Palladium-catalyzed alkoxycarbonylation of conjugated enyne oxiranes: A diastereoselective method for the synthesis of 7-hydroxy-2,3,5-trienoates

Article abstract of DOI:10.1021/acs.joc.5b00382

Palladium-catalyzed alkoxycarbonylative 1,5-substitution of conjugated enyne oxiranes provides a diastereoselective route to (E)-configured 7-hydroxy-2,3,5-trienoates. The reactions proceeded in a highly stereoselective manner, possibly through sequential

Full text of DOI:10.1021/acs.joc.5b00382

Article
pubs.acs.org/joc
Palladium-Catalyzed Alkoxycarbonylation of Conjugated
Enyne Oxiranes: A Diastereoselective Method for the Synthesis
of 7‑Hydroxy-2,3,5-trienoates
Melih Kus,† Levent Artok,*,† and Muhittin Aygun‡
̧
̈
†Department of Chemistry, Faculty of Science, Izmir Institute of Technology, Urla, 35430 Izmir, Turkey
‡Department of Physics, Faculty of Science, Dokuz Eylul University, Buca, Izmir, Turkey
S
* Supporting Information
ABSTRACT: Palladium-catalyzed alkoxycarbonylative 1,5-substitution of conjugated enyne oxiranes provides a diastereose-
lective route to (E)-configured 7-hydroxy-2,3,5-trienoates. The reactions proceeded in a highly stereoselective manner, possibly
through sequential formation of π-allylpalladium and σ-vinylallenyl palladium complexes. The major diastereomeric form of the
product is determined by the configuration of the alkenyl moiety of the substrate.
Encouraged by these findings, we have decided to extend
the methodology to enyne oxiranes in order to obtain more
functionalized vinylallene structures. To the best of our
knowledge, the only coupling method that involved the use
of enyne oxiranes was their reactions with organocuprates,
which led to alkyl-substituted vinylallenes that bear a hydroxyl
group in the allylic position (Scheme 2).3e However, this
INTRODUCTION
■
Vinylallenes are, interestingly, reactive compounds toward
various cycloaddition and cyclization reactions.1 They exhibit
particularly higher activity and selectivity with Diels−Alder
reactions, because their configurational equilibrium is more on
the side of s-cis conformera prerequisite for a [4 + 2] cyclo-
addition reaction to occur effectivelythan for 1,3-dienes.2 In
spite of their synthetic utility in organic reactions, there are only
a few methods that can generate vinylallene structures.1j,o,r,3
Recently, we introduced new methods for the construction of
functionalized vinylallenes, which involved palladium- or
rhodium-catalyzed reactions of carbonate or acetate derivatives
of 2-en-4-yne alcohols.4 2,3,5-Trienoates were a form of the
vinylallene structure that was accomplished via palladium-
catalyzed alkoxycarbonylation of 2,4-enyne carbonates (Scheme 1).4a
Scheme 2. Previous Study: 1,5-(SN2″)-Substitution
Reactions of Enyne Oxiranes with Organocuprates3e
Scheme 1. Previous Study: Alkoxycarbonylation of Enyne
Carbonates4a,c
method provided a very limited scope for both enyne substrates
and their reacting partners, and moreover, the diastereoselec-
tivity of this method, in terms of relative configuration of allenyl
moiety and allylic carbon, could not be probed.
We describe here for the first time that conjugated enynes
carrying an oxirane moiety as a leaving group undergo
It was later found that in some cases, this reaction proceeds
with high center-to-axial chirality transfer.4c
Received: February 17, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00382
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a
Table 1. Methoxycarbonylation of Enyne Oxirane (Z)-1a
b
entry
Pd %
PPh3%
t (h)
yield %
c
1
2
3
4
5
6
0.5
0.25
0.5
0.25
1
2
1
2
>99
1
>99
>99
>99
0
3
3
0.5
0
5
16
0
4
16
0
a
b
Reaction conditions: 0.3 mmol of (Z)-1a, 2 mL of MeOH, under CO filled balloon, 25 °C. Determined by 1H NMR analysis using benzaldehyde
c
as the internal standard. Isolated yield.
a
Table 2. Effect of Ligand on Methoxycarbonylation of (Z)-1b
b
c
entry
ligand
PPh3
t (h)
yield %
dr
1
2
1
4
96
89
92
97
95
81
94
92:8
92:8
d
PPh3
3
P(2-MeC6H4)3
P(2-OMeC6H4)3
P(4-OMeC6H4)3
PPh2Me
0.5
0.5
1
92:8
4
87:13
86:14
80:20
83:17
94:6
5
6
2.5
1
7
Tri(2-furyl)phosphine
P(4-CF3C6H4)3
dppf
e
8
0.5
1
94
9
72
96
89
92
90:10
86:14
86:14
86:14
85:15
−
10
11
12
13
14
dppe
3
dppb
1.5
1.5
9.5
10
Xantphos
f
( )-BINAP
BIPHEP
44
0
a
Reaction conditions: 0.1 mmol of (Z)-1b, 2 mL of MeOH, 1 mol % of Pd, P/Pd ratio is 4:1, under CO-filled balloon, 25 °C. dppf: 1,1′-
bis(diphenylphosphino)ferrocene; dppe: 1,2-bis(diphenylphosphino)ethane; dppb: 1,4-bis(diphenylphosphino)butane; Xanthphos: 4,5-bis-
(diphenylphosphino)-9,9-dimethylxanthene; BINAP: 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene; BIPHEP: 2,2′-bis(diphenylphosphino)-1,1′-
b
c
1
1
biphenyl. Determined by H NMR analysis using benzaldehyde as the internal standard. Diastereomeric ratio (dr) was determined by H NMR.
d
e
f
Pd(PPh3)4 was the catalyst of this reaction. Isolated yield. The conversion of (Z)-1b was 49%.
alkoxycarbonylation in the presence of palladium under fairly
mild conditions, forming hydroxy-functionalized 2,3,5-trienoates
usually with high diastereoselectivities.
reduced by half (0.25% Pd, 1% PPh3) without compromising
the product yield (entry 2). The optimum PPh3/Pd ratio appears
to be 4:1, because any deviation from this ratio resulted in a
decrease in the reaction rate (entries 1−4). Finally, the controlled
experiments proved that no conversion for the substrate would be
possible in the absence of a phosphine ligand or a palladium
source (entries 5 and 6).
Having determined that the enyne oxirane (Z)-1a is a
perfectly amenable reagent toward palladium catalysis as a
means to synthesize vinylallene structures, we next probed the
diastereoselectivitydirectly associated with the level of
center-to-axial chirality transferof the method over the sub-
strate (Z)-1b, using a variety of mono- and bidentate ligands.
The corresponding vinylallene product 2ba was in 96% yield
with a good diastereomeric ratio (92:8) when PPh3 was used as
the ligand (Table 2, entry 1). The relative configuration of its
RESULTS AND DISCUSSION
■
We initiated our study using the enyne oxirane (Z)-1a whose
oxirane terminus is dimethyl-substituted. We were pleased to
observe that, with just our first attempt, the substrate (Z)-1a
was converted to the desired 2,3,5-trienoate product 2aa, which
is exclusively in (E)-configuration, and carries a hydroxyl group
on the allylic position, almost quantitatively under very mild
reaction conditions; the conversion was complete within just
1 h, when the reaction was performed in the presence of a
Pd2dba3−CHCl3 (0.5 mol % Pd) and PPh3 (2 mol %)
combination in MeOH, and under balloon pressure of CO at
25 °C (Table 1, entry 1). The catalyst loading could even be
B
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a
Table 3. Alkoxycarbonylation of Enyne Oxirane (Z)-1a
b
entry
ROH
product
t (h)
yield %
dr
1
2
3
4
5
6
EtOH
PrOH
2bb
2bc
2bd
2be
2bf
1
3
84
87
83
88
0
80:20
88:12
86:14
86:14
−
BuOH
4
i-PrOH
2
t-BuOH
allyl alcohol
10
6
c
2bg
25
93:7
d
7
1
91
93:7
a
b
c
d
1
Performed under the conditions of Table 2. Determined by H NMR. The conversion of (Z)-1b was 75%. Reaction was performed with
3 mol % of Pd and 12 mol % of ligand.
Scheme 3. Methoxycarbonylation of (E)-1b
major diastereomer was determined by X-ray crystallography of
its phenylcarbamate derivative (see the Supporting Information).5
Typically, comparable yields are obtained with a variety of
monodentate phosphine ligands tested herein, with varying
reaction times required for a full conversion. However, it has
been found that the level of the chirality transfer is strongly
dependent on the ligand type that is used. The reactions in the
presence of a prepared catalyst Pd(PPh3)4 or P(2-MeC6H4)3
ligand proceeded with similar selectivities when compared with
PPh3 (entries 2 and 3), whereas electron-rich phosphines and a
heteroaryl-substituted phosphine all showed inferior stereo-
selectivities (entries 4−7). The best diastereoselectivity was
obtained with the use of an electron-poor phosphine ligand,
P(4-CF3C6H4)3, which afforded 2ba with 94% yield and 94:6 dr
within just 30 min (entry 8). Finally, the use of bidentate
ligands brought about dismal selectivities or low activities in
some cases (entries 9−14).
Having determined P(4-CF3C6H4)3 as the optimal ligand,
next we explored the suitability of a number of alcohol reagents
for their reactions with (Z)-1b. Except those with t-BuOH
(Table 3, entry 5), the vinylallene products could be obtained
at yields within the range of 83−91% with all alcohol reagents
tested herein. Surprisingly, however, the reactions performed
with alkyl alcohols, including EtOH, PrOH, BuOH, and i-PrOH,
all proceeded with relatively lower stereoselectivities (entries
1−5). Nevertheless, gratifyingly an additional functionality
could be introduced to a 7-hydroxy-2,3,5-trienoate structure
with the use of allyl alcohol, which yielded the corresponding
product 2bg in 91% yield and with 93:7 dr, albeit with higher
Pd loading to complete the reaction (entries 6−7).
reaction period for complete conversion and resulted in a
diastereomer of 2ba (2ba′) with a high yield, but slightly
decreased selectivity of 92:8 dr (Scheme 3). This result also
proves that the configuration of alkenyl moiety of substrate
regulates the stereomeric outcome of the product. Nonetheless,
because of some difficulties encountered during the synthesis
of enyne oxiranes with (E)-alkenyl group, such as partial
isomerization of the alkenyl group, further studies were
continued using only (Z)-configured reagents.
Next we explored the scope of the protocol over a variety of
substrates containing (Z)-alkenyl and (E)-oxirane moieties.
Except in one case, alkoxycarbonylation reactions proceeded
rather smoothly and provided the expected products at yields
within the range of 81−92%.
It was interesting to observe that the form of pendant oxygen
functionality within R3 group is an important factor for the
stereoselectivity of the process. Substituting the methoxymethyl
group in R3 position with a benzyloxymethyl group ((Z)-1c)
had no detectable effect on both the reactivity and stereo-
selectivity (Table 4, entry 1). However, when R3 was a carbinol
group ((Z)-1d) or its hydroxyl group was silyl-protected
((Z)-1e), the corresponding methoxycarbonylated products
2da and 2ea were obtained with 90:10 and 89:11 dr, respec-
tively (entries 2 and 3).
The same trend was also obvious for the reactions of (Z)-1f
and (Z)-1g, where R3 is dimethylcarbinol and dimethylmethoxy
methyl, respectively. Though comparably good yields could be
achieved with both reagents, the products 2fa and 2ga were
obtained with significantly different level of stereoselectivities,
85:15 and 95:5 dr, respectively (entries 4 and 5).
It seems that the method is also suitable for enyne oxiranes
containing an (E)-configured alkenyl moiety; a carbonylation
reaction of (E)-1b in MeOH under the standard conditions
(conditions denoted in Table 2) required remarkably longer
It seems that for an effective stereoselectivity, the alkenyl
carbon that is proximal to the alkynyl moiety is required to be
fully substituted, because the carbonylative reaction of the enyne
oxirane containing a disubstituted alkenyl moiety ((Z)-1h) with
C
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a
Table 4. Alkoxycarbonylation of Enyne Oxiranes
a
b
c
1
Performed under the conditions of Table 2. Determined by H NMR. Reaction was performed with 3 mol % of Pd and 12 mol % of ligand.
MeOH proceeded with an inferior stereoselectivity (entry 6).
As a model for substrates with all alkyl substituents, the enyne
oxirane (Z)-1i, where all R1, R2, and R3 positions were occupied
by butyl groups, also gave rise to the expected product 2ia with
a high selectivity of 93:7 dr (entry 7). However, (Z)-1j pos-
sessing a methyl group in the R3 interestingly afforded the
lowest dr (82:18) as compared to other enyne oxiranes tested
herein (entry 8).6 While the method tolerated a larger cyclohexyl
D
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group in the R2 (entry 9) under the reaction conditions, the
presence of the tert-butyl group at this position ((Z)-1l)
brought about the formation of an allylic esterified byproduct
(3la) along with the desired product 2la with a high dr (entry 10).7
It was also intriguing to find that there appears to be a direct
relation between the diastereoselectivity and the size of R1
(entries 11−13).8 For instance, when (Z)-1m, which contains a
terminal alkynyl moiety, was subjected to the methoxycarbo-
nylation, the product 2ma was obtained with only 88:12
dr. Nevertheless, the substrate (Z)-1o (R1 = t-Bu) afforded the
expected product 2oa in an excellent level of selectivity (97:3 dr).
