Multidirectional cobalt-catalyzed diels-alder/1,4-hydrovinylation sequences

Article abstract of DOI:10.1021/jo301028b

The combination of two powerful cobalt-catalyzed carbon-carbon bond forming transformations, namely, the Diels-Alder and the 1,4-hydrovinylation reaction, in a tandem or a sequential one-pot procedure, opened up a concise and efficient route to polysubstituted aromatic systems and cyclohex-3-enone derivatives. Furthermore, ozonolysis of the latter products led to polycarbonyl compounds with tailored carbonyl group distances which could be characterized via their respective BF₂-borinane complexes. The cobalt catalysts tolerated several functional groups, and a flexible approach to polyfunctionalized compounds in concise fashion was described.

Full text of DOI:10.1021/jo301028b

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pubs.acs.org/joc
Multidirectional Cobalt-Catalyzed Diels−Alder/1,4-Hydrovinylation
Sequences
Florian Erver, Julian R. Kuttner, and Gerhard Hilt*
Fachbereich Chemie, Philipps-Universitat Marburg, Hans-Meerwein-Str. 35043 Marburg, Germany
̈
S
* Supporting Information
ABSTRACT: The combination of two powerful cobalt-catalyzed carbon−carbon bond forming transformations, namely, the
Diels−Alder and the 1,4-hydrovinylation reaction, in a tandem or a sequential one-pot procedure, opened up a concise and
efficient route to polysubstituted aromatic systems and cyclohex-3-enone derivatives. Furthermore, ozonolysis of the latter
products led to polycarbonyl compounds with tailored carbonyl group distances which could be characterized via their respective
BF2-borinane complexes. The cobalt catalysts tolerated several functional groups, and a flexible approach to polyfunctionalized
compounds in concise fashion was described.
Scheme 1
INTRODUCTION
■
The increasing portfolio of cobalt-catalyzed transformations for
the selective formation of carbon−carbon bonds and carbon−
heteroatom bonds for the synthesis of increasingly complex
structures is a constant driving force for chemists involved in
the development of new synthetic methods. Cobalt catalysts
have found a number of applications for the construction of
cyclic products as well as for the generation of acyclic
derivatives via carbon−carbon bond formation processes.1
However, a transition-metal-catalyzed method is usually very
selective for a specific type of bond formation. In contrast, very
few catalysts have been identified that are able to initiate
multiple conceptionally different transformations, and an even
smaller number of catalysts are able to initiate carbon−carbon
bond formations by different types of reactions.2
pattern), the 1,4-hydrovinylation reaction of two unsymmetrical
starting materials can generate up to four isomers (3−6)
concerning the site (α or β on the terminal alkene as well as C1
versus C4 on the 1,3-diene) of the carbon−carbon bond
formation. Additionally, taking all possible E- and Z-
combinations of the corresponding 1,4-dienes into account,
the total number of isomers for the 1,4-hydrovinylation
reaction, without even considering the also possible 1,2-
hydrovinylation reactions,6 rises to 12.
In the past, we reported several types of cycloaddition
reactions and formation of acyclic products based on the
application of different cobalt catalysts. Alternation of the
ligands, the type of starting materials applied, or the solvent led,
in some cases, to the formation of alternative regioisomers in
cobalt-catalyzed reactions. Among the transformations de-
scribed thus far, the cobalt-catalyzed regiodiverse cyclo-
trimerization of alkynes,3 the regiodiverse Diels−Alder
reaction,4 as well as the regioselective 1,4-hydrovinylation
reaction5 have attracted considerable interest (Scheme 1).
While the cobalt-catalyzed cycloaddition process led to two
different regioisomers 1 and 2 (para- and meta-substitution
Received: May 18, 2012
Published: June 14, 2012
© 2012 American Chemical Society
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In an effort to combine different types of cobalt-catalyzed
carbon−carbon bond formation processes, we initiated a
project for the synthesis of more complex structures by
applying simple cobalt catalysts in Diels−Alder and 1,4-
hydrovinylation reactions in a one-pot reaction sequence.
Thereby, multicomponent reactions should be realized and
aspects of chemo- and regioselective carbon−carbon bond
formations investigated.
Table 1. Scope of the Diels−Alder/1,4-Hydrovinylation/
Oxidation Strategy
RESULTS AND DISCUSSION
■
We began our studies by exploring the application of internal
nonconjugated enynes (7a−o; see Experimental Section) with
symmetrical 1,3-dienes such as 2,3-dimethyl-1,3-butadiene
(DMB) in order to reduce the number of possible regioisomers
for both types of reactions. The catalyst system of choice for
this initial study comprises CoBr2(dppe),7 zinc powder, and
zinc iodide, which has proven to be an active catalyst system for
both transformations. Furthermore, the crude dihydroaromatic
intermediate obtained after cobalt catalysis should be directly
oxidized to its corresponding aromatic derivative 8 by using
DDQ (2,3-dichloro-4,5-dicyano-1,4-benzoquinone). For this
purpose, different enynes of type 7 were applied in the cobalt-
catalyzed one-pot reaction sequence for the synthesis of
products such as 8 in a straightforward fashion (Scheme 2).
Scheme 2
The results of the cobalt-catalyzed Diels−Alder/1,4-hydro-
vinylation/oxidation one-pot reaction sequence are summarized
in Table 1.
The GC−MS analysis of a reaction around 50% conversion
revealed that the cobalt-catalyzed Diels−Alder reaction and the
1,4-hydrovinylation proceeded with similar relative rates.
Aromatic enynes proved to be very suitable substrates for this
type of one-pot sequence (entries 6−8). The chain unit length
of the enyne seems to have no significant influence on the
yields obtained after three formal steps. All possible carbon
oxidation states could be realized next to the aromatic core
using the appropriate enyne. While the enyne ester was
converted into 8a in excellent yield (entry 1), phenone 8b
(entry 2) could be obtained only in a moderate yield. As known
from previous reactions, substrates with ketone functionality are
more difficult to convert and generally lower yields are
obtained. However, an unprotected hydroxyl-functionalized
enyne (entry 3) was converted without difficulties, and the
benzaldehyde derivative 8c was obtained directly upon
overoxidation with DDQ (entry 3), whereas the acylated
enynol could be transformed in the usual manner (entry 4). A
trimethylsilyl-functionalized enyne delivered the silylated
aromatic compound 8e in a good yield (entry 5). Furthermore,
the reaction sequence was tested upon compatibility with
heteroatoms in the enyne chain unit. Therefore, an allyl
propargyl ether and a sulfonamide derivative were subjected to
the sequence. The sulfonamide generated the corresponding
product 8j in a comparable good yield (entry 10), whereas the
product 8i (entry 9) could only be obtained in a moderate
a
Reaction conditions: Diels−Alder/1,4-hydrovinylation reaction:
CoBr2(dppe) (10 mol %), ZnI2 (20 mol %), Zn powder (20 mol
%), alkyne (1 M), DMB (2.4 M) in dichloromethane, room
temperature; oxidation: cycloaddition product (0.1 M), DDQ (0.2
M; 0.3 M for compound 8c) in benzene, room temperature.
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yield, possibly due to partial oxidative cleavage of the benzylic
ether with DDQ, as known for electron-rich PMB derivatives.8
In the case of unsymmetrical 1,3-dienes, the cobalt catalyst
systems investigated by us in the past gave excellent
regioselectivities for the cobalt-catalyzed Diels−Alder reactions
in favor of the para-substituted cycloaddition product 1 (see
Scheme 1) with bisphosphine ligands as well as for the meta-
substituted product 2 when pyridine imine ligands (py-imine)
were applied.4
Table 2. Scope of the Diels−Alder/1,4-Hydrovinylation/
Hydrolysis Strategy
When cobalt catalysts are applied in the 1,4-hydrovinylation
reaction, the proposed active catalyst [Co(dppe)+] exhibits
excellent regioselectivity for the carbon−carbon bond for-
mation at the α-carbon atom of the terminal alkene while a
similar cobalt complex utilizing a more complex bidentate
phosphine−phosphite ligand (SchmalzPhos) forms the new
carbon−carbon bond with high selectivity at the β-carbon.9
The advantage of the one-pot sequence presented here is
exemplified by the variability of the coupling partners. For
example, the replacement of DMB with the unsymmetrical 2-
(trimethylsilyloxy)buta-1,3-diene (TMSO-diene) led to com-
pletely different types of products. After hydrolysis of the silyl
enol ether intermediates, cyclic enones were generated10 while
acyclic enones were formed via the 1,4-hydrovinylation process
(9 in Scheme 3). Moreover, when pyridine imine type ligands11
Scheme 3
were applied in the Diels−Alder reactions, the meta-substituted
regioisomer 10 was formed instead of the para-regioisomer.4c,d
In addition to this remarkable regioselectivity in the Diels−
Alder reaction, pyridine imine type cobalt catalysts are
unreactive in the 1,4-hydrovinylation reaction. Accordingly,
the terminal alkene moiety remains unchanged, and the
application of the CoBr2(dppe) catalyst can be used to generate
an acyclic enone unit after hydrolysis in product 11. Therefore,
it is possible to form either the para-substituted cyclohex-3-
enone product 9 via a tandem Diels−Alder/1,4-hydrovinylation
reaction or the meta-substituted derivative 11 via a sequential
Co(py-imine)-catalyzed Diels−Alder and Co(dppe)-catalyzed
1,4-hydrovinylation reaction approach (Scheme 3).
a
A: Diels−Alder/1,4-hydrovinylation reaction: CoBr2(dppe) (10 mol
%), ZnI2 (20 mol %), Zn powder (20 mol %), alkyne (1 M), TMSO-
diene (2.4 M) in dichloromethane, room temperature; hydrolysis:
substrate (0.125 M), aqueous HCl (2 M) in THF/water, room
temperature. B: Diels−Alder reaction: CoBr2(py-imine) (10 mol %),
ZnI2 (20 mol %), Zn powder (20 mol %), alkyne (1 M), TMSO-diene
(1.5 M) in dichloromethane, room temperature; 1,4-hydrovinylation
reaction: CoBr2(dppe) (10 mol %), ZnI2 (20 mol %), Zn powder (20
mol %), TMSO-diene (1.5 M) in dichloromethane, room temperature;
hydrolysis: substrate (0.1 M), TBAB (0.06 M), KF (saturated aqueous
solution, buffered to pH = 7) in THF/water/dichloromethane, room
temperature.
The results of the cobalt-catalyzed Diels−Alder/1,4-hydro-
vinylation/hydrolysis one-pot reaction sequence are summar-
ized in Table 2.
