm. IR
–1
UV/Vis (CH
2
Cl
ATR): ν˜ = 3077 (w), 3045 (w), 2985 (w), 1717 (s), 1631 (s), 1552
s), 1444 (w), 1408 (w), 1356 (m), 1243 (m), 1208 (m), 1178 (m),
2
(
(
2
2
1
092 (s), 983 (m), 918 (m), 874 (m), 849 (m), 802 (s), 724 (m), 678 give 30 as a pale-yellow oil, yield 422 mg (1.3 mmol, 68%). R =
f
–1 1
(m), 562 (s), 546 (s) cm . H NMR (400 MHz, CDCl
3
, TMS): δ =
0.44 (CH Cl /MeOH, 10:1). IR (ATR): ν˜ = 3084 (w), 2984 (w),
2911 (w), 1724 (s), 1635 (m), 1554 (m), 1445 (w), 1394 (w), 1356
(w), 1241 (m), 1202 (w), 1163 (w), 1087 (w), 1016 (s), 961 (s), 806
2
2
3
7
.30 (dd, JH,H = 9.2, 6.8 Hz, 1 H, CH), 6.31–6.28 (m, 2 H, 2ϫ
CH), 4.17 (s, 2 H, CH
1
2
) ppm. 13C NMR (100 MHz, CDCl
3
): δ =
–
1 1
61.1 (C), 159.3 (C), 142.8 (CH), 116.2 (CH), 104.8 (CH), 26.7
(m), 779 (m), 738 (m), 642 (w) cm . H NMR (400 MHz, CDCl ,
3
+
3
(
(
(
CH
2
) ppm. MS (EI, 70 eV): m/z (%) = 188 (1) [M ], 162 (2), 146 TMS): δ = 7.30 (dd, J
H,H
= 6.6, 9.4 Hz, 1 H, CH), 6.24–6.21 (m,
2
3), 109 (18), 95 (60), 81 (90), 79 (27), 62 (14), 53 (73), 42 (34), 39 2 H, 2ϫ CH), 4.21–4.11 (m, 4 H, 2ϫ CH ), 3.08 (d, JP,H
100).
=
2
3
22.0 Hz, 2 H, CH ), 1.34 (t, J
C NMR (100 MHz, CDCl
2
H,H 3
= 7.1 Hz, 6 H, 2ϫ CH ) ppm.
3
, TMS): δ = 161.7 (C), 156.8 (d, JC,P
1
3
2
Preparation of Alkenyl Pyrones: As reported by Thibonnet et al.,[26]
=
10.0 Hz, C), 143.4 (d, JC,P = 3.7 Hz, CH), 114.0 (d, JC,P = 3.7 Hz,
to a solution of freshly distilled acid chloride 26a–c (15 mmol) in
abs. dioxane (50 mL), was added dropwise tributylstannyl 4-(tri-
butylstannyl)but-3-enoate (6.64 g, 10 mmol), followed by the
addition of tetrakis(triphenylphosphane)palladium(0) (5 mol-%,
2
CH), 105.2 (d, JC,P = 8.2 Hz, CH), 62.7 (d,
CH
CH
JC,P = 6.6 Hz, 2ϫ
), 32.3 (d, JC,P = 39.3 Hz, CH ), 16.2 (d, JC,P = 6.0 Hz, 2ϫ
2
1
3
2
3
) ppm.
570 mg). After stirring for 6 h at 50 °C, the mixture was hydrolysed Preparation of Alkenylpyrones by Horner–Wadsworth–Emmons Re-
by addition of a saturated solution of ammonium chloride, and
extracted with diethyl ether. The organic layer was washed with
brine, dried, and concentrated under reduced pressure. Purification
by column chromatography on silica gel containing 10% potassium
action: To a solution of diisopropylamine (137 mg, 1.36 mmol,
1.05 equiv.) in anhydrous THF (4 mL) was added dropwise at 0 °C
a solution of nBuLi (1.6 m in hexane, 0.85 mL, 1.36 mmol,
1.05 equiv.), and the reaction mixture was stirred for 45 min at
2912
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2906–2913

2H-Pyran-2-ones from Trichoderma viride and asperellum
0
1
°C. After cooling to –78 °C, phosphonate 30 (0.41 g, 1.28 mmol,
equiv.) in anhydrous THF (2 mL) was added dropwise. The mix-
[7] J. R. Bamburg, F. M. Strong, Phytochemistry 1969, 8, 2405–
410.
2
[8] C. McKean, L. Tang, M. Billam, M. Tang, C. W. Theodorakis,
R. J. Kendall, J. S. Wang, J. Appl. Toxicol. 2006, 26, 139–147.
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Tubaki, Chem. Pharm. Bull. 1995, 43, 1035–1038.
[10] N. Stoppacher, B. Kluger, S. Zeilinger, R. Krska, R. Schu-
macher, J. Microbiol. Methods 2010, 81, 187–193.
[11] R. P. Collins, A. F. Halim, J. Agric. Food Chem. 1972, 20, 437–
438.
ture was further stirred for 1 h, maintaining the temperature below
20 °C. After cooling to –78 °C, freshly distilled butyric aldehyde
121 mg, 1.68 mmol, 1.3 equiv.) or hexanal (168 mg, 1.68,
.3 equiv.), respectively, was added. Stirring was continued over-
night, while the mixture was allowed to slowly warm to room tem-
perature. The reaction was quenched by the addition of water, fol-
lowed by extraction with diethyl ether (3ϫ 20 mL). The combined
–
(
1
extracts were dried with MgSO
cation by column chromatography on silica gel yielded 7 (152 mg,
.93 mmol, 73%) and 13 (169 mg, 0.88 mmol, 69%) as pale-yellow
4
and concentrated in vacuo. Purifi-
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[
[
[
13] N. Claydon, M. Allan, J. R. Hanson, A. G. Avent, Trans. Br.
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Mycol. Soc. 1987, 88, 503–513.
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Motta, J. Agric. Food Chem. 2003, 51, 6957–6960.
15] N. Kishimoto, S. Sugihara, K. Mochida, T. Fujita, Biocontrol
Sci. 2005, 10, 31–36.
Supporting Information (see footnote on the first page of this arti-
cle): Tabulated results of headspace analyses, synthetic procedures
1
13
for compounds 24, 26a–c, and 27, and copies of H and C NMR
spectra of synthetic compounds.
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Acknowledgments
[
This work was funded by an Emmy Noether fellowship of the
Deutsche Forschungsgemeinschaft (DFG) (DI1536/1-3, to J. S. D.).
We thank Prof. Gabriele König (University of Bonn) for the kind
gift of Trichoderma strains and Prof. Stefan Schulz (TU
Braunschweig) for support of our group.
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Received: January 11, 2013
Published Online: March 18, 2013
Eur. J. Org. Chem. 2013, 2906–2913
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2913