The remarkable improvement on the stereoselectivity of the
process that was gained with the presence of the tert-butyl
group on the alkynyl moiety appears enduring; in contrast to
the results obtained with (Z)-1b, when R1 = tert-butyl, the
replacement of the methoxy group with benzyloxy- ((Z)-1p),
hydroxyl- ((Z)-1q), or silyl-protected ((Z)-1r) groups within
R3 only slightly impacted the dr of the corresponding prod-
ucts (entries 14−16). Moreover, the carbonylative reaction of
(Z)-1o with other alcohols also provided the corresponding
vinylallenes with high dr values (entries 17−19).
The loss of stereochemical integrity of the resulting products
should take place during the course of the reaction cycle
because subjecting the purified 2ba again to the standard con-
ditions for 4 h had no influence on its original diastereomeric
ratio.13 Though we cannot completely disregard the occurrence of
the π-allylpalladium isomerization or its formation through syn-
attack of the palladium, the back side migration of the palladium
over the alkynyl side (by inversion of configuration) could be the
primary basis for the formation of the minor diastereomeric form
in each case, and particularly increased sizes of R1 and R2 might
have limited the occurrence of such transitions in an inverted
manner. However, the presence of a highly encumbered group,
such as tert-butyl, at R2 also retards the effective migration of the
π-allyl coordinated palladium, and as a result (Z)-1l partly
underwent allylic alkoxycarbonylation to form the byproduct 3la.
Finally, the enyne oxirane (Z)-1i′ containing a (Z)-configured
oxirane moiety was also subjected to the standard reaction
conditions. The reaction proceeded smoothly in accordance
to the proposed mechanism, and thus yielded the vinylallene
product 2ia′, which is the diastereomer of 2ia (see entry 7 of
Table 4), with a high level of dr (Scheme 6).
The enyne oxirane (Z)-1s with a phenyl substituent at
alkynyl terminus yielded the product 2sa with 88:12 dr (entry 20),
and the substrate 1t having an endocyclic double bond also
successfully underwent methoxycarbonylation to generate an
exocyclic conjugated vinylallene structure 2ta with a relatively
lower but synthetically still useful dr (Scheme 4).
CONCLUSION
■
In summary, we have established an unprecedented, mild, and
efficient palladium-catalyzed diastereoselective 1,5-type alkox-
ycarbonylative substitution over conjugated enyne oxiranes,
which provides a highly selective route to anti-substituted
(E)-configured vinylallenes bearing a hydroxyl group on the
allylic position. The reactions proceeded through successive for-
mation of zwitterionic π-allyl- and σ-allenylpalladium complexes.
Scheme 4. Methoxycarbonylation of 1t
EXPERIMENTAL SECTION
■
General Methods. THF, DMF, and DCM solvents were all
purified by a solvent purification system. Et2O was distilled from
benzophenone-ketyl under argon prior to use. Methanol and ethanol
were dried over Mg turnings in the presence of iodine and stored on
molecular sieve 3 Å under Ar. 1-Propanol and 2-propanol were dried
first by stirring over anhydrous CaO followed by refluxing over Mg
turnings in the presence of iodine. 1-Butanol was dried first by stirring
over anhydrous MgSO4 and then refluxed over Mg turnings in the
presence of iodine. tert-BuOH was stirred over CaH2 (5% w/v),
distilled, and stored on molecular sieve 3 Å under Ar.
The mechanisms illustrated in Scheme 5 are proposed to
account for the stereoselective formation of 2 and 2′.9 The
reaction cycle should begin with ring-opening by the attack of a
palladium complex to both (Z)-1 and (E)-1 in anti-mode,10
leading to the formation of π-allylpalladium complexes A and
A′, respectively,10d,11 Given the formation of vinylallenes exclu-
sively in (E)-configuration for both intermediates (A and A′),
the alkanolate group (CHR3O−) on the planar allyl ligand
should be oriented syn with respect to the middle allylic C−H.
These intermediates additionally undergo a palladium shift to
the far alkynyl carbon proceeding mainly with retention to form
vinylallenyl palladium complexes B and B′, respectively. The
relative position of the R2 group and alkynyl moiety on A and
A′ may also be inverted via the π−σ−π interconversion into C
and C′,4c,10c respectively, before undergoing such a Pd shift.
The favored configuration of this side of the complex should be
regulated by the inherent structure of R2. For instance, when R2
is hydrogen the thermodynamically more stable π-allyl com-
plexes should bear alkynyl and CHR3O− moieties in syn,syn
positions (A′ and C).10c,d,11
Syntheses of all enyne oxirane starting materials (1 and 1′) were
performed under Ar gas, and purification of all synthesized molecules
was performed by column chromatography on silica gel. Silica gel
material used for the purification of enyne oxirane substrates had a
particle size range of 60−200 mesh and was treated by NEt3 before
use. It must be noted that the column chromatography of the substrate
1 and 1′ on an untreated silica gel always resulted in decomposi-
tion. All other column purifications were performed on silica gel
60 (35−70 μm). All substrates and vinylallene products appeared
either colorless or as pale yellow oils.
The synthesized reactants and carbonylation products were
analyzed by GC and GC-MS. NMR spectra were recorded on a
400 MHz spectrometer. Chemical shifts are reported in ppm
downfield from Me4Si. Infrared spectra were obtained by ATR
method with neat samples. High-resolution mass spectral analyses of
new compounds were performed using EI-High Resolution Double
Focusing Magnetic Sector (ionization mode: 70 eV, emission current:
1 mA, source temperature: 160 °C, resolution: 10 000 (10% valley
definition)) and ESI-LTQ Orbitrap (source voltage: +3.8 kV, capillary
voltage: 41 V, capillary temperature: 275 °C, tube lens voltage: 140 V,
system resolution: 60 000 (10% valley definition)).
However, such configurational transitions cannot alter the
outcome of the reaction, because both isomeric intermediates
C and C′ would also lead to B and B′, respectively. These
σ-allenylpalladium complexes undergo successive CO insertion
and reductive elimination, as verified previously,4,12 to yield 2
and 2′ stereoselectively.
The Pd2(dba)3−CHCl3 complex was synthesized in the laboratory.14
Synthesis of (Z)-1i and (Z)-1i′. 1-Hexyne (2.3 mL, 20 mmol) was
added dropwise to a solution of BBr3 (22 mL, 22 mmol, 1 M) in dry
E
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Scheme 5. Mechanism of Alkoxycarbonylation of Conjugated Enyne Oxiranes
Scheme 6. Methoxycarbonylation of (Z)-1i′
DCM at −78 °C. The mixture was allowed to warm to 0 °C and
stirred for 1 h. The reaction mixture was recooled to −78 °C, and a
solution of 2,3-dimethylbutan-2,3-diol (2.84g, 24 mmol) in dry DCM
(20 mL) was added dropwise. Following this addition, the mixture was
warmed to ambient temperature and stirred for 1 h. Then, the mixture
was quenched by brine and extracted with DCM. The combined
organic layers were dried over MgSO4, filtered, and evaporated. The
residue was purified on silica gel column to afford S1 as a colorless oil
(hexane−EtAc, yield: 3.57 g, 62%).15
To a stirred solution of S1 (4.64 g, 16 mmol) and PdCl2(PPh3)2
(1 mol %, 112 mg, 0.16 mmol) in dry THF (20 mL) was added a
solution of 1-hexynylzinc chloride, which was generated by treatment
of 1-hexyne (1.6 g, 19.2 mmol) with BuLi (8.5 mL, 20.7 mmol, 2.5 M
in hexane) in dry THF (20 mL) for 30 min at −78 °C and following
treatment with ZnCl2 (2.72 g, 19.2 mmol) for 30 min at 0 °C. The
resultant reaction mixture was stirred at room temperature (rt) for 1 h
before quenching by 0.5 M HCl(aq). The content of the reaction
medium was extracted with ether, washed with saturated NaHCO3 and
brine, dried over MgSO4, filtered, and concentrated under reduced
pressure. The residue was purified on silica gel column to afford S2 as
a colorless oil (hexane−EtAc, yield: 3.9 g, 84%).15
stirred for 30 min at room temperature. After the completion of the
reaction, water was added to the resulting mixture before extracting
with ether. The combined extracts were dried over MgSO4, filtered,
and concentrated under reduced pressure. The residue was purified on
silica gel column to afford the (5E,7Z)-8-butyltetradeca-5,7-dien-9-yne
(S3i) or (5Z,7Z)-8-butyltetradeca-5,7-dien-9-yne (S3i′) as yellowish
oil products (hexane−EtAc, yield of S3i: 1.89 g, 77%; yield of S3i′:
1.25 g, 51%).18
To a solution of S3i or S3i′ (492 mg, 2 mmol) in DCM (30 mL)
was added 12 mL solution of Na2CO3 (25%) followed by 3.4 mmol
(587 mg) of m-CPBA dropwise at 0 °C. The mixture was stirred at the
same temperature and monitored with TLC until the reactant was
consumed completely. At the end of the epoxidation process, the
mixture was extracted with DCM, dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The crude mixture
was chromatographed on NEt3-pretreated short silica gel column
which afforded the enyne oxirane (Z)-1i or (Z)-1i′ in about 85%
purities as pale yellow oil products (hexane−EtAc, yield of (Z)-1i: 300 mg,
57%; yield of (Z)-1i′: 158 mg, 30%).
1
(Z)-1i: H NMR (400 MHz, C6D6) δ: 5.32 (d, J = 8.7 Hz, 1H),
3.90 (dd, J = 8.7, 2.3 Hz, 1H), 2.71 (td, J = 5.5, 2.3 Hz, 1H), 2.11 (t,
J = 6.8 Hz, 2H), 2.10 (t, J = 6.4 Hz, 2H), 1.54−1.15 (m, 14H), 0.84−
0.70 (m, 9H); 13C{1H} NMR (100 MHz, C6D6) δ: 137.5, 133.3, 95.7,
78.6, 59.6, 56.4, 37.4, 31.8, 30.7, 30.3, 28.0, 22.4, 22.0, 21.8, 19.0, 13.7,
13.6, 13.3.
A mixture of 1.5 mol % of Pd2(dba)3 (137 mg, 0.15 mmol), 6 mol %
of AsPh3 (184 mg, 0.6 mmol), and 15 mL of 1 M KOH(aq) in 50 mL
of THF was cooled to 0 °C before the addition of the compound S2
(2.9 g, 10 mmol). Then, a THF solution (10 mL) of trans-16 or cis-1-
iodo-1-hexene17 (2.52 g, 12 mmol), which were synthesized according
to the literature procedures, was added dropwise, and the reaction
(Z)-1i′: 1H NMR (400 MHz, CDCl3) δ: 5.38 (d, J = 9.0, 1H), 3.90
(dd, J = 9.0, 4.8 Hz, 1H), 3.11 (q, J = 4.8 Hz, 1H), 2.37 (t, J = 6.8 Hz,
F
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R1 = Bu, R2 = Me, (Z)-1d, 0.23 g, 60%; R1= H, R2 = Me, 0.17 g, 60%;
R1 = Bu, R2 = H, 0.19 g, 55%; R1 = Bu, R2 = Cy, 0.26 g, 49%; R1 = Cy,
R2 = Me, 0.25 g, 57%; R1 = t-Bu, R2 = Me, (Z)-1o, 0.25 g, 65%; R1 =
Bu, R2 = t-Bu, 0.24 g, 50%; R1 = Ph, R2 = Me, 0.26 g, 60%).
As for the alkylation of the pendant hydroxyl group of S7, a
suspension of sodium hydride (1.1 equiv) in DMF (1 mL) was added
to a solution of S7 (1 mmol) in DMF (1 mL/mmol S7) at −20 °C.
The mixture was stirred for further 30 min before the addition of
methyl iodide (1.2 equiv) or benzyl bromide (1.2 equiv). The mixture
was stirred for 4 h at the same temperature, and then the reaction was
terminated by the addition of MeOH (5 mL) and brine (5 mL) and
extracted with DCM. The combined extracts were dried over MgSO4,
filtered, and concentrated under reduced pressure. The crude mixture
was subjected to column chromatography over NEt3-pretreated short
silica gel column to afford the corresponding alkoxy-substituted enyne
oxirane products as colorless oil (hexane−EtOAc, yields (Z)-1b,
0.18 g, 87%; (Z)-1c, 0.22 g, 77%; (Z)-1h, 0.17 g, 90%; (Z)-1k, 0.24 g,
87%; (Z)-1l, 0.21 g, 83%; (Z)-1m, 0.13 g, 87%; (Z)-1n, 0.19 g; 84%;
(Z)-1o, 0.19 g, 90%; (Z)-1p, 0.24 g, 85%; (Z)-1s, 0.20 g, 87%).22
A mixture of (Z)-1d (194, mg, 1 mmol) or (Z)-1q (227 mg,
1.17 mmol), Et3N (0.18 mL, 1.3 mmol), t-butyldimethylsilyl chloride
(0.2 g, 1.3 mmol), and 4-dimethylaminopyridine (DMAP) (15 mg,
0.12 mmol) in CH2Cl2 (12 mL) was stirred at room temperature for
24 h. Then, the reaction was terminated by water, and the content
of the reaction flask was extracted with DCM. The organic solution
was dried with MgSO4, filtered, and evaporated. The residue was
chromatographed over NEt3-pretreated short silica gel column to
afford silylated enyne oxiranes as a colorless oil (hexane−EtOAc, yields
(Z)-1e, 0.28 g, 79%; (Z)-1r, 0.25 g, 81%).23
2H), 2.15 (td, J = 7.6, 0.8 Hz, 2H), 1.60−1.25 (m, 14H), 0.95−0.88
(m, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ: 130.8, 128.9, 96.4, 78.1,
59.1, 55.4, 37.5, 30.8, 30.2, 28.5, 28.2, 22.5, 21.9, 21.9, 19.2, 14.0, 13.9, 13.8.