The yields obtained for the tandem Diels−Alder/1,4-
hydrovinylation/hydrolysis sequence range from moderate to
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Scheme 4
good and are slightly lower compared to the reactions involving
DMB (entries 1−5). Nevertheless, different types of enynes
were accepted, and unprecedented polyfunctionalized products
were obtained. The use of the cobalt pyridine imine catalyst
successfully enabled the synthesis of the corresponding
cyclohexenone derivatives of type 11 with excellent regiocon-
trol. The overall yields for the reaction sequence are acceptable
to good concerning the formation of three new carbon−carbon
bonds and a single workup after hydrolysis of the silyl enol
ether intermediates.
the use of different butadiene derivatives. Thereby, it is easily
imaginable that a concise approach to complex organic
structures can be realized using rather simple building blocks
and their proper combination with each other.
Table 3. Results of the Sequential Diels−Alder/1,4-
Hydrovinylation Strategy
The use of a sequential Diels−Alder/1,4-hydrovinylation
strategy bears a further advantage. In principal, it should be
possible to obtain mixed products using different 1,3-dienes in
the cobalt-catalyzed reactions. Therefore, the cobalt pyridine
imine catalyst system initiates the Diels−Alder reaction of the
first 1,3-diene (12) and the alkyne subunit of 13, leaving the
terminal double bond of intermediate 14 untouched (Scheme
4). Then the second 1,3-diene 15 is added, and the cobalt-
catalyzed 1,4-hydrovinylation reaction is initiated by the cobalt
bisphosphine catalyst system now added to the reaction
mixture. The workup of the dihydroaromatic intermediate 16
can either generate the corresponding aromatic products, when
16 is treated with DDQ (compare to Scheme 2), or the
hydrolysis strategy is used as before for the production of
ketone substructures (compare to Scheme 3). Although the
variation of the substituents R1, R2 and R4, R5 of the dienes 12
and 15 would have allowed the synthesis of a huge variety of
different products, we concentrated our attention on the use of
DMB (R1 = R2 = Me) and TMSO-diene (R4 = H, R5 =
OSiMe3). Nevertheless, still a wide variety of products 17
became accessible, and the results of these multicomponent
one-pot reaction sequences utilizing two different cobalt
catalysts are summarized in Table 3.
In two examples (entries 1 and 2), an aromatic and an ester-
substituted enyne provided the aromatic products 17a and 17b
after Diels−Alder reaction with DMB, 1,4-hydrovinylation with
TMSO-diene, and subsequent hydrolysis in moderate yields. As
a side product of the DDQ oxidation of 17b, an overoxidized
derivative was also observed (∼15%), where an additional
double bond was introduced between the ketone functionality
and the exo-chain double bond. Unfortunately, this derivative
could not be isolated in pure form, but it clearly indicated that
the corresponding intermediate for the generation of 17b was
originally formed in higher yield.
The inversion of the reaction sequence using first TMSO-
diene in the regioselective Diels−Alder reaction then DMB in
the 1,4-hydrovinylation and subsequent hydrolysis furnished
the corresponding products 17c−17f in moderate to excellent
yields (entries 3−6). The flexibility of this approach lies in the
possibility for variation of the enyne functionality, the chain
length, or incorporation of heteroatoms between as well as in
a
Reaction conditions: Diels−Alder reaction: CoBr2(py-imine) (10 mol
%), ZnI2 (20 mol %), Zn powder (20 mol %), alkyne (1 M), diene
(1.2−1.5 M) in dichloromethane, room temperature; 1,4-hydro-
vinylation reaction: CoBr2(dppe) (10 mol %), ZnI2 (20 mol %), Zn
powder (20 mol %), 1,3-diene (1.2−1.5 M) in dichloromethane, room
temperature; hydrolysis: substrate (0.1 M), TBAB (0.06 M), KF
(saturated aqueous solution, buffered to pH = 7) in THF/water/
dichloromethane, room temperature.
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Scheme 5
Finally, we envisaged the possibility to generate polycarbonyl
derivatives upon ozonolysis from the cyclohex-3-enone
products formed via the regioselective cobalt-catalyzed tandem
Diels−Alder/1,4-hydrovinylation/hydrolysis sequence. One
valuable aspect in this approach is the flexibility in which the
carbonyl group distance within the pentacarbonyl derivatives
can be varied. This is made possible first by the control of the
Diels−Alder reaction, second by the chain length between
alkyne and alkene subunit (X), and third the type of 1,3-diene
(e.g., 12 or 15) used in the 1,4-hydrovinylation reaction.
In these studies, we concentrated our attention on the
sequentially produced cyclohex-3-enones of type 11, varying
only the enynes and the second introduced 1,3-diene.
Accordingly, the hypothetical products such as 11x, which is
accessible with DMB in the cobalt-catalyzed 1,4-hydro-
vinylation reaction, would lead to a 1,3-dicarbonyl unit in the
eastern part of 18x (Scheme 5). The oxidative cleavage of the
cyclohex-3-enone subunit in 11x would also lead to a 1,3,6-
tricarbonyl substructure in the western section of 18x. The
synthesis of a 1,4-dicarbonyl subunit in the eastern section
could be realized when hypothetical products such as 11y,
generated from the TMSO-diene in the 1,4-hydrovinylation
step, would be submitted to ozonolysis to afford products such
as 18y. Herein, also the 1,3,6-tricarbonyl substructure in the
western section of 18y would be generated by ozonolysis.
Accordingly, two pentacarbonyl products 18x and 18y would
be obtainable with tailored carbonyl distances in the eastern
part, and the chain length determined by X is decisive for the
carbonyl distances toward the western part with its 1,3,6-
tricarbonyl units.
solids. The tautomeric forms are annihilated in the BF2 adduct,
and the NMR signals can be assigned doubtlessly.
The results of these reaction sequences are summarized in
Table 4.
The isolation of the mono- and bis-BF2-borinane adducts
19a−19c and 19d was accomplished in only moderate yields by
column chromatography over silica gel. At this point, we were
interested to find ways to isolate and characterize the
polycarbonyl compounds regardless of the yields. The BF2-
borinane adducts seem to be an appropriate way not only for
the isolation of the compounds but also for the determination
of the identity of the desired products. In the absence of the
tautomeric forms, unambiguous assignment of the NMR signals
was possible. The 1,3-dicarbonyl units were all converted into
the corresponding BF2-borinane adducts, while the 1,4-
dicarbonyl substructures remained unchanged. Accordingly,
the 1,3-dicarbonyl subunits are protected, while the other
carbonyl groups are now available for follow-up chemical
transformations. In order to prove that the initial yields for the
ozonolysis are much higher, we attempted to isolate some of
the pentacarbonyl compounds. Product 18c could be isolated
by chromatography on silica gel after reduction by either PPh3
or P(OMe)3 in acceptable yield (50−59%). Product 18e, which
consists of a 1,3-dicarbonyl and a 1,3,5-tricarbonyl subunit,
could also be isolated by chromatography but only in a poor
yield of 18%, while aqueous extraction of the phosphate
byproduct by using P(OMe)3 as the reducing agent delivered
18e in good yield. This showed that we were able to generate
several pentacarbonyl derivatives from nonconjugated enynes
in only two to three steps based on the versatile and
regiodiverse application of cobalt catalysts.
The isolation and characterization of such pentacarbonyl
derivatives is nontrivial as we reported earlier.12 The keto−enol
tautomers are relatively polar, and the yields are generally
reduced by purification using column chromatography on
regular silica gel. Also, the tautomeric forms give rise to
multiple sets of signals in NMR analysis, which makes the
assignment of signals more complicated. Therefore, we decided
to transform the polycarbonyl derivatives in most cases into
their corresponding borinane derivatives of type 19 via reaction
with BF3. These BF2 adducts can be isolated by column
chromatography on regular silica gel and are mostly yellowish
CONCLUSION
■
In conclusion, we have demonstrated that different cobalt-
catalyzed transformations as the Diels−Alder and the 1,4-
hydrovinylation reaction can be combined in a one-pot
procedure. Moreover, the sequences described here allow a
very flexible product assembly as there are a lot of possibilities
given for substructure variations. We could show that the
nature of the product is strongly dependent on the diene(s)
used for the cobalt-catalyzed transformations as the reaction
with DMB in the Diels−Alder reaction led to aromatic
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with subsequent heating by using a heat-gun. 1H and 13C NMR spectra
were obtained using CDCl3 as a solvent and tetramethylsilane as
internal standard. Chemical shifts δ are reported in parts per million
downfield from tetramethylsilane. Coupling constants are indicated in
hertz with multiplicities denoted as s (singlet), d (doublet), t (triplet),
q (quartet), p (pentet), sext (sextet), and m (multiplet). Broad singlets
are reported as bs. IR spectra were measured on an FT-IR
spectrometer and are reported in wave numbers (cm−1). High-
resolution mass spectra were acquired using electron impact ionization
(EI) or atmospheric pressure chemical ionization (APCI).
Table 4. Results of the Ozonolysis/Borinane Formation of
Polycarbonyl Derivatives
General Procedure for the Preparation of 1,4-Enynes 7a−7i.
Following a literature procedure,13 CuI (10 mol %), Na2SO3 (0.5
equiv), and K2CO3 (1.0 equiv) were dissolved in the indicated solvent
at 50 °C. Then the terminal alkyne (1.0 equiv) was added to form a
bright yellow suspension. Upon treatment with allylbromide (1.2
equiv), the color changes to orange. The resulting suspension was
stirred overnight at 50 °C. The reaction mixture was then transferred
into a 1:1 solution of saturated aqueous NH4Cl/water and extracted
with diethyl ether. The combined organic phases were dried over
MgSO4 followed by evaporation of the solvent. The crude product was
then purified by flash column chromatography (silica gel) to obtain the
products of type 7. For the synthesis of aryl-substituted enynes 7a and
7b, dimethylformamide was used as the solvent and 1,8-
diazabicyclo[5.4.0]undec-7-ene (10 mol %, DBU) was added to the
reaction mixture. The ester-substituted 1,4-diene 7f was generated in
dimethyl sulfoxide, and KHCO3 was used instead of K2CO3. The acyl-
substituted 1,4-enyne 7g was obtained via allylation of but-3-yn-2-ol in
water and subsequent oxidation with pyridinium chlorochromate (2.0
equiv, PCC) in dichloromethane.14 The products 1-fluoro-4-(pent-4-
en-1-ynyl)benzene (7c), pent-4-en-1-ynylbenzene (7d), trimethyl-
(pent-4-en-1-ynyl)silane (7e), hex-5-en-2-yn-1-ol (7h), and hex-5-en-
2-ynyl acetate (7i) are known. The analytical data for these
compounds are in accordance with the literature; the analytical data
for new enyne compounds are given below.
