Ene-Yne Metathesis of Allylphosphonates and Allylphosphates: Synthesis of Phosphorus-Containing 1,3-Dienes

Article abstract of DOI:10.1021/acs.joc.0c02886

A variety of ene-yne cross metathesis reactions were performed using unsaturated phosphonate and phosphate reagents, affording the corresponding phosphorylated 1,3-diene products in good to excellent yields. These difficult ene-yne metatheses employed a Grubbs catalyst bearing a cyclic amino alkyl carbene ligand. A variety of terminal alkynes of varying substitution underwent the reaction, and different phosphorus-containing alkenes were found to give the conjugated diene products in high yields. The resulting dienes were further transformed by Horner-type Wittig reactions and a Diels-Alder cycloaddition.

Full text of DOI:10.1021/acs.joc.0c02886

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Ene−Yne Metathesis of Allylphosphonates and Allylphosphates:
Synthesis of Phosphorus-Containing 1,3-Dienes
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̀
Laurence N. Rohde, Jr., Therese H. Wild, and Steven T. Diver*
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ABSTRACT: A variety of ene−yne cross metathesis reactions were
performed using unsaturated phosphonate and phosphate reagents,
affording the corresponding phosphorylated 1,3-diene products in good
to excellent yields. These difficult ene−yne metatheses employed a
Grubbs catalyst bearing a cyclic amino alkyl carbene ligand. A variety of
terminal alkynes of varying substitution underwent the reaction, and
different phosphorus-containing alkenes were found to give the
conjugated diene products in high yields. The resulting dienes were
further transformed by Horner-type Wittig reactions and a Diels−Alder
cycloaddition.
Scheme 1. Desired Cross Ene−Yne Metathesis to Provide
Dienylphosphonates
INTRODUCTION
■
Organophosphorus compounds are useful reagents in organic
synthesis and comprise a privileged class of compounds that
have numerous applications in industry as agrochemicals, fire
retardants and medicines. In catalysis, phosphines R3P are
widely used as ligands, coveted because of their ability to fine
tune a metal’s performance in catalysis. Phosphorus-stabilized
carbanions such as those used in the Horner−Wadsworth−
Emmons olefination1−4 are not only classical reagents for
alkene bond synthesis but also widely used for stereoselective
alkene synthesis in complex molecule total synthesis.
1,3-Dienes are versatile building blocks, but unsaturated
phosphorus(V) compounds were perceived to be difficult
substrates for metathesis chemistry due to their potential to
coordinate through the PO bond. This might be especially
disruptive to intermolecular reactions, especially in ene−yne
metathesis where alkyne concentrations must be low to avoid
oligomerization side reactions.5 There are many traditional
methods for 1,3-diene functionalization, like the Diels−Alder
reaction, and diverse metal-catalyzed reactions have emerged
that can functionalize the ends of the diene with various
heteroatoms. However, there are a limited number of examples
of allylphosphonate reagents undergoing intermolecular
(cross) alkene metathesis6−9 and no examples of these reagents
giving cross ene−yne metathesis. Early examples by Hanson
and co-workers used unsaturated phosphonates and related
compounds to construct P-heterocycles by ring-closing meta-
thesis (RCM)10−13 and later developed this procedure to
synthesize alkenes in complex molecule synthesis.14,15
Governeur,16 van Boom,17 and Schmidt18 also made P-
heterocycles by RCM or ring-closing EYM, respectively.
Some of the Grubbs catalysts used for alkene and ene−yne
metathesis are shown in Scheme 1 below. The second-
generation Grubbs catalyst Ru1 and the Hoveyda−Grubbs
catalysts Ru2 are typically used for most challenging
applications. Hoveyda’s related chiral molybdenum catalysts
have been used for asymmetric RCM to construct P-
heterocycles.19 Pietrusiewicz and Grela employed vinyl
Received: December 4, 2020
Published: January 5, 2021
https://dx.doi.org/10.1021/acs.joc.0c02886
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phosphine oxides in cross metathesis using the more active
Grela catalyst Ru2B.20 Bowen et al. dimerized diethyl
allylphosphonate with Ru1.21 More recently, Spilling and co-
workers utilized substituted allylphosphonates in the cross
alkene metathesis with the Grubbs complex Ru1.22 Coordina-
tion of the PO bond to the ruthenium carbene could
deactivate catalytic intermediates, cause catalyst decomposi-
tion, or simply decrease the reaction rate, resulting in a
synthetically impractical reaction. With low alkyne concen-
trations, these interactions could be particularly debilitating.
Though active Grela catalysts have been used for difficult cross
alkene metathesis, new catalysts have seldom been applied to
problematic cross ene−yne metathesis. Recent work by Fogg
has shown that CAAC-containing Ru carbene catalysts may
overcome decomposition in alkene metathesis.23 We specu-
lated that Ru catalysts such as Ru3 and Ru4 bearing CAAC
ligands instead of the N-heterocyclic carbene ligand (which
characterizes the second generation Grubbs complex) might be
useful in encouraging difficult cross ene−yne metathesis.
In this work, we report that unsaturated phosphorus-
containing functional groups, such as allylphosphonates and
homoallylphosphonates, can be joined to alkynes by ene−yne
metathesis (EYM) by use of a CAAC-containing Grubbs
catalyst. With this method, it is possible to access a variety of
new phosphorus compounds containing the valuable 1,3-diene
subunit (Scheme 1). We envisioned use of these novel
products for both Wittig-type reactions and reactions of the
1,3-diene, such as Diels−Alder reactions.
the unbranched alkyne 2c, also possessing a benzoate group at
the propargylic position, failed to react using either the Grubbs
or Hoveyda−Grubbs catalysts (entries 3 and 4). Similarly, no
reaction was observed for either 2d or 2e (entries 5 and 6).
Previous mechanistic work in our group explains the poor
reactivity of unbranched terminal alkynes such as 2c and 2e.26
Alkyne branching was found to accelerate the slow step in the
ene−yne metathesis catalytic cycle.26,27 If there is no branching
in the alkyne side chain, the overall reaction rate slows down. If
this critical step in the catalytic cycle becomes too slow,
decomposition may occur,5 as we found when studying the
kinetics of EYM promoted by the phosphine-free Hoveyda−
Grubbs complex, Ru2.27 Grubbs and Bertrand et al.28 showed
that use of Bertrand’s CAAC ligand29 in a series of novel Ru
complexes resulted in a Grubbs catalyst that registered the
highest turnover observed for an ethenolysis. In recent
mechanistic studies, Fogg et al. found that CAAC Ru carbene
catalysts can resist decomposition of ruthenacycles,23 which
can explain their increased reactivity in alkene metathesis.
Lemcoff and co-workers found reduced side reactions due to
isomerization when using CAAC Ru carbenes.30 Aware of
these developments and applications of CAAC Ru carbenes in
challenging alkene metathesis,28,31 we surmised that CAAC Ru
carbenes might be useful for difficult cross ene−yne metathesis
since some of the Ru carbene intermediates are the same. We
focused our attention on the problematic coupling of
phosphonate 1a to linear alkyne 2c.
Catalyst optimization studies determined that a CAAC-
containing catalyst was superior for this ene−yne metathesis
using less reactive, linear terminal alkynes (Table 2). We
RESULTS AND DISCUSSION
■
Initial experiments with the Grubbs catalysts gave mixed
results in the cross ene−yne metathesis of allylphosphonates
(Table 1). Allylphosphonate 1a was chosen to investigate ene−
yne metathesis (EYM) using various terminal alkynes. For 2a
and 2b, excellent yields were obtained using equimolar
quantities of alkene 1a and alkyne 2 (entries 1 and 2, Table
1). Use of equimolar stoichiometry is unusual in cross EYM24
and is highly appealing due to its atom economy.25 However,
Table 2. Catalyst Optimization Studies
a
entry
RuX (mol %)
Y
temp (°C), time (h)
yield (%)
1
2
3
4
5
6
7
8
Ru1 (10)
Ru1 (10)
Ru2A (5)
Ru2A (5)
Ru2A (5)
Ru2A (5)
Ru3 (5)
Ru4 (5)
Ru3 (5)
Ru3 (5)
Ru3 (1)
Ru3 (5)
Ru3 (5)
Ru3 (5)
Ru3 (5)
1
4
1
1
4
9
4
4
3
2
4
4
4
3
2
60, 24
60, 3
60, 3
80, 3
60, 3
60, 3
60, 3
60, 3
60, 3
60, 3
60, 3
rt, 3
<10
44
<10
<10
32
Table 1. Initial Studies of Allylphosphonate−Alkyne
Metathesis
71
>95
<10
>95
21
<10
>95
>95
>95
25
9
10
11
12
13
14
15
rt, 1
rt, 1
rt, 1
a
NMR yields based on integration vs mesitylene internal standard.
focused on the combination of alkene 1a and linear
(unbranched) alkyne 2c. With a high 10 mol % catalyst
loading of Grubbs’ catalyst Ru1, increasing alkene equivalents
helped but still did not give a good yield (entries 1 and 2,
Table 2). The more thermally robust Hoveyda−Grubbs
catalyst Ru2A was investigated in more detail, where low
conversions were found at 60 and 80 °C, but increased yields
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were found at 4 and 9 equiv of alkene (entries 3−6). We
considered 4 equiv to be the upper limit for excess alkene
because it is both wasteful and produces significantly more of
the unwanted alkene homodimer. The CAAC catalysts Ru3
and Ru4 were next screened. The smaller Ru3 promoted the
reaction and gave greater than 95% NMR yield, but the bulkier
Ru4 gave unsatisfactory results (entries 7 and 8, respectively).
Using Ru3, the alkene equivalents could be reduced to 3 with
equal results, but the yield was found to plummet if only 2
equiv of 1a was used (entries 9 and 10). Reduction in catalyst
loading to 1 mol % was not possible (entry 11). Surprisingly,
excellent reactivity was found at room temperature, and similar
attempts to drop the alkene equivalents paralleled the
observations at 60 °C (entries 12−15). This led us to settle
on the conditions in either entry 9 or entry 14, with 3 equiv of
the phosphorus reagent at either 60 °C or 25 °C.
alkene. Z-Selectivity is unprecedented in ene−yne metathesis,
so we took a closer look at the reaction. Early aliquots showed
that the reaction was not stereoselective: an initial E/Z
isomeric mixture was produced; however, the E-isomer quickly
and selectively decomposed, which upgraded the Z-isomer.
Next, we found that the ene−yne metathesis was general
with respect to the phosphorus-containing alkene (Table 4).
Table 4. Variation of Phosphonate Alkene Partner
With a suitable catalyst and lower temperature found, we
investigated a variety of terminal alkynes bearing various
functional groups (Table 3). Because of the lower temper-
Table 3. Alkyne Scope
We investigated two additional phosphonates bearing different
esters, 1b and 1c; a homoallyl diethylphosphonate 1d; an
allylated β-ketophosphonate reagent 1e; and allylphosphate 1f
(see bottom of Table 4). These alkene-containing reactants
were subjected to intermolecular ene−yne metathesis with a
variety of alkynes using the standard conditions from the table
above. Dimethyl allylphosphonate gave results similar to those
of the diethyl ester (entries 1 and 2, Table 4). Next, we
investigated bis(trifluoroethyl)phosphonate esters, since these
phosphonate reagents are valuable for stereoselective Z-alkene
synthesis via the Still−Gennari modification32 of the Horner−
Wadsworth−Emmons (HWE) reaction. The presence of
electron-withdrawing groups on the phosphonate was well
tolerated but required higher reaction temperatures (entries
3−5). As expected, extending the allyl chain by one carbon did
not perturb the reaction and resulted in very good yields of the
expected 1,3-dienes (entries 6 and 7). Next, considering the
utility of the HWE, we wanted to try an β-ketophosphonate 1e,
which could be used for subsequent olefination of aldehydes.
Previously, we had difficulty bringing about cross ene−yne
metathesis in the presence of malonates.33 Fortunately, no
difficulties were observed with this alkene, and the products
were obtained in very good yields (entries 8 and 9). Finally, we
examined allylphosphate as a partner. The products in entries
10 and 11 were attractive since cross coupling or substitution
a
4 equiv of 1a used.
atures possible with the CAAC catalyst, we elected to use
dichloromethane as the reaction solvent for preparative runs.
With the problematic linear alkyne 2c, a high yield of the diene
3ac was obtained after only 1 h in CH2Cl2 at rt (entry 1). The
branched TBS ether worked well, providing a 68% yield of
diene 3ad (entry 2). Other linear alkynes underwent the cross
metathesis to give the expected products in excellent yields
(entries 3 and 4). Branching at the propargylic position of the
alkyne was well tolerated (entries 5 and 6). Trimethylsilyla-
cetylene was a good substrate and gave the product 3ai in an
unusually high 9:1 E/Z ratio (entry 7). Nitrogen functionality
was tolerated (entries 8 and 9). Last, methyl propiolate 2l
underwent reaction to give the corresponding product 3al in
moderate yield, but remarkably as solely the Z-isomer, as
evidenced by the magnitude of the coupling constant (3JHH
10.1 Hz) for the vinylic hydrogens of the 1,2-disubstituted
=
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of these products would be possible, thereby extending
synthetic utility of the 1,3-diene products. In the event,
allylphosphate 1f was found to be a willing partner in the cross
ene−yne metathesis under the standard conditions using the
CAAC catalyst Ru3. In all cases, the 1,3-diene products were
produced as E/Z mixtures.
diene 3ef underwent facile [4 + 2] cycloaddition with phenyl-
1,3,4-triazol-2,5-dione (PTAD);40−43 subsequent deprotona-
tion and Horner−Wadsworth−Emmons reaction with benzal-
dehyde afforded cycloadduct 4ef with the trisubstituted alkene
in the side chain formed as a 3:1 E/Z mixture.
While not fully explored, atom economy could be achieved
in some of these ene−yne metatheses. For example, in entry 3
of Table 4, 1 equiv of bis(trifluoroethyl)phosphonate 1c was
subjected to cross metathesis with 1 equiv of alkyne 2b using
catalyst Ru2A to give product 3cb in 89% yield. This provides
an additional example of atom economy (cf. entries 1 and 2 in
Table 1).
Sulfur functionality is particularly problematic in cross
metathesis since sulfur has a strong affinity for late metals
such as Ru.34−37 Since thiophosphonates are known to give
higher yields in Horner−Wittig reactions,38 we decided to
investigate the compatibility of the PS functional group with
the Ru-catalyzed ene−yne metathesis. We explored the
thiophosphonate 1g under analogous conditions as given
above to find excellent conversion in the ene−yne metathesis.