Synthesis of (Z)-1a. A hexane solution of BuLi (4.8 mL, 12 mmol,
2.5 M) was added dropwise to a solution of isopropyl(triphenyl)-
phosphonium iodide (4.32 g, 10 mmol) in THF (30 mL) at 0 °C and
stirred for further 1 h. The enyne aldehyde (Z)-S4a (1.8 g, 12 mmol),
which was synthesized as prescribed elsewhere,4a,b was added dropwise
to the resulting mixture and stirred for 1 h at rt. The reaction was
quenched by the addition of saturated NH4Cl(aq) solution, and the
organic layer was extracted with diethyl ether. The combined extracts
were dried over MgSO4 and chromatographed on a silica gel column
to obtain pure S3a (hexane/EtOAc, yield: 1.65 g, 78%).19
The epoxidation of S3a (352 mg, 2 mmol) and isolation of the
product (Z)-1a was performed as specified for (Z)-1i (hexane−EtOAc,
yield: 0.27 g, 70%).
1
(Z)-1a: H NMR (400 MHz, CDCl3) δ: 5.38 (dq, J = 8.9, 1.5 Hz,
1H), 3.65 (d, J = 8.9 Hz, 1H), 2.34 (t, J = 6.8 Hz, 2H), 1.87 (s, 3H),
1.56−1.36 (m, 4H), 1.35 (s, 3H), 1.27 (s, 3H), 0.9 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ: 130.7, 125.5, 95.9, 79.1, 62.6,
60.5, 30.9, 24.9, 24.2, 22.1, 19.6, 19.3, 13.7.
Syntheses of (Z)-1b-e,h,k-s. A general procedure for the syntheses
of noncyclic enyne aldehydes (S4) used here was reported elsewhere.4a,b
To a solution of NaH (1.1 equiv) in THF (2.5 mL/mmol S4) was
added triethyl phosphonoacetate (1.2 equiv) at 0 °C, and the mixture
stirred for 1 h at room temperature. Subsequently, to the reaction
mixture was added S4 (6.5−10 mmol) dropwise at −78 °C and stirred
for 1 h at room temperature. The reaction was terminated by the
addition of saturated NH4Cl and extracted with Et2O. The organic
layer was dried over MgSO4, filtered, and concentrated under reduced
pressure to obtain S5 with E/Z isomeric ratios varying in the range of
97:3 to 95:5.20 The crude mixture was purified on silica gel column
(hexane−EtAc) to obtain S5 in pure isomeric form (yields of (2E,4Z)-
S5: R1 = Bu, R2 = Me, 3.17 g, 72%; R1 = H, R2 = Me, 2.30 g, 70%; R1 =
Bu, R2 = H, 1.48 g, 72%; R1 = Bu, R2 = Cy, 1.4 g, 68%; R1 = Cy, R2 =
Me, 1.97 g, 80%; R1 = t-Bu, R2 = Me, 1.80 g, 82%; R1 = Bu, R2 = t-Bu,
2.12 g, 81%; R1 = Ph, R2 = Me, 2.04 g, 85%).
A DIBALH (∼3 eq, 1.0 M in cyclohexane) solution was added
dropwise to the solution of S5 in DCM (∼6 mL/mmol S5) at −78 °C.
After the reaction mixture was stirred for 4 h at the same temperature,
1 M HCl(aq) solution was added before extracting with DCM. The
organic layers were combined, washed with brine, dried over MgSO4,
filtered, and concentrated under reduced pressure. The crude mixture
was subjected to silica gel column chromatography to purify the
corresponding S6 compound (hexane−EtOAc; yields of (2E,4Z)-S6:
R1 = Bu, R2 = Me, 2.18 g, 85%; R1 = H, R2 = Me, 1.45 g, 85%; R1 = Bu,
R2 = H, 1.12 g, 95%; R1 = Bu, R2 = Cy, 1.1 g, 94%; R1 = Cy, R2 = Me,
1.55 g, 95%; R1 = t-Bu, R2 = Me, 1.39 g, 95%; R1 = Bu, R2 = t-Bu, 1.6 g,
90%; R1 = Ph, R2 = Me, 1.6 g, 92%).21
Synthesis of (E)-1b. Synthesis of (E)-1b was performed starting
from (E)-configured S4 following the same method employed for the
synthesis of (Z)-1b. Yields: (R1 = Bu, R2 = Me): (2E,4E)-S5b, 1.12 g,
79%; (2E,4E)-S6b, 0.83 g, 91%; (E)-S7b (produced from 4.6 mmol
of (2E,4E)-S6b), 0.43 g, 47%; (E)-1b (produced from 2.2 mmol of
(E)-S7b), 0.40 g, 88%.
1
(Z)-1b: H NMR (400 MHz, CDCl3) δ: 5.23 (dd, J = 8.9, 1.2 Hz,
1H), 3.74 (dd, J = 8.9, 2.4 Hz, 1H), 3.71 (dd, J = 11.6, 3.2 Hz, 1H),
3.40 (dd, J = 11.6, 5.7 Hz, 1H), 3.40 (s, 3H), 3.08 (ddd, J = 5.7, 3.2,
2.4 Hz, 1H), 2.35 (t, J = 7.2 Hz, 2H), 1.87 (d, J = 1.2 Hz, 3H), 1.55−
1.40 (m, 4H), 0.92 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ: 131.5, 125.7, 95.9, 78.7, 72.5, 59.2, 58.3, 54.2, 30.7, 23.8,
21.9, 19.1, 13.6.
(E)-1b: (400 MHz, CDCl3) δ: 5.35 (dd, J = 9.0, 1.0 Hz, 1H), 3.67
(dd, J = 11.3, 3.0 Hz, 1H), 3.48 (dd, J = 9.0, 2.2 Hz, 1H), 3.44 (dd, J =
11.3, 5.1 Hz, 1H), 3.38 (s, 3H), 3.06 (ddd, J = 5.1, 3.0, 2.2 Hz, 1H),
2.28 (t, J = 6.8 Hz, 2H), 1.93 (d, J = 1.0 Hz, 3H), 1.54−1.37 (m, 4H),
0.90 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 131.3,
125.2, 90.3, 82.4, 80.0, 59.2, 58.6, 51.9, 30.7, 21.9, 18.9, 18.2, 13.6.
1
(Z)-1c: H NMR (400 MHz, C6D6) δ: 7.24−7.22 (m, 2H), 7.14−
7.10 (m, 2H), 7.05 (dt, J = 7.2, 1.6 Hz, 1H), 5.14 (dd, J = 8.9, 1.6 Hz,
1H), 4.35 (d, A of AB, JAB = 12.1 Hz, 1H), 4.31 (d, B of AB, JAB = 12.1
Hz, 1H), 4.01 (dd, J = 8.9, 2.2 Hz, 1H), 3.45 (dd, J = 11.4, 3.0 Hz,
1H), 3.25 (dd, J = 11.4, 5.5 Hz, 1H), 2.95 (ddd, J = 5.5, 3.0, 2.2 Hz,
The epoxidation of S6 (2 mmol) and isolation of the corresponding
S7 products were performed as specified for (Z)-1i (yields of (Z)-S7:
G
DOI: 10.1021/acs.joc.5b00382
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1H), 2.06 (t, J = 6.8 Hz, 2H), 1.71 (d, J = 1.6 Hz, 3H), 1.29−1.16 (m,
4H), 0.7 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6) δ:
138.5, 132.8, 128.2, 127.4, 127.3, 124.8, 95.5, 79.1, 72.8, 70.0, 58.2,
53.8, 30.6, 23.5, 21.8, 18.9, 13.3.
(Z)-1s: 1H NMR (400 MHz, CDCl3) δ: 7.46−7.44 (m, 2H), 7.34−
7.32 (m, 3H), 5.38 (dq, J = 9.0, 1.5 Hz, 1H), 3.84 (dd, J = 9.0, 2.4 Hz,
1H), 3.74 (dd, J = 11.7, 3.2 Hz, 1H), 3.43 (dd, J = 11.7, 6.0 Hz, 1H),
3.42 (s, 3H) 3.14 (ddd, J = 6.0, 3.2, 2.4 Hz, 1H), 2.00 (d, J = 1.5 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 133.1, 131.5, 128.5, 128.3,
124.9,122.9, 94.5, 87.3, 72.5, 59.2, 58.5, 54.1, 23.4.
Synthesis of (Z)-1f and (Z)-1g. To the dry Et2O (15 mL) solution
of S5b (1.1 g, 5 mmol) was added an ethereal (15 mL) solution of
2.1 eq. MeMgI (5.25 mL, 10.5 mmol, 2 M) dropwise at −50 °C, and
then the mixture stirred for 6 h at the same temperature. The mixture
was allowed to warm to 0 °C and quenched by the addition of 30 mL
of saturated NH4Cl(aq) solution before extracting with Et2O. The
combined extracts were dried over MgSO4, filtered, and evaporated.
The resulting residue was purified on a silica gel column to afford S8
(hexane−EtAc, yield: 0.49 g, 80%).
1
(Z)-1d: H NMR (400 MHz, CDCl3) δ: 5.25 (dd, J = 9.0, 1.4 Hz,
1H), 3.96 (dd, J = 12.6, 2.3 Hz, 1H), 3.87 (dd, J = 9.0, 2.3 Hz, 1H),
3.68 (dd, J = 12.6, 4.1 Hz, 1H), 3.11−3.09 (m, 1H), 2.36 (t, J = 7.0 Hz,
2H), 1.88 (d, J = 1.4 Hz, 3H), 1.56−1.39 (m, 4H), 0.92 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (100 MHz, C6D6) δ: 132.5, 124.8, 95.7, 79.1,
61.1, 59.5, 53.7, 30.6, 23.5, 21.8, 19.0, 13.3.
1
(Z)-1e: H NMR (400 MHz, CDCl3) δ: 5.22 (dd, J = 9.1, 1.5 Hz,
1H), 3.86 (dd, J = 12.1, 3.2 Hz, 1H), 3.76 (dd, J = 9.1, 2.4 Hz, 1H),
3.71 (dd, J = 12.1, 4.8 Hz, 1H), 3.00 (ddd, J = 4.8, 3.2, 2.4 Hz, 1H),
2.33 (t, J = 7.2 Hz, 2H), 1.86 (d, J = 1.5 Hz, 3H), 1.56−1.37 (m, 4H),
0.91 (t, J = 6.8 Hz, 3H), 0.89 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ: 131.9, 125.3, 95.7, 78.7, 63.0,
60.1, 54.3, 30.8, 25.8, 23.8, 22.0, 19.1, 18.3, 13.6, −5.3, −5.4.
The epoxidation of S8 (412 mg, 2 mmol) and isolation of the prod-
uct (Z)-1f were performed as specified for (Z)-1i (hexane−EtOAc,
yield: 0.27 g, 60%).
The hydroxyl group of (Z)-1f (222 mg, 1.0 mmol) was methylated
as described above furnishing the enyne oxirane (Z)-1g in 90% yield
(0.21 g).
(Z)-1h: 1H NMR (400 MHz, CDCl3) δ: 5.75 (dtd, J = 10.8, 2.4, 0.8
Hz, 1H), 5.44 (dd, J = 10.8, 8.8 Hz, 1H), 3.80 (dd, J = 8.8, 2.2 Hz,
1H), 3.74 (dd, J = 11.2, 2.8 Hz, 1H), 3.44−3.38 (m, 1H), 3.41 (s, 3H),
3.11 (dt, J = 5.4, 2.6 Hz, 1H), 2.36 (td, J = 6.8, 2.3 Hz, 2H), 1.58−1.41
(m, 4H), 0.92 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ: 137.2, 115.4, 97.1, 72.3, 59.2, 58.2, 53.3, 50.4, 30.6, 21.9, 19.2, 13.5.
1
(Z)-1k: H NMR (400 MHz, CDCl3) δ: 5.21 (d, J = 8.7 Hz, 1H),
3.77 (dd, J = 8.7, 2.4 Hz, 1H), 3.72 (dd, J = 11.5, 3.1 Hz, 1H), 3.38
(dd, J = 11.5, 5.7 Hz, 1H), 3.40 (s, 3H), 3.07 (dt, J = 5.7, 2.4 Hz, 1H),
2.37 (t, J = 7.2 Hz, 2H), 2.02−1.97 (m, 1H), 1.76−1.20 (m, 14H),
0.92 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 136.3,
129.1, 97.0, 76.7, 72.6, 59.2, 58.5, 54.3, 45.4, 31.7, 31.6, 30.8, 29.7,
26.2, 26.0, 22.0, 19.2, 13,6.