1-Methoxy-3-(pent-4-en-1-ynyl)benzene (7a): colorless liquid; 463
mg (2.69 mmol, 85%); eluent, pentane/diethyl ether = 10:1; 1H NMR
(300 MHz, CDCl3) δ 7.20 (t, J = 7.9 Hz, 1H), 7.02 (dt, J = 7.6, 1.1 Hz,
1H), 6.96 (dd, J = 2.5, 1.4 Hz, 1H), 6.85 (ddd, J = 8.3, 2.6, 0.9 Hz,
1H), 5.90 (ddt, J = 17.0, 10.0, 5.3 Hz, 1H), 5.41 (dq, J = 17.0, 1.7 Hz,
1H), 5.17 (dq, J = 10.0, 1.7 Hz, 1H), 3.80 (s, 3H), 3.20 (dt, J = 5.3, 1.8
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 159.3, 132.4, 129.3, 124.7,
124.2, 116.5, 116.3, 114.4, 86.4, 82.8, 55.2, 23.7; MS (EI) m/z (%) 172
(M+, 100), 157 (12), 141 (12), 128 (29), 115 (8); HRMS (EI, ICP,
m/z) calcd for C12H12O 172.0888, found 172.0877; IR (film, cm−1)
3078, 3006, 2940, 2911, 2835, 2236, 1640, 1598, 1576, 1484, 1421,
1317, 1282, 1203, 1167, 1083, 1042, 990, 915, 853, 780, 685, 630, 561,
518, 464.
a
The yield refers to the formation of the BF2 adduct from the
previously isolated 1,3-dicarbonyl compound 18c with BF3 etherate in
dichloromethane. The reduction of the ozonide was performed using
triphenylphosphine. The product was purified by column chromatog-
raphy. The reduction of the ozonide was performed using trimethyl
b
c
phosphite. The product was purified by column chromatography.
d
The reduction of the ozonide was performed using trimethyl
phosphite. The product was purified by extraction.
compounds, while the TMSO-diene led to the synthesis of
cyclohex-3-enones accessible in a regiodivergent fashion,
dependent on the cobalt catalyst used. Furthermore, the
modular and sequential approach for these three-component
reactions enables the formation of pentacarbonyl compounds
with tailored functional group distances. The products, which
look hardly approachable by other methods, could be isolated
and undoubtedly characterized via their respective BF2
complexes. Our future work will focus on exploring the
chemistry of these interesting polycarbonyl compounds.
1,2,3-Trimethoxy-5-(pent-4-en-1-ynyl)benzene (7b): colorless oil;
1
470 mg (2.02 mmol, 94%); eluent, pentane/diethyl ether = 4:1; H
NMR (300 MHz, CDCl3) δ 6.66 (s, 2H), 5.91 (ddt, J = 17.0, 10.0, 5.3
Hz, 1H), 5.39 (dq, J = 17.0, 1.7 Hz, 1H), 5.17 (dq, J = 10.0, 1.7 Hz,
1H), 3.84 (s, 9H), 3.19 (dt, J = 5.3, 1.8 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 153.0, 138.5, 132.4, 118.7, 116.3, 108.8, 85.6, 82.8, 60.9,
56.1, 23.7; MS (EI) m/z (%) 232 (M+, 100), 231 (98), 217 (81), 189
(11), 172 (16), 128 (16); HRMS (EI, ICP, m/z) calcd for C14H16O3
232.1099, found 232.1096; IR (film, cm−1) 2938, 2835, 1574, 1501,
1456, 1408, 1348, 1314, 1284, 1233, 1165, 1122, 999, 917, 831, 769,
737, 626, 560, 526.
EXPERIMENTAL SECTION
■
General Methods. All reactions were carried out under an argon
atmosphere in heat-gun-dried glassware and were stirred magnetically.
Unless otherwise noted, all reactions were performed with anhydrous
solvents, and ZnI2 was dried in vacuo at 150 °C prior to use.
Commercially available materials were used without further
purification. Ozonolysis was conducted using an ozone generator,
and O2/O3 mixture was dried by a P4O5 column. Flash
chromatography was performed on silica gel 60 (230−400 mesh),
and analytical thin layer chromatography (TLC) was carried out on
silica gel 60 F-254 precoated aluminum plates. The TLC plates were
analyzed by short-wave UV illumination and by dipping in CAM stain
(composed of 40 g of ammonium molybdate, 1.6 g of ceric ammonium
molybdate, 80 mL of concentrated sulfuric acid, and 720 mL of water)
Methyl Hex-5-en-2-ynoate (7f): colorless liquid; 1.91 g (15.36
1
mmol, 77%); eluent, pentane/diethyl ether = 20:1; H NMR (300
MHz, CDCl3) δ 5.83−5.70 (m, 1H), 5.33 (d, J = 17.0 Hz, 1H), 5.17
(d, J = 11.7 Hz, 1H), 3.75 (s, 3H), 3.10 (td, J = 3.6, 1.9 Hz, 2H); 13C
NMR (75 MHz, CDCl3) δ 154.0, 129.7, 117.7, 85.9, 74.7, 52.5, 22.8;
MS (EI) m/z (%) 124 (M+, 23), 109 (1), 93 (100), 79 (11), 65 (58),
53 (13); HRMS (EI, ICP, m/z) calcd for C7H8O2 124.0524, found
124.0526; IR (film, cm−1) 3414, 3089, 3020, 2988, 2956, 2901, 2844,
2243, 1716, 1643, 1507, 1436, 1417, 1324, 1258, 1090, 1074, 1042,
992, 929, 816, 753, 663, 564.
Hept-6-en-3-yn-2-one (7g): colorless liquid; 533 mg (4.93 mmol,
25%, two steps); eluent, pentane/diethyl ether = 10:1; 1H NMR (300
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MHz, CDCl3) δ 5.85−5.72 (m, 1H), 5.32 (dd, J = 17.0, 1.1 Hz, 1H),
5.18 (dd, J = 10.2, 1.5 Hz, 1H), 3.13 (td, J = 3.5, 1.7 Hz, 2H), 2.33 (s,
3 H); 13C NMR (75 MHz, CDCl3) δ 184.6, 130.0, 117.6, 89.9, 83.0,
32.7, 23.1; MS (EI) m/z (%) 108 (M+, 6), 93 (100), 77 (4), 65 (52),
62 (5), 53 (6), 50 (4); HRMS (EI, ICP, m/z) calcd for C7H8O
108.0575, found 108.0569; IR (film, cm−1) 3336, 3089, 2986, 2920,
2214, 1678, 1643, 1416, 1360, 1321, 1285, 1230, 1107, 1077, 1019,
992, 965, 929, 712, 620, 583, 561.
were added, and the mixture was stirred at room temperature for 16 h.
Afterward, the suspension was filtered over a short pad of silica gel,
and the solvent was removed under vacuum. The residue was dissolved
in benzene (10 mL) and was treated with 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (2.0 mmol, 3.0 mmol for 8c, DDQ). The mixture was
stirred for 1 h at room temperature and was then filtered over a short
pad of deactivated silica gel. The solvent was removed in vacuo, and
the residue was purified by flash column chromatography.
General Procedure for the Preparation of 1,5-Enynes 7j−7l.
Following a literature procedure,15 pent-4-yn-1-ol (1.0 equiv) and the
arylhalide (1.0 equiv) were added to a degassed solution of CuI (4 mol
%) and (PPh3)2PdCl2 (2 mol %) in triethylamine (0.375 M). The
reaction mixture was then heated to 60 °C and stirred overnight.
Afterward, the suspension was filtered over a small plug of silica gel
and flashed with diethyl ether. After evaporation of the solvent, the
crude product was dissolved in anhydrous dichloromethane (0.2 M).
The solution was treated with pyridinium chlorochromate (1.5 equiv,
PCC) and stirred at room temperature overnight.16 The resulting
suspension was filtered over silica gel, followed by evaporation of the
solvent. The crude product was then purified by flash column
chromatography. From a known procedure,9 methyltriphenylphos-
phonium bromide (2.0 equiv) was dissolved in tetrahydrofuran (0.18
M). To this suspension was added dropwise n-butyllithium (2.5 M, 2.0
equiv) at 0 °C and stirred for 30 min at room temperature. The
resulting solution was treated with a solution of the pure aldehyde in 5
mL of tetrahydrofuran at 0 °C. The reaction mixture was gradually
warmed to room temperature and stirred overnight. After hydrolysis
with half-concentrated aqueous NH4Cl solution and extraction with
diethyl ether, the combined organic phases were dried over MgSO4
followed by evaporation of the solvent. The crude product was then
purified by flash column chromatography to obtain a colorless liquid.
The products 1-(hex-5-en-1-ynyl)-4-methoxybenzene (7k), hex-5-
en-1-ynylbenzene (7l), and 3-(prop-2-ynyloxy)prop-1-ene (7n) are
known. The analytical data for these compounds are in accordance
with the literature; the analytical data for new enyne compounds are
given below.
2-(Hex-5-en-1-ynyl)thiophene (7j): colorless liquid; 662 mg (4.08
mmol, 41%, three steps); eluent, pentane; 1H NMR (300 MHz,
CDCl3) δ 7.17 (dd, J = 5.3, 1.1 Hz, 1H), 7.12 (dd, J = 3.4, 1.1 Hz, 1H),
6.94 (dd, J = 5.3, 3.8 Hz, 1H), 5.98−5.84 (m, 1H), 5.16−5.03 (m,
2H), 2.54−2.49 (m, 2H), 2.40−2.32 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 136.8, 131.0, 126.7, 126.0, 124.0, 115.8, 93.6, 74.1, 32.7,
19.5; MS (EI) m/z (%) 162 (M+, 22), 147 (7), 134 (7), 128 (3), 121
(100), 115 (2), 108 (2), 93 (2), 87 (1), 77 (21), 69 (6), 63 (6), 51
(5); HRMS (EI, ICP, m/z) calcd for C10H10S 162.0503, found
162.0497; IR (film, cm−1) 3438, 3106, 3077, 2980, 2921, 2844, 2227,
1796, 1642, 1519, 1428, 1355, 1328, 1238, 1191, 1080, 1044, 994, 916,
848, 830, 699.
Methyl 2-(4,5-Dimethyl-2-methylenehex-4-enyl)-4,5-dimethyl-
benzoate (8a): colorless oil; 230 mg (0.80 mmol, 80%); eluent,
pentane/diethyl ether = 20:1; 1H NMR (300 MHz, CDCl3) δ 7.65 (s,
1H), 7.00 (s, 1H), 4.71 (s, 1H), 4.41 (s, 1H), 3.83 (s, 3H), 3.59 (s,
2H), 2.76 (s, 2H), 2.26 (s, 6H), 1.68 (s, 3H), 1.61−1.59 (m, 6H); 13C
NMR (75 MHz, CDCl3) δ 168.3, 147.6, 140.7, 138.5, 134.3, 132.8,
131.6, 127.6, 126.1, 125.1, 110.5, 51.6, 41.6, 39.9, 20.5, 20.3, 19.7, 19.1,
18.4; MS (EI) m/z (%) 286 (M+, 6), 271 (2), 254 (4), 239 (39), 224
(10), 211 (11), 203 (100), 186 (13), 173 (10), 165 (3), 157 (7), 141
(8), 128 (12), 119 (7), 109 (20), 91 (13), 77 (8), 67 (12), 55 (14);
HRMS (EI, ICP, m/z) calcd for C19H26O2 286.1933, found 286.1934;
IR (film, cm−1) 3077, 2986, 2919, 2861, 1723, 1643, 1616, 1563, 1502,
1434, 1372, 1293, 1267, 1233, 1189, 1138, 1049, 1022, 1002, 955, 892,
833, 792.