However, in these two examples (Scheme 2), it proved difficult
CONCLUSION
■
In conclusion, dienes can be synthesized by ene−yne
metathesis between phosphorus-containing alkenes and
alkynes using a suitable Grubbs catalyst bearing a cyclic alkyl
amino carbene (CAAC) ligand. In the best cases, atom-
economical coupling of 1 equiv of alkene and 1 equiv of alkyne
could be achieved. Mostly, diethyl allylphosphonate and
diethyl homoallyl phosphonate were used as alkene reactants,
but other phosphorus-containing functional groups were also
found to be good substrates. The superiority of a CAAC-
containing Grubbs catalyst had not been demonstrated
previously for ene−yne metathesis. Most likely, the superior
performance of this catalyst is due to improved catalyst lifetime
through analogy to alkene metathesis; however, no kinetic or
mechanistic studies were done in this work. The usefulness of
these catalysts may extend to other problematic metatheses; on
the basis of this work, it seems prudent to consider the use of
CAAC types of Ru catalysts (Bertrand−Grubbs catalysts) in
cross ene−yne metathesis. Synthetic utility of the products was
demonstrated through condensation of phosphorus-stabilized
carbanions with aldehydes, through diene functionalization, or
both.
Scheme 2. Thiophosphonate Ene−Yne Metathesis and
Protecting Group Removal
EXPERIMENTAL SECTION
■
A. General Information. Unless stated otherwise, all reactions
were performed in oven-dried glassware equipped with a magnetic stir
bar and carried out under a nitrogen atmosphere. CH2Cl2, Et2O, and
THF were degassed by bubbling the solvent with argon gas and
subsequently dried by passage through an activated alumina column
while under an argon atmosphere via a solvent purification system.
Benzene was degassed similarly and subsequently dried by passage
through an activated alumina and Q5 column via a solvent
purification system. All reagents used were purchased from
commercial vendors and used without further purification, unless
otherwise noted. Reactions carried out at −78 °C, 0 °C, and
temperatures above room temperature were accomplished using a dry
ice/acetone, ice/water and a mineral oil (up to 80 °C)/sand bath
(>80 °C), respectively. Flash column chromatography was carried out
on SiliCycle 60 Å (230−400 mesh) silica gel. TLC analysis was
performed on glass-backed EM Sciences F254 silica plates and were
visualized using a UV lamp and/or developed in a potassium
permanganate stain.
to separate the diene products from the unreacted alkene 1g or
its homodimer. Accordingly, either a saponification or mild
desilylation was conducted to give the corresponding alcohols
3gb and 3gf in good isolated yields over the two steps.
Last, we found that dienyl phosphonates underwent
Horner−Wittig reactions and a Diels−Alder reaction (Scheme
3). Deprotonation of dienyl phosphonate 3ab with KHMDS
and subsequent condensation with benzaldehyde provided the
expected triene in good yield (eq 3). The newly formed alkene
was formed as the E-isomer, and the 2:1 E/Z mixture of the
middle double bond was the same 2:1 E/Z isomeric
composition as found in the starting diene.39 In eq 4, the
The ruthenium carbene catalysts used were obtained from Umicore
and used as received. Catalytic reactions were terminated by the
addition of either ethyl vinyl ether (0.15 mL per mmol of alkyne) or a
methanolic solution of potassium isocyanoacetate (KO2CCH2NC).
Potassium isocyanoacetate was prepared and used as previously
reported (0.20 equiv in methanol).44
Scheme 3. Reactions of Dienyl Phosphonates
1H, 13C, and 31P NMR spectra were recorded on either a 300 MHz,
400 or 500 MHz Varian spectrometer with the appropriate frequency
reported. 1H and 13C NMR spectra obtained in CDCl3 were internally
standardized via the trace chloroform signals at 7.26 and 77.0 ppm,
respectively. 31P NMR spectra obtained in CDCl3 were standardized
by use of triphenylphosphine in CDCl3 as an external reference set to
1
−6.0 ppm. E/Z ratios were based on integrations in the H spectra.
Integrations for 31P NMR signals were found to agree closely with the
1
E/Z ratios determined by H NMR spectroscopy; however, here we
report major and minor 31P resonances since the integrations are only
approximate due to short relaxation delays (2 s) used.
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B. Preparation of Starting Materials. Diethyl Allylphospho-
nate (1a). Freshly distilled triethyl phosphite (7.95 mL, 46.4 mmol)
and allyl bromide (7.80 mL, 90.1 mmol) were added to a 50 mL
round bottom (rb) flask. The flask was then equipped with a reflux
condenser and heated to reflux (ca. 70 °C) for 18 h with vigorous
stirring. Volatile organics were then removed via rotatory evaporation,
and the crude oil was then fractionally distilled (bp 86−90 °C/6
mmHg) under high vacuum to afford 1a as a clear colorless oil (7.31
g, 89%). Spectral data obtained match literature reports.45
Dimethyl Allylphosphonate (1b). Compound 1b was prepared
similarly to 1a. Freshly distilled trimethyl phosphite (5.30 mL, 44.9
mmol) and allyl bromide (7.80 mL, 90.1 mmol) were added to a 50
mL rb flask while under a nitrogen atmosphere. The flask was then
equipped with a reflux condenser and heated to reflux (ca. 70 °C) for
18 h with vigorous stirring. Volatile organics were then removed via
rotatory evaporation, and the crude oil was then fractionally distilled
(bp 64−67 °C/6 mmHg) under high-vacuum. Initial fractions (ca. 3
mL) were liberally discarded, and distillation was stopped early prior
to distilling the remaining oil (ca. 1 mL) to afford 1b as a clear
colorless oil (1.92 g, 28%). Spectral data obtained match literature
reports.46
Bis(2,2,2-trifluoroethyl) Allylphosphonate (1c). Compound 1c
was prepared similarly to a previous report.7 Tris(2,2,2-trifluoroethyl)
phosphite (95% purity, 1.10 mL, 5.0 mmol), allyl bromide (0.89 mL,
10.3 mmol), and tetrabutylammonium iodide (93 mg, 0.25 mmol)
were added to a 25 mL PTFE sealed heavy glass walled reaction
vessel. The reaction mixture was then heated (ca. 140 °C) for 18 h
with vigorous stirring. Volatile organics were removed via rotatory
evaporation, and the crude oil was then purified by flash column
chromatography on silica gel (eluent: 20% to 25% ethyl acetate in
hexanes) to afford 1c as a clear pale-yellow oil (893 mg, 63%).
Analytical TLC: Rf = 0.28 (25% ethyl acetate in hexanes). Spectral
data obtained matched the literature.7
Diethyl But-3-enyl-1-phosphonate (1d). Freshly distilled triethyl
phosphite (4.25 mL, 24.6 mmol) and 4-bromo-1-butene (7.50 mL,
73.5 mmol) were added to a 50 mL round bottomed flask, which was
then equipped with a reflux condenser. The reaction mixture was then
heated (ca. 140 °C) to reflux for 48 h with vigorous stirring. Volatile
organics were removed via rotatory evaporation, and the crude oil was
then fractionally distilled (bp 106−110 °C/8 mmHg) under high
vacuum to afford 1d as a clear colorless oil (2.74 g, 58%). Spectral
data obtained match literature reports.47
Ethyl 2-(Diethoxyphosphoryl)pent-4-enoate (1e). 1e was pre-
pared using a modified procedure from literature. Sodium hydride
(60% dispersion in oil, 401 mg, 10.0 mmol) was added to a 50 mL
round bottomed flask and suspended in THF (20 mL). Triethyl
phosphonoacetate (5.00 mL, 25.0 mmol) was added dropwise, which
resulted in a clear solution. The mixture was allowed to stir for 30 min
at room temperature and allyl bromide (0.87 mL, 10.1 mmol) was
then added. The reaction mixture was then allowed to stir overnight;
A white precipitate had formed after 5 min of adding the alkyl halide.
A saturated aqueous solution of NH4Cl (10 mL) was then added and
the organic layer was removed. The aqueous layer was then extracted
with Et2O (3x, 15 mL) and the organic layers were combined. The
organic layer was then extracted with water (10 mL) and then brine
(10 mL). The organic layer was then dried with MgSO4, which was
subsequently removed via gravity filtration through filter paper. The
dried organic layer was then concentrated and purified by flash
column chromatography on silica gel (eluent: 40−45% ethyl acetate
in hexanes) to afford 1e as a clear colorless oil (1.77 g, 67%).
Analytical TLC: Rf = 0.21 (50% ethyl acetate in hexanes). Spectral
data obtained match literature reports.48
Diethyl Allylphosphate (1f). Compound 1f was prepared using a
modified procedure from the literature. Anhydrous ethanol (6.10 mL,
104.5 mmol) and anhydrous triethylamine (14.50 mL, 104.0 mmol)
were added to a 250 mL three-necked rb flask and were subsequently
dissolved in Et2O (ca. 1.0 M). The flask was then cooled to 0 °C and
was equipped with an addition funnel, which was then charged with
freshly distilled phosphoryl chloride (4.65 mL, 49.9 mmol).
Phosphoryl chloride was then slowly added (ca. 1 drop every 10 s).
After addition, the reaction mixture was allowed to warm to room
temperature and stir overnight. The reaction mixture was then filtered
through a 2 cm pad of Celite, which was then washed with Et2O (20
mL). The filtrate was then concentrated via rotatory evaporation to
afford crude diethyl chlorophosphate, which was used immediately in
the next step. 31P NMR of the crude product showed a 94:6 ratio of
diethyl chlorophosphate/triethyl phosphate.
Allyl alcohol (2.70 mL, 39.7 mmol), triethylamine (8.50 mL, 61.0
mmol), and DMAP (1.23 g, 10.0 mmol) were added to a 250 mL
three-necked rb flask and were subsequently dissolved in CH2Cl2 (ca.
0.25 M). The flask was then cooled to 0 °C and was equipped with an
addition funnel, which was charged with the crude diethyl
chlorophosphate prepared in the previous step. Crude diethyl
chlorophosphate was then slowly added (ca. 1 drop every 20 s).
After addition, the reaction mixture was allowed to warm to room
temperature and stir overnight. The reaction mixture was then
extracted with a saturated aqueous solution of sodium bicarbonate
(150 mL), and the organic layer was removed. The aqueous layer was
then extracted with CH2Cl2 (2×, 30 mL). The organic layers were
then combined and extracted with water (150 mL) and then brine
(150 mL). The organic layer was then dried with MgSO4, which was
subsequently removed via gravity filtration through filter paper. The
dried organic layer was then concentrated via rotatory evaporation
and passed through a silica plug (eluent: 50% ethyl acetate in
hexanes). This afforded 1f as a clear colorless oil (3.69 g, 48%).
Spectral data obtained match literature reports.49
O,O-Diethyl Allylphosphonothioate (1g). Compound 1a (902 mg,
5.06 mmol) and freshly recrystallized Lawesson’s reagent (2.03 g, 5.02
mmol) were added to a 50 mL rb flask, and toluene (20 mL) was
subsequently added. The flask was then equipped with a reflux
condenser and heated to reflux. Solids had dissolved after 30 min of
refluxing, and the reaction mixture was then allowed to stir overnight.
The reaction mixture was then cooled to room temperature, and a
precipitate formed upon exposure to air. The reaction mixture was
then filtered through a 2 cm pad of Celite, which was then washed
with toluene (2×, 20 mL). The foul smelling filtrates were then
combined and carefully concentrated via rotatory evaporation under
high vacuum. The crude residue was then purified by flash column
chromatography on silica gel (eluent: 0−2% ethyl acetate in hexanes)
to afford 1g as a clear colorless oil with a slight rotten egg smell (614
mg, 63%). Analytical TLC: Rf = 0.45 (5% ethyl acetate in hexanes).
1H NMR (300 MHz, CDCl3, ppm): δ 5.92−5.70 (m, 1H), 5.28−5.12
(m, 2H), 4.24−3.98 (m, 4H), 2.81 (dd, 2JHP = 19.5 Hz, 3JHH = 7.3 Hz,
3
2H), 1.30 (t, JHH = 7.1 Hz, 6H). 13C{1H} NMR (75 MHz, CDCl3,
ppm): δ 127.9 (d, 2JCP = 10.4 Hz), 120.3 (d, 3JCP = 15.3 Hz), 62.8 (d,
1
3
2JCP = 7.0 Hz), 40.8 (d, JCP = 109.8 Hz), 16.3 (d, JCP = 6.9 Hz).
31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ 93.13 (s). FT-IR (neat,
cm−1): 2954, 2929, 2856, 2252, 1773, 1709, 1631, 1601, 1503, 1471,
1458, 1412, 1291, 1252, 1219, 1201, 1174, 1134, 1096, 1027, 1006,
974, 912, 835, 811, 775, 766, 731, 689, 663, 645, 617, 574, 506.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C7H15O2PSNa
217.0423, found 217.0430.
C. Optimization Procedure. Compounds 1a (9 mg, 0.05 mmol)
and 3c (8 mg, 0.05 mmol) were added to an oven-dried 1 dram vial. A
solution of Ru1 (ca. 5.0 μM in C6D6, 1 mL) was added to the vial.
The empty space of the vial was purged with a stream of nitrogen gas
and was subsequently capped and sealed with parafilm. The vial was
then heated to 60 °C and allowed to stir for 24 h. Mesitylene (2.3 μL,
1
0.17 mmol) was then added to the mixture and stirred for 1 min. H
NMR and 31P NMR of the reaction mixture was then taken with a 25
1
s relaxation delay between scans; olefinic signals in H NMR were
compared to mesitylene for yield and 31P NMR was qualitatively used
to observe any new signals that may be representative to product/
byproduct formation.
D. General Procedures for Ene−Yne Metathesis. General
Procedure A. Compounds 1 and 2 were added to a rb flask and were
subsequently dissolved in benzene (ca. 0.05−0.10 M) while under a
nitrogen atmosphere. RuX (ca. 5 mol %) was then added, and the
flask was subsequently equipped with a reflux condenser. The reaction
mixture was then heated to 60 °C and allowed to stir for 3 h. The
1375
https://dx.doi.org/10.1021/acs.joc.0c02886
J. Org. Chem. 2021, 86, 1371−1384

The Journal of Organic Chemistry
pubs.acs.org/joc
Featured Article
catalytic reaction was then terminated by the addition of ethyl vinyl
ether or a methanolic solution of potassium isocyanoacetate followed
by an additional 0.5 h of stirring. The reaction mixture was then
concentrated via rotatory evaporation and purified by flash column
chromatography on silica gel to afford 3.
General Procedure B. Compounds 1 and 2 were added to a rb flask
and were subsequently dissolved in CH2Cl2 (ca. 0.05 M) while under
a nitrogen atmosphere. RuX (ca. 5 mol %) was then added, and the
reaction mixture was stirred for 1−3 h at room temperature. The
catalytic reaction was then terminated by the addition of ethyl vinyl
ether or a methanolic solution of potassium isocyanoacetate followed
by an additional 0.5 h of stirring. The reaction mixture was then
concentrated via rotatory evaporation and purified by flash column
chromatography on silica gel to afford 3.
TOF) m/z: [M + Na]+ calcd for C18H25O5PNa 375.1332, found
375.1339.