1
(Z)-1f: H NMR (400 MHz, CDCl3) δ: 5.26 (dd, J = 8.8, 1.6 Hz,
1H), 3.89 (dd, J = 8.8, 2.3 Hz, 1H), 2.88 (d, J = 2.3 Hz, 1H), 2.36 (t,
J = 7.0 Hz, 2H), 1.87 (d, J = 1.6 Hz, 3H), 1.78 (d, J = 0.8 Hz, 1H),
1.57−1.40 (m, 4H), 1.31 (s, 3H), 1.25 (s, 3H), 0.92 (t, J = 6.8 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 132.0, 125.1, 78.8, 73.8,
64.7, 53.3, 50.7, 30.7, 23.7, 22.2, 21.9, 21.0, 19.1, 13.5.
1
(Z)-1l: H NMR (400 MHz, CDCl3) δ: 5.24 (d, J = 8.9 Hz, 1H),
3.81 (dd, J = 8.9, 2.4 Hz, 1H), 3.74 (dd, J = 11.2, 3.1 Hz, 1H), 3.42−
3.38 (m, 1H), 3.41 (s, 3H), 3.10 (ddd, J = 5.6, 3.1, 2.4 Hz, 1H), 2.39
(t, J = 7.2 Hz, 2H), 1.59−1.41 (m, 4H), 1.11 (s, 9H), 0.93 (t, J = 7.6
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 140.2, 127.4, 97.4,
72.7, 59.2, 58.5, 54.7, 36.1, 30.8, 28.9, 21.9, 19.2, 13.6.
1
(Z)-1g: H NMR (400 MHz, CDCl3) δ: 5.24 (dd, J = 8.9, 1.5 Hz,
1H), 3.69 (dd, J = 8.9, 2.3 Hz, 1H), 3.29 (s, 3H), 2.87 (d, J = 2.3 Hz,
1H), 2.36 (t, J = 6.7 Hz, 2H), 1.87 (d, J = 1.5 Hz, 3H), 1.56−1.39 (m,
4H), 1.18 (s, 3H), 1.15 (s, 3H), 0.92 (t, J = 7.2 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ: 132.2, 125.3, 95.8, 79.0, 74.0, 64.9, 53.4,
50.9, 30.9, 23.9, 22.4, 22.0, 21.1, 19.2, 13.7.
1
(Z)-1m: H NMR (400 MHz, C6D6) δ: 5.10 (dq, J = 8.9, 1.0 Hz,
1H), 3.84 (dd, J = 8.9, 2.0 Hz, 1H), 3.25 (dd, J = 11.5, 3.0 Hz, 1H),
3.06−2.99 (m, 1H), 3.05 (s, 3H), 2.83 (ddd, J = 5.5, 3.0, 2.0 Hz, 1H),
2.74 (s, 1H), 1.57 (d, J = 1.0 Hz, 3H); 13C{1H} NMR (100 MHz,
C6D6) δ: 136.0, 122.9, 82.4, 81.5, 72.2, 58.4, 58.0, 53.2, 22.7.
Synthesis of (Z)-1j. To a stirred solution of diphenylethylphosphine
oxide (4.6 g, 20 mmol) in dry THF (70 mL) was added BuLi (2.5 M
in hexane, 8.8 mL) dropwise at 0 °C and stirred for a further 30 min.
The solution was cooled to −78 °C, and then the dienyne ester S5b
(3.88 g, 20 mol) was added dropwise. The solution was allowed to
warm to ambient temperature and subsequently stirred overnight.
Saturated NH4Cl solution was added, and subsequently its THF
content was removed under reduced pressure. The aqueous residue
was diluted with brine (20 mL) and extracted with DCM. The com-
bined organic phases were dried over MgSO4, filtered, and con-
centrated under reduced pressure. The product S9 was purified
by column chromatography on silica gel (hexane−EtAc, yield:
1.9 g, 25%).24
To a stirred solution of S9 (1.9 g, 5 mmol) in ethanol (50 mL) was
added NaBH4 (189 mg, 5 mmol) in one portion and stirred for a
further 8 h at ambient temperature. The reaction afforded S10 en-
riched in threo form. Saturated NH4Cl (15 mL) was added, and
subsequently its ethanol content was removed under reduced pressure.
The aqueous mixture was diluted with brine (20 mL) and extracted
with DCM. The combined organic layers were dried over MgSO4,
filtered, and concentrated under reduced pressure. The product S10
was isolated in pure threo form by column chromatography on silica
gel (hexane/EtAc, yield: 1.31 g, 69%).24
1
(Z)-1n: H NMR (400 MHz, C6D6) δ: 5.14 (dq, J = 9.0, 1.4 Hz,
1H), 4.01 (dd, J = 9.0, 2.0 Hz, 1H), 3.35 (dd, J = 11.3, 3.2 Hz, 1H),
3.16 (dd, J = 11.3, 5.5 Hz, 1H), 3.09 (s, 3H), 2.91 (ddd, J = 5.5, 3.2,
2.0 Hz, 1H), 2.34 (m, 1H), 1.71 (d, J = 1.4 Hz, 3H), 1.66−1.03 (m,
10H); 13C{1H} NMR (100 MHz, C6D6) δ: 132.7, 124.7, 99.5, 79.2,
72.4, 58.5, 58.1, 53.7, 32.5, 32.4, 29.6, 25.7, 24.6, 23.5.
1
(Z)-1o: H NMR (400 MHz, C6D6) δ: 5.12 (dd, J = 8.5, 1.3 Hz,
1H), 3.95 (dd, J = 8.5, 2.3 Hz, 1H), 3.34 (dd, J = 11.5, 3.1 Hz, 1H),
3.16 (dd, J = 11.5, 5.5 Hz, 1H), 3.09 (s, 3H), 2.90 (ddd, J = 5.5, 3.1,
2.3 Hz, 1H), 1.68 (d, J = 1.3 Hz, 3H), 1.12 (s, 9H); 13C{1H} NMR
(100 MHz, C6D6) δ: 132.8, 124.5, 103.4, 77.7, 72.4, 58.5, 58.0, 53.7,
30.6, 27.9, 23.4.
1
(Z)-1p: H NMR (400 MHz, CDCl3) δ: 7.35−7.28 (m, 5H), 5.22
(dq, J = 8.9, 1.4 Hz, 1H), 4.61 (d, A of AB, JAB = 12.0 Hz, 1H), 4.57
(d, B of AB, JAB = 12.0 Hz, 1H), 3.81 (dd, J = 11.3, 3.0 Hz, 1H), 3.76
(dd, J = 8.9, 2.2 Hz, 1H), 3.53 (dd, J = 11.3, 5.5 Hz, 1H), 3.13 (ddd,
J = 5.5, 3.0, 2.2 Hz, 1H), 1.86 (d, J = 1.4 Hz, 3H), 1.24 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3) δ: 140.0, 137.9, 131.3, 128.4,
127.7, 125.7, 104.0, 77.1, 73.3, 70.1, 58.6, 54.3, 31.0, 28.1, 23.8.
1
(Z)-1q: H NMR (400 MHz, C6D6) δ: 5.17 (dd, J = 8.9, 1.1 Hz,
1H), 4.1 (dd, J = 8.9, 2.3 Hz, 1H), 3.54−3.48 (m, 1H), 3.34−3.30 (m,
1H), 2.75−2.73 (m, 1H), 1.73 (d, J = 1.1 Hz, 3H), 1.17 (s, 9H);
13C{1H} NMR (100 MHz, C6D6) δ: 132.5, 124.6, 103.7, 77.6, 61.0,
59.4, 53.6, 30.6, 27.9, 23.4.
To a stirred solution of S10 (1.31 g, 3.45 mmol) in DMF (50 mL)
was added NaH (60% dispersion in oil; 138 mg, 3.45 mmol) in one
portion at ambient temperature and stirred for a further 3 h. The
reaction was quenched by the addition of 25 mL of water and 15 mL
of brine and subsequently extracted with Et2O. The combined extracts
were washed with water, dried over MgSO4, filtered, and concentrated
under reduced pressure. The product S3j was purified by column
chromatography on silica gel (hexane, yield: 330 mg, 59%).24
1
(Z)-1r: H NMR (400 MHz, CDCl3) δ: 5.21 (d, J = 9.0 Hz, 1H),
3.87 (dd, J = 12.0, 3.2 Hz, 1H), 3.74 (m, 2H), 3.01 (m, 1H), 1.86 (s,
3H), 1.26 (s, 9H), 0.90 (s, 9H), 0.08 (s, 6H); 13C{1H} NMR: (100
MHz, CDCl3) δ: 131.6, 125.3, 103.8, 77.1, 62.9, 60.2, 54.3, 31.0, 28.1,
25.9, 23.9, 18.3, −5,3.
H
DOI: 10.1021/acs.joc.5b00382
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The Journal of Organic Chemistry
Article
The epoxidation of S3j (162 mg, 1 mmol) and isolation of the
product (Z)-1j were performed as specified for (Z)-1i (hexane−EtAc,
yield: 35.6 mg, 20%).
reaction vessel, and 1 mL of alcohol solution of the substrate 1 or 1′
was added. When the reaction was complete as judged by TLC
analysis, the solvent content was evaporated and the residue was
purified by column chromatography on silica gel to afford 2 or 2′ as a
pale yellow oil. The coupling constants of olefinic protons and NOE
studies confirmed (E)-configured structures. 1H NMR analyses of
vinylallene products, except that of 2ia′, were performed in C6D6.
With this solvent, the 1H NMR signals of diastereomers were resolved
adequately, allowing to determine diastereomeric ratios smoothly. In
contrast, when using CDCl3 solvent, diastereomeric signals were all
overlapped.
S9: 1H NMR (400 MHz, CDCl3) δ: 7.86−7.74 (m, 4H), 7.55−7.43
(m, 6H), 6.34 (d, J = 1.2 Hz, 1H), 3.99 (dq, J = 13.5, 7.0 Hz, 1H), 2.42
(t, J = 7.0 Hz, 2H), 1.89 (d, J = 1.2 Hz, 3H), 1.60−1.51 (m, 2H),
1.47−1.38 (m, 5H), 0.92 (t, J = 7.0 Hz, 3H).
1
S10: H NMR (400 MHz, CDCl3) δ: 7.83−7.71 (m, 4H), 7.56−
7.43 (m, 6H), 5.53 (dd, J = 8.3, 1.2 Hz, 1H), 4.80 (dt, J = 13.8, 8.3 Hz,
1H), 2.82−2.71 (m, 1H), 2.15 (t, J = 7.2 Hz, 2H), 1.65 (d, J = 1.2 Hz,
3H), 1.40−1.28 (m, 4H), 1.04 (dd, J = 17.2, 7.4 Hz, 3H), 0.78 (t, J =
7.2 Hz, 3H).
1
S3j: H NMR (400 MHz, CDCl3) δ: 6.48 (ddq, J = 15.4, 10.8, 1.6
1
Hz, 1H), 6.11 (d, J = 10.8 Hz, 1H), 4.80 (dq, J = 15.4, 7.0 Hz, 1H),
2.39 (t, J = 6.8 Hz, 2H), 1.86 (s, 3H), 1.79 (d, J = 7.0 Hz, 3H), 1.60−
1.52 (m, 2H), 1.51−1.44 (m, 2H), 0.94 (t, J = 6.8 Hz, 3H).
Product Data. 2aa: Yield: 24.9 mg (99%); H NMR (400 MHz,
CDCl3) δ: 6.13 (d, J = 16.0 Hz, 1H), 5.76 (d, J = 16.0 Hz, 1H), 3.67
(s, 3H), 2.22 (t, J = 7.6 Hz, 2H), 1.85 (s, 3H), 1.37−1.27 (m, 10H),
0.86 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 213.4,
167.7, 137.8, 122.9, 103.1, 99.7, 70.9, 52.0, 30.1, 29.8, 28.6, 22.1, 14.8,
13.8; FTIR (νmax/cm−1): 3409, 2957, 2930, 2871, 1940, 1714, 1436,
1378, 1264, 1133, 1083, 1019, 966, 912, 723, 696; MS (EI, m/z): 252
(1, M+), 234 (2), 205 (7), 194 (7), 179 (5), 151 (23), 135 (35), 121
(15), 107 (32), 91 (43), 77 (25), 65 (15), 59 (46), 43 (100); HRMS
(ESI) C15H25O3 (MH)+, 253.1798 (calculated); 253.1799 (found).
1
(Z)-1j: H NMR (400 MHz, C6D6) δ: 5.16 (dd, J = 8.9, 1.4 Hz,
1H), 3.75 (dd, J = 8.9, 2.1 Hz, 1H), 2.64 (qd, J = 5.4, 2.1 Hz, 1H), 2.08
(t, J = 6.8 Hz, 2H), 1.73 (d, J = 1.4 Hz, 3H), 1.31−1.20 (m, 4H), 1.04
(d, J = 5.2 Hz, 3H), 0.72 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100
MHz, C6D6) δ: 133.7, 123.9, 95.2, 79.3, 57.4, 55.2, 30.6, 23.4, 21.8,
19.0, 17.3, 13.2.
Synthesis of (Z)-1t. PBr3 (1.4 mL, 13.8 mmol) was added dropwise
to a mixture of DMF (1.2 mL, 15.3 mmol) and chloroform (10 mL)
at 0 °C, and then the resulting mixture stirred for 1 h. Subsequently,
0.5 g of cyclohexanone (6 mmol) was added dropwise and stirred for
8 h at room temperature. The reaction was terminated with water, neu-
tralized with the addition of solid NaHCO3, and extracted with DCM.