1-(2-(4,5-Dimethyl-2-methylenehex-4-enyl)-4,5-dimethylphenyl)-
ethanone (8b): yellow oil; 121 mg (0.45 mmol, 45%); eluent,
pentane/diethyl ether = 10:1; 1H NMR (300 MHz, CDCl3) δ 7.41 (s,
1H), 7.00 (s, 1H), 4.71 (s, 1H), 4.40 (s, 1H), 3.50 (s, 2H), 2.75 (s,
2H), 2.51 (s, 3H), 2.28−2.27 (m, 6H), 1.68 (s, 3H), 1.60 (s, 6H); 13C
NMR (75 MHz, CDCl3) δ 201.8, 147.8, 140.2, 136.8, 136.3, 134.1,
133.1, 130.4, 126.2, 125.1, 110.7, 41.7, 39.5, 29.6, 20.6, 20.4, 19.7, 19.3,
18.4; MS (EI) m/z (%) 270 (M+, 2), 252 (8), 237 (10), 227 (6), 211
(5), 195 (2), 187 (100), 170 (4), 160 (6), 152 (2), 141 (4), 128 (6),
115 (5), 105 (2), 91 (5), 83 (3), 67 (3), 55 (5); HRMS (EI, ICP, m/
z) calcd for C19H26O 270.1984, found 270.2001; IR (film, cm−1) 3077,
2983, 2919, 2861, 1685, 1643, 1612, 1557, 1498, 1449, 1385, 1372,
1354, 1291, 1263, 1231, 1199, 1132, 1020, 948, 887, 656, 635.
2-(4,5-Dimethyl-2-methylenehex-4-enyl)-4,5-dimethylbenzalde-
hyde (8c): colorless oil; 188 mg (0.73 mmol, 73%); eluent, pentane/
1
diethyl ether = 10:1; H NMR (300 MHz, CDCl3) δ 10.11 (s, 1H),
7.63 (s, 1H), 7.01 (s, 1H), 4.80 (s, 1H), 4.41 (s, 1H), 3.59 (s, 2H),
2.80 (s, 2H), 2.30 (s, 6H), 1.69 (s, 3H), 1.61 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 191.7, 147.7, 143.5, 139.8, 135.2, 132.9, 132.2, 131.0,
126.6, 124.8, 112.1, 41.7, 37.8, 20.6, 20.4, 20.0, 19.2, 18.3; MS (EI) m/
z (%) 256 (M+, 5), 241 (46), 223 (56), 208 (21), 193 (19), 181 (10),
173 (100), 159 (16), 141 (11), 128 (18), 115 (14), 105 (5), 91 (12),
77 (8), 67 (5), 55 (6); HRMS (EI, ICP, m/z) calcd for C18H24O
256.1827, found 256.1816; IR (film, cm−1) 3079, 2983, 2919, 2859,
2755, 1690, 1643, 1611, 1560, 1499, 1450, 1399, 1373, 1295, 1258,
1184, 1070, 1023, 895, 778, 693, 629.
2-(4,5-Dimethyl-2-methylenehex-4-enyl)-4,5-dimethylbenzyl ac-
etate (8d): yellow oil; 207 mg (0.70 mmol, 70%); eluent, pentane/
diethyl ether = 10:1; 1H NMR (300 MHz, CDCl3) δ 7.11 (s, 1H), 6.95
(s, 1H), 5.01 (s, 2H), 4.77 (s, 1H), 4.47 (s, 1H), 3.27 (s, 2H), 2.75 (s,
2H), 2.25−2.23 (m, 6H), 2.06 (s, 3H), 1.70 (s, 3H), 1.62−1.60 (m,
6H); 13C NMR (75 MHz, CDCl3) δ 170.9, 146.7, 136.8, 135.8, 134.5,
131.9, 131.5, 131.2, 126.4, 125.0, 111.4, 64.3, 41.4, 38.7, 21.0, 20.6,
20.4, 19.4, 19.2, 18.3; MS (EI) m/z (%) 300 (M+, 1), 240 (92), 225
(100), 210 (16), 197 (38), 183 (61), 170 (77), 157 (47), 141 (31),
128 (20), 115 (19), 105 (12), 91 (18), 77 (8), 67 (5), 55 (10); HRMS
(EI, ICP, m/z) calcd for C20H28O2 300.2089, found 300.2097; IR
(film, cm−1) 3466, 3077, 2980, 2919, 2861, 2728, 1742, 1643, 1506,
1451, 1376, 1331, 1228, 1119, 1073, 1022, 959, 895, 749, 631, 605.
(2-(4,5-Dimethyl-2-methylenehex-4-enyl)-4,5-dimethylphenyl)-
trimethylsilane (8e). colorless oil; 200 mg (0.67 mmol, 67%); eluent:
The 1,5-enyne 7m was prepared in two steps via Williamson’s ether
synthesis17 and subsequent functionalization of the terminal alkyne
subunit of 7n with ethyl carbonochloridate,18 whereas the sulfonamide
7o was obtained via tosylation of allylamine and subsequent
propargylation following a literature procedure.19
Ethyl 4-(Allyloxy)but-2-ynoate (7m): colorless liquid; 1.20 g (7.14
mmol, 47%, two steps); eluent, pentane/diethyl ether = 10:1; 1H
NMR (300 MHz, CDCl3) δ 5.94−5.82 (m, 1H), 5.32 (dq, J = 17.2, 1.6
Hz, 1H), 5.26−5.21 (m, 1H), 4.27−4.20 (m, 4H), 4.07 (d, J = 6.0 Hz,
2H), 1.30 (t, J = 6.99 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 153.1,
133.4, 118.4, 83.1, 78.1, 71.0, 62.1, 56.7, 14.0; MS (EI) m/z (%) 168
(M+, 2), 139 (4), 122 (4), 111 (30), 95 (30), 84 (45), 66 (100), 55
(67); HRMS (ESI, FT-ICR, m/z) calcd for C9H12O3Na 191.0679,
found 191.0680; IR (film, cm−1) 3477, 3084, 2985, 2941, 2906, 2860,
2236, 1716, 1649, 1466, 1447, 1384, 1367, 1251, 1157, 1096, 1057,
1019, 931, 863, 751.
1
pentane; H NMR (300 MHz, CDCl3) δ 7.24 (s, 1H), 6.97 (s, 1H),
4.82 (s, 1H), 4.50 (s, 1H), 3.36 (s, 2H), 2.77 (s, 2H), 2.26 (s, 3H),
2.24 (s, 3H), 1.71 (s, 3H), 1.64 (s, 3H), 1.62 (s, 3H), 0.29 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ 147.4, 142.5, 137.4, 135.8, 135.7, 133.2,
131.0, 126.3, 125.1, 111.9, 42.2, 41.7, 20.6, 20.4, 19.6, 19.3, 18.6, 0.4;
MS (EI) m/z (%) 300 (M+, 29), 285 (6), 257 (54), 241 (12), 227 (7),
211 (16), 201 (4), 183 (21), 173 (12), 161 (12), 143 (5), 133 (4), 119
General Procedure for the Tandem Diels−Alder/1,4-Hydro-
vinylation/DDQ Oxidation Sequence with 2,3-Dimethylbuta-
1,3-diene. Zinc iodide (20 mol %), zinc powder (20 mol %), and
CoBr2(1,2-bis(diphenylphosphino)ethane) (10 mol %) were sus-
pended in dichloromethane (1 mL) under argon atmosphere. Then
2,3-dimethyl-1,3-butadiene (2.4 mmol) and the enyne 7 (1.0 mmol)
8381
dx.doi.org/10.1021/jo301028b | J. Org. Chem. 2012, 77, 8375−8385

The Journal of Organic Chemistry
Featured Article
(10), 107 (11), 93 (2), 83 (18), 73 (100), 55 (14); HRMS (EI, ICP,
m/z) calcd for C20H32Si 300.2273, found 300.2260; IR (film, cm−1)
3079, 2918, 2861, 2728, 1768, 1643, 1604, 1550, 1489, 1448, 1407,
1379, 1330, 1248, 1179, 1119, 1021, 896, 837, 759, 713, 688, 646.
2-(4,5-Dimethyl-2-methylenehex-4-enyl)-3′-methoxy-4,5-dime-
thylbiphenyl (8f): colorless oil; 136 mg (0.41 mmol, 81%); eluent,
(75 MHz, CDCl3) δ 143.0, 141.4, 137.9, 136.4, 135.9, 133.2, 130.0,
129.5, 129.4, 127.3, 126.7, 126.3, 124.2, 112.8, 52.1, 50.5, 38.6, 21.5,
20.5, 20.3, 19.6, 19.4, 18.4; MS (EI) m/z (%) 411 (M+, 6), 292 (9),
256 (86), 240 (9), 225 (1), 212 (1), 184 (10), 171 (1), 155 (13), 136
(21), 119 (100), 107 (14), 91 (32), 77 (5), 65 (4), 53 (1); HRMS (EI,
ICP, m/z) calcd for C25H33NO2S 411.2232, found 411.2232; IR (film,
cm−1) 2921, 2860, 1649, 1598, 1505, 1448, 1341, 1305, 1215, 1160,
1119, 1094, 1072, 1020, 909, 815, 778, 752, 735, 708, 693, 656, 600,
547.
General Procedure for the Tandem Diels−Alder/1,4-Hydro-
vinylation Sequence with 2-(Trimethylsilyloxy)buta-1,3-diene.
Zinc iodide (20 mol %), zinc powder (20 mol %), and CoBr2(1,2-
bis(diphenylphosphino)ethane) (10 mol %) were suspended in
dichloromethane (1 mL) under argon atmosphere. Then 2-
(trimethylsilyloxy)buta-1,3-diene (2.4 mmol) and the enyne 7 (1.0
mmol) were added, and the mixture was stirred at room temperature
for 16 h. Afterward, the suspension was filtered over a short pad of
silica gel, and the solvent was removed under vacuum. The residue was
dissolved in tetrahydrofuran (8 mL) and was treated with aqueous
HCl (2 mL, 2 M). The mixture was stirred for 1 h at room
temperature and was then filtered over a short pad consisting of a silica
gel/MgSO4 mixture. The solvent was removed in vacuo, and the
residue was purified by flash column chromatography.