5-(Diethoxyphosphoryl)-2-methylenepent-3-en-1-yl Benzoate
(3ac). Compounds 1a (273 mg, 1.53 mmol), 2c (83 mg, 0.52
mmol), and Ru3 (16 mg, 0.026 mmol) were used following general
procedure B for 1 h. The catalyst was quenched with potassium
isocyanoacetate, which afforded 3ac after flash chromatography on
silica gel (eluent: 80% ethyl acetate in hexanes) as a pale-yellow oil
with a 1.5:1 E/Z ratio (135 mg, 77%). Analytical TLC: Rf = 0.60
1
(100% ethyl acetate). H NMR (500 MHz, CDCl3, ppm): δ 8.00−
7.89 (m, 2H), 7.50−7.43 (m, 1H), 7.37−7.31 (m, 2H), 6.16 (dd, 3JHH
= 16.0 Hz, 4JHP = 5.0 Hz, 0.6H), 6.02 (dd, 3JHH = 11.6 Hz, 4JHP = 4.5
3
3
3
Hz, 0.4H), 5.68 (ddt, JHH = 15.8 Hz, JHH = 7.7 Hz, JHP = 7.7 Hz,
0.6H), 5.59 (ddt, 3JHH = 11.5 Hz, 3JHH = 7.6 Hz, 3JHP = 7.6 Hz, 0.4H),
5.32 (s, 0.4H), 5.25 (s, 0.4H), 5.23 (s, 0.6H), 5.13 (s, 0.6H), 4.89 (s,
E. New Organophosphorus Compounds by Ene−Yne Cross
Metathesis. Diethyl (4-Phenylpenta-2,4-dien-1-yl)phosphonate
(3aa). Compounds 1a (546 mg, 3.06 mmol), freshly distilled 2a
(314 mg, 3.07 mmol), and Ru1 (135 mg, 0.16 mmol) were used
following general procedure A (ca. 0.10 M). The catalyst was
quenched with ethyl vinyl ether, which afforded 3aa after flash
chromatography on silica gel (eluent: ethyl acetate) as a dark brown
oil with a 2:1 E/Z ratio (780 mg, 91%). Analytical TLC: Rf = 0.46
2
1.2H), 4.73 (s, 0.8H), 4.06−3.93 (m, 4H), 2.75 (dd, JHP = 22.6 Hz,
3JHH = 8.1 Hz, 0.8H), 2.57 (dd, 2JHP = 22.4 Hz, 3JHH = 7.6 Hz, 1.2H),
1.21 (t, 3JHH = 7.1 Hz, 2.4H), 1.17 (t, 3JHH = 7.1 Hz, 3.6H). 13C{1H}
4
NMR (75 MHz, CDCl3, ppm): δ 166.3, 166.2, 140.0 (d, JCP = 4.2
Hz), 139.2, 134.2 (d, 3JCP = 14.8 Hz), 133.20, 133.18, 130.8 (d, 3JCP
=
14.7 Hz), 130.14, 130.13, 129.8, 129.7, 128.52, 128.50, 122.4 (d, 2JCP
= 11.1 Hz), 120.0 (d, 2JCP = 11.9 Hz), 117.9 (d, 5JCP = 3.8 Hz), 117.2
1
5
5
2
(100% ethyl acetate). H NMR (500 MHz, CDCl3, ppm): δ 7.40−
(d, JCP = 3.0 Hz), 67.0 (d, JCP = 1.9 Hz), 64.5, 62.13 (d, JCP = 6.7
Hz), 62.09 (d, 2JCP = 6.8 Hz), 31.3 (d, 1JCP = 138.9 Hz), 27.4 (d, 1JCP
= 140.0 Hz), 16.6, 16.5. 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ
26.50 (s, minor), 26.00 (s, major). FT-IR (neat, cm−1): 3444, 2982,
2932, 2907, 1718, 1649, 1602, 1584, 1451, 1392, 1368, 1315, 1263,
1176, 1163, 1110, 961, 804, 783, 712, 688, 674, 617, 530. HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C17H23NaO5PNa 361.1175,
found 361.1181.
3
4
4
7.21 (m, 5H), 6.38 (dddt, JHH = 15.6 Hz, JHP = 5.1 Hz, JHH = 1.4
Hz, 4JHH = 0.6 Hz, 0.65H), 6.31 (dddt, 3JHH = 11.4 Hz, 4JHP = 4.3 Hz,
4JHH = 1.7 Hz, 4JHH = 1.5 Hz, 0.35H), 5.73 (ddt, 3JHH = 11.4 Hz, 3JHH
= 7.8 Hz, 3JHP = 7.0 Hz, 0.35H), 5.55 (ddt, 3JHH = 15.6 Hz, 3JHH = 7.6
3
Hz, JHP = 7.6 Hz, 0.65H), 5.55 (s, 0.35H), 5.28−5.25 (m, 0.35H),
5.19−5.17 (m, 0.65H), 5.10−5.07 (m, 0.65H), 4.08−3.97 (m, 4H),
2.69 (ddd, 2JHP = 22.3 Hz, 3JHH = 7.8 Hz, 4JHH = 1.6 Hz, 0.75H), 2.60
2
3
4
(ddd, JHP = 22.4 Hz, JHH = 7.7 Hz, JHH = 1.4 Hz, 1.5H), 1.27 (t,
3JHH = 7.1 Hz, 6H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 147.2
(d, 4JCP = 4.2 Hz), 143.3 (d, 4JCP = 3.6 Hz), 139.8 (d, 5JCP = 0.6 Hz),
Diethyl (5-((tert-Butyldimethylsilyl)oxy)-4-methylenehex-2-en-1-
yl)phosphonate (3ad). Compounds 1a (268 mg, 1.50 mmol),
( )-2d (91 mg, 0.50 mmol), and Ru3 (16 mg, 0.025 mmol) were
used following general procedure B for 1 h. The catalyst was
quenched with ethyl vinyl ether, which afforded 3ad after flash
chromatography on silica gel (eluent: 40% ethyl acetate in hexanes) as
a dark-brown oil with a 1.5:1 E/Z ratio (122 mg, 68%). Analytical
TLC: Rf = 0.23 (50% ethyl acetate in hexanes). 1H NMR (500 MHz,
CDCl3, ppm): δ 6.10 (dd, 3JHH = 16.0 Hz, 4JHP = 5.2 Hz, 0.6H), 6.06
(ddt, 3JHH = 11.6 Hz, 4JHP = 4.1 Hz, 4JHH = 1.2 Hz, 0.4H), 5.70 (ddt,
5
3
3
139.7 (d, JCP = 1.6 Hz), 136.1 (d, JCP = 14.7 Hz), 133.0 (d, JCP
=
=
14.6 Hz), 128.2, 128.01, 127.98, 127.7, 127.4, 126.4, 122.1 (d, 2JCP
2
5
12.0 Hz), 121.9 (d, JCP = 10.7 Hz), 116.1 (d, JCP = 4.1 Hz), 115.4
(d, JCP = 2.8 Hz), 61.8 (d, JCP = 6.7 Hz), 61.7 (d, JCP = 6.5 Hz),
2
2
2
1
1
3
30.7 (d, JCP = 138.7 Hz), 26.8 (d, JCP = 139.4 Hz), 16.3 (d, JCP
=
5.7 Hz), 16.3 (d, 3JCP = 5.5 Hz). 31P{1H} NMR (121.5 MHz, CDCl3,
ppm): δ 26.88 (s, minor), 26.20 (s, major). FT-IR (neat, cm−1): 2982,
2938, 2908, 1738, 1726, 1494, 1443, 1390, 1369, 1054, 1032, 963,
777, 703. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C15H21NaO3PNa 303.1121, found 303.1117.
3JHH = 15.9 Hz, 3JHH = 7.7 Hz, 3JHP = 7.7 Hz, 0.6H), 5.62 (ddt, 3JHH
=
11.5 Hz, 3JHH = 7.5 Hz, 3JHP = 7.5 Hz, 0.4H), 5.24 (s, 0.4H), 5.17 (s,
3
0.6H), 5.04 (s, 0.4H), 4.97 (s, 0.6H), 4.46 (q, JHH = 6.3 Hz, 0.6H),
3
( )-6-(Diethoxyphosphoryl)-3-methylenehex-4-en-2-yl Benzoate
(3ab). Compounds 1a (357 mg, 2.00 mmol), ( )-2b (350 mg, 2.01
mmol), and Ru2 (64 mg, 0.10 mmol) were used following general
procedure A (ca. 0.10 M). The catalyst was quenched with ethyl vinyl
ether, which afforded 3ab after flash chromatography on silica gel
(eluent: ethyl acetate) as a dark brown oil with a 2:1 E/Z ratio (641
4.20 (q, JHH = 6.3 Hz, 0.4H), 4.15−4.00 (m, 4H), 2.81−2.72 (m,
0.8H), 2.61 (dd, 2JHP = 22.2 Hz, 3JHH = 7.5 Hz, 0.8H), 1.31−1.26 (m,
3
3
6H), 1.25 (d, JHH = 6.3 Hz, 1.8H), 1.16 (d, JHH = 6.4 Hz, 1.8H),
0.86 (s, 9.0H), 0.02 (s, 1.2H), 0.02 (s, 1.8H), 0.01 (s, 1.2H), 0.01 (s,
4
1.8H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 150.0 (d, JCP
=
2.4 Hz), 148.2 (d, 4JCP = 2.0 Hz), 134.2 (d, 3JCP = 14.9 Hz), 131.2 (d,
3JCP = 14.8 Hz), 121.2 (d, 2JCP = 10.8 Hz), 118.7 (d, 2JCP = 12.0 Hz),
113.0 (d, 5JCP = 3.8 Hz), 112.4 (d, 5JCP = 2.7 Hz), 71.6 (d, 5JCP = 1.8
Hz), 69.0, 62.04 (d, 2JCP = 6.7 Hz), 62.01 (d, 2JCP = 6.6 Hz), 61.93 (d,
1
mg, 91%). Analytical TLC: Rf = 0.47 (100% ethyl acetate). H NMR
(500 MHz, CDCl3, ppm): δ 8.08−8.02 (m, 2H), 7.58−7.53 (m, 1H),
3
7.46−7.41 (m, 2H), 6.22−6.13 (m, 1H), 5.84 (ddt, JHH = 15.9 Hz,
3JHH = 7.4 Hz, 3JHP = 7.4 Hz, 0.65H), 5.80 (q, 3JHH = 6.6 Hz, 0.65H),
5.73 (ddt, 3JHH = 11.5 Hz, 3JHH = 7.9 Hz, 3JHP = 6.8 Hz, 0.35H), 5.56
2JCP = 6.7 Hz), 61.89 (d, JCP = 6.6 Hz), 31.3 (d, JCP = 138.9 Hz),
2
1
27.4 (d, 1JCP = 140.4 Hz), 25.91, 25.90, 24.8, 23.8, 18.3, 16.54 (d, 3JCP
3
3
(q, JHH = 6.6 Hz, 0.35H), 5.39 (s, 0.35H), 5.29 (s, 0.65H), 5.25 (s,
= 5.9 Hz), 16.52 (d, JCP = 6.0 Hz), −4.78, −4.83, −4.9, −5.0.
31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ 27.08 (s, minor), 26.38
0.35H), 5.15 (s, 0.65H), 4.16−4.01 (m, 4H), 2.90−2.74 (m, 0.7H),
3
3
4
(s, major). FT-IR (neat, cm−1): 2956, 2930, 2899, 2857, 1635, 1473,
1463, 1444, 1390, 1368, 1251, 1163, 1114, 1095, 1054, 1027, 963,
834, 814, 775, 668, 593, 526. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C17H35NaO4PSiNa 385.1934, found 385.1945.
2.70 (ddt, JHP = 22.2 Hz, JHH = 7.7 Hz, JHH = 1.3 Hz, 1.3H), 1.53
3
3
(d, JHH = 6.6 Hz, 2H), 1.45 (d, JHH = 6.6 Hz, 1H), 1.33−1.20 (m,
6H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 165.74, 165.72,
4
4
145.7 (d, JCP = 3.9 Hz), 144.0 (d, JCP = 3.3 Hz), 133.7, 133.6 (d,
3JCP = 14.9 Hz), 133.1, 130.57, 130.55, 130.3 (d, JCP = 14.7 Hz),
3
Diethyl (7-(Benzyloxy)-4-methylenehept-2-en-1-yl)phosphonate
(3ae). Compounds 1a (268 mg, 1.50 mmol), 2e (88 mg, 0.51 mmol),
and Ru3 (16 mg, 0.025 mmol) were used following general procedure
B for 1 h. The catalyst was quenched with methanolic potassium
isocyanoacetate, which afforded 3ae after flash chromatography on
silica gel (eluent: 80% ethyl acetate in hexanes) as a pale-yellow oil
with a 1.5:1 E/Z ratio (145 mg, 81%). Analytical TLC: Rf = 0.35
2
129.73, 129.68, 128.47, 128.47, 122.7 (d, JCP = 10.8 Hz), 112.0 (d,
2JCP = 12.0 Hz), 114.9 (d, JCP = 2.9 Hz), 114.6 (d, JCP = 4.0 Hz),
5
5
73.3 (d, 5JCP = 2.0 Hz), 70.6, 62.2 (d, 2JCP = 3.3 Hz), 62.10 (d, 2JCP
=
3.3 Hz), 62.05 (d, 2JCP = 1.0 Hz), 62.0 (d, 2JCP = 1.0 Hz), 31.3 (d, 1JCP
= 139.7 Hz), 27.3 (d, 1JCP = 141.3 Hz), 20.4, 19.8, 16.6, 16.5. 31P{1H}
NMR (121.5 MHz, CDCl3, ppm): δ 26.77 (s, minor), 26.10 (s,
major). FT-IR (neat, cm−1): 3443, 2982, 2934, 2907, 1716, 1647,
1602, 1584, 1478, 1451, 1392, 1369, 1315, 1267, 1176, 1163, 1099,
1054, 1024, 961, 867, 728, 794, 713, 688, 593, 530. HRMS (ESI-
1
(100% ethyl acetate). H NMR (500 MHz, CDCl3, ppm): δ 7.35−
3
4
7.29 (m, 4H), 7.29−7.23 (m, 1H) 6.18 (dd, JHH = 15.8 Hz, JHP
=
3
4
5.0 Hz, 0.6H), 6.00 (dd, JHH = 11.5 Hz, JHP = 4.3 Hz, 0.4H), 5.65
1376
https://dx.doi.org/10.1021/acs.joc.0c02886
J. Org. Chem. 2021, 86, 1371−1384

The Journal of Organic Chemistry
pubs.acs.org/joc
Featured Article
2
2
(ddt, 3JHH = 15.6 Hz, 3JHH = 7.6 Hz, 3JHP = 7.5 Hz, 0.6H), 5.54 (ddt,
127.6, 127.2, 122.7 (d, JCP = 10.6 Hz), 120.9 (d, JCP = 11.8 Hz),
116.1 (d, 5JCP = 3.8 Hz), 115.7 (d, 5JCP = 2.9 Hz), 77.5 (d, 5JCP = 1.8
Hz), 74.9, 62.01 (d, 2JCP = 6.7 Hz), 61.95 (d, 2JCP = 6.5 Hz), 61.9 (d,
3
3
3JHH = 11.5 Hz, JHH = 7.7 Hz, JHP = 7.7 Hz, 0.7H), 5.02 (s, 0.4H),
5.02 (s, 0.4H), 5.02 (s, 0.4H), 4.95 (s, 0.6H), 4.93 (s, 0.6H), 4.49 (s,
1
1
2JCP = 6.8 Hz), 31.2 (d, JCP = 138.6 Hz), 27.2 (d, JCP = 140.1 Hz),
3
1.2H), 4.48 (s, 0.8H), 4.41−4.02 (m, 4H), 3.48 (t, JHH = 6.4 Hz,
1.2H), 3.45 (t, 3JHH = 6.4 Hz, 0.8H), 2.79 (ddd, 2JHP = 22.3 Hz, 3JHH
21.20, 21.19, 16.5 (d, 3JCP = 6.0 Hz), 16.4 (d, 3JCP = 5.9 Hz). 31P{1H}
NMR (121.5 MHz, CDCl3, ppm): δ 26.81 (s, minor), 25.78 (s,
major). FT-IR (neat, cm−1): 2982, 2931, 1739, 1647, 1495, 1455,
1392, 1370, 1228, 1163, 1097, 1021, 961, 865, 847, 761, 700, 607,
536. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C18H25O5PNa
375.1332, found 375.1343.