The extract was washed with brine, dried over MgSO4, filtered, and con-
centrated under reduced pressure. The purification on short silica gel
column provided the compound S11 (hexane/EtAC, 0.92 g, 81%).25
A mixture of S11 (945 mg, 5 mmol), Pd(PPh3)4 (123 mg, 0.1 mmol,
2 mol % of Pd), and CuI (21 mg, 0.1 mmol, 2 mmol % of Cu) in
10 mL of Et3N was stirred for 10 min at room temperature followed by
the addition of 1-hexyne (0.5 g, 6 mmol). After being stirred for 3 h at
room temperature, water was added and extracted with Et2O. The
combined organic phases were dried over MgSO4, filtered, and con-
centrated under reduced pressure. The residue was purified by column
chromatography on silica gel to obtain endocyclic enyne aldehyde S4t
(hexane/EtAc, 0.84 g, 90%).25
1
2ba: Yield: 25.2 mg (94%); H NMR (400 MHz, C6D6) δ: 6.43
(dd, J = 15.7, 1.6 Hz, 1H, major), 6.41 (dd, J = 15.7, 1.6 Hz, 1H,
minor), 5.51 (dd, J = 15.7, 5.5 Hz, 1H, major), 5.51 (dd, J = 15.7, 5.5
Hz, 1H, minor), 4.23−4.19 (m, 1H), 3.36 (s, 3H, major), 3.35 (s, 3H,
minor), 3.03 (dd, A of ABX, JAB = 9.2 Hz, JAX = 4.0 Hz, 1H), 2.98 (dd,
B of ABX, JAB = 9.2 Hz, JBX = 7.2 Hz, 1H), 2.95 (s, 3H), 2.39 (td, J =
7.5, 2.2 Hz, 2H), 2.23 (bs, 1H), 1.69 (s, 3H), 1.47−1.39 (m, 2H), 1.23
(sext, J = 7.6 Hz, 2H), 0.78 (t, J = 7.2 Hz, 3H, major), 0.78 (t, J = 7.2
Hz, 3H, minor); 13C{1H} NMR: (100 MHz, C6D6) δ: 213.5, 166.9,
129.2, 127.3, 103.1, 76.5, 70.6, 58.2, 51.3, 30.3, 28.9, 22.2, 14.5, 13.7;
FTIR (νmax/cm−1): 3419, 2955, 2928, 2870, 1943, 1715, 1456, 1436,
1379, 1266, 1241, 1193, 1129, 1016, 966; MS (EI, m/z): 268 (1, M+),
236 (1), 223 (4), 205 (1), 191 (6), 151 (2), 135 (7), 121 (6), 93 (8),
91 (14), 77 (10), 59 (6), 45 (100); HRMS (ESI): C15H25O4 (MH)+,
269.1747 (calculated); 269.1747 (found).
1
2ba′: Yield: 23.3 mg, (87%); H NMR (400 MHz, C6D6) δ: 6.42
(dd, J = 15.7, 1.6 Hz, 1H, major), 6.40 (dd, J = 15.7, 1.6 Hz, 1H,
minor), 5.52 (dd, J = 15.7, 5.7 Hz, 1H), 4.22−4.20 (m, 1H), 3.37 (s,
3H, major), 3.35 (s, 3H, minor), 3.03 (dd, A of ABX, JAB = 9.6 Hz,
JAX = 4.0 Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6 Hz, JBX = 8.0 Hz, 1H),
2.96 (s, 3H), 2.38 (td, J = 7.6 Hz, 1.8 Hz, 2H), 2.29 (bs, 1H), 1.70 (s,
3H), 1.48−1.40 (m, 2H), 1.25 (sext, J = 7.6 Hz, 2H), 0.79 (t, J = 7.6
Hz, 3H); 13C{1H} NMR (100 MHz, C6D6) δ: 213.5, 166.9, 129.2,
103.1, 100.0, 76.5, 70.6, 58.2, 51.3, 30.3, 28.9, 22.2, 14.5, 13.7; FTIR
(νmax/cm−1): 3419, 2955, 2928, 2870, 1943, 1715, 1456, 1436, 1379,
1266, 1241, 1193, 1129, 1016, 966; MS (EI, m/z): 268 (1, M+), 236
(1), 223 (4), 205 (1), 191 (6), 151 (2), 135 (7), 121 (6), 93 (8), 91
(14), 77 (10), 59 (6), 45 (100); HRMS (ESI): C15H25O4 (MH)+,
269.1747 (calculated); 269.1747 (found).
The conversion of S4t (840 mg, 4.42 mmol) to dienyne ester S5t
was performed by HWE reaction as described above (hexane/EtAc,
0.96 g, 84%). Further successive synthetic procedures, which involved
the reduction of the ester S5t (960 mg, 3.7 mmol) to the enyne
alcohol S6t (730 mg, 91% yield), the epoxidation of S6t (436 mg,
2 mmol) to S7t (260 mg, 55% yield), and finally methyl derivatization
of hydroxyl group of S7t (260 mg, 1.1 mmol) to obtain (Z)-1t (0.22 g,
90%) were all conducted as described above.
1
(Z)-1t: H NMR (400 MHz, CDCl3) δ: 4.00−3.97 (m, 1H), 3.73
(dt, J = 11.2, 2.8 Hz, 1H), 3.45−3.30 (m, 4H), 3.20 (sext, J = 2.8 Hz,
1H), 2.34 (t, J = 6.8 Hz, 2H), 2.21−2.10 (m, 2H), 2.02−1.91 (m, 2H),
1.79−1.32 (m, 6H), 0.98−0.79 (m, 5H); 13C{1H} NMR (100 MHz,
CDCl3) δ: 137.3, 121.7, 94.2, 79.5, 73.1, 59.2, 56.2, 55.2, 30.9, 30.8,
22.4, 22.2, 21.9, 21.7, 19.2, 13.6.
1
2bb: Yield: 23.7 mg (84%); H NMR (400 MHz, C6D6) δ: 6.44
(dd, J = 15.4, 1.6 Hz, 1H, major), 6.43 (dd, J = 15.4, 1.6 Hz, 1H,
minor), 5.54 (dd, J = 15.4, 5.6 Hz, 1H), 4.24−4.18 (m, 1H), 3.99
(q, J = 7.1 Hz, 2H), 3.03 (dd, A of ABX, JAB = 9.6 Hz, JAX = 4.0 Hz,
1H), 2.98 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.6 Hz, 1H), 2.95 (s, 3H),
2.41 (td, J = 7.2, 2.4 Hz, 2H) 2.28 (bs, 1H), 1.71 (s, 3H), 1.49−1.41
Carbonylation Reactions. A palladium complex, phosphine
ligand, and 1 mL of alcohol were added successively to a Schlenck
apparatus that is attached to an Ar line and stirred 1 h at 25 °C before
the addition of the substrate. A CO full balloon was then fixed to the
I
DOI: 10.1021/acs.joc.5b00382
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(m, 2H), 1.25 (sext, J = 7.2 Hz, 2H), 0.92 (t, J = 7.1 Hz, 3H, major), 0.91
(t, J = 7.1 Hz, 3H, minor) 0.79 (t, J = 7.2 Hz, 3H, major), 0.79 (t, J =
7.2 Hz, 3H, minor); 13C{1H} NMR: (100 MHz, CDCl3) δ: 213.5, 167.1,
128.7, 127.8, 103.1, 100.3, 76.4, 71.1, 60.8, 59.1, 30.2, 28.6, 22.2, 14.7,
14.3, 13.9; FTIR (νmax/cm−1): 3418, 2956, 2926, 2858, 1940, 1708, 1458,
1367, 1322, 1261, 1240, 1172, 1118, 1062, 1023, 965, 864, 713. MS
(EI, m/z): 282 (1, M+), 238 (1), 237 (4), 209 (2), 191 (5), 135 (3),
121 (5), 107 (6), 93 (8), 91 (12), 77 (7), 65 (5), 55 (7), 45 (100); HRMS
(ESI): C16H26O4 (MH)+, 283.1904 (calculated); 283.1909 (found).
2bc: Yield: 25.8 mg (87%); 1H NMR (400 MHz, C6D6) δ: 6.44 (dd,
J = 15.8, 1.6 Hz, 1H, major), 6.43 (dd, J = 15.8, 1.6 Hz, 1H, minor),
5.53 (dd, J = 15.8, 5.6 Hz, 1H), 4.23−4.19 (m, 1H), 4.02−3.92 (m,
2H), 3.03 (dd, A of ABX, JAB = 9.6 Hz, JAX = 4.4 Hz, 1H), 2.98 (dd, B
of ABX, JAB = 9.6 Hz, JBX = 7.2 Hz, 1H), 2.94 (s, 3H), 2.41 (td, J = 7.3,
1.6 Hz, 2H), 2.22 (bs, 1H), 1.72 (s, 3H), 1.49−1.33 (m, 4H), 1.25
(sext, J = 7.4 Hz, 2H), 0.79 (t, J = 7.4 Hz, 3H, major), 0.80 (t, J = 7.4
Hz, 3H, minor), 0.66 (t, J = 7.3 Hz, 3H, major), 0.65 (t, J = 7.3 Hz,
3H, minor); 13C{1H} NMR (100 MHz, CDCl3) δ: 213.6, 167.2,
128.6, 127.9, 103.1, 100.3, 76.5, 71.1, 66.3, 59.1, 30.2, 28.5, 22.2, 22.0,
14.7, 13.9, 10.3; FTIR (νmax/cm−1): 3406, 2958, 2928, 1941, 1709,
1458, 1397, 1322, 1263, 1172, 1132, 1062, 1015, 965, 713; MS (EI,
m/z): 296 (1, M+), 278 (1), 251 (3), 236 (1), 209 (3), 191 (5), 135
(4), 121 (5), 91 (10), 79 (6), 65 (3), 45 (100); HRMS (ESI):
C17H28O4 (MH)+, 297.2060 (calculated), 297.2065 (found).
165 (3), 121 (6), 91 (11), 77 (9), 65 (4), 55 (7), 45 (100); HRMS
(ESI): C17H27O4 (MH)+, 295.1904 (calculated), 295.1910 (found).
1
2ca: Yield: 31.0 mg (90%); H NMR (400 MHz, C6D6) δ: 7.24−
7.01 (m, 5H), 6.44 (dd, J = 15.8, 1.6 Hz, 1H, major), 6.42 (dd, J =
15.8, 1.6 Hz, 1H, minor), 5.49 (dd, J = 15.8, 5.7 Hz, 1H), 4.29−4.23
(m, 1H), 4.21 (d, A of AB, JAB = 12.0 Hz, 1H), 4.19 (d, B of AB, JAB
=
12.0 Hz, 1H), 3.36 (s, 3H, major) 3.34 (s, 3H, minor), 3.18 (dd, A of
ABX, JAB = 9.2 Hz, JAX= 3.6 Hz, 1H), 3.11 (dd, B of ABX, JAB = 9.2 Hz,
JBX = 7.6 Hz, 1H), 2.38 (td, J = 7.6, 2.8 Hz, 2H), 1.69 (s, 3H), 1.42
(quint, J = 7.6 Hz, 2H), 1.23 (sext, J = 7.6 Hz, 2H), 0.78 (t, J = 7.6 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 213.6, 167.6, 137.7, 128.5,
128.4, 128.0, 127.9, 127.8, 103.2, 99.9, 74.0, 73.4, 71.2, 52.1, 30.1, 28.6,
22.2, 14.7, 13.9; FTIR (νmax/cm−1): 3416, 2954, 2928, 2869, 1943,
1714, 1454, 1435, 1379, 1322, 1266, 1134, 1016, 965, 738, 698. MS
(EI, m/z): 344 (1, M+), 312 (1), 279 (3), 253 (2), 191 (2), 167 (20),
149 (77), 113 (10), 104 (12), 91 (65), 70 (35), 57 (42), 57 (54),
43 (80), 41 (100); HRMS (ESI): C21H29O4 (MH)+, 345.2060
(calculated); 345.2065 (found).
2da: Yield: 21.3 mg (84%); 1H NMR (400 MHz, C6D6): δ: 6.35 (d,
J = 16.0 Hz, 1H, major), 6.34 (d, J = 16.0 Hz, 1H, minor), 5.48 (dd,
J = 16.0, 5.9 Hz, 1H), 4.10−4.04 (m, 1H), 3.44−3.24 (m, 2H), 3.37 (s,
3H), 2.39 (td, J = 7.6, 3.2 Hz, 2H), 1.70 (s, 3H), 1.44 (quint, J = 7.6
Hz, 2H), 1.25 (sext, J = 7.6 Hz, 2H), 0.80 (t, J = 7.6 Hz, 3H, major),
0.80 (t, J = 7.2 Hz, 3H, minor); 13C{1H} NMR: (100 MHz, C6D6) δ:
213.6, 167.0, 129.2, 128.0, 103.2, 100.1, 72.8, 66.3, 51.4, 30.3, 28.9,
22.2, 14.5, 13.7; FTIR (νmax/cm−1): 3384, 2954, 2928, 2871, 1940,
1715, 1436, 1379, 1265, 1240, 1131, 1076, 1017, 965, 875; LC-MS/
MS: 255 (100, MH+), 237 (20), 227 (8), 225 (20), 223 (42), 207
(12), 205 (50), 195 (12), 193 (15), 177 (18), 175 (18), 163 (15), 149
(8); HRMS (ESI): C14H23O4 (MH)+, 255.1596 (calculated); 255.1591
(found).