Methyl 2-(2-Methylene-5-oxohexyl)-4-oxocyclohex-1-enecarbox-
ylate (9a): pale yellow oil; 159 mg (0.60 mmol, 60%); eluent, diethyl
ether; 1H NMR (300 MHz, CDCl3) δ 4.78 (s, 1H), 4.73 (s, 1H), 3.71
(s, 3H), 3.36 (s, 2H), 3.18 (s, 2H), 2.62 (td, J = 7.5, 2.1 Hz, 2H), 2.51
(t, J = 6.4 Hz, 2H), 2.42−2.38 (m, 2H), 2.26 (t, J = 7.4 Hz, 2H), 2.15−
2.14 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 208.7, 207.9, 166.7,
148.9, 145.1, 123.4, 111.3, 51.6, 41.7, 41.0, 40.7, 37.5, 30.1, 29.9, 29.6;
MS (EI) m/z (%) 264 (M+, 2), 249 (7), 232 (29), 215 (8), 204 (4),
193 (100), 175 (42), 161 (21), 147 (36), 133 (22), 119 (25), 105
(31), 91 (29), 77 (17), 65 (8), 55 (6); HRMS (EI, ICP, m/z) calcd for
C15H20O4 264.1362, found 264.1366; IR (film, cm−1) 3417, 3079,
2952, 2905, 2844, 1716, 1642, 1435, 1361, 1322, 1233, 1190, 1162,
1095, 1058, 1022, 995, 953, 896, 847, 766, 634, 589.
1
pentane/diethyl ether = 10:1; H NMR (300 MHz, CDCl3) δ 7.29−
7.23 (m, 1H), 7.04 (d, J = 5.3 Hz, 2H), 6.90−6.85 (m, 3H), 4.76 (s,
1H), 4.51 (s, 1H), 3.81 (s, 3H), 3.17 (s, 2H), 2.64 (s, 2H), 2.29 (s,
6H), 1.64 (s, 3H), 1.52 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 159.2,
147.9, 143.2, 139.7, 135.4, 134.1, 134.0, 131.6, 131.1, 128.7, 126.1,
125.0, 121.7, 114.8, 112.2, 111.4, 55.2, 41.5, 39.4, 20.5, 20.3, 19.4, 19.3,
18.3; MS (EI) m/z (%) 334 (M+, 65), 319 (23), 304 (1), 291 (48),
276 (22), 263 (18), 250 (100), 236 (45), 223 (39), 210 (16), 195
(16), 178 (16), 165 (18), 152 (9), 141 (2), 128 (3), 107 (9), 91 (4),
79 (4), 67 (4), 55 (6); HRMS (EI, ICP, m/z) calcd for C24H30O
334.2297, found 334.2284; IR (film, cm−1) 3442, 2917, 1643, 1600,
1580, 1481, 1452, 1430, 1385, 1315, 1286, 1240, 1212, 1179, 1117,
1051, 1021, 985, 892, 859, 781, 753, 734, 703.
2-(2-(5, 6-Dimethyl-3-methylenehept-5-enyl)-4, 5-
dimethylphenyl)thiophene (8g): colorless oil; 110 mg (0.34 mmol,
1
68%); eluent, pentane; H NMR (300 MHz, CDCl3) δ 7.31 (dd, J =
5.3, 1.1 Hz, 1H), 7.17 (s, 1H), 7.08−7.06 (m, 2H), 7.00 (dd, J = 3.4,
1.1 Hz, 1H), 4.71 (s, 1H), 4.66 (s, 1H), 2.84−2.79 (m, 2H), 2.71 (s,
2H), 2.29 (s, 3H), 2.26 (s, 3H), 2.19−2.14 (m, 2H), 1.68 (s, 3H), 1.62
(s, 3H), 1.57 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 147.5, 142.9,
138.0, 136.5, 134.0, 132.3, 131.2, 131.0, 126.9, 126.0, 125.9, 125.2,
124.8, 109.5, 41.4, 37.8, 31.9, 20.6, 20.4, 19.4, 19.1, 18.3; MS (EI) m/z
(%) 324 (M+, 24), 281 (7), 254 (3), 239 (8), 225 (2), 213 (4), 201
(100), 186 (31), 171 (19), 152 (3), 141 (4), 123 (5), 109 (1), 93 (2),
81 (2), 67 (1), 55 (2); HRMS (EI, ICP, m/z) calcd for C22H28S
324.1912, found 324.1924; IR (film, cm−1) 3073, 2919, 2861, 2727,
1785, 1643, 1495, 1451, 1384, 1372, 1264, 1225, 1192, 1151, 1103,
1076, 1021, 886, 847, 830, 734, 694, 659.
2-(5,6-Dimethyl-3-methylenehept-5-enyl)-4′-methoxy-4,5-dime-
thylbiphenyl (8h): colorless oil; 173 mg (0.50 mmol, 99%); eluent,
1
pentane/diethyl ether = 20:1; H NMR (300 MHz, CDCl3) δ 7.24−
3-(3-Methylene-6-oxoheptyl)-4-(thiophen-2-yl)cyclohex-3-enone
(9b): orange oil; 70 mg (0.23 mmol, 46%); eluent, pentane/diethyl
7.22 (m, 2H), 7.06 (s, 1H), 7.00 (s, 1H), 6.95−6.92 (m, 2H), 4.63 (s,
1H), 4.61 (s, 1H), 3.86 (s, 3H), 2.71−2.67 (m, 2H), 2.64 (s, 2H), 2.30
(s, 3H), 2.27 (s, 3H), 2.12−2.06 (m, 2H), 1.67 (s, 3H), 1.59 (s, 3H),
1.53 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 158.4, 147.6, 139.0,
137.2, 135.3, 134.3, 133.8, 131.6, 130.6, 130.2, 125.8, 125.2, 113.4,
109.4, 55.3, 41.3, 37.7, 31.6, 20.6, 20.4, 19.4, 19.2, 18.2; MS (EI) m/z
(%) 348 (M+, 27), 305 (4), 278 (3), 263 (18), 250 (2), 237 (3), 225
(100), 210 (59), 195 (29), 179 (11), 165 (10), 152 (7), 115 (1), 93
(2), 79 (1), 67 (1), 55 (1); HRMS (EI, ICP, m/z) calcd for C25H32O
348.2453, found 348.2446; IR (film, cm−1) 2917, 2862, 1643, 1608,
1570, 1495, 1448, 1378, 1287, 1241, 1175, 1107, 1035, 965, 885, 832,
646, 564, 523, 488, 413.
1
ether = 1:1; H NMR (300 MHz, CDCl3) δ 7.27−7.24 (m, 1H),
7.02−6.98 (m, 1H), 6.88−6.85 (m, 1H), 4.74−4.66 (m, 2H), 3.20 (s,
1H), 3.01 (s, 1H), 2.80 (t, J = 6.8 Hz, 1H), 2.59−2.49 (m, 5H), 2.45−
2.32 (m, 2H), 2.25−2.10 (m, 7H); 13C NMR (75 MHz, CDCl3) δ
209.9, 209.5, 147.3, 142.9, 136.9, 133.5, 126.8, 125.3, 124.5, 109.8,
46.2, 43.9, 41.7, 38.6, 38.3, 34.7, 32.5, 29.5; MS (EI) m/z (%) 302
(M+, 20), 284 (3), 269 (2), 256 (3), 244 (7), 231 (9), 215 (4), 203
(4), 191 (100), 178 (7), 163 (16), 149 (19), 134 (13), 115 (10), 97
(11), 77 (5), 65 (4), 55 (5); HRMS (EI, ICP, m/z) calcd for
C18H22O2S 302.1341, found 302.1349; IR (film, cm−1) 3411, 3076,
2922, 2853, 2253, 1716, 1646, 1625, 1578, 1432, 1359, 1297, 1238,
1196, 1162, 1082, 1050, 964, 895, 842, 702, 588, 525.
Ethyl 2-((4,5-dimethyl-2-methylenehex-4-enyloxy)methyl)-4,5-di-
methylbenzoate (8i): colorless oil; 151 mg (0.46 mmol, 46%); eluent,
pentane/diethyl ether = 10:1; 1H NMR (300 MHz, CDCl3) δ 7.72 (s,
1H), 7.47 (s, 1H), 5.09 (s, 1H), 4.88 (s, 1H), 4.85 (s, 2H), 4.32 (q, J =
7.2 Hz, 2H), 3.98 (s, 2H), 2.82 (s, 2H), 2.31−2.25 (m, 6H), 1.68 (s,
3H), 1.66 (s, 3H), 1.62 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 167.2, 144.3, 141.4, 138.5, 135.0, 131.5, 128.8,
126.4, 125.6, 124.6, 111.6, 73.5, 69.8, 60.6, 38.4, 20.6, 20.4, 20.0, 19.2,
18.4, 14.3; MS (EI) m/z (%) 330 (M+, 1), 251 (5), 223 (2), 207 (6),
191 (28), 177 (7), 163 (100), 146 (25), 133 (9), 121 (13), 107 (40),
91 (19), 79 (13), 67 (5), 55 (6); HRMS (ESI, FT-ICR, m/z) calcd for
C21H30O3Na 353.2087, found 353.2101; IR (film, cm−1) 2981, 2919,
2860, 1713, 1650, 1615, 1565, 1052, 1449, 1385, 1367, 1301, 1267,
1230, 1190, 1137, 1097, 1050, 902, 782, 631.
4-((2-Methylene-5-oxohexyloxy)methyl)cyclohex-3-enone (9c):
yellow oil; 110 mg (0.47 mmol, 47%); eluent, diethyl ether; 1H
NMR (300 MHz, CDCl3) δ 5.73 (s, 1H), 5.02 (s, 1H), 4.87 (s, 1H),
3.89 (s, 4H), 2.88 (s, 2H), 2.66−2.59 (m, 2H), 2.52−2.48 (m, 4H),
2.33 (t, J = 7.4 Hz, 2H), 2.15 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
210.0, 207.9, 144.6, 135.6, 121.1, 112.0, 73.2, 73.0, 41.6, 39.3, 38.3,
29.8, 26.9, 26.0; MS (EI) m/z (%) 236 (M+, 1), 178 (1), 160 (1), 125
(10), 111 (100), 97 (32), 79 (62), 53 (25); HRMS (ESI, FT-ICR, m/
z) calcd for C14H20O3Na 259.1305, found 259.1308; IR (film, cm−1)
3465, 3080, 2918, 2852, 1716, 1654, 1424, 1359, 1230, 1192, 1161,
1086, 1051, 962, 903, 809, 783, 589.