2
2
= 7.9 Hz, JHH = 1.6 Hz, 0.8H), 2.63 (dd, JHP = 22.2 Hz, 3JHH = 7.6
3
3
Hz, 1.2H), 2.29 (t, JHH = 7.7 Hz, 1.2H), 2.18 (t, JHH = 7.7 Hz,
0.8H), 1.80 (tt, 3JHH = 7.7, 6.5 Hz, 1.2H), 1.72 (tt, 3JHH = 7.7, 6.4 Hz,
3
3
0.8H), 1.30 (t, JHH = 7.1 Hz, 3.6H), 1.29 (t, JHH = 7.1 Hz, 2.4H).
13C{1H} NMR (125 MHz, CDCl3, ppm): δ 145.1 (d, 4JCP = 4.1 Hz),
4
3
(E)-tert-Butyldimethyl((1-phenylpent-1-en-4-yn-3-yl)oxy)silane
(2h). Alkynol 2h was prepared using a modified procedure from the
literature.50 Trimethylsilylacetylene (4.30 mL, 31.0 mmol) was added
to a 250 mL rb flask and was subsequently dissolved in THF (ca. 0.38
M). The flask was then cooled to −78 °C, and n-butyllithium (11.0
mL, 2.2 M in hexanes, 24.2 mmol) was added dropwise. The reaction
mixture was allowed to stir for 30 min, and a solution of
cinnamaldehyde (2.55 g, 19.3 mmol) in THF (10 mL) was added
dropwise. The reaction mixture was then allowed to stir for an
additional 30 min and was warmed to 0 °C. K2CO3 (700 mg, 5.06
mmol) in methanol (40 mL) was then added, and the reaction
mixture was allowed to stir and warm to room temperature overnight.
A saturated aqueous solution of NH4Cl (40 mL) was then added, and
the organic layer was removed. The aqueous layer was then extracted
with Et2O (3×, 40 mL) and the organic layers were combined. The
organic layer was then extracted with water (80 mL) and brine (80
mL). The organic layer was then dried with MgSO4, which was
subsequently removed via gravity filtration through filter paper. The
dried organic layer was then concentrated via rotatory evaporation
and passed through a silica plug (eluent: 10% ethyl acetate in
hexanes). This afforded the alcohol as a clear yellow oil (2.34 g, 77%).
Analytical TLC: Rf = 0.25 (20% ethyl acetate in hexanes). Spectral
data match the literature report.50
The alcohol (790 mg, 4.99 mmol) was added to a 100 mL rb flask
and was subsequently dissolved in CH2Cl2 (ca. 0.13 M). The flask was
then cooled to 0 °C, and DMAP (37 mg, 0.29 mmol),
diisopropylethylamine (4.40 mL, 25.3 mmol), and TBSCl (1.58 g,
10.5 mmol) were added. The reaction mixture was then allowed to
stir and warm to room temperature overnight. A saturated aqueous
solution of NH4Cl (20 mL) was then added, and the organic layer was
removed. The aqueous layer was then extracted with CH2Cl2 (3×, 20
mL), and the organic layers were combined. The organic layer was
then extracted with water (40 mL) and brine (40 mL). The organic
layer was then dried with MgSO4, which was subsequently removed
via gravity filtration through filter paper. The dried organic layer was
then concentrated via rotatory evaporation and purified by flash
column chromatography on silica gel (eluent: 15% to 20% ethyl
acetate in hexanes) to afford 2h as a clear yellow oil (1.23 g, 90%).
144.0 (d, JCP = 3.5 Hz), 138.7, 138.6, 136.9 (d, JCP = 14.6 Hz),
3
134.2 (d, JCP = 14.7 Hz), 128.4, 128.4, 127.68, 127.67, 127.58,
127.56, 120.0 (d, 2JCP = 10.7 Hz), 118.2 (d, 2JCP = 12.0 Hz), 115.4 (d,
5JCP = 3.8 Hz), 114.5 (d, 5JCP = 2.7 Hz), 73.0, 73.0, 69.9, 69.7, 62.0 (d,
2JCP = 6.7 Hz), 61.9 (d, JCP = 6.7 Hz), 33.5 (d, 5JCP = 1.9 Hz), 30.9
4
(d, 1JCP = 139.7 Hz), 28.5, 28.3, 28.2, 27.2 (d, 1JCP = 140.8 Hz), 16.52
(d, JCP = 6.0 Hz), 16.50 (d, JCP = 6.1 Hz). 31P{1H} NMR (121.5
MHz, CDCl3, ppm): δ 27.06 (s, minor), 26.50 (s, major). FT-IR
(neat, cm−1): 2980, 2930, 2856, 2100, 1719, 1605, 1496, 1478, 1454,
1392, 1366, 1249, 1163, 1099, 1023, 961, 781, 737, 698, 606, 530.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C19H29O4PNa
375.1696, found 375.1694.
3
3
Diethyl (6-((tert-Butyldimethylsilyl)oxy)-4-methylenehex-2-en-1-
yl)phosphonate (3af). Compounds 1a (719 mg, 4.03 mmol), 2f (185
mg, 1.00 mmol) and Ru3 (31 mg, 0.050 mmol) were used following
general procedure B for 1 h. The catalyst was quenched with
methanolic potassium isocyanoacetate, which afforded 3af after flash
chromatography on silica gel (eluent: 40% ethyl acetate in hexanes) as
a pale-yellow oil with a 2:1 E/Z ratio (306 mg, 88%). Analytical TLC:
Rf = 0.48 (100% ethyl acetate). 1H NMR (500 MHz, CDCl3, ppm): δ
3
4
3
6.11 (dd, JHH = 15.8 Hz, JHP = 4.9 Hz, 0.65H), 5.96 (ddt, JHH
=
11.5 Hz, 4JHP = 4.2 Hz, 4JHH = 1.2 Hz, 0.35H), 5.59 (ddt, 3JHH = 15.6
Hz, 3JHH = 7.6 Hz, 3JHP = 7.6 Hz, 0.65H), 5.48 (ddt, 3JHH = 11.5 Hz,
3JHH = 7.8 Hz, 3JHP = 7.8 Hz, 0.35H), 5.03 (s, 0.35H), 5.00 (s, 0.35H),
3
4.94 (s, 0.65H), 4.91 (s, 0.65H), 4.12−3.95 (m, 4H), 3.65 (t, JHH
7.2 Hz, 1.3H), 3.59 (t, JHH = 7.0 Hz, 0.7H), 2.75 (ddd, JHP = 22.3
=
3
2
3
4
2
Hz, JHH = 7.9 Hz, JHH = 1.5 Hz, 0.7H), 2.58 (dd, JHP = 22.3 Hz,
3JHH = 7.6 Hz, 1.3H), 2.37 (t, 3JHH = 7.2 Hz, 1.3H), 2.24 (t, 3JHH = 6.9
3
3
Hz, 0.7H), 1.25 (t, JHH = 7.1 Hz, 2.1H), 1.25 (t, JHH = 7.1 Hz,
3.9H), 0.82 (s, 5.85H), 0.81 (s, 3.15H), −0.02 (s, 3.9H), −0.03 (s,
4
2.1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 142.3 (d, JCP
=
4.2 Hz), 141.5 (d, 4JCP = 3.6 Hz), 136.9 (d, 3JCP = 14.7 Hz), 134.2 (d,
3JCP = 14.7 Hz), 119.8 (d, 2JCP = 10.8 Hz), 118.2 (d, 2JCP = 12.0 Hz),
116.8 (d, 5JCP = 4.0 Hz), 116.0 (d, 5JCP = 2.8 Hz), 62.2, 62.0, 61.9 (d,
2
1
2JCP = 6.7 Hz), 61.8 (d, JCP = 6.7 Hz), 40.4, 35.7, 30.9 (d, JCP
=
1
139.0 Hz), 27.1 (d, JCP = 140.2 Hz), 26.0, 25.9, 18.32, 18.27, 16.47
(d, JCP = 5.9 Hz), 16.45 (d, JCP = 6.0 Hz), −5.27, −5.30. 31P{1H}
NMR (121.5 MHz, CDCl3, ppm): δ 27.15 (s, minor), 26.50 (s,
major). FT-IR (neat, cm−1): 3456, 2954, 2929, 2904, 2857, 2084,
1737, 1607, 1472, 1463, 1444, 1390, 1362, 1251, 1164, 1095, 1054,
1025, 963, 890, 834, 812, 775, 731, 663, 523. HRMS (ESI-TOF) m/z:
[M + Na]+ calcd for C17H35O4PSiNa 385.1934, found 385.1927.
5-(Diethoxyphosphoryl)-2-methylene-1-phenylpent-3-en-1-yl
Acetate (3ag). Compounds 1a (269 mg, 1.51 mmol), ( )-2g (87
mg, 0.50 mmol), and Ru3 (17 mg, 0.026 mmol) were used following
general procedure B for 1 h. The catalyst was quenched with
methanolic potassium isocyanoacetate, which afforded 3ag after flash
chromatography on silica gel (eluent: 5% to 10% ethanol in hexanes)
as a pale-yellow oil with a 2:1 E/Z ratio (148 mg, 84%). Analytical
3
3
1
Analytical TLC: 0.60 (20% ethyl acetate in hexanes). H NMR (500
MHz, CDCl3, ppm): δ 7.43−7.37 (m, 2H), 7.35−7.29 (m, 2H),
3
4
7.28−7.22 (m, 1H), 6.72 (dd, JHH = 15.8 Hz, JHH = 1.0 Hz, 1H),
3
3
3
6.25 (dd, JHH = 15.8 Hz, JHH = 5.6 Hz, 1H), 5.08 (ddd, JHH = 5.6
3
4
3
Hz, JHH = 2.3 Hz, JHH = 1.3 Hz, 1H), 2.56 (d, JHH = 2.2 Hz, 1H),
0.96 (s, 9H), 0.19 (s, 3H), 0.18 (s, 3H). 13C{1H} NMR (125 MHz,
CDCl3, ppm): δ 136. 6, 130.7, 129.0, 128.7, 128.0, 126. 9, 83.7, 73. 7,
63.5, 26.0, 18.5, −4.4, −4.6. FT-IR (neat, cm−1): 3308, 3028, 2955,
2930, 2886, 2857, 1737, 1601, 1578, 1496, 1472, 1463, 1449, 1390,
1362, 1297, 1252, 1204, 1113, 1060, 1005, 964, 939, 909, 870, 834,
812, 778, 733, 692, 651, 580, 554. HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C17H24OSiNa 295.1489, found 295.1494.
Diethyl ((6E)-5-((tert-butyldimethylsilyl)oxy)-4-methylene-7-phe-
nylhepta-2,6-dien-1-yl)phosphonate (3ah). Compounds 1a (140
mg, 0.78 mmol), ( )-2h (70 mg, 0.26), and Ru3 (8 mg, 0.012 mmol)
were used following general procedure B for 1 h. The catalyst was
quenched with ethyl vinyl ether, which afforded 3ah after flash
chromatography on silica gel (eluent: 40% ethyl acetate in hexanes) as
a dark-brown oil with a 1.5:1 E/Z ratio (96 mg, 84%). Analytical
1
TLC: Rf = 0.26 (10% ethanol in hexanes). H NMR (300 MHz,
CDCl3, ppm): δ 7.41−7.26 (m, 5H), 6.51 (s, 0.65H), 6.21 (s, 0.35H),
6.12 (dd, 3JHH = 16.2 Hz, 4JHP = 5.1 Hz, 0.65H), 5.93 (dd, 3JHH = 11.4
Hz, 4JHP = 3.4 Hz, 0.35H), 5.76−5.53 (m, 1H), 5.41 (s, 0.35H), 5.34
(s, 0.35H), 5.29 (s, 1.3H), 4.13−3.83 (m, 4H), 2.84−2.62 (m, 0.7H),
2.56 (dd, 2JHP = 22.4 Hz, 3JHH = 7.5 Hz, 1.3H), 2.12 (s, 1H), 2.11 (s,
3
3
2H), 1.30 (t, JHH = 7.1 Hz, 2.1H), 1.22 (t, JHH = 7.0 Hz, 3.9H).
13C{1H} NMR (75 MHz, CDCl3, ppm): δ 169.78, 169.76, 143.4 (d,
1
TLC: Rf = 0.77 (100% ethyl acetate). H NMR (500 MHz, CDCl3,
ppm): δ 7.38−7.33 (m, 2H), 7.32−7.25 (m, 2H), 7.24−7.17 (m, 1H),
6.59 (d, JHH = 16.0 Hz, 0.6H), 6.55 (d, JHH = 16.0 Hz, 0.4H), 6.18
4JCP = 4.1 Hz), 142.3 (d, 4JCP = 3.3 Hz), 138.2, 138.1, 133.3 (d, 3JCP
=
3
3
3
14.8 Hz), 130.1 (d, JCP = 14.7 Hz), 128.51, 128.46, 128.3, 128.2,
1377
https://dx.doi.org/10.1021/acs.joc.0c02886
J. Org. Chem. 2021, 86, 1371−1384

The Journal of Organic Chemistry
pubs.acs.org/joc
Featured Article
3
(dd, 3JHH = 15.9 Hz, JHH = 5.8 Hz, 0.6H), 6.16−6.10 (m, 1H), 6.11
ppm): δ 150.80, 150.78, 144.4, 144.3, 140.3 (d, 4JCP = 3.9 Hz), 139.8
4
3
(dd, 3JHH = 15.9 Hz, 3JHH = 5.9 Hz, 0.4H), 5.89 (ddt, 3JHH = 15.9 Hz,
(d, JCP = 3.6 Hz), 137.1, 137.0, 134.7 (d, JCP = 14.8 Hz), 131.2 (d,
2
3JCP = 14.5 Hz), 129.22, 129.21, 128.3, 128.2, 122.4 (d, JCP = 10.9
3JHH = 7.5 Hz, 3JHP = 7.2 Hz, 0.6H), 5.65 (ddt, 3JHH = 11.5 Hz, 3JHH
=
2
5
3
Hz), 118.9 (d, JCP = 11.5 Hz), 115.3 (d, JCP = 3.0 Hz), 114.6 (d,
7.6 Hz, JHP = 7.6 Hz, 0.4H), 5.39 (s, 0.4H), 5.29 (s, 0.6H), 5.22 (s,
0.4H), 5.13 (s, 0.6H), 4.96 (d, JHH = 5.7 Hz, 0.6H), 4.72 (d, JHH
5JCP = 3.9 Hz), 84.37, 84.35, 62.1 (d, JCP = 6.8 Hz), 62.0 (d, JCP
=
2
2
3
3
=
6.5 Hz), 50.8 (d, 5JCP = 2.3 Hz), 47.8, 31.2 (d, 1JCP = 139.2 Hz), 27.9,
27.8, 27.3 (d, 1JCP = 139.8 Hz), 21.65, 21.65, 16.50 (d, 3JCP = 6.0 Hz),
16.47 (d, 3JCP = 6.0 Hz). 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ
26.59 (s, minor), 25.94 (s, major). FT-IR (neat, cm−1): 3453, 2981,
2933, 2103, 1728, 1644, 1597, 1495, 1478, 1443, 1394, 1355, 1285,
1248, 1187, 1148, 1090, 1024, 962, 939, 849, 806, 772, 718, 675, 659,
591, 545. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C22H34NO7PSNa 510.1686, found 510.1701.