1
2bd: Yield: 25.7 mg (83%); H NMR (400 MHz, C6D6) δ: 6.45
(dd, J = 16.0, 1.2 Hz, 1H, major), 6.43 (dd, J = 16.0, 1.2 Hz, 1H,
minor), 5.53 (dd, J = 16.0, 5.6 Hz, 1H, major), 5.53 (dd, J = 16, 5.6
Hz, 1H, minor), 4.24−4.19 (m, 1H), 4.09−3.99 (m, 2H), 3.04 (dd, A
of ABX, JAB = 9.6 Hz, JAX = 4.0 Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6
Hz, JBX = 7.6 Hz, 1H), 2.95 (s, 3H), 2.41 (td, J = 7.4, 2.4 Hz, 2H) 2.26
(bs, 1H), 1.75 (s, 3H, minor), 1.73 (s, 3H, major), 1.46 (quint, J = 7.2
Hz, 2H), 1.36 (quint, J = 7.4 Hz, 2H), 1.25 (sext, J = 7.2 Hz, 2H), 1.12
(sext, J = 7.4 Hz, 2H), 0.80 (t, J = 7.2 Hz, 3H, minor), 0.79 (t, J = 7.2
Hz, 3H, major), 0.68 (t, J = 7.4 Hz, 3H, major), 0.67 (t, J = 7.4 Hz, 3H,
minor); 13C{1H} NMR (100 MHz, CDCl3) δ: 213.6, 167.2, 128.6,
127.8, 103.1, 100.3, 76.4, 71.1, 64.7, 59.1, 30.6, 30.2, 28.5, 22.2, 19.2,
14.7, 13.9, 13.7; FTIR (νmax/cm−1): 3428, 2958, 2929, 2873, 1940,
1710, 1458, 1379, 1322, 1261, 1131, 1062, 1016, 965, 713; MS (EI, m/z):
310 (1, M+), 293 (1), 265 (1), 235 (2), 207 (4), 191 (4), 161 (3), 121
(3), 105 (5), 91 (10), 79 (5), 57 (15), 45 (100); HRMS (ESI):
C18H31O4 (MH)+, 311.2217 (calculated), 311.2219 (found).
2ea: Yield: 30.2 mg (82%); 1H NMR (400 MHz, C6D6) δ: 6.45 (dd,
J = 15.8, 1.6 Hz, 1H, major), 6.34 (dd, J = 15.8, 1.6 Hz, 1H, minor)
5.54 (dd, J = 15.8, 5.6 Hz, 1H, major), 5.50 (dd, J = 15.8, 5.6 Hz, 1H,
minor), 4.19−4.10 (m, 1H), 3.42 (dd, A of ABX, JAB = 9.6 Hz, JAX
=
4.4 Hz, 1H), 3.37 (s, 3H), 3.31 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.2
Hz, 1H), 2.39 (td, J = 7.2, 1.6 Hz, 2H), 2.24 (d, J = 3.6 Hz, 1H), 1.72
(s, 3H, major), 1.69 (s, 3H, minor), 1.44 (quint, J = 7.2 Hz, 2H), 1.24
(sext, J = 7.2 Hz, 2H), 0.89 (s, 9H, minor), 0.85 (s, 9H, major), 0.79
(t, J = 7.2 Hz, 3H), −0.06 (s, 6H); 13C{1H} NMR (100 MHz, C6D6)
δ: 213.5, 166.9, 129.2, 127.5, 103.1, 100.0, 72.4, 67.2, 51.3, 30.3, 28.9,
25.6, 22.2, 18.1, 14.5, 13.7, −5.6, −5.7; FTIR (νmax/cm−1): 3465, 2954,
2928, 2858, 1940, 1716, 1463, 1435, 1361, 1258, 1118, 963, 837, 777;
MS (EI, m/z): 368 (1, M+), 339 (1), 311 (2), 279 (1), 249 (3), 219
(2), 191 (4), 175 (5), 159 (6), 145 (3), 121 (5), 117 (15), 105 (30),
91 (20), 77 (20), 75 (100), 73 (50), 57 (85), 41 (60); HRMS (ESI):
C20H37O4Si (MH)+, 369.2456 (calculated), 369.2470 (found).
2fa: Yield: 25.4 mg (90%); 1H NMR (400 MHz, C6D6) δ: 6.29 (dd,
J = 15.7, 1.2 Hz, 1H, minor), 6.28 (dd, J = 15.7, 1.2 Hz, 1H, major),
5.63 (dd, J = 15.7, 6.6 Hz, 1H, minor), 5.62 (dd, J = 15.7, 6.6 Hz, 1H,
major), 3.73 (d, J = 6.6 Hz, 1H), 3.36 (s, 3H, major), 3.34 (s, 3H,
minor), 2.38 (td, J = 7.2, 1.6 Hz, 2H), 2.15 (bs, 1H), 2.00 (bs, 1H),
1.71 (s, 3H, minor), 1.71 (s, 3H, major), 1.43 (quint, J = 7.2 Hz, 2H),
1.23 (sext, J = 7.2 Hz, 2H), 1.06 (s, 3H, major), 1.05 (s, 3H, minor),
1.03 (s, 3H, minor), 1.02 (s, 3H, major), 0.78 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, C6D6) δ: 213.5, 166.9, 129.3, 128.4, 103.2,
100.0, 79.2, 72.3, 51.3, 30.3, 28.8, 26.1, 23.8, 22.1, 14.5, 13.6; FTIR
(νmax/cm−1): 3407, 2956, 2929, 2860, 1940, 1714, 1436, 1377, 1265,
1242, 1133, 1015, 965, 898; MS (EI, m/z): 282 (2, M+), 250 (2), 222
(1), 191 (3), 164 (4), 134 (4), 121 (20), 91 (7), 77 (16), 65 (5), 59
(100), 43 (37); HRMS (ESI): C16H27O4 (MH)+: 283.1904
(calculated), 283.1908 (found).
1
2be: Yield: 26.1 mg (88%); H NMR (400 MHz, C6D6) δ: 6.43
(dd, J = 16.0, 1.6 Hz, 1H), 5.51 (dd, J = 16.0, 5.6 Hz, 1H), 5.05 (sept,
J = 6.4 Hz, 1H, major), 5.05 (sept, J = 6.4 Hz, 1H, minor), 4.23−4.16
(m, 1H), 3.02 (dd, A of ABX, JAB = 9.2 Hz, JAX = 4.0 Hz, 1H), 2.97
(dd, B of ABX, JAB = 9.2 Hz, JBX = 7.6 Hz, 1H), 2.94 (s, 3H), 2.42 (td,
J = 7.6, 2.0 Hz, 2H), 2.21 (bs, 1H), 1.71 (s, 3H), 1.45 (quint, J = 7.6
Hz, 2H), 1.25 (sext, J = 7.6 Hz, 2H), 1.02 (d, J = 6.4 Hz, 3H), 1.01
(d, J = 6.4 Hz, 3H), 0.79 (t, J = 7.6 Hz, 3H, major), 0.79 (t, J = 7.6 Hz,
3H, minor); 13C{1H} NMR (100 MHz, CDCl3) δ: 213.5, 166.7,
128.9, 127.6, 103.0, 100.7, 76.5, 71.1, 68.1, 59.1, 30.2, 28.6, 22.2, 21.9,
21.8, 14.7, 13.9; FTIR (νmax/cm−1) δ: 3442, 2957, 2927, 1942, 1706,
1457, 1373, 1322, 1264, 1107, 1062, 1014, 966,831,713; MS (EI, m/z):
296 (1, M+), 282 (1), 251 (2), 209 (3), 191 (4), 180 (1), 121 (6), 107
(4), 91 (7), 77 (6), 55 (4), 45 (100); HRMS (ESI): C17H29O4 (MH)+,
297.2060 (calculated), 297.2060 (found).
1
2bg: Yield: 26.8 mg (91%); H NMR (400 MHz, C6D6) δ: 6.43
(dd, J = 15.6, 0.8 Hz, 1H), 5.72−5.62 (m, 1H), 5.52 (dd, J = 15.6, 5.6
Hz, 1H), 5.08 (dq, J = 18.8, 1.6 Hz, 1H), 4.89 (dq, J = 6.4, 1.6 Hz,
1H), 4.53−4.41 (m, 2H), 4.23−4.19 (m, 1H), 3.04 (dd, A of ABX,
JAB = 9.6 Hz, JAX= 4.0 Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6 Hz, JBX
=
2ga: Yield: 26.3 mg (89%); 1H NMR (400 MHz, C6D6) δ: 6.45 (dd,
J = 15.8, 1.6 Hz, 1H), 5.68 (dd, J = 15.8, 6.2 Hz, 1H), 3.96 (d, J = 6.2
Hz, 1H), 3.36 (s, 3H, major), 3.33 (s, 3H, minor), 2.86 (s, 3H), 2.44
(bs, 1H), 2.38 (td, J = 7.6, 1.6 Hz, 2H), 1.72 (s, 3H), 1.43 (quint, J =
7.6 Hz, 2H), 1.23 (sext, J = 7.6 Hz, 2H), 0.93 (s, 3H), 0.88 (s, 3H),
0.78 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6) δ: 213.4,
166.9, 129.1, 103.2, 99.9, 77.6, 77.1, 51.3, 48.6, 30.3, 28.9, 22.1, 20.2,
19.2, 14.6, 13.7; FTIR (νmax/cm−1): 3446, 2953, 2928, 2859, 1939,
7.2 Hz, 1H), 2.95 (s, 3H), 2.39 (td, J = 7.2, 2.0 Hz, 2H), 2.31 (bs, 1H),
1.70 (s, 3H), 1.44 (quint, J = 7.2 Hz, 2H), 1.24 (sext, J = 7.2 Hz, 2H),
0.79 (t, J = 7.2 Hz, 3H, minor), 0.78 (t, J = 7.2 Hz, 3H, major);
13C{1H} NMR (100 MHz, CDCl3) δ: 213.7, 166.8, 132.4, 128.5,
128.1, 117.4, 103.2, 100.0, 76.4, 71.1, 65.2, 59.1, 30.1, 28.5, 22.2, 14.7,
13.9; FTIR (νmax/cm−1): 3417, 2956, 2928, 2873, 1939, 1710, 1647,
1456, 1379, 1322, 1259, 1236, 1172, 1129, 1062, 1015, 965, 928, 837,
713. MS (EI, m/z): 294 (1, M+), 261 (1), 249 (2), 221 (1), 191 (5),
J
DOI: 10.1021/acs.joc.5b00382
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1712, 1459, 1435, 1380, 1321, 1264, 1241, 1118, 1062, 1015, 965, 861,
833, 740, 713; MS (EI, m/z): 296 (1, M+), 265 (1), 233 (1), 221 (1),
191 (1), 121 (3), 91 (5), 74 (4), 73 (100), 59 (5), 43 (20); HRMS
(ESI): C17H29O4 (MH)+: 297.2060 (calculated), 297.2063 (found).
2la: Yield: 21.1 mg (68%); 1H NMR (400 MHz, C6D6) δ: 6.22 (dd,
J = 15.6, 1.6 Hz, 1H, major), 6.21 (dd, J = 15.6, 1.6 Hz, 1H, minor),
5.92 (dd, J = 15.6, 5.2 Hz, 1H), 4.23−4.15 (m, 1H), 3.38 (s, 3H), 3.01
(dd, A of ABX, JAB = 9.2 Hz, JAX = 3.6 Hz, 1H), 2.95 (dd, B of ABX,
JAB = 9.2 Hz, JBX = 7.6 Hz, 1H), 2.92 (s, 3H), 2.44−2.37 (m, 2H), 2.29
(bs, 1H), 1.51−1.46 (m, 2H), 1.26 (sext, J =7.2 Hz, 2H), 1.07 (s, 9H),
0.81 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6) δ: 208.6,
167.4, 132.0, 123.6, 117.1, 102.7, 76.4, 70.6, 58.2, 51.3, 33.8, 30.5, 30.1,
28.9, 22.4, 13.7; FTIR (νmax/cm−1): 3455, 2957, 2929, 2871, 1940,
1713, 1459, 1435, 1395, 1363, 1322, 1264, 1239, 1195, 1172, 1132,
1062, 1017, 963, 713; LC-MS/MS: 311 (67, MH+), 292 (19), 279
(80), 261 (27), 255 (10), 251 (5), 247 (10), 237 (9), 229 (60), 223
(100), 219 (8), 205 (8), 201 (9), 191 (8), 179 (26), 177 (8), 169
(10); HRMS (ESI): C18H31O4 (MH)+: 311.2223 (calculated),
311.2220 (found).