4-Methyl-N-(2-methylene-5-oxohexyl)-N-((4-oxocyclohex-1-
enyl)methyl)benzene-sulfonamide (9d): colorless oil; 180 mg (0.46
1
mmol, 46%); eluent, diethyl ether; H NMR (300 MHz, CDCl3) δ
N-(4,5-Dimethyl-2-methylenehex-4-enyl)-N-(3,4-dimethylbenzyl)-
4-methylbenzene Sulfonamide (8j): colorless oil; 268 mg (0.65
7.68 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 5.56 (s, 1H), 4.86
(s, 1H), 4.84 (s, 1H), 3.70 (s, 4H), 2.82−2.81 (m, 2H), 2.54 (t, J = 7.4
Hz, 2H), 2.42 (s, 3H), 2.41−2.34 (m, 4H), 2.23−2.18 (m, 2H), 2.13
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 209.5, 207.4, 143.5, 143.1,
136.7, 133.8, 129.7, 127.3, 123.2, 113.9, 53.2, 53.1, 41.3, 39.3, 38.1,
29.8, 26.9, 26.3, 21.5; MS (EI) m/z (%) 389 (M+, 1), 281 (1), 263 (5),
1
mmol, 70%); eluent, pentane/diethyl ether = 10:1; H NMR (300
MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H),
6.84 (d, J = 7.6 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 6.80 (s, 1H), 4.77
(s, 1H), 4.73 (s, 1H), 4.28 (s, 2H), 3.68 (s, 2H), 2.55 (s, 2H), 2.43 (s,
3H), 2.20 (s, 3H), 2.14 (s, 3H), 1.64 (s, 3H), 1.49 (s, 6H); 13C NMR
8382
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Featured Article
248 (3), 238 (1), 224 (17), 198 (2), 184 (3), 172 (1), 155 (57), 139
(8), 126 (100), 109 (33), 91 (75), 81 (11), 65 (20), 55 (3); HRMS
(ESI, FT-ICR, m/z) calcd for C21H27NO4SNa 412.1553, found
412.1552; IR (film, cm−1) 3412, 2922, 1716, 1652, 1598, 1495, 1442,
1339, 1036, 1290, 1190, 1160, 1094, 1035, 1019, 987, 911, 817, 770,
710, 657, 586, 549.
136.6, 132.4, 131.7, 110.8, 104.8, 60.8, 56.1, 45.7, 41.6, 40.7, 38.5, 29.8,
29.6, 28.6; MS (EI) m/z (%) 372 (19, M+), 301 (58), 270 (22), 140
(16), 97 (51), 83 (75), 43 (100); HRMS (EI, ICP, m/z) calcd for
C22H28O5 372.1937, found 372.1939; IR (film, cm−1) 2939, 1715,
1581, 1506, 1452, 1412, 1363, 1241, 1167, 1127, 1007, 896, 840, 756.
4-[2-(3-Oxobutyl)prop-2-en-1-yl]-3-phenylcyclohex-3-en-1-one
(11h): yellow oil; 192 mg (0.68 mmol, 68%); eluent, pentane/ethyl
4-(4-Methoxyphenyl)-3-(3-methylene-6-oxoheptyl)cyclohex-3-
1
enone (9e): pale yellow oil; 107 mg (0.33 mmol, 66%); eluent,
acetate = 3:1; H NMR (300 MHz, CDCl3) δ 7.38−7.29 (m, 2H),
1
pentane/diethyl ether = 1:1; H NMR (300 MHz, CDCl3) δ 7.08−
7.29−7.22 (m, 1H), 7.18−7.11 (m, 2H), 4.83−4.76 (m, 2H), 3.16 (s,
2H), 2.76 (s, 2H), 2.60−2.45 (m, 4H), 2.39−2.32 (m, 2H), 2.19−2.12
(m, 2H), 2.06 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 210.2, 207.8,
146.1, 141.0, 132.4, 131.7, 128.4, 127.7, 127.0, 111.0, 45.7, 41.6, 40.3,
38.6, 29.8, 29.7, 28.5; MS (EI) m/z (%) 282 (12, M+), 264 (8), 249
(8), 224 (16), 211 (100), 193 (34), 181 (52), 167 (80), 155 (80), 141
(41), 128 (44), 115 (34); HRMS (EI, ICP, m/z) calcd for C19H22O2
282.1620, found 282.1631; IR (film, cm−1) 2915, 1716, 1442, 1361,
1161, 895, 759, 704.
7.02 (m, 2H), 6.90−6.85 (m, 2H), 4.63−4.61 (m, 2H), 3.81 (s, 3H),
2.97 (s, 2H), 2.69 (t, J = 6.6 Hz, 2H), 2.59−2.54 (m, 2H), 2.45−2.40
(m, 2H), 2.14−2.04 (m, 9H); 13C NMR (75 MHz, CDCl3) δ 210.7,
208.0, 158.4, 147.4, 134.3, 133.7, 130.2, 129.0, 113.7, 109.7, 55.2, 43.3,
41.7, 38.9, 34.7, 32.2, 32.0, 29.8, 29.4; MS (EI) m/z (%) 326 (M+, 92),
308 (1), 268 (23), 255 (24), 237 (4), 225 (8), 215 (100), 197 (14),
187 (14), 173 (35), 159 (30), 141 (12), 128 (19), 115 (22), 103 (5),
91 (9), 77 (7), 65 (2), 55 (14); HRMS (EI, ICP, m/z) calcd for
C21H26O3 326.1882, found 326.1872; IR (film, cm−1) 2915, 2844,
2359, 1711, 1647, 1606, 1508, 1444, 1357, 1288, 1242, 1175, 1111,
1031, 952, 890, 829, 556, 506.
4-[3-(3-Oxobutyl)but-3-en-1-yl]-3-phenylcyclohex-3-en-1-one
(11i): yellow oil; 186 mg (0.63 mmol, 55%); eluent, pentane/ethyl
1
acetate = 3:1; H NMR (300 MHz, CDCl3) δ 7.39−7.29 (m, 2H),
7.29−7.20 (m, 1H), 7.15−7.08 (m, 2H), 4.67−4.56 (m, 2H), 3.10 (s,
2H), 2.56 (s, 4H), 2.46−2.37 (m, 2H), 2.21−2.01 (m, 9H); 13C NMR
(75 MHz, CDCl3) δ 210.3, 208.0, 147.5, 141.3, 133.8, 131.0, 128.4,
128.0, 126.8, 109.6, 45.8, 41.6, 38.6, 34.9, 32.1, 29.8, 29.4, 28.9; MS
(EI) m/z (%) 296 (12, M+), 278 (20), 238 (22), 225 (20), 185 (68),
167 (43), 141 (46), 128 (74), 115 (43), 55 (100); HRMS (EI, ICP,
m/z) calcd for C20H24O2 296.1776, found 296.1785; IR (film, cm−1)
2918, 1710, 1439, 1358, 1160, 890, 757, 702.
General Procedure for the Sequential Diels−Alder/1,4-
Hydrovinylation Sequence with 2,3-Dimethylbuta-1,3-diene
and 2-(Trimethylsilyloxy)buta-1,3-diene. Zinc iodide (20 mol %),
zinc powder (20 mol %), iron powder (20 mol %), and CoBr2(2,4,6-
trimethylphenyl-N-(pyridin-2-ylmethylene)aniline) (10 mol %) were
suspended in dichloromethane (1 mL) under argon atmosphere. Then
2,3-dimethylbuta-1,3-diene or 2-(trimethylsilyloxy)buta-1,3-diene
(1.2−1.5 mmol) and the enyne 7 (1.0 mmol) were added, and the
mixture was stirred at room temperature for 16 h. Then the suspension
was further treated with zinc iodide (20 mol %), zinc powder (20 mol
%), CoBr2(1,2-bis(diphenylphosphino)ethane) (10 mol %), and the
other 1,3-diene (1.2−1.5 mmol) followed by stirring for 16 h at room
temperature. Afterward, the suspension was filtered over a short pad of
silica gel, and the solvent was removed under vacuum. If 2,3-
dimethylbuta-1,3-diene was used in the first case, the residue was
oxidized by DDQ as described in the appropriate general procedure
above. In the other case, hydrolysis was performed utilizing a buffered
KF solution as described in the general procedure above.
Methyl 4,5-Dimethyl-2-(2-methylene-5-oxohexyl)benzoate (17a):
yellow oil; 140 mg (0.51 mmol, 51%); eluent, pentane/diethyl ether =
1:1; 1H NMR (300 MHz, CDCl3) δ 7.66 (s, 1H), 6.99 (s, 1H), 4.73 (s,
1H), 4.44 (s, 1H), 3.83 (s, 3H), 3.66 (s, 2H), 2.64−2.59 (m, 2H),
2.34−2.29 (m, 2H), 2.26−2.25 (m, 6H), 2.14 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 208.4, 168.0, 148.3, 141.0, 138.2, 134.5, 132.9, 131.8,
127.3, 110.5, 51.7, 41.9, 39.9, 30.2, 29.8, 19.7, 19.1; MS (EI) m/z (%)
274 (M+, 1), 256 (19), 242 (14), 224 (36), 199 (100), 185 (34), 171
(32), 156 (26), 141 (20), 115 (13), 91 (10), 77 (6), 59 (3); HRMS
(EI, ICP, m/z) calcd for C17H22O3 274.1569, found 274.1577; IR
(film, cm−1) 3415, 2949, 1719, 1672, 1647, 1615, 1596, 1563, 1503,
1435, 1359, 1295, 1268, 1237, 1190, 1140, 1047, 1003, 955, 893, 834,
792.
General Procedure for the Sequential Diels−Alder/1,4-
Hydrovinylation Sequence with 2-(Trimethylsilyloxy)buta-
1,3-diene. Zinc iodide (20 mol %), zinc powder (20 mol %), and
CoBr2(2,4,6-trimethylphenyl-N-(pyridin-2-ylmethylene)aniline) (10
mol %) were suspended in dichloromethane (1 mL) under argon
atmosphere. Then 2-(trimethylsilyloxy)buta-1,3-diene (1.5 mmol) and
the enyne 7 (1 mmol) were added, and the mixture was stirred at
room temperature for 16 h. Then the suspension was treated with
further zinc iodide (20 mol %), zinc powder (20 mol %), CoBr2(1,2-
bis(diphenylphosphino)ethane) (10 mol %), and 2-
(trimethylsilyloxy)buta-1,3-diene (1.5 mmol) followed by stirring for
16 h at room temperature. The mixture was taken up in THF/water
(5:1, 10 mL) and treated with tetrabutylammonium bromide (200 mg,
0.62 mmol) and a saturated aqueous solution of KF (2 mL; buffered to
pH = 7 by addition of 1 M acetic acid). The suspension was stirred for
1 h at room temperature, and the phases were separated. The aqueous
phase was extracted twice with diethyl ether (20 mL), and the
combined organic phases were washed with brine (20 mL) and dried
over MgSO4. After filtration, the solvent was removed in vacuo and the
residue was purified by flash column chromatography.