5.9 Hz, 0.4H), 4.15−3.95 (m, 4H), 2.90−2.70 (m, 0.8H), 2.63 (ddd,
3
4
3
2JHP = 22.3 Hz, JHH = 7.5 Hz, JHH = 1.1 Hz, 1.2H), 1.28 (t, JHH
=
3
3
7.1 Hz, 1.2H), 1.27 (t, JHH = 7.1 Hz, 1.2H), 1.23 (t, JHH = 7.1 Hz,
3
1.8H), 1.20 (t, JHH = 7.1 Hz, 1.8H), 0.93 (s, 5.4H), 0.92 (s, 3.6H),
0.09 (s, 2H), 0.08 (s, 2H), 0.08 (s, 2H). 13C{1H} NMR (125 MHz,
4
4
CDCl3, ppm): δ 147.2 (d, JCP = 4.0 Hz), 145.7 (d, JCP = 3.4 Hz),
137.04, 137.01, 133.5 (d, 3JCP = 15.0 Hz), 131.8, 131.4, 130.9 (d, 3JCP
= 14.7 Hz), 129.8, 129.7, 128.6, 128.6, 127.6, 127.5, 126.59, 126.57,
121.6 (d, 2JCP = 10.6 Hz), 119.9 (d, 2JCP = 11.8 Hz), 114.2 (d, 5JCP
=
Diethyl (6-(1,3-Dioxoisoindolin-2-yl)-4-methylenehex-2-en-1-yl)-
phosphonate (3ak). Compounds 1a (137 mg, 0.77 mmol), 2b (50
mg, 0.25 mmol), and Ru3 (8 mg, 0.013 mmol) were used following
general procedure B for 1 h. The catalyst was quenched with ethyl
vinyl ether, which afforded 3ak after flash chromatography on silica
gel (eluent: 5% to 10% ethanol in hexanes) as a dark-brown oil with a
1:1 E/Z ratio (71 mg, 75%). Analytical TLC: Rf = 0.23 (10% ethanol
3.6 Hz), 113.8 (d, 5JCP = 2.8 Hz), 76.6 (d, 5JCP = 1.8 Hz), 74.2 (d, 5JCP
= 0.8 Hz), 62.1 (d, 2JCP = 6.5 Hz), 62.04 (d, 2JCP = 6.5 Hz), 61.97 (d,
2JCP = 6.6 Hz), 61.96 (d, JCP = 6.7 Hz), 31.5 (d, JCP = 138.6 Hz),
27.5 (d, 1JCP = 140.3 Hz), 25.96, 25.94, 18.5, 16.53 (d, 3JCP = 4.5 Hz),
16.51 (d, 3JCP = 5.8 Hz), 16.48 (d, 3JCP = 4.4 Hz), 16.46 (d, 3JCP = 5.7
Hz), −4.58, −4.65, −4.72, −4.73. 31P{1H} NMR (121.5 MHz,
CDCl3, ppm): δ 27.16 (s, minor), 26.36 (s, major). FT-IR (neat,
cm−1): 3027, 2955, 2929, 2901, 2857, 2103, 1601, 1495, 1472, 1463,
1448, 1390, 1361, 1250, 1163, 1099, 1055, 1025, 962, 904, 881, 833,
814, 776, 747, 693, 590, 532. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C24H39O4PSiNa 473.2247, found 473.2247.
2
1
1
in hexanes). H NMR (500 MHz, CDCl3, ppm): δ 7.84−7.76 (m,
3
4
2H), 7.71−7.65 (m, 2H), 6.17 (dd, JHH = 15.8 Hz, JHP = 4.6 Hz,
0.5H), 6.05 (dd, 3JHH = 11.4 Hz, 4JHP = 3.2 Hz, 0.5H), 5.79 (ddt, 3JHH
= 15.5 Hz, 3JHH = 7.6 Hz, 3JHP = 7.6 Hz, 0.5H), 5.55 (ddt, 3JHH = 11.4
3
3
Hz, JHH = 7.5 Hz, JHP = 7.4 Hz, 0.5H), 5.10 (s, 0.5H), 5.05 (s,
0.5H), 4.98 (s, 0.5H), 4.96 (s, 0.5H), 4.16−3.95 (m, 4H), 3.80 (t,
3JHH = 7.5 Hz, 1H), 3.75 (t, 3JHH = 7.3 Hz, 1H), 2.77 (dd, 2JHP = 22.4
Hz, 3JHH = 7.9 Hz, 1H), 2.65 (dd, 2JHP = 22.2 Hz, 3JHH = 7.5 Hz, 1H),
2.56 (t, 3JHH = 7.5 Hz, 1H), 2.46 (t, 3JHH = 7.3 Hz, 1H), 1.30 (t, 3JHH
Diethyl (4-(Trimethylsilyl)penta-2,4-dien-1-yl)phosphonate (3ai).
Compounds 1a (294 mg, 1.65 mmol), 2i (52 mg, 0.52 mmol), and
Ru3 (17 mg, 0.026) were used following general procedure B for 1 h.
The catalyst was quenched with methanolic potassium isocyanoace-
tate, which afforded 3ai after flash chromatography on silica gel
(eluent: ethyl acetate) as a pale-yellow oil with a 9:1 E/Z ratio (107
3
= 7.0 Hz, 3H), 1.27 (t, JHH = 7.0 Hz, 3H). 13C{1H} NMR (125
MHz, CDCl3, ppm): δ 168.23, 168.22, 142.0 (d, 4JCP = 4.3 Hz), 140.
4
3
Eight (d, JCP = 3.6 Hz), 136.0 (d, JCP = 14.8 Hz), 134.00, 133.98,
1
mg, 74%). Analytical TLC: Rf = 0.39 (100% ethyl acetate). H NMR
133.3 (d, 3JCP = 14.6 Hz), 132.2, 132.1, 123.3 (2 C), 121.0 (d, 2JCP
11.0 Hz), 119.1 (d, JCP = 12.0 Hz), 117.3 (d, JCP = 4.3 Hz), 116.9
=
3
4
(500 MHz, CDCl3, ppm): δ 6.20 (dd, JHH = 15.9, JHP = 5.1 Hz,
2
5
0.9H), 6.17−6.12 (m, 0.1H), 5.62−5.60 (m, 0.9H), 5.59 (ddt, 3JHH
=
5
2
2
(d, JCP = 2.8 Hz), 62.1 (d, JCP = 6.7 Hz), 62.0 (d, JCP = 6.7 Hz),
3
3
15.8 Hz, JHH = 7.3 Hz, JHP = 7.3 Hz, 0.9H), 5.46−5.44 (m, 0.1H),
37.1, 36.9, 35.7, 31.1, 30.9 (d, 1JCP = 138.8 Hz), 27.3 (d, 1JCP = 140.2
5.43 (ddt, 3JHH = 11.3 Hz, 3JHH = 7.5 Hz, 3JHP = 7.5 Hz, 0.1H), 5.34−
Hz), 16.6 (d, JCP = 5.6 Hz), 16.5 (d, JCP = 5.5 Hz). 31P{1H} NMR
(121.5 MHz, CDCl3, ppm): δ 26.86 (s, 0.5P), 26.22 (s, 0.5P). FT-IR
(neat, cm−1): 3464, 2981, 2933, 2103, 1772, 1709, 1613, 1467, 1439,
1394, 1361, 1297, 1247, 1188, 1163, 1099, 1023, 961, 870, 793, 720,
629, 530. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C19H24NO5PNa 400.1283, found 400.1295.
3
3
5.29 (m, 1H), 4.13−3.96 (m, 4H), 2.64 (ddd, 2JHP = 22.1 Hz, 3JHH
=
2
2
3
7.7 Hz, JHH = 1.6 Hz, 0.2H), 2.57 (ddd, JHP = 22.1 Hz, JHH = 7.5
Hz, 2JHH = 1.5 Hz, 1.8H), 1.25 (t, 3JHH = 7.0 Hz, 0.6H), 1.24 (t, 3JHH
= 7.1 Hz, 5.4H), 0.10 (s, 8.1H), 0.02 (s, 0.9H). 13C{1H} NMR (75
4
4
MHz, CDCl3, ppm): δ 148.8 (d, JCP = 3.1 Hz), 148.4 (d, JCP = 3.8
3
3
Hz), 139.5 (d, JCP = 14.8 Hz), 135.4 (d, JCP = 14.8 Hz), 127.8 (d,
Methyl (Z)-5-(Diethoxyphosphoryl)-2-methylenepent-3-enoate
(3al). Compounds 1a (269 mg, 1.51 mmol), 2l (44 mg, 0.53
mmol), and Ru3 (16 mg, 0.025 mmol) were used following general
procedure B for 1 h. The catalyst was quenched with ethyl vinyl ether,
which afforded 3al after flash chromatography on silica gel (eluent:
5% to 10% ethanol in hexanes) as a dark-brown oil as the Z-isomer
only (72 mg, 52%). Analytical TLC: Rf = 0.11 (10% ethanol in
5JCP = 4.2 Hz), 126.7 (d, JCP = 3.9 Hz), 120.4 (d, JCP = 12.2 Hz).
5
2
117.5 (d, 2JCP = 10.4 Hz), 61.9 (d, 2JCP = 6.6 Hz), 61.7 (d, 2JCP = 6.7
1
1
Hz), 31.2 (d, JCP = 138.6 Hz), 26.4 (d, JCP = 140.6 Hz), 16.4 (d,
3JCP = 5.9 Hz), 16.3 (d, JCP = 6.3 Hz), −1.0, −2.1. 31P{1H} NMR
3
(121.5 MHz, CDCl3, ppm): δ 27.58 (s, minor), 26.52 (s, major). FT-
IR (neat, cm−1): 3463, 2981, 2957, 2904, 2100, 1723, 1635, 1479,
1444, 1393, 1368, 1295, 1248, 1164, 1098, 1024, 962, 837, 800, 759,
721, 692, 655, 618, 527. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C12H25O3PSiNa 299.1203, found 299.1208.
1
hexanes). H NMR (500 MHz, CDCl3, ppm): δ 6.37 (s, 1H), 5.91
3
4
4
4
(dddt, JHH = 11.6 Hz, JHP = 4.9 Hz, JHH = 1.6 Hz, JHH = 1.5 Hz,
1H), 5.96 (s, 1H), 5.71 (ddt, 3JHH = 11.6 Hz, 3JHH = 8.1 Hz, 3JHP = 6.4
Hz, 1H), 4.15−3.98 (m, 4H), 3.73 (s, 3H), 2.71 (ddd, 2JHP = 22.6 Hz,
tert-Butyl (5-(Diethoxyphosphoryl)-2-methylenepent-3-en-1-yl)-
(tosyl)carbamate (3aj). Compounds 1a (272 mg, 1.53 mmol), 2j
(156 mg, 0.50 mmol), and Ru3 (16 mg, 0.026 mmol) were used
following general procedure B for 1 h. The catalyst was quenched with
methanolic potassium isocyanoacetate, which afforded 3aj after flash
chromatography on silica gel (eluent: ethyl acetate) as a pale-yellow
oil with a 1.5:1 E/Z ratio (232 mg, 95%). Analytical TLC: Rf = 0.28
3JHH = 8.1 Hz, JHH = 1.6 Hz, 2H), 1.28 (t, JHH = 7.1 Hz, 6H).
4
3
13C{1H} NMR (75 MHz, CDCl3, ppm): δ 166.8 (d, JCP = 2.0 Hz),
5
4
3
5
135.1 (d, JCP = 3.5 Hz), 128.6 (d, JCP = 14.5 Hz), 128.3 (d, JCP
=
2.9 Hz), 122. Seven (d, 2JCP = 11.0 Hz), 62.1 (d, 2JCP = 6.6 Hz), 52.2,
27.1 (d, JCP = 140.1 Hz), 16.5 (d, JCP = 6.0 Hz). 31P{1H} NMR
(121.5 MHz, CDCl3, ppm): δ 26.27 (s). FT-IR (neat, cm−1): 3444,
2983, 2954, 2910, 2088, 1720, 1641, 1614, 1438, 1392, 1369, 1302,
1245, 1198, 1161, 1139, 1097, 1051, 1023, 960, 879, 844, 815, 768,
709, 636. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C11H19O5PNa
285.0862, found 285.0868.