1
2ha: Yield: 22.1 mg (87%): H NMR (400 MHz, C6D6) δ: 6.24
(ddd, J = 15.2, 10.6, 1.6 Hz, 1H), 5.98 (dt, J = 10.6, 2.7 Hz, 1H), 5.46
(ddd, J = 15.2, 4.8, 0.8 Hz, 1H), 4.16−4.08 (m, 1H), 3.36 (s, 3H,
major), 3.35 (s, 3H, minor), 2.99 (dd, A of ABX, JAB = 9.6 Hz, JAX
=
4.0 Hz, 1H), 2.93 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.6 Hz, 1H), 2.93
(s, 3H), 2.41−2.29 (m, 2H), 2.20 (bs, 1H), 1.42 (quint, J = 7.2 Hz,
2H), 1.23 (sext, J = 7.2 Hz, 2H), 0.79 (t, J = 7.2 Hz, 3H, minor), 0.78
(t, J = 7.2 Hz, 3H, major); 13C{1H} NMR (100 MHz, C6D6) δ: 213.8,
166.6, 132.7, 124.1, 101.9, 97.0, 76.3, 70.3, 58.2, 51.3, 30.2, 28.6, 22.1,
13.6. FTIR (νmax/cm−1): 3423, 2955, 2930, 2872, 1941, 1716, 1436,
1322, 1268, 1133, 1062, 967, 853, 713; MS (EI, m/z): 254 (1, M+),
223 (1), 209 (2), 177 (4), 149 (3), 135 (4), 125 (6), 107 (8), 91 (7),
77 (10), 65 (5), 59 (10), 45 (100); HRMS (ESI): C14H23O4 (M)+:
255.1591 (calculated), 255.1593 (found).
2ma: Yield: 17.2 mg (81%); 1H NMR (400 MHz, C6D6) δ: 6.29 (d,
J = 16.0 Hz, 1H, major), 6.26 (d, J = 15.9 Hz, 1H, minor), 5.69−5.66
(m, 1H), 5.47 (ddd, J = 15.9, 5.2, 1.2 Hz, 1H), 4.17−4.12 (m, 1H),
3.32 (s, 3H, major), 3.31 (s, 3H, minor), 3.00 (dd, A of ABX, JAB = 9.6
Hz, JAX = 4.0 Hz, 1H), 2.95 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.2 Hz,
1H), 2.95 (s, 3H), 2.08 (bs, 1H), 1.55 (d, J = 2.7 Hz, 3H); 13C{1H}
NMR (100 MHz, C6D6) δ: 216.1, 165.0, 130.2, 126.0, 103.5, 87.5,
76.3, 70.5, 58.2, 51.1, 14.0; FTIR (νmax/cm−1): 3429, 2925, 1944,
1721, 1438, 1395, 1260, 1196, 1153, 1126, 1028, 966, 840; MS (EI,
m/z): 212 (2, M+), 193 (1), 167 (3), 135 (6), 110 (6), 107 (11), 81
(5), 77 (20), 67 (6), 59 (11), 45 (100); HRMS (ESI): C11H17O4
(MH+): 213.1121 (calculated), 213.1120 (found).
2ia: Yield: 26.4 mg (82%); 1H NMR (400 MHz, CDCl3) δ: 6.08 (d,
J = 15.8 Hz, 1H), 5.72 (dd, J = 15.8, 6.8 Hz, 1H), 4.16 (q, J = 6.8 Hz,
1H), 3.70 (s, 3H), 2.31−2.15 (m, 4H), 1.62−1.28 (m, 16H), 0.93 (m,
9H); 13C{1H} NMR: (100 MHz, CDCl3) δ: 213.1, 167.8, 132.8,
126.2, 108.2, 101.4, 73.1, 52.0, 37.0, 30.3, 29.6, 28.7, 28.3, 27.6, 22.6,
22.4, 22.3, 14.0, 13.9, 13.8; FTIR (νmax/cm−1): 3418, 2956, 2929,
2860, 1937, 1716, 1465, 1435, 1378, 1265, 1133, 1072, 964; MS (EI,
m/z): 322 (1, M+), 236 (3), 194 (5), 163 (5), 119 (5), 105 (6), 91
(17), 85 (12), 69 (30), 57 (50), 41 (100); HRMS (ESI): C20H35O3
(MH)+: 323.2581 (calculated), 323.2584 (found).
1
2na: Yield: 27.0 mg (92%); H NMR (400 MHz, C6D6) δ: 6.46
1
(dd, J = 15.7, 1.6 Hz, 1H), 5.53 (dd, J = 15.7, 5.5 Hz, 1H), 4.27−4.20
(m, 1H), 3.36 (s, 3H, major), 3.35 (s, 3H, minor), 3.05 (dd, A of ABX,
2ia′: Yield: 25.5 mg (80%); H NMR (400 MHz, CDCl3) δ: 6.08
(d, J = 15.7 Hz, 1H), 5.72 (dd, J = 15.7, 6.7 Hz, 1H), 4.17 (q, J = 6.7
Hz, 1H), 3.71 (s, 3H), 2.30−2.14 (m, 4H), 1.71−1.18 (m, 15H),
0.97−0.82 (m, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ: 213.1,
167.8, 132.8, 126.1, 108.2, 101.4, 73.0, 52.0, 37.1, 30.4, 29.6, 28.7, 28.4,
27.6, 22.6, 22.4, 22.3, 14.0, 13.9; FTIR (νmax/cm−1): 3422, 2956, 2928,
2859, 1937, 1716, 1465, 1435, 1379, 1264, 1132, 1074, 963; MS (EI,
m/z): 322 (1, M+), 236 (20), 231 (21), 205 (20), 195 (36), 194 (90),
179 (35), 177 (42), 165 (39), 163 (50), 152 (38), 135 (55), 121
(61),107 (68), 105 (60), 93(72), 91 (74), 85 (69), 79 (62), 57 (100),
55 (41); HRMS (ESI) C20H35O3 (MH)+: 323.2581 (calculated),
323.2584 (found).
JAB = 9.6 Hz, JAX = 4.0 Hz, 1H), 3.00 (dd, B of ABX, JAB = 9.6 Hz, JBX
=
7.2 Hz, 1H), 2.96 (s, 3H), 2.64 (tt, J = 11.4, 3.4 Hz, 1H), 2.33 (bs,
1H), 1.95 (d, J = 11.4 Hz, 2H), 1.71 (s, 3H), 1.64−1.55 (m, 2H),
1.53−1.45 (m, 1H), 1.30−0.94 (m, 5H); 13C NMR (100 MHz, C6D6)
δ: 213.2, 166.6, 129.1, 105.9, 104.3, 76.5, 70.6, 58.2, 51.2, 37.6, 32.8,
26.4, 26.3, 26.0, 14.6; FTIR (νmax/cm−1): 3420, 2924, 2851, 1936,
1712, 1435, 1369, 1322, 1254, 1228, 1192, 1128, 1093, 1071, 1026,
997, 965, 891, 872, 780; MS (EI, m/z): 294 (2, M+), 262 (1), 249 (2),
217 (3), 189 (1), 171 (4), 135 (2), 119 (3), 105 (5), 91 (6), 77 (6), 67
(4), 55 (8), 45 (100); HRMS (ESI): C17H27O4 (MH)+: 295.1904
(calculated), 295.1908 (found).
2ja: Yield: 20.7 mg (87%); 1H NMR (400 MHz, C6D6) δ: 6.16 (dd,
J = 15.6, 1.2 Hz, 1H), 5.50 (dd, J = 15.6, 6.2 Hz, 1H, minor), 5.49 (dd,
J = 15.6, 6.2 Hz, 1H, major), 4.03 (quint, J = 6.2 Hz, 1H), 3.38 (s, 3H,
major), 3.37 (s, 3H, minor), 2.39 (td, J = 7.4, 1.2 Hz, 2H), 1.70 (s,
3H), 1.49−1.41 (m, 2H), 1.25 (sext, J = 7.4 Hz, 2H), 1.04 (d, J = 6.2
Hz, 3H), 0.80 (t, J = 7.4 Hz, 3H, minor), 0.80 (t, J = 7.4 Hz, 3H,
major); 13C{1H} NMR (100 MHz, C6D6) δ: 213.3, 166.9, 134.7,
125.2, 103.1, 99.9, 68.0, 51.2, 30.3, 28.9, 23.1, 22.1, 14.5, 13.6; FTIR
(νmax/cm−1): 3410, 2956, 2928, 1941, 1715, 1436, 1322, 1266, 1135,
1062, 1016, 965, 714; MS (EI, m/z): 238 (3, M+), 205 (5), 194,(15),
181 (15), 164 (13), 151 (55), 135 (45), 121 (100), 107 (30), 93 (90),
77 (45), 65 (10), 55 (14), 43 (92); HRMS (ESI): C14H23O3 (MH)+:
239.1648 (calculated), 239.1652 (found).
1
2oa: Yield: 23.9 mg (89%); H NMR (400 MHz, C6D6) δ: 6.43
(dd, J = 15.8, 1.6 Hz, 1H), 5.51 (dd, J = 15.8, 5.6 Hz, 1H), 4.25−4.20
(m, 1H), 3.32 (s, 3H, major), 3.30 (s, 3H, minor), 3.04 (dd, A of ABX,
JAB = 9.6 Hz, JAX = 4.4 Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6 Hz, JBX
=
7.2 Hz, 1H), 2.96 (s, 3H), 2.34 (bs, 1H), 1.68 (s, 3H), 1.29 (s, 9H);
13C{1H} NMR (100 MHz, C6D6) δ: 212.4, 165.9, 128.9, 108.8, 103.2,
76.5, 70.7, 58.2, 50.9, 34.2, 29.3, 14.6; FTIR (νmax/cm−1): 3419, 2955,
2870, 1934, 1717, 1435, 1362, 1322, 1258, 1226, 1132, 1062, 965; MS
(EI, m/z): 268 (1, M+), 236 (1), 223 (2), 191 (3), 163 (5), 145 (5),
135 (15), 119 (5), 105 (6), 91 (12), 79 (15), 65 (5), 59 (7), 57 (25),
45 (100); HRMS (ESI): C15H25O4 (MH)+: 269.1747 (calculated),
269.1748 (found).
2ka: Yield: 29.9 mg (89%): 1H NMR (400 MHz, C6D6) δ: 6.27 (dd,
J = 15.8, 1.4 Hz, 1H, major), 6.26 (dd, J = 15.8, 1.4 Hz, 1H, minor),
5.78 (dd, J = 15.8, 5.5 Hz, 1H), 4.27−4.23 (m, 1H), 3.38 (s, 3H,
1
2ob: Yield: 25.7 mg (91%): H NMR (400 MHz, C6D6) δ: 6.44
(dd, J = 15.5, 1.6 Hz, 1H, major), 6.42 (dd, J = 15.5, 1.6 Hz, 1H,
minor), 5.52 (dd, J = 15.5, 6.0 Hz, 1H), 4.23−4.19 (m, 1H), 3.95 (qd,
J = 7.2 Hz, 1.2 Hz, 2H), 3.03 (dd, A of ABX, JAB = 9.6 Hz, JAX = 4.0
Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.2 Hz, 1H), 2.95 (s,
3H), 2.32 (bs, 1H), 1.70 (s, 3H), 1.31 (s, 9H), 0.89 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ: 212.1, 166.2, 129.0, 127.4,
109.2, 103.1, 76.5, 71.1, 60.3, 59.1, 34.2, 29.5, 14.8, 14.2; FTIR
(νmax/cm−1): 3420, 2959, 1939, 1713, 1459, 1366, 1322, 1255, 1223,
1112, 1060, 965; MS (EI, m/z): 282 (2, M+), 249 (1), 237 (3), 208
(2), 191 (4), 163 (6), 135 (15), 105 (7), 91 (11), 77 (16), 65 (4), 57
(18), 45 (100); HRMS (ESI): C16H27O4 (MH)+; 283.1904
(calculated), 283.1908 (found).
major), 3.37 (s, 3H, minor), 3.05 (dd, A of ABX, JAB = 9.6 Hz, JAX
=
4.0 Hz, 1H), 3.02 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.2 Hz, 1H), 2.94
(s, 3H), 2.46−2.41 (m, 2H), 2.34 (bs, 1H), 2.16−2.09 (m, 1H), 2.03−
1.99 (m, 1H), 1.92−1.87 (m, 1H), 1.66−1.60 (m, 2H), 1.54−1.45 (m,
3H), 1.33−1.01 (m, 7H), 0.81 (t, J = 7.2 Hz, 3H, major), 0.81 (t, J =
7.2 Hz, 3H, minor); 13C NMR (100 MHz, C6D6) δ: 212.3, 167.1,
129.0, 125.9, 113.8, 102.7, 76.5, 70.8, 58.2, 51.3, 38.0, 32.8, 32.4, 30.6,
29.0, 26.4, 26.4, 26.2, 22.4, 13.7; FTIR (νmax/cm−1): 3426, 2925, 2853,
1924, 1713, 1435, 1322, 1263, 1240, 1195, 1173, 1119, 1062, 1016,
964, 890, 841, 713; MS (EI, m/z): 336 (2, M+), 291 (60), 273 (8), 259
(100), 241 (20), 231 (30), 213 (27), 203 (30), 189 (19), 175 (21),
161 (22), 145 (21), 133 (21), 119 (19), 105 (25), 91(47), 79 (33), 67
(21), 55 (45), 45 (65); HRMS (ESI): C20H33O4 (MH)+: 337.2380
(calculated), 337.2384 (found).