3-(4-Methoxyphenyl)-4-(3-methylene-6-oxoheptyl)cyclohex-3-
enone (11e): yellow oil; 121 mg (0.37 mmol, 37%); eluent, pentane/
1
ethyl acetate = 3:1; H NMR (300 MHz, CDCl3) δ 7.06−6.99 (m,
2H), 6.89−6.82 (m, 2H), 4.66−4.55 (m, 2H), 3.78 (s, 3H), 3.06 (s,
2H), 2.52 (s, 4H), 2.45−2.37 (m, 2H), 2.21−1.98 (m, 9H); 13C NMR
(75 MHz, CDCl3) δ 210.4, 208.0, 158.3, 147.5, 133.6, 130.4, 129.03,
128.96, 113.7, 109.5, 55.1, 45.9, 41.6, 38.5, 34.9, 32.1, 29.7, 29.4, 28.8;
MS (EI) m/z (%) 326 (M+, 14), 295 (7), 253 (8), 215 (100), 197 (8),
171 (21), 159 (13), 115 (11); HRMS (ESI, FT-ICR, m/z) calcd for
C21H26O3Na 349.1774, found 349.1777; IR (film, cm−1) 1712, 1607,
1510, 1442, 1359, 1287, 1245, 1176, 1161, 1034, 891, 834, 733, 702.
3-(3-Methoxyphenyl)-4-[2-(3-oxobutyl)prop-2-en-1-yl]cyclohex-
3-en-1-one (11f): yellow oil; 218 mg (0.70 mmol, 70%); eluent,
1
pentane/ethyl acetate = 3:1; H NMR (300 MHz, CDCl3) δ 7.28−
7.19 (m, 1H), 6.80 (ddd, J = 8.3, 2.6, 0.9 Hz, 1H), 6.73 (dt, J = 7.6, 1.4
Hz, 1H), 6.69 (dd, J = 2.4, 1.6 Hz, 1H), 4.87−4.73 (m, 2H), 3.78 (s,
3H), 3.15 (s, 2H), 2.77 (s, 2H), 2.58−2.44 (m, 4H), 2.42−2.34 (m,
2H), 2.20−2.12 (m, 2H), 2.07 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
210.2, 207.8, 159.5, 146.2, 142.4, 132.3, 131.7, 129.4, 120.1, 113.4,
112.5, 111.0, 55.1, 45.6, 41.6, 40.4, 38.6, 29.8, 29.7, 28.5; MS (EI) m/z
(%) 312 (M+, 6), 254 (10), 241 (100), 211 (23), 185 (44), 171 (18),
115 (20), 83 (36); HRMS (EI, ICP, m/z) calcd for C20H24O3
312.1725, found 312.1728; IR (film, cm−1) 2939, 1716, 1598, 1577,
1485, 1427, 1360, 1286, 1265, 1211, 1163, 1046, 893, 788, 704.
4-[2-(3-Oxobutyl)prop-2-en-1-yl]-3-(3,4,5-trimethoxyphenyl)-
cyclohex-3-en-1-one (11g): yellow oil; 246 mg (0.66 mmol, 82%);
5-((4′-Fluoro-4,5-dimethylbiphenyl-2-yl)methyl)hex-5-en-2-one
(17b): yellow oil; 48 mg (0.16 mmol, 31%); eluent, pentane/diethyl
1
ether = 5:1; H NMR (300 MHz, CDCl3) δ 7.48−7.41 (m, 2H),
7.30−7.23 (m, 2H), 7.21 (s, 1H), 7.20 (s, 1H), 4.97 (s, 1H), 4.74 (s,
1H), 3.40 (s, 2H), 2.62−2.57 (m, 2H), 2.49 (s, 3H), 2.47 (s, 3H),
2.38−2.33 (m, 2H), 2.28 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
208.0, 161.9 (d, JCF = 243.8 Hz), 148.2, 138.7, 137.6 (d, JCF = 3.8 Hz),
135.7, 134.5, 133.6, 131.6, 131.3, 130.7 (d, JCF = 7.5 Hz), 114.7 (d, JCF
= 20.3 Hz), 111.5, 41.7, 39.4, 29.8, 29.7, 19.3, 19.2; MS (EI) m/z (%)
310 (M+, 40), 295 (3), 277 (4), 267 (3), 252 (19), 239 (100), 225
(27), 211 (49), 196 (22), 183 (31), 170 (4), 157 (2), 146 (1), 133 (2),
1
eluent, pentane/ethyl acetate = 3:2; H NMR (300 MHz, CDCl3) δ
6.36 (s, 2H), 4.85−4.76 (m, 2H), 3.83 (s, 3H), 3.81 (s, 6H), 3.16 (s,
2H), 2.78 (s, 2H), 2.56−2.37 (m, 6H), 2.21−2.15 (m, 2H), 2.08 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 210.1, 207.7, 153.1, 146.4, 136.9,
8383
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Featured Article
109 (2), 97 (2), 77 (1), 65 (1), 53 (1); HRMS (EI, ICP, m/z) calcd
for C21H23FO 310.1733, found 310.1720; IR (film, cm−1) 3077, 2920,
1714, 1646, 1601, 1493, 1443, 1357, 1295, 1221, 1157, 1092, 1017,
971, 889, 839, 754, 650, 620, 562, 530, 419.
temperature and was stirred for additional 3−15 h after which it was
directly subjected to column chromatography for isolation of the
respective BF2 complex.
1-Phenyldodecane-1,3,6,8,11-pentone BF2 Complex (19a): yellow
solid; 45 mg (0.11 mmol, 23%); eluent, ethyl acetate/pentane = 2:1;
4-(4,5-Dimethyl-2-methylenehex-4-enyl)-3-(4-fluorophenyl)-
1
cyclohex-3-enone (17c): yellow oil; 155 mg (0.50 mmol, 99%);
mp = 106 °C; H NMR (300 MHz, CDCl3) δ 8.11−8.03 (m, 2H),
1
eluent, pentane/diethyl ether = 5:1; H NMR (300 MHz, CDCl3) δ
7.75−7.63 (m, 1H), 7.58−7.48 (m, 2H), 6.65 (s, 1H), 6.11 (s, 1H),
3.09−2.94 (m, 4H), 2.91−2.83 (m, 2H), 2.81−2.73 (m, 2H), 2.14 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 205.2, 196.1, 190.9, 190.7, 184.3,
135.9, 131.0, 129.4, 129.3, 101.5, 97.4, 38.0, 32.7, 32.4, 31.3, 29.4; 11B
NMR (128 MHz, CDCl3) δ 0.6, 0.3; 19F NMR (282 MHz, CDCl3) δ
−138.7, −139.2; HRMS (ESI, FT-ICR, m/z) calcd for
C18H18B2F4O5Na 435.1170, found 435.1172; IR (KBr, cm−1) 3156,
2921, 1713, 1542, 1493, 1416, 1396, 1377, 1162, 1045, 986, 823, 785.
1-(4-Methoxyphenyl)-dodecane-1,3,6,8,11-pentone BF2 Complex
(19b): yellow solid; 78 mg (0.18 mmol, 36%); eluent, ethyl acetate/
7.16−7.12 (m, 2H), 7.04−6.97 (m, 2H), 4.81 (s, 1H), 4.76 (s, 1H),
3.16 (s, 2H), 2.66 (s, 2H), 2.63 (s, 2H), 2.58−2.49 (m, 4H), 1.64 (s,
3H), 1.57 (s, 3H), 1.54 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 210.3,
161.8 (d, JCF = 244.5 Hz), 145.7, 136.9 (d, JCF = 3.0 Hz), 132.8, 131.0,
129.2 (d, JCF = 8.3 Hz), 126.5, 124.6, 115.2 (d, JCF = 21.0 Hz), 110.5,
45.6, 41.7, 40.3, 38.6, 28.9, 20.5, 20.4, 18.3; MS (EI) m/z (%) 312
(M+, 57), 297 (20), 283 (4), 269 (100), 255 (33), 242 (33), 227 (39),
213 (32), 199 (57), 185 (79), 172 (40), 159 (72), 146 (72), 133 (59),
121 (24), 109 (77), 91 (24), 77 (14), 67 (16), 55 (17); HRMS (EI,
ICP, m/z) calcd for C21H25FO 312.1889, found 312.1908; IR (film,
cm−1) 3072, 2981, 2911, 2859, 1716, 1642, 1599, 1506, 1435, 1364,
1296, 1223, 1156, 1103, 1018, 969, 894, 836, 730, 650, 559, 497.
4-(4,5-Dimethyl-2-methylenehex-4-en-1-yl)-3-phenylcyclohex-3-
en-1-one (17d): yellow oil; 442 mg (1.50 mmol, 74%); eluent,
1
pentane = 2:1; mp = 118−119 °C; H NMR (300 MHz, CDCl3) δ
7.63 (d, J = 8.3 Hz, 1H), 7.57−7.52 (m, 1H), 7.42 (t, J = 8.1 Hz, 1H),
7.24−7.19 (m, 1H), 6.63 (s, 1H), 6.11 (s, 1H), 3.86 (s, 3H), 3.08−
2.94 (m, 4H), 2.91−2.84 (m, 2H), 2.80−2.74 (m, 2H), 2.14 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 205.2, 196.1, 190.9, 190.8, 184.1, 160.1,
132.3, 130.2, 122.8, 122.0, 113.1, 101.5, 97.6, 55.6, 38.0, 32.6, 32.4,
31.3, 29.4; 11B NMR (128 MHz, CDCl3) δ 0.8, 0.5; 19F NMR (282
MHz, CDCl3) δ −138.6, −139.1; HRMS (ESI, FT-ICR, m/z) calcd
for C19H20B2F4O6Na 465.1281, found 465.1276; IR (KBr, cm−1) 3151,
2919, 1719, 1542, 1495, 1469, 1436, 1388, 1255, 1055, 983, 817, 739.
1-Phenyltridecane-1,3,6,9,12-pentaone BF2 Complex (19c).
brown oil; 9 mg (0.024 mmol, 20%); eluent, ethyl acetate/pentane
= 2:1; 1H NMR (300 MHz, CDCl3) δ 8.12−8.02 (m, 2H), 7.73−7.64
(m, 1H), 7.58−7.49 (m, 2H), 6.63 (s, 1H), 3.04−2.96 (m, 2H), 2.95−
2.87 (m, 2H), 2.84−2.76 (m, 2H), 2.76−2.68 (m, 6H), 2.16 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 207.8, 207.0, 206.6, 194.1, 182.9, 135.4,
131.3, 129.13, 129.09, 97.1, 37.6, 37.0, 36.3, 35.9, 35.8, 31.6, 29.8; 11B
NMR (128 MHz, CDCl3) δ 0.8; 19F NMR (282 MHz, CDCl3) δ
−139.1; HRMS (ESI, FT-ICR, m/z) calcd for C19H21BF2O5Na
401.1346, found 401.1342; IR (film, cm−1) 2922, 2855, 1709, 1594,
1535, 1494, 1453, 1368, 1313, 1172, 1086, 1052, 997, 784, 714, 689.