1
3
1
(100% ethyl acetate). H NMR (500 MHz, CDCl3, ppm): δ 7.85−
3
4
7.78 (m, 2H), 7.34−7.28 (m, 2H), 6.29 (dd, JHH = 16.1 Hz, JHP
=
3
4
4
4.8 Hz, 0.6H), 6.08 (ddd, JHH = 11.4 Hz, JHP = 4.4 Hz, JHH = 1.0
Hz, 0.4H), 5.70 (ddt, JHH = 15.5 Hz, JHH = 7.7 Hz, JHP = 7.6 Hz,
0.6H), 5.69 (ddd, JHH = 11.5 Hz, JHH = 7.9 Hz, JHP = 6.8 Hz,
3
3
3
3
3
3
Dimethyl (6-((tert-Butyldimethylsilyl)oxy)-4-methylenehex-2-en-
1-yl)phosphonate (3bf). Compounds 1b (225 mg, 1.50 mmol), 2f
(94 mg, 0.51 mmol), and Ru3 (16 mg, 0.026 mmol) were used
following general procedure B for 1 h. The catalyst was quenched with
ethyl vinyl ether, which afforded 3bf after flash chromatography on
silica gel (eluent: 70% to 100% ethyl acetate in hexanes) as a dark-
brown oil with a 1.5:1 E/Z ratio (95 mg, 56%). Analytical TLC: Rf =
0.4H), 5.30 (s, 0.4H), 5.26 (s, 0.4H), 5.57 (s, 0.6H), 5.08 (s, 0.6H),
4.63 (s, 1.2H), 4.46 (s, 0.8H), 4.18−4.05 (m, 4H), 2.82 (ddd, 2JHP
=
22.4 Hz, 3JHH = 8.0 Hz, 2JHH = 1.5 Hz, 0.8H), 2.67 (ddd, 2JHP = 22.3
3
4
Hz, JHH = 7.5 Hz, JHH = 0.9 Hz, 1.2H), 2.45 (s, 1.8H), 2.44 (s,
3
1.2H), 1.35 (s, 3.6H), 1.35 (s, 5.4H), 1.33 (t, JHH = 7.1 Hz, 2.4H),
3
1.32 (t, JHH = 7.1 Hz, 3.6H). 13C{1H} NMR (75 MHz, CDCl3,
1378
https://dx.doi.org/10.1021/acs.joc.0c02886
J. Org. Chem. 2021, 86, 1371−1384

The Journal of Organic Chemistry
pubs.acs.org/joc
Featured Article
0.43 (100% ethyl acetate). 1H NMR (500 MHz, CDCl3, ppm): δ 6.15
(ddt, 3JHH = 15.8 Hz, 4JHP = 4.9 Hz, 4JHH = 1.1 Hz, 0.6H), 6.00 (ddt,
3JCP = 15.6 Hz), 133.0 (s), 132.3 (d, JCP = 15.8 Hz), 130.4, 130.3,
3
1
3
129.60, 129.56, 128.4, 122.60 (dq, JCF = 275.8 Hz, JCP = 7.7 Hz),
3JHH = 11.5 Hz, 4JHP = 4.4 Hz, 4JHH = 1.6 Hz, 0.4H), 5.60 (ddt, 3JHH
=
1
3
2
122.58 (dq, JCF2 = 275.8 Hz, JCP = 7.5 Hz), 119.8 (d, JCP = 11.4
5
15.6 Hz, 3JHH = 7.5 Hz, 3JHP = 7.5 Hz, 0.6H), 5.49 (ddt, 3JHH = 11.5,
Hz), 116.8 (d, JCP = 13.1 Hz), 115.8 (d, JCP = 4.3 Hz), 115.1 (d,
5JCP = 1.9 Hz), 73.0 (d, 5JCP = 2.1 Hz), 70.3, 63.2−61.2 (m), 30.7 (d,
3
3JHH = 7.9 Hz, JHP = 7.0 Hz, 0.4H), 5.04 (s, 0.4H), 5.03 (s, 0.4H),
1
1JCP = 140.7 Hz), 26.9 (d, JCP = 142.1 Hz), 20.1, 19.6. [Note: The
4.98 (s, 0.6H), 5.94 (s, 0.6H), 3.71 (d, 3JHP = 10.9 Hz, 2.4H), 3.70 (d,
3JHP = 10.9 Hz, 3.6H), 3.68 (d, 3JHH = 7.2 Hz, 1.2H), 3.62 (d, 3JHH
7.0 Hz, 0.8H), 2.79 (ddd, JHP = 22.4 Hz, JHH = 8.0 Hz, JHH = 1.7
=
multiplet reported at δC 63.2−61.2 ppm appears as complex overlap
of two doublet-of-quartets expected to be observed from the
methylene carbon in the 2,2,2-trifluoroethoxy moiety for both E
and Z-isomers. An expansion is provided within its spectrum.]
31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ 30.06 (s, minor), 29.26
2
3
4
2
3
4
Hz, 0.8H), 2.39 (ddd, JHP = 22.4 Hz, JHH = 7.6 Hz, JHH = 1.2 Hz,
3
3
1.2H), 2.39 (t, JHH = 7.2 Hz, 1.2H), 2.26 (d, JHH = 7.0 Hz, 0.8H),
0.84 (s, 5.4H), 0.83 (s, 3.6H), −0.00 (s, 3.6H), −0.01 (s, 2.4H).
13C{1H} NMR (75 MHz, CDCl3, ppm): δ 142.3 (d, JCP = 4.2 Hz),
(s, major). FT-IR (neat, cm−1): 2972, 2252, 1715, 1603, 1585, 1492,
1452, 1418, 1377, 1264, 1168, 1104, 1069, 1026, 963, 909, 881, 843,
733, 712, 688, 658, 649, 555, 518. HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C18H19F6O5PNa 483.0766, found 483.0780.
4
4
3
3
141.5 (d, JCP = 3.6 Hz), 137.2 (d, JCP = 14.8 Hz), 134.6 (d, JCP
=
14.7 Hz), 119.4 (d, 2JCP = 10.9 Hz), 117.8 (d, 2JCP = 12.1 Hz), 117.1
(d, 5JCP = 3.9 Hz), 116.1 (d, 5JCP = 2.8 Hz), 62.3, 62.0, 52.8 (d, 2JCP
=
6.6 Hz), 52.7 (d, 2JCP = 6.7 Hz), 40.4 (d, 5JCP = 1.6 Hz), 35.6, 29.9 (d,
Bis(2,2,2-trifluoroethyl) (5-((tert-butyldimethylsilyl)oxy)-4-meth-
ylenehex-2-en-1-yl)phosphonate (3cd). Compounds 1c (216 mg,
0.75 mmol), ( )-2d (47 mg, 0.25 mmol), and Ru3 (8 mg, 0.013
mmol) were used following general procedure A (ca. 0.05 M). The
catalyst was quenched with ethyl vinyl ether, which afforded 3 cd after
flash chromatography on silica gel (eluent: 15% ethyl acetate in
hexanes) as a pale-yellow oil with a 1.2:1 E/Z ratio (88 mg, 74%).
Analytical TLC: Rf = 0.35 and 0.29 for the Z and E-isomer,
1JCP = 139.2 Hz), 26.2 (d, JCP = 140.1 Hz), 26.01, 25.97, 18.4, 18.3,
1
−5.2, −5.26. 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ 29.64 (s,
minor), 28.94 (s, major). FT-IR (neat, cm−1): 2953, 2929, 2896,
2856, 1723, 1607, 1472, 1463, 1389, 1361, 1253, 1174, 1095, 1057,
1029, 967, 936, 888, 832, 811, 775, 724, 663, 520. HRMS (ESI-TOF)
m/z: [M + Na]+ calcd for C15H31O4PSiNa 357.1621, found 357.1623.
tert-Butyl (5-(Dimethoxyphosphoryl)-2-methylenepent-3-en-1-
yl)(tosyl)carbamate (3bj). Compounds 1b (226 mg, 1.50 mmol),
2j (155 mg, 0.50 mmol), and Ru3 (16 mg, 0.026 mmol) were used
following general procedure B for 1 h. The catalyst was quenched with
ethyl vinyl ether, which afforded 3bj after flash chromatography on
silica gel (eluent: 5% to 10% ethanol in hexanes) as a dark-brown oil
with a 1.2:1 E/Z ratio (185 mg, 80%). Analytical TLC: Rf = 0.13
1
respectively (20% ethyl acetate in hexanes). H NMR (500 MHz,
3
CDCl3, ppm): δ 6.23−6.17 (m, 0.45H), 6.18 (ddd, JHH = 16.0 Hz,
3JHP = 5.5 Hz, 4JHH = 0.6 Hz, 0.55H), 5.68 (ddt, 3JHH = 15.9 Hz, 3JHH
= 7.5 Hz, 3JHP = 7.5 Hz, 0.55H), 5.57 (ddt, 3JHH = 11.5 Hz, 3JHH = 7.6
3
Hz, JHP = 7.6 Hz, 0.45H), 5.28 (s, 0.45H), 5.22 (s, 0.55H), 5.02 (s,
3
0.55H), 5.00 (s, 0.45H), 4.46 (q, JHH = 6.4 Hz, 0.55H), 4.43−4.31
3
1
(m, 4H), 4.24 (q, JHH = 6.3 Hz, 0.45H), 3.05−2.88 (m, 0.9H), 2.79
(10% ethanol in hexanes). H NMR (500 MHz, CDCl3, ppm): δ
2
3
4
3
(ddd, JHP = 22.9 Hz, JHH = 7.6 Hz, JHH = 0.6 Hz, 1.1H), 1.25 (d,
7.84−7.77 (m, 2H), 7.35−7.27 (m, 2H), 6.23 (dd, JHH = 16.0 Hz,
3
3JHH = 6.4 Hz, 1.65H), 1.16 (d, JHH = 6.4 Hz, 1.35H), 0.87 (s,
3JHP = 4.7 Hz, 0.55H), 6.09 (ddt, 3JHH = 11.4 Hz, 3JHP = 3.6 Hz, 4JHH
= 1.3 Hz, 0.45H), 5.74−5.63 (m, 1H), 5.27 (s, 0.45H), 5.26 (0.45H),
5.17 (s, 0.55H), 5.10 (s, 0.55H), 4.64 (s, 1.1H), 4.46 (s, 0.9H), 3.77
(d, 3JHP = 10.9 Hz, 2.7H), 3.76 (d, 3JHP = 10.8 Hz, 3.3H), 2.85 (ddd,
4.05H), 0.87 (s, 4.95H), 0.04 (s, 1.35H), 0.03 (s, 1.65H), 0.02 (s,
1.35H), −0.0 (s, 1.65H). 13C{1H} NMR (75 MHz, CDCl3, ppm): δ
4
4
3
149.6 (d, JCP = 4.7 Hz), 148.1 (d, JCP = 3.7 Hz), 136.6 (d, JCP
=
15.8 Hz), 133.4 (d, 3JCP = 15.9 Hz), 122.67 (dq, 1JCF = 275.8 Hz, 3JCP
= 7.6 Hz), 122.66 (dq, 1JCF = 275.9 Hz, 3JCP = 7.6 Hz), 118.3 (d, 2JCP
= 11.3 Hz), 115.8 (d, 2JCP = 13.1 Hz), 114.2 (d, 5JCP = 4.3 Hz), 112.9
(d, 5JCP = 3.0 Hz), 71.5 (d, 5JCP = 2.0 Hz), 69.2, 62.4 (dq, 2JCF = 37.8
2JHP = 22.4 Hz, 3JHH = 8.0 Hz, 4JHH = 1.4 Hz, 0.9H), 2.69 (dd, 2JHP
=
22.2 Hz, 3JHH = 7.5 Hz, 1.1H), 2.45 (s, 1.65H), 2.45 (s, 1.35H), 1.36
(s, 4.95H), 1.35 (s, 4.05H). 13C{1H} NMR (75 MHz, CDCl3, ppm):
δ 150.79, 150.77, 144.4, 144.3, 140.3 (d, 4JCP = 3.9 Hz), 139.8 (d, 4JCP
2
2
2
3
3
Hz, JCP = 6.2 Hz), 62.28 (dq, JCF = 37.7 Hz, JCP = 6.3 Hz), 62.24
(dq, 2JCF = 37.7 Hz, 2JCP = 6.3 Hz), 30.9 (d, 1JCP = 140.5 Hz), 27.2 (d,
1JCP = 142.2 Hz), 26.9, 24.6, 23.7, 18.3, −4.85, −4.93, −5.1. 31P{1H}
NMR (121.5 MHz, CDCl3, ppm): δ 30.39 (s, minor), 29.55 (s,
major). FT-IR (neat, cm−1): 2958, 2932, 2859, 2253, 1721, 1473,
1417, 1299, 1258, 1174, 1106, 1074, 964, 906, 836, 777, 730, 650,
554, 518. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C17H29F6O4PSiNa 493.1385, found 493.1369.
Bis(2,2,2-trifluoroethyl) ((6E)-5-((tert-Butyldimethylsilyl)oxy)-4-
methylene-7-phenylhepta-2,6-dien-1-yl)phosphonate (3ch). Com-
pounds 1c (432 mg, 1.51 mmol), ( )-2h (153 mg, 0.56 mmol), and
Ru3 (17 mg, 0.026 mmol) were used following general procedure A
(ca. 0.05M). The catalyst was quenched with ethyl vinyl ether, which
afforded 3ch after flash chromatography on silica gel (eluent: 15%
ethyl acetate in hexanes) as a pale-yellow oil with a 1.3:1 E/Z ratio
(250 mg, 80%). Analytical TLC: Rf = 0.17 and 0.15 for the Z and E-
= 3.6 Hz), 137.1, 137.0, 134.9 (d, JCP = 14.9 Hz), 131.5 (d, JCP
=
2
14.6 Hz), 129.23 129.22, 128.22, 128.17, 122.0 (d, JCP = 11.0 Hz),
2
5
5
118.5 (d, JCP = 11.9 Hz), 115.4 (d, JCP = 2.7 Hz), 114.9 (d, JCP
=
3.6 Hz), 84.42, 84.38, 52.8 (d, 2JCP = 6.1 Hz), 52.7 (d, 2JCP = 6.1 Hz),
5
1
50.8 (d, JCP = 2.3 Hz), 47.8, 30.2 (d, JCP = 139.4 Hz), 27.9, 27.8,
1
26.3 (d, JCP = 139.8 Hz), 21.65, 21.65. 31P{1H} NMR (121.5 MHz,
CDCl3, ppm): δ 29.07 (s, minor), 28.38 (s, major). FT-IR (neat,
cm−1): 2981, 2954, 2852, 1728, 1597, 1495, 1456, 1396, 1354, 1251,
1187, 1153, 1089, 1030, 937, 881, 848, 8076, 771, 720, 675, 591, 545.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C20H30NO7PSNa
482.1373, found 482.1385.