2oe: Yield: 26.0 mg (88%) 1H NMR (400 MHz, C6D6) δ: 6.43 (dd,
J = 15.6, 1.6 Hz, 1H), 5.53 (dd, J = 15.6, 5.6 Hz, 1H), 5.01 (sept, J =
6.4 Hz, 1H), 4.22−4.19 (m, 1H), 3.03 (dd, A of ABX, JAB = 9.6 Hz,
JAX = 4.4 Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6 Hz, JBX = 7.6 Hz, 1H),
K
DOI: 10.1021/acs.joc.5b00382
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
2.95 (s, 3H, major), 2.94 (s, 3H, minor), 2.26 (bs, 1H), 1.71 (s, 3H),
1.31 (s, 9H), 1.00 (d, J = 6.4 Hz, 3H), 0.99 (d, J = 6.4 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ: 211.8, 165.9, 129.1, 127.3,
109.7, 103.1, 76.5, 71.1, 67.8, 59.0, 34.1, 29.5, 21.8, 21.8, 14.7; FTIR
(νmax/cm−1): 3410, 2960, 2926, 2896, 2825, 1935, 1708, 1458, 1373,
1322, 1255, 1226, 1049, 1021, 964, 833, 783, 713; MS (EI, m/z): 296
(1, M+), 278 (1), 251 (2), 236 (2), 191 (6), 163 (7), 135 (15), 105
(14), 91 (17), 77 (16), 65 (5), 57 (40), 45 (100); HRMS (ESI):
C17H29O4 (MH)+: 297.2060 (calculated); 297.2064 (found).
1.68 (s, 3H); 13C{1H} NMR (100 MHz, C6D6) δ: 215.9, 165.8, 133.2,
130.5, 128.7, 128.2, 127.5, 126.2, 104.4, 102.7, 76.4, 70.6, 58.2, 51.5,
14.2; FTIR (νmax/cm−1): 3419, 2922, 2851, 1926, 1716, 1492, 1434,
1369, 1321, 1273, 1195, 1171, 1123, 1062, 1039, 964, 918, 898, 781,
694; MS (EI, m/z): 288 (2, M+), 256 (3), 211 (5), 183(5), 155 (17),
115 (8), 89 (4), 77 (9), 51 (5), 45 (100); HRMS (ESI): C17H21O4
(MH)+: 289.1434 (calculated), 289.1439 (found).
1
2ta: Yield: 25.4 mg (82%); H NMR (400 MHz, C6D6) δ: 5.80 (d,
J = 8.2, 1.6 Hz, 1H, minor), 5.75 (dt, J = 8.2, 1.6 Hz, 1H, major),
4.55−4.50 (m, 1H), 3.36 (s, 3H), 3.08−3.03 (m, 2H), 2.96 (s, 3H),
2.40 (td, J = 7.6, 2.8 Hz, 2H), 2.25−2.11 (m, 4H), 1.60−1.20 (m, 4H),
0.86−0.78 (m, 5H); 13C{1H} NMR (100 MHz, C6D6) δ: 207.1, 167.4,
137.2, 125.6, 109.3, 99.6, 76.3, 66.9, 58.3, 51.4, 30.7, 30.5, 28.9, 28.5,
25.6, 25.5, 22.2, 13.9; FTIR (νmax/cm−1): 3456, 2928, 2857, 2859,
1946, 1713, 1436, 1436, 1266, 1241, 1128, 1063, 957; MS (EI, m/z):
308 (1, M+), 276 (25), 231 (65), 201 (35), 175 (40), 161 (50), 117
(55), 91 (95), 77 (40), 55 (30), 45 (100); HRMS (ESI): C18H29O4
(MH)+: 310.2067 (calculated), 310.2067 (found).
Carbamate Derivatization of 2ba and Crystal Growth for
X-ray Analysis. The mixture of vinylallene ester (45.2 mg, 0.2 mmol),
phenyl isocyanate (31 mg, 0.26 mmol), and dry pyridine (15.8 mg,
0.2 mmol) in 2 mL of toluene was stirred at room temperature for
5 days. The mixture was taken into Et2O and washed with brine, dried
over MgSO4, and filtered. The solvent was removed in vacuum, and
the crude residue was purified by column chromatography on silica gel
(hexane−EtAc; 5:1, yield: 0.62 g, 80%).26 The pure white solid
material was dissolved in a boiled hexane and gradually cooled down
to 30 ° overnight.
1
2og: Yield: 25.9 mg (88%); H NMR (400 MHz, C6D6) δ: 6.42
(dd, J = 15.6, 1.6 Hz, 1H, major), 6.40 (dd, J = 15.6, 1.6 Hz, 1H,
minor), 5.64 (ddt, J = 17.2, 10.8, 4.8 Hz, 1H,), 5.53 (dd, J = 15.6, 5.6
Hz, 1H), 5.08 (dq, J = 17.2, 1.6 Hz, 1H), 4.87 (dq, J = 10.8, 1.6 Hz,
1H), 4.48−4.37 (m, 2H), 4.24−4.19 (m, 1H), 3.03 (dd, A of ABX, JAB
= 9.6 Hz, JAX = 4.0 Hz, 1H), 2.99 (dd, B of ABX, JAB = 9.6 Hz, JBX
=
7.2 Hz, 1H), 2.95 (s, 3H, major), 2.94 (s, 3H, minor), 2.28 (bs, 1H),
1.69 (s, 3H), 1.30 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ:
212.4, 165.7, 132.5, 128.7, 127.7, 117.1, 108.9, 103.2, 76.5, 71.1, 64.7,
59.1, 34.2, 29.4, 14.8; FTIR (νmax/cm−1): 3410, 2957, 2927, 1935,
1713, 1647, 1457, 1398, 1362, 1321, 1252, 1217, 1172, 1131, 1061,
1027, 1016, 964, 928, 836, 781, 713; MS (EI, m/z): 294 (1, M+), 249
(3), 236 (2), 191 (4), 163 (5), 135 (6), 105 (5), 91 (10), 77 (9), 65
(3), 57 (16), 45 (100); HRMS (EI): C17H27O4 (MH)+: 295.1904
(calculated), 295.1907 (found).
1
2pa: Yield: 29.6 mg (86%); H NMR (400 MHz, C6D6) δ: 7.17−
7.05 (m, 5H), 6.43 (dd, J = 15.8, 1.6 Hz, 1H), 5.49 (dd, J = 15.8, 5.6
Hz, 1H), 4.28−4.24 (m, 1H), 4.20 (s, 2H, major), 4.17 (s, 2H, minor),
3.31 (s, 3H), 3.19 (dd, A of ABX, JAB = 9.2 Hz, JAX = 3.6 Hz, 1H), 3.12
(dd, B of ABX, JAB = 9.2 Hz, JBX = 7.2 Hz, 1H), 2.32 (bs, 1H), 1.67 (s,
3H), 1.34 (s, 9H, minor), 1.29 (s, 9H, major); 13C{1H} NMR: (100
MHz, CDCl3) δ: 212.4, 166.5, 137.8, 128.8, 128.5, 127.9, 127.8, 127.7,
108.8, 103.1, 74.0, 73.4, 71.2, 51.6, 34.2, 29.4, 14.8; FTIR (νmax/cm−1):
3422, 2954, 2865, 1934, 1715, 1496, 1479, 1454, 1434, 1391, 1362,
1257, 1225, 1104, 1060, 1029, 965, 781, 737, 698; MS (EI, m/z): 344
(2, M+), 311 (2), 296 (2), 223 (2), 191 (3), 168 (4), 135 (11), 107
(7), 91 (100), 57 (50), 41 (25); HRMS (ESI): C21H29O4 (MH)+:
345.2060 (calculated), 345.2068 (found).
4ba: M.P.: 67−69 °C; 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J =
7.6 Hz, 2H), 7.32−7.28 (m, 2H), 7.06 (tt, J = 7.6, 1.2 Hz, 1H), 6.72
(bs, 1H), 6.33 (dd, J = 15.8, 1.2 Hz, 1H), 5.70 (dd, J = 15.8 Hz, 6.4
Hz, 1H), 5.53 (qd, J = 5.6, 1.2 Hz, 1H), 3.70 (s, 3H), 3.60 (d, J = 2.4
Hz, 1H), 3.59 (d, J = 0.8 Hz, 1H), 3.42 (s, 3H), 2.25 (t, J = 7.6 Hz,
2H), 1.89 (s, 3H), 1.40−1.28 (m, 4H), 0.88 (t, J = 7.6 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ: 213.8, 167.5, 152.6, 137.7,
130.0, 129.1, 124.8, 123.5, 118.6, 103.0, 100.0, 74.1, 73.5, 59.3, 52.1,
30.1, 28.6, 22.1, 14.7, 13.9.
1
2qa: Yield: 22.1 mg (87%); H NMR (400 MHz, C6D6) δ: 6.32
(dd, J = 15.8, 1.6 Hz, 1H, major), 6.09 (dd, J = 15.8, 6.0 Hz, 1H,
minor), 5.74 (dd, J = 15.8, 1.6 Hz, 1H, minor), 5.43 (dd, J = 15.8, 6.0
Hz, 1H, major), 4.03−3.99 (m, 1H), 3.35 (dd, A of ABX, JAB = 11.2
Hz, JAX = 3.6 Hz, 1H), 3.32 (s, 3H), 3.23 (dd, B of ABX, JAB = 11.2 Hz,
JBX = 7.2 Hz, 1H), 2.44 (bs, 1H), 2.22 (bs, 1H), 1.67 (s, 3H, major),
1.57 (s, 3H, minor), 1.34 (s, 9H, minor), 1.29 (s, 9H, major); 13C
NMR (100 MHz, C6D6) δ: 212.4, 165.9, 128.9, 108.9, 103.2, 72.8,
66.3, 50.9, 34.1, 29.3, 14.6; NMR (100 MHz, CDCl3) δ: 212.4, 166.5,
129.2, 127.9, 108.9, 103.1, 73.0, 66.4, 51.7, 34.2, 29.4, 14.8; FTIR
(νmax/cm−1): 3368, 2955, 2926, 2865, 1934, 1717, 1641, 1458, 1434,
1363, 1257, 1225, 1060, 1029, 965, 925, 862, 781; MS (EI, m/z): 254
(3, M+): 207 (7), 194 (11), 179 (10), 148 (13), 119 (15), 105 (20), 91
(35), 73 (20), 59 (20), 57 (100), 41 (50); HRMS (EI): C14H23O4
(MH)+: 255.1591 (calculated), 255.1590 (found).
ASSOCIATED CONTENT
■
S
* Supporting Information
1
X-ray crystallographic data of 4ba and copies of H NMR and
13C NMR spectra for the substrates 1 and 1′, the products 2
and 2′, and 4ba. The Supporting Information is available free of
charge on the ACS Publications website at DOI: 10.1021/
acs.joc.5b00382.
1
2ra: Yield: 30.9 mg, (84%): H NMR (400 MHz, C6D6) δ: 6.43
AUTHOR INFORMATION
Corresponding Author
*E-mail: leventartok@iyte.edu.tr
(dd, J = 15.6, 1.6 Hz, 1H, major), 6.41 (dd, J = 15.6, 1.6 Hz, 1H,
minor), 5.53 (dd, J = 15.6, 5.6 Hz, 1H), 4.17−4.12 (m, 1H), 3.42 (dd,
■
A of ABX, JAB = 10.0 Hz, JAX = 4.0 Hz, 1H), 3.32 (dd, B of ABX, JAB
=
10.0 Hz, JBX = 7.6 Hz, 1H), 3.32 (s, 3H), 2.23 (bs, 1H), 1.71 (s, 3H),
1.29 (s, 9H), 0.85 (s, 9H), −0.06 (s, 6H); 13C{1H} NMR (100 MHz,
C6D6) δ: 212.4, 165.9, 129.1, 108.8, 103.2, 72.5, 67.2, 50.9, 34.1, 29.3,
25.6, 18.1, 14.6, −5.6, −5.7; FTIR (νmax/cm−1): 3467, 2954, 2927,
2857, 1935, 1718, 1462, 1434, 1362, 1256, 1225, 1111, 1062, 1005,
963, 837, 777; MS (EI, m/z): 368 (1, M+), 351 (1), 311 (3), 279 (2),
237 (10), 223 (8), 191 (10), 177 (15), 163 (20), 159 (43), 145 (20),
135 (25), 105 (30), 89 (45), 75 (85), 73 (100), 57 (55), 41 (38); HRMS
(ESI): C20H37O4Si (MH)+: 369.2456 (calculated), 369.2463 (found).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The financial support of the Scientific and Technological
Research Council of Turkey and Federal Ministry of Education
and Research (Germany) via the Intensified Cooperation
Program (210T092) is gratefully acknowledged. We thank the
Biological Mass and Proteomics Facility of Izmir Institute of
Technology for MS/MS analyses and the Mass Spectrometry
Laboratory of Dortmund University of Technology for HRMS
analyses.
1
2sa: Yield: 25.1 mg (87%); H NMR (400 MHz, C6D6) δ: 7.71−
7.67 (m, 2H), 7.14−7.11 (m, 2H), 7.03−6.99 (m, 1H), 6.41 (dd, J =
15.8, 1.2 Hz, 1H, major), 6.38 (dd, J = 15.8, 1.2 Hz, 1H, minor), 5.56
(dd, J = 15.8, 5.6 Hz, 1H), 4.21−4.16 (m, 1H), 3.38 (s, 3H, major),
3.36 (s, 3H, minor), 3.03−2.96 (m, 2H), 2.96 (s, 3H), 2.30 (bs, 1H),
L
DOI: 10.1021/acs.joc.5b00382
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
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DEDICATION
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Dedicated to the memory of Prof. Dr. Ayhan S. Demir.
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DOI: 10.1021/acs.joc.5b00382
J. Org. Chem. XXXX, XXX, XXX−XXX