1-Phenyltridecane-1,3,6,9,12-pentaone (18c): colorless solid; 79
mg (0.24 mmol, 59%); eluent, pentane/ethyl acetate = 1:1; mp = 77−
1
pentane/diethyl ether = 4:1; H NMR (300 MHz, CDCl3) δ 7.37−
7.29 (m, 2H), 7.29−7.22 (m, 1H), 7.22−7.14 (m, 2H), 4.88−4.71 (m,
2H), 3.20 (s, 2H), 2.70 (s, 2H), 2.64 (s, 2H), 2.60−2.43 (m, 4H), 1.64
(s, 3H), 1.57 (s, 3H), 1.54 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
210.6, 145.7, 141.0, 132.3, 131.9, 128.3, 127.6, 126.9, 126.4, 124.7,
110.5, 45.6, 41.6, 40.3, 38.7, 28.9, 20.5, 20.4, 18.3; MS (EI) m/z (%)
294 (19, M+), 251 (34), 224 (30), 181 (24), 167 (31), 155 (100), 128
(60), 115 (63); HRMS (EI, ICP, m/z) calcd for C21H26O 294.1984,
found 294.1981; IR (film, cm−1) 2916, 1718, 1680, 1443, 1372, 1195,
894, 761, 702.
4-(5,6-Dimethyl-3-methylenehept-5-en-1-yl)-3-phenylcyclohex-3-
en-1-one (17e): yellow oil; 197 mg (0.64 mmol, 64%); eluent,
1
pentane/diethyl ether = 5:1; H NMR (300 MHz, CDCl3) δ 7.38−
7.30 (m, 2H), 7.29−7.22 (m, 1H), 7.16−7.09 (m, 2H), 4.70−4.54 (m,
2H), 3.12 (s, 2H), 2.66−2.49 (m, 6H), 2.24−2.13 (m, 2H), 2.08−1.97
(m, 2H), 1.65 (s, 3H), 1.53 (s, 3H), 1.51 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 210.5, 147.2, 141.4, 134.2, 130.7, 128.4, 128.1, 126.8, 126.0,
125.0, 109.9, 45.9, 41.0, 38.6, 34.4, 32.4, 28.8, 20.6, 20.4, 18.2; MS (EI)
m/z (%) 308 (15, M+), 265 (20), 224 (40), 183 (100), 165 (36), 141
(48), 129 (38); HRMS (EI, ICP, m/z) calcd for C22H28O 308.2140,
found 308.2123; IR (film, cm−1) 2922, 1715, 1671, 1443, 1266, 892,
761, 702.
1
78 °C; H NMR (300 MHz, CDCl3) δ 15.77 (bs, 0.7H), 8.00−7.81
(m, 2H), 7.62−7.38 (m, 3H), 6.18 (s, 0.7H), 4.13 (s, 0.2H), 3.34−3.27
(m, 0.2H), 2.99−2.58 (m, 11.6H), 2.22−2.08 (m, 3H); 13C NMR (75
MHz, CDCl3) δ 207.8, 207.6, 207.0, 197.7, 180.0, 134.2, 132.1, 128.5,
126.8, 96.3, 37.0, 36.9, 36.1, 36.04, 35.98, 33.4, 29.8 (enol form only);
HRMS (ESI, FT-ICR, m/z) calcd for C19H22O5Na 353.1359, found
353.1369; IR (film, cm−1) 2910, 1696, 1626, 1576, 1458, 1408, 1357,
1327, 1276, 1094, 1074, 759, 688.
4-(5,6-Dimethyl-3-methylenehept-5-enyl)-3-(4-methoxyphenyl)-
cyclohex-3-enone (17f): yellow oil; 94 mg (0.28 mmol, 56%); eluent,
1
pentane/diethyl ether = 4:1; H NMR (300 MHz, CDCl3) δ 7.07−
7.04 (m, 2H), 6.89−6.86 (m, 2H), 4.62−4.61 (m, 2H), 3.81 (s, 3H),
3.09 (s, 2H), 2.60 (s, 2H), 2.54 (s, 4H), 2.22−2.17 (m, 2H), 2.05−
1.99 (m, 2H), 1.65 (s, 3H), 1.54 (s, 3H), 1.52 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 210.8, 158.4, 147.2, 134.0, 133.7, 130.1, 129.2, 126.0,
125.0, 113.8, 109.9, 55.2, 46.1, 41.0, 38.6, 34.4, 32.4, 28.8, 20.6, 20.4,
18.2; MS (EI) m/z (%) 338 (M+, 38), 323 (1), 307 (2), 295 (28), 280
(5), 268 (6), 254 (25), 240 (4), 227 (6), 215 (100), 202 (23), 187 (7),
171 (27), 159 (16), 145 (8), 128 (12), 115 (13), 103 (2), 91 (8), 77
(6), 55 (21); HRMS (EI, ICP, m/z) calcd for C23H30O2 338.2246,
found 338.2262; IR (film, cm−1) 3328, 2912, 2851, 1713, 1668, 1605,
1508, 1447, 1366, 1289, 1244, 1177, 1111, 1033, 889, 833, 563, 512,
414.
1-Phenyldodecane-1,3,6,9,11-pentone BF2 Complex (19d): or-
ange solid; 101 mg (0.25 mmol, 38%); eluent, ethyl acetate/pentane =
1
2:1; mp = 108−109 °C; H NMR (400 MHz, CDCl3) δ 8.04 (d, J =
7.3 Hz, 2H), 7.67 (t, J = 7.4 Hz, 2H), 7.55−7.47 (m, 2H), 6.66 (s,
1H), 6.02 (s, 1H), 3.02−2.88 (m, 6H), 2.79 (t, J = 6.4 Hz, 2H), 2.27
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 205.4, 193.8, 193.5, 192.8,
182.9, 135.5, 131.1, 129.2, 129.0, 101.4, 97.2, 37.0, 36.8, 31.5, 30.9,
24.1; 11B NMR (128 MHz, CDCl3) δ 0.8, 0.5; 19F NMR (376 MHz,
CDCl3) δ −138.1, −138.7; HRMS (ESI, FT-ICR, m/z) calcd for
C18H18B2F4O5Na 435.1170, found 435.1167; IR (KBr, cm−1) 3156,
2917, 1717, 1558, 1494, 1391, 1181, 1051, 822, 792, 709, 681.
1-Phenylundecane-1,3,6,8,10-pentaone (18e): pale yellow solid;
26 mg (0.086 mmol, 18%); eluent, pentane/ethyl acetate/methanol =
General Procedure for the Ozonolysis Reaction and BF2
Complexation. The polyene was dissolved in dichloromethane (0.1
M), and the solution was cooled to −78 °C. A mixture of oxygen and
ozone was bubbled through the solution until a blue color appeared.
The mixture was purged with oxygen for 5−10 min to obtain a
colorless or slightly yellowish solution, which was directly treated with
triphenyl phosphine (1.1 equiv per double bond) and allowed to warm
to room temperature. After 30 min of stirring, the mixture was purged
with argon for 5−10 min and cooled to −78 °C. BF3 etherate (3 equiv
per 1,3-dicarbonyl unit) and triethylamine (1 equiv per 1,3-dicarbonyl
unit) were added, and the mixture was stirred for 30 min to form a
colorless precipitate. The mixture was allowed to warm slowly to room
1
66:32:1; mp = 51−53 °C; H NMR (300 MHz, CDCl3) δ 15.99−
15.62 (m, 0.7H), 15.37−14.89 (m, 0.6H), 14.34−14.07 (m, 0.3H),
7.99−7.79 (m, 2H), 7.65−7.39 (m, 3H), 6.24−6.16 (m, 0.8H), 5.65−
5.54 (m, 0.7H), 5.30−5.13 (m, 0.4H), 4.18−4.12 (m, 0.2H), 3.81−
3.67 (m, 0.3H), 3.53−3.33 (m, 1.5H), 2.99−2.53 (m, 4.1H), 2.29−
1.93 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 202.5, 197.5, 196.5,
195.6, 194.9, 193.8, 190.8, 187.0, 183.4, 182.0, 180.9, 179.8, 179.4,
178.9, 134.1, 133.8, 132.33, 132.29, 132.2, 128.8, 128.6, 126.94,
126.88, 126.8, 101.1, 100.8, 98.8, 98.3, 96.3, 96.2, 57.5, 57.2, 53.7, 53.6,
53.1, 52.9, 37.8, 37.6, 36.9, 36.8, 35.6, 34.3, 33.6, 33.5, 30.9, 30.3, 24.5,
8384
dx.doi.org/10.1021/jo301028b | J. Org. Chem. 2012, 77, 8375−8385

The Journal of Organic Chemistry
Featured Article
21.8 (resolved signals of all possible tautomers); HRMS (ESI, FT-ICR,
m/z) calcd for C17H18O5Na 325.1046, found 325.1046; IR (film,
cm−1) 2913, 1721, 1595, 1392, 1298, 1134, 754, 688.
T.; Wang, C.-C.; Cheng, C.-H. J. Am. Chem. Soc. 2007, 129, 12032.
(k) Grutters, M. M. P.; Muller, C.; Vogt, D. J. Am. Chem. Soc. 2006,
̈
128, 7414. (l) Wang, C.-C.; Lin, T.-S.; Cheng, C.-H. J. Am. Chem. Soc.
2002, 124, 9696.
(7) dppe = 1,2-bis(diphenylphosphino)ethane.
ASSOCIATED CONTENT
■
(8) (a) Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett.
1982, 23, 885. (b) Horita, K.; Yoshioka, T.; Tanaka, T.; Oikawa, Y.;
Yonemitsu, O. Tetrahedron 1986, 42, 3021.
(9) Arndt, M.; Dindaroglu, M.; Schmalz, H.-G.; Hilt, G. Org. Lett.
̆
2011, 13, 6236.
S
* Supporting Information
1H and 13C NMR spectra for selected compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(10) Kuttner, J. R.; Warratz, S.; Hilt, G. Synthesis 2012, 44, 1293.
(11) py-imine = 2,4,6-trimethylphenyl-N-(pyridin-2-ylmethylene)
aniline.
(12) Kersten, L.; Hilt, G. Adv. Synth. Catal. 2012, 354, 863.
(13) Bieber, L. W.; da Silva, M. F. Tetrahedron Lett. 2007, 48, 7088.
(14) Snider, B. B.; Zhou, J. Org. Lett. 2006, 8, 1283.
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7871.
(16) Horino, Y.; Nakashima, Y.; Hashimoto, K.; Kuroda, S. Synlett
2010, 2879.
(17) Pandey, G.; Sekhar, B. B. V. S. Tetrahedron 1995, 51, 1483.
(18) Zhao, L.; Lu, X.; Xu, W. J. Org. Chem. 2005, 70, 4059.
(19) Patel, M. C.; Livinghouse, T.; Pagenkopf, B. L. Org. Synth. 2003,
80, 93.
AUTHOR INFORMATION
Corresponding Author
*E-mail: hilt@chemie.uni-marburg.de.
■
ACKNOWLEDGMENTS
■
We thank the Fonds der Chemischen Industrie for a fellowship
(F.E.) and the Deutsche Forschungsgemeinschaft for financial
support.
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