6-(Bis(2,2,2-trifluoroethoxy)phosphoryl)-3-methylenehex-4-en-
2-yl Benzoate (3cb). Compounds 1c (145 mg, 0.51 mmol), ( )-2b
(89 mg, 0.51 mmol), and Ru2A (16 mg, 0.025 mmol) were used
following general procedure A (ca. 0.10 M). The catalyst was
quenched with ethyl vinyl ether, which afforded 3cb after flash
chromatography on silica gel (eluent: 20% ethyl acetate in hexanes) as
a pale-yellow oil with a 1.5:1 E/Z ratio (208 mg, 89%). Analytical
TLC: Rf: 0.38 and 0.29 for the Z and E-isomer, respectively (20%
ethyl acetate in hexanes). 1H NMR (500 MHz, CDCl3, ppm): δ
8.07−8.00 (m, 2H), 7.58−7.50 (m, 1H), 7.45−7.40 (m, 2H), 6.28−
6.24 (m, 0.4H), 6.25 (ddd, 3JHH = 15.9 Hz, 4JHP = 5.8 Hz, 4JHH = 0.6
1
isomer, respectively (15% ethyl acetate in hexanes). H NMR (500
MHz, CDCl3, ppm): δ 7.38−7.34 (m, 2H), 7.32−7.27 (m, 2H),
3
7.24−7.18 (m, 1H), 6.60 (dd, JHH = 16.0 Hz, J = 1.1 Hz, 0.57H),
3
3
6.57 (dd, JHH = 15.8 Hz, J = 0.7 Hz, 0.43H), 6.22 (ddt, JHH = 11.7
Hz, 4JHP = 4.4 Hz, 4JHH = 1.3 Hz, 0.43H), 6.20 (ddt, 3JHH = 16.1 Hz,
4JHP = 5.2 Hz, 4JHH = 0.5 Hz, 0.57H), 6.17 (dd, 3JHH = 15.9 Hz, 3JHH
=
5.8 Hz, 0.57H), 6.11 (dd, 3JHH = 15.9 Hz, 3JHH = 6.0 Hz, 0.43H), 5.86
(ddt, 3JHH = 15.8 Hz, 3JHH = 7.5 Hz, 3JHP = 7.5 Hz, 0.57H), 5.58 (ddt,
3JHH = 11.5 Hz, 3JHH = 7.5 Hz, 3JHP = 7.5 Hz, 0.43H), 5.43 (s, 0.43H),
5.35 (s, 0.57H), 5.17 (d, J = 1.7 Hz, 0.57H), 5.17 (s, 0.43H), 4.97 (d,
3JHH = 5.8 Hz, 0.57H), 4.74 (d, 3JHH = 5.9 Hz, 0.43H), 4.40−4.16 (m,
4H), 3.08−2.88 (m, 0.86H), 2.78 (ddd, 2JHP = 23.0 Hz, 3JHH = 7.6 Hz,
4JHH = 0.9 Hz, 1.14H), 0.94 (s, 9H), 0.11 (s, 1.29H), 0.09 (s, 2.85H),
0.09 (s, 1.29H), 0.08 (s, 0.57H). 13C{1H} NMR (75 MHz, CDCl3,
3
3
3
Hz, 0.6H), 5.78 (ddt, JHH = 15.9 Hz, JHH = 7.5 Hz, JHH = 7.4 Hz,
0.6H), 5.77 (q, 3JHH = 6.6 Hz, 0.6H), 5.49 (ddt, 3JHH = 11.4 Hz, 3JHH
= 7.6 Hz, 3JHP = 7.6 Hz, 0.4H), 5.53 (q, 3JHH = 6.6 Hz, 0.4H), 5.39 (s,
0.4H), 5.33 (s, 0.6H), 5.19−5.16 (m, 1H), 5.17 (s, 0.5H), 4.40−4.26
(m, 4H), 3.07−2.89 (m, 0.8H), 2.81 (ddd, 2JHP = 23.1 Hz, 3JHH = 7.6
Hz, 4JHH = 0.7 Hz, 1.2H), 1.83 (d, 3JHH = 6.6 Hz, 1.8H), 1.43 (d, 3JHH
= 6.6 Hz, 1.2H). 13C{1H} NMR (75 MHz, CDCl3, ppm): δ 165.60,
4
4
165.59, 145.4 (d, JCP = 4.8 Hz), 143.8 (d, JCP = 3.7 Hz), 135.5 (d,
1379
https://dx.doi.org/10.1021/acs.joc.0c02886
J. Org. Chem. 2021, 86, 1371−1384

The Journal of Organic Chemistry
pubs.acs.org/joc
Featured Article
4
4
3
3
ppm): δ 146.7 (d, JCP = 4.7 Hz), 145.5 (d, JCP = 4.7 Hz), 136.7,
18.49, 18.47, 16.57 (d, JCP = 6.0 Hz), 16.55 (d, JCP = 6.0 Hz),
−4.60, −4.64, −4.7. 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ
30.80 (s, 0.5P), 30.67 (s, 0.5P). FT-IR (neat, cm−1): 3449, 2955,
2929, 2857, 1601, 1495, 1472, 1463, 1448, 1390, 1361, 1248, 1164,
1099, 1056, 1028, 963, 900, 882, 834, 776, 747, 693, 588, 534. HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C25H41O4PSiNa 487.2404,
found 487.2417.
3
3
136.7, 135.2 (d, JCP = 15.9 Hz), 132.9 (d, JCP = 15.8 Hz), 131.5,
130.9, 128.53, 128.51, 127.5, 126.44, 126.39, 122.52 (dq, 1JCF = 275.9
3
1
3
Hz, JCP = 7.6 Hz), 122.48 (dq, JCF = 275.9 Hz, JCP = 7.6 Hz),
1
3
2
122.47 (dq, JCF2 = 275.9 Hz, JCP = 7.4 Hz), 118.5 (d, JCP = 11.4
5
Hz), 117.0 (d, JCP = 13.0 Hz), 115.4 (d, JCP = 4.3 Hz), 114.0 (d,
5JCP = 3.0 Hz), 76.40 (d, 5JCP = 2.0 Hz), 74.37 (d, 5JCP = 0.6 Hz), 62.2
(dq, 2JCF = 37.7 Hz, 2JCP = 6.5 Hz), 62.13 (dq, 2JCF = 37.7 Hz, 2JCP
=
=
( )-Ethyl 8-((tert-Butyldimethylsilyl)oxy)-2-(diethoxyphosphor-
yl)-6-methyleneoct-4-enoate (3ec). Compounds 1e (203 mg, 0.77
mmol), 2c (40 mg, 0.25 mmol), and Ru3 (8 mg, 0.013 mmol) were
used following general procedure A (ca. 0.05 M). The catalyst was
quenched with methanolic potassium isocyanoacetate, which afforded
3ec after flash chromatography on silica gel (eluent: 20% to 30%
acetone in hexanes) as a pale-yellow oil with a 1.5:1 E/Z ratio (74 mg,
70%). Analytical TLC: Rf = 0.25 (30% acetone in hexanes). 1H NMR
(500 MHz, CDCl3, ppm): δ 8.06−7.99 (m, 2H), 7.56−7.49 (m, 1H),
2
2
1
6.4 Hz), 62.10 (dq, JCF = 37.7 Hz, JCP = 6.9 Hz), 30.8 (d, JCP
1
140.5 Hz), 27.1 (d, JCP = 142.3 Hz), 25.7, 18.3, −4.8, −4. 9, −4.98,
−5.01. 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ 30.30 (s, minor),
29.35 (s, major). FT-IR (neat, cm−1): 2957, 2931, 2859, 2251, 1720,
1601, 1495, 1472, 1463, 1417, 1362, 1290, 1256, 1171, 1105, 1071,
1006, 963, 908, 880, 835, 777, 732, 693, 649, 602, 556, 520. HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C24H33F6O4PSiNa 581.1682,
found 581.1690.
3
3
7.44−7.38 (m, 2H), 6.18 (d, JHH = 16.0 Hz, 0.6H), 5.94 (d, JHH
=
Diethyl (7-((tert-Butyldimethylsilyl)oxy)-5-methylenehept-3-en-
1-yl)phosphonate (3df). Compounds 1d (194 mg, 1.01 mmol), 2f
(47 mg, 0.26 mmol), and Ru3 (8 mg, 0.13 mmol) were used
following general procedure B for 3 h. The catalyst was quenched with
methanolic potassium isocyanoacetate, which afforded 3df after flash
chromatography on silica gel (eluent: 40% to 50% ethyl acetate in
hexanes) as a pale-yellow oil with a 1:1.2 E/Z ratio (67 mg, 70%).
11.8 Hz, 0.4H), 5.71 (dt, 3JHH = 16.0 Hz, 3JHH = 7.1 Hz, 0.6H), 5.52
3
3
(dt, JHH = 11.6 Hz, JHH = 6.9 Hz, 0.4H), 5.39 (s, 0.4H), 5.25 (s,
0.6H), 5.16 (s, 1.0H), 4.91 (s, 1.2H), 4.81 (s, 0.8H), 4.20−4.05 (m,
6H), 3.07−2.57 (m, 3H), 1.33−1.26 (m, 6H), 1.23 (t, J = 7.1 Hz,
1.2H), 1.19 (t, J = 7.1 Hz, 1.8H). 13C{1H} NMR (75 MHz, CDCl3,
2
2
ppm): δ 168.6 (d, JCP = 4.7 Hz), 168.5 (d, JCP = 4.7 Hz), 166.2,
166.1, 139.9, 139.5, 133.1 (d, 5JCP = 2.0 Hz), 132.0 (d, 5JCP = 0.5 Hz),
1
Analytical TLC: Rf = 0.20 (50% ethyl acetate in hexanes). H NMR
3
(500 MHz, CDCl3, ppm): δ 6.04 (d, 3JHH = 15.8 Hz, 0.45H), 5.78 (d,
130.10, 130.05, 129.8 (d, JCP = 17.0 Hz), 129.7, 129.91, 129.89,
3
3JHH = 11.6 Hz, 0.55H), 5.67 (dt, JHH = 15.7 Hz, JHH = 6.8 Hz,
3
3
128.43, 128.42, 126.9 (d, JCP = 16.1 Hz), 117.3, 117.1, 67.0, 64.4,
62.9 (d, 2JCP = 6.3 Hz), 62.8 (d, 2JCP = 6.8 Hz), 61.52, 61.46, 46.0 (d,
3
3
0.45H), 5.43 (dt, JHH = 11.6 Hz, JHH = 7.3 Hz, 0.55H), 5.00 (s,
0.55H), 4.92 (s, 0.45H), 4.87 (s, 0.45H), 4.85 (s, 0.55H), 4.12−3.98
(m, 4H), 3.67 (t, 3JHH = 7.2 Hz, 0.9H), 3.62 (t, 3JHH = 7.1 Hz, 1.1H),
1JCP = 130.3 Hz), 45.6 (d, JCP = 129.6 Hz), 30.5 (d, JCP = 4.3 Hz),
1
2
26.3 (d, 2JCP = 4.2 Hz), 16.41 (d, 3JCP = 6.0 Hz), 16.39 (d, 3JCP = 6.0
Hz), 14.16. 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ 21.28 (s,
major), 21.25 (s, minor). FT-IR (neat, cm−1): 3451, 2982, 2932,
2109, 1721, 1602, 1584, 1451, 1392, 1368, 1315, 1255, 1175, 1153,
1110, 1098, 1022, 967, 860, 792, 713, 688, 674, 651, 559. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C21H30O7P 425.1714, found
425.1714.
3
2.52−2.43 (m, 1.1H), 2.41−2.31 (m, 0.9H), 2.38 (t, JHH = 7.2 Hz,
0.9H), 2.27 (t, 3JHH = 7.1 Hz, 1.1H), 1.83−1.71 (m, 2H), 1.28 (t, 3JHH
= 7.1 Hz, 2.7H), 1.27 (t, 3JHH = 7.1 Hz, 3.3H), 0.84 (s, 4.05H), 0.84
(s, 4.95H), −0.00 (s, 2.7H), −0.00 (s, 3.3H). 13C{1H} NMR (75
5
MHz, CDCl3, ppm): δ 142.7, 142.0, 132.9 (d, JCP = 1.1 Hz), 131.0
5
3
3
(d, JCP = 1.8 Hz), 130.6 (d, JCP = 17.3 Hz), 128.4 (d, JCP = 17.1
Hz), 115.9, 115.6, 62.5, 62.3, 61.59 (d, 2JCP = 6.4 Hz), 61.58 (d, 2JCP
Ethyl 8-((tert-butyldimethylsilyl)oxy)-2-(diethoxyphosphoryl)-6-
methyleneoct-4-enoate (3ef). Compounds 1e (266 mg, 1.01
mmol), 2f (49 mg, 0.26 mmol), and Ru3 (8 mg, 0.013 mmol)
were used following general procedure A (ca. 0.05 M). The catalyst
was quenched with methanolic potassium isocyanoacetate, which
afforded 3ef after flash chromatography on silica gel (eluent: 45%
ethyl acetate in hexanes) as a pale-yellow oil with a 1.5:1 E/Z ratio
(100 mg, 84%). Analytical TLC: Rf = 0.41 (50% ethyl acetate in
hexanes). 1H NMR (500 MHz, CDCl3, ppm): δ 6.09 (d, 3JHH = 15.8
Hz, 0.6H), 5.85 (d, JHH = 11.7 Hz, 0.4H), 5.59 (dt, JHH = 15.7 Hz,
3JHH = 7.1 Hz, 0.6H), 5.37 (dt, 3JHH = 11.6 Hz, 3JHH = 7.1 Hz, 0.4H),
5.05−5.02 (m, 0.4H), 4.95−4.93 (m, 0.6H), 4.92−4.88 (m, 1H),
4.22−4.07 (m, 6H), 3.66 (t, 3JHH = 7.3 Hz, 1.2H), 3.64 (t, 3JHH = 7.2
Hz, 0.8H), 2.98 (ddd, 2JHP = 22.2 Hz, 3JHH = 11.1 Hz, 3JHH = 4.0 Hz,
1
= 6.4 Hz), 40.7, 35.8, 26.3 (d, JCP = 139.3 Hz), 26.0, 26.0, 25.8 (d,
2JCP = 4.5 Hz), 25.7 (d, JCP = 139.1 Hz), 21.9 (d, JCP = 4.4 Hz),
1
2
18.4, 18.4, 16.6 (d, JCP = 7.0 Hz), −5.16, −5.21. 31P{1H} NMR
3
(121.5 MHz, CDCl3, ppm): δ 30.66 (s, minor), 30.65 (s, major). FT-
IR (neat, cm−1): 3451, 2954, 2929, 2857, 1636, 1472, 1463, 1443,
1390, 1361, 1248, 1164, 1096, 1055, 1027, 962, 894, 834, 813, 775,
736, 663, 542. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C18H37O4PSiNa 399.2091, found 399.2102.
3
3
( )-Diethyl ((7E)-6-((tert-Butyldimethylsilyl)oxy)-5-methylene-8-
phenylocta-3,7-dien-1-yl)phosphonate (3dh). Compounds 1d (149
mg, 0.77 mmol), ( )-2h (68 mg, 0.25 mmol), and Ru3 (8 mg, 0.13
mmol) were used following general procedure B for 3 h. The catalyst
was quenched with methanolic potassium isocyanoacetate, which
afforded 3dh after flash chromatography on silica gel (eluent: 35% to
40% ethyl acetate in hexanes) as a pale-yellow oil with a 1:1 E/Z ratio
(92 mg, 79%). Analytical TLC: Rf = 0.30 (50% ethyl acetate in
hexanes). 1H NMR (500 MHz, CDCl3, ppm): δ 7.37−7.32 (m, 2H),
2
3
3
0.6H), 2.94 (ddd, JHP = 22.2 Hz, JHH = 11.1 Hz, JHH = 4.0 Hz,
0.6H), 2.89−2.81 (m, 0.4H), 2.81−2.67 (m, 1H), 2.65−2.56 (m,
3
3
0.6H), 2.36 (t, JHH = 7.3 Hz, 1.2H), 2.29 (t, JHH = 7.1 Hz, 1.8H),
0.86 (s, 9H), 0.02 (s, 2.4H), 0.01 (s, 3.6H). 13C{1H} NMR (75 MHz,
2
2
3
CDCl3, ppm): δ 168.8 (d, JCP = 4.7 Hz), 168.6 (d, JCP = 4.3 Hz),
142.4, 141.8, 134.8 (d, 5JCP = 0.8 Hz), 132.5 (d, 5JCP = 1.4 Hz), 127.6
(d, 3JCP = 15.9 Hz), 125.4 (d, 3JCP = 16.1 Hz), 116.5, 115.9, 62.92 (d,
2JCP = 6.4 Hz), 62.89 (d, 2JCP = 6.2 Hz), 62.8 (d, 2JCP = 6.9 Hz), 62.7
(d, JCP = 7.1 Hz), 62.35, 62.33, 61.49, 61.46, 46.2 (d, JCP = 130.3
Hz), 45.9 (d, JCP = 129.4 Hz), 40.6, 35.7, 30.4 (d, JCP = 4.3 Hz),
7.32−7.27 (m, 2H), 7.23−7.18 (m, 1H), 6.58 (d, JHH = 15.7 Hz,
0.5H), 6.54 (d, 3JHH = 15.8 Hz, 0.5H), 6.19 (dd, 3JHH = 15.8 Hz, 3JHH
= 5.7 Hz, 0.5H), 6.11 (dd, 3JHH = 15.8 Hz, 3JHH = 5.9 Hz, 0.5H), 6.03
3
3
3
(d, JHH = 16.0 Hz, 0.5H), 5.94 (dt, JHH = 15.9 Hz, JHH = 6.6 Hz,
0.5H), 5.89 (d, 3JHH = 11.7 Hz, 0.5H), 5.58 (dt, 3JHH = 11.7 Hz, 3JHH
= 7.2 Hz, 0.5H), 5.36 (s, 0.5H), 5.21 (s, 0.5H), 5.08 (s, 0.5H), 4.98
2
1
1
2
3
3
2
2
(s, 0.5H), 4.93 (d, JHH = 5.5 Hz, 0.5H), 4.71 (d, JHH = 5.7 Hz,
0.5H), 4.13−3.98 (m, 4H), 2.56−2.46 (m, 1H), 2.42−2.32 (m, 1H),
1.85−1.70 (m, 2H), 1.30 (t, 3JHH = 6.9 Hz, 1.5H), 1.30 (t, 3JHH = 7.3
26.2 (d, JCP = 4.3 Hz), 26.0, 18.40, 18.37, 16.46 (d, JCP = 6.0 Hz),
16.44 (d, JCP = 6.2 Hz), 14.25, 14.23, −5.20, −5.23. 31P{1H} NMR
2
(121.5 MHz, CDCl3, ppm): δ 21.42 (s, minor), 21.37 (s, major). FT-
IR (neat, cm−1): 2955, 2930, 2857, 1734, 1607, 1472, 1444, 1390,
1368, 1327, 1252, 1152, 1096, 1023, 967, 894, 834, 812, 775, 732,
663, 602, 566. High-resolution MS HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C21H41O6PSiNa 471.2302, found 471.2314.
3
3
Hz, 1.5H), 1.29 (t, JHH = 7.0 Hz, 1.5H), 1.28 (t, JHH = 7.3 Hz,
1.5H), 0.92 (s, 9H), 0.8 (s, 4H), 0.7 (s, 2H). 13C{1H} NMR (75
3
MHz, CDCl3, ppm): δ 147.5, 146.2, 137.1, 137.0, 132.3 (d, JCP
=
17.8 Hz), 132.1, 132.0, 129.9 (d, 3JCP = 17.5 Hz), 129.6, 129.5, 129.4
(d, 5JCP = 1.4 Hz), 128.61, 128.59, 127.51, 127.49, 127.4 (d, 5JCP = 1.9
Hz), 126.57, 126.57, 113.3, 113.1, 76.7, 74.4, 61.60 (d, 2JCP = 6.5 Hz),
6-((tert-Butyldimethylsilyl)oxy)-4-methylenehex-2-en-1-yl dieth-
yl Phosphate (3ff). Compounds 1f (198 mg, 1.02 mmol), 2f (48 mg,
0.26 mmol), and Ru3 (8 mg, 0.013 mmol) were used following
general procedure A (ca. 0.05 M). The catalyst was quenched with
2
2
1
61.57 (d, JCP = 6.4 Hz), 26.21 (d, JCP = 1.1 Hz), 26.17 (d, JCP
139.1 Hz), 26.0, 25.6 (d, JCP = 139.0 Hz), 21.1 (d, JCP = 1.1 Hz),
=
1
5
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Featured Article
methanolic potassium isocyanoacetate, which afforded 3ff after flash
chromatography on silica gel (eluent: 40% ethyl acetate in hexanes) as
a pale-yellow oil with a 2:1 E/Z ratio (75 mg, 77%). Analytical TLC:
Rf = 0.30 (30% ethyl acetate in hexanes). 1H NMR (500 MHz,
CDCl3, ppm): δ 6.30 (ddt, 3JHH = 15.8 Hz, 4JHP = 1.5 Hz, 4JHH = 0.5
Hz, 0.65H), 6.02 (ddt, 3JHH = 11.7 Hz, 3JHP = 1.9 Hz, 4JHH = 1.0 Hz,
brine (10 mL). The organic layer was then dried with MgSO4, which
was subsequently removed via gravity filtration through filter paper.
The dried organic layer was then concentrated via rotatory
evaporation and purified by flash column chromatography on silica
gel (eluent: 15% to 20% ethyl acetate in hexanes) to afford 3gb as a
clear colorless oil with a 2:1 E/Z ratio (50 mg, 75% over two steps).
3
3
1
0.35H), 5.79 (dt, JHH = 15.8 Hz, JHP = 6.3 Hz, 0.65H), 5.67 (dt,
Analytical TLC: Rf = 0.19 (20% ethyl acetate in hexanes). H NMR
3
3JHH = 11.7 Hz, JHP = 6.4 Hz, 0.35H), 5.09−5.07 (m, 1H), 5.05 (s,
3
(500 MHz, CDCl3, ppm): δ 6.18−6.11 (m, 0.35H), 6.13 (dd, JHH
=
2
3
0.65H), 4.80−4.77 (m, 0.35H), 4.71 (ddd, JHP = 8.1 Hz, JHH = 6.5
15.8 Hz, 4JHP = 6.0 Hz, 0.65H), 5.75 (ddt, 3JHH = 15.9 Hz, 3JHH = 7.6
2
2
3
Hz, 3JHP = 7.6 Hz, 0.65H), 5.69 (ddt, JHH = 11.5 Hz, 3JHH = 7.8 Hz,
3
Hz, JHH = 1.7 Hz, 0.7H), 4.57 (ddd, JHP = 8.1 Hz, JHH = 6.4 Hz,
2JHH = 1.2 Hz, 1.3H), 4.13−4.05 (m, 4H), 3.71 (t, JHH = 7.1 Hz,
3
3JHP = 7.8 Hz, 0.35H), 5.24 (s, 0.35H), 5.21 (s, 0.65H), 5.09 (s,
0.35H), 5.05 (s, 0.65H), 4.56 (q, 3JHH = 6.3 Hz, 0.65H), 4.28 (q, 3JHH
= 6.5 Hz, 0.35H), 4.19−3.99 (m, 35H), 3.09−2.93 (m, 0.7H), 2.82
(dd, 2JHP = 19.8 Hz, 3JHH = 7.6 Hz, 1.3H), 1.95 (bs, 0.35H), 1.79 (bs,
3
3
2
1.3H), 3.64 (t, JHH = 6.9 Hz, 0.7H), 2.42 (dt, JHH = 7.1 Hz, JHH
=
3
2
0.9 Hz, 1.3H), 2.29 (dt, JHH = 6.9 Hz, JHH = 0.9 Hz, 0.7H), 1.33−
1.29 (m, 6H), 0.86 (s, 5.85H), 0.86 (s, 3.15H), 0.02 (s, 3.3H), 0.02
(s, 2.7H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 142.0, 141.6,
136.2, 134.0, 126.6 (d, J = 7.3 Hz), 123.1 (d, J = 6.8 Hz), 118.7,
117.0, 68.0, 67.9, 63.9 (d, 2JCP = 5.7 Hz), 63.8 (d, 2JCP = 5.1 Hz), 62.2,
0.66H), 1.34 (d, JHH = 6.4 Hz, 1.95H), 1.30−1.24 (m, 7.05H). 13C
3
NMR (125 MHz, CDCl3, ppm): δ 149.7 (d, 4JCP = 4.8 Hz), 148.2 (d,
4JCP = 3.8 Hz), 134.5 (d, JCP = 15.8 Hz), 131.2 (d, JCP = 15.6 Hz),
3
3
2
122.4 (d, 2JCP = 9.6 Hz), 119.5 (d, 2JCP = 11.3 Hz), 112.9, 112.9, 70.8
62. 40.2, 35.6, 26.00, 25.98, 18.4, 18.3, 16.2 (d, JCP = 6.7 Hz), −5.2,
−5.3. 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ −1.28 (s, major),
−1.30 (s, minor). FT-IR (neat, cm−1): 2954, 2930, 2857, 1608, 1583,
1473, 1444, 1418, 1392, 1370, 1257, 1192, 1167, 1097, 1027, 969,
900, 833, 775, 732, 663, 631, 518. HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C17H35O6PSiNa 401.1884, found 401.1881.
5
2
2
(d, JCP = 1.9 Hz), 67.7, 62.9 (d, JCP = 7.1 Hz), 62.83 (d, JCP = 6.8
Hz), 62.82 (d, 2JCP = 7.1 Hz), 62.77 (d, 2JCP = 6.8 Hz), 40.0 (d, 1JCP
=
1
3
109.8 Hz), 35.6 (d, JCP = 111.1 Hz), 22.9, 22.3, 16.29 (d, JCP = 6.7
Hz), 16.26 (d, JCP = 7.0 Hz). 31P{1H} NMR (121.5 MHz, CDCl3,
3
ppm): δ 93.48 (s, minor), 92.81 (s, major). FT-IR (neat, cm−1): 3412,
2979, 1444, 1389, 1160, 1099, 1024, 957, 869, 841, 780, 598. HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C11H21O3PSNa 287.0841,
found 287.0841.
(6E)-5-((tert-Butyldimethylsilyl)oxy)-4-methylene-7-phenylhep-
ta-2,6-dien-1-yl Diethyl Phosphate (3fh). 1f (152 mg, 0.78 mmol),
( )-2h (71 mg, 0.26 mmol), and Ru3 (8 mg, 0.013 mmol) were used
following general procedure A (ca. 0.05 M). The catalyst was
quenched with methanolic potassium isocyanoacetate, which afforded
3fh after flash chromatography on silica gel (eluent: 25% to 30% ethyl
acetate to hexanes) as a pale-yellow oil with a 2:1 E/Z ratio (77.8 mg,
O,O-Diethyl (6-Hydroxy-4-methylenehex-2-en-1-yl)-
phosphonothioate (3gf). Compounds 1g (151 mg, 0.78 mmol), 2f
(47 mg, 0.26 mmol), and Ru3 (8.0 mg, 0.013 mmol) were used
following general procedure A (ca. 0.05 M). The catalyst was
quenched with methanolic potassium isocyanoacetate, which afforded
3gf after flash chromatography on silica gel (eluent: 2% to 3% ethyl
acetate in hexanes) as a mixture with 1g as a clear colorless oil upon
isolation. Analytical TLC: Rf = 0.45 (5% ethyl acetate in hexanes).
The isolated mixture was added to a 25 mL of rb flask and
subsequently dissolved in anhydrous ethanol (5 mL). Pyridinium p-
toluenesulfonate (26 mg, 0.10 mmol) was then added, and the
reaction mixture was allowed to stir overnight (ca. 18 h). The reaction
mixture was then concentrated and purified by flash column
chromatography on silica gel (eluent: 20% to 25% ethyl acetate in
hexanes) to afford 3gf as a clear colorless oil with a 5:1 E/Z ratio (41
mg, 61% over two steps). Analytical TLC: Rf = 0.23 (20% ethyl
1
64%). Analytical TLC: Rf = 0.16 (30% ethyl acetate in hexanes). H
NMR (500 MHz, CDCl3, ppm): δ 7.37−7.33 (m, 2H), 7.31−7.26
(m, 2H), 7.23−7.18 (m, 1H), 6.59 (d, 3JHH = 15.9 Hz, 0.6H), 6.56 (d,
3JHH = 15.8 Hz, 0.4H), 6.27 (d, 3JHH = 16.0 Hz, 0.6H), 6.18 (dd, 3JHH
= 15.8 Hz, 3JHH = 5.6 Hz, 0.6H), 6.13 (d, 3JHH = 11.9 Hz, 0.4H), 6.10
3
(dd, 3JHH = 15.9 Hz, 3JHH = 5.9 Hz, 0.4H), 6.03 (dt, JHH = 16.0 Hz,
3JHH = 6.2 Hz, 0.6H), 5.79 (dt, 3JHH = 11.7 Hz, 3JHH = 6.4 Hz, 0.4H),
5.40 (s, 0.4H), 5.36 (s, 0.6H), 5.21 (s, 0.6H), 4.96 (d, 3JHH = 5.8 Hz,
0.6H), 4.88 (s, 0.4H), 4.76−4.69 (m, 1.2H), 4.58−4.53 (m, 1.2H),
4.11−3.99 (m, 4H), 1.31−1.24 (m, 6H), 0.92 (s, 9H), 0.09 (s, 2H),
0.08 (s, 2H), 0.07 (s, 2H). 13C{1H} NMR (125 MHz, CDCl3, ppm):
4
δ 146.7, 145.8, 136.92, 136.85, 132.4, 131.6, 131.1, 130.5 (d, JCP
=
3
1
0.9 Hz), 130.0, 129.8, 128.59, 128.57, 128.1 (d, JCP = 7.6 Hz),
acetate in hexanes). H NMR (500 MHz, CDCl3, ppm): δ 6.17 (dd,
127.61, 127.57, 126.59, 126.56, 124.7 (d, 3JCP = 6.6 Hz), 115.8, 114.8,
3JHH = 15.8 Hz, 3JHH = 5.8 Hz, 0.83H), 6.04 (dd, 3JHH = 4.6 Hz, 3JHH
2
2
76.3, 74.3, 68.11, 68.07, 68.09 (d, JCP = 5.5 Hz), 64.4 (d, JCP = 5.3
3
3
3
= 11.5 Hz, 0.17H), 5.68 (ddt, JHH = 15.7 Hz, JHH = 7.6 Hz, JHP
=
2
3
Hz), 63.8 (d, JCP = 5.8 Hz), 25.90, 25.89, 18.4, 16.2 (d, JCP = 6.7
Hz), 16.1 (d, 2JCP = 6.6 Hz), −4.6, −4.7, −4.8. 31P{1H} NMR (121.5
MHz, CDCl3, ppm): δ −1.39 (s, major), −1.42 (s, minor). FT-IR
(neat, cm−1): 2955, 2930, 2857, 2112, 1601, 1495, 1472, 1463, 1449,
1391, 1369, 1258, 1166, 1101, 1026, 967, 902, 881, 834, 776, 747,
693, 597, 528. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C24H39O5PSiNa 489.2186, found 489.2191.
3
3
3
7.6 Hz, 0.83H), 5.60 (ddt, JHH = 11.5 Hz, JHH = 7.9 Hz, JHP = 7.9
Hz, 0.17H), 5.10 (s, 0.34H), 5.07 (s, 0.83H), 5.02 (s, 0.83H), 4.16−
4.00 (m, 4H), 3.73 (t, JHH = 6.4 Hz, 1.66H), 3.68 (t, 3JHH = 6.2 Hz,
3
2
3
0.34H), 3.04 (dd, JHP = 20.0 Hz, JHH = 7.9 Hz, 0.34H), 2.83 (dd,
2JHP = 19.9 Hz, 3JHH = 7.6 Hz, 1.66H), 2.49 (t, 3JHH = 6.4 Hz, 1.66H),
2.35 (t, 3JHH = 6.1 Hz, 0.34H), 1.28 (t, 3JHH = 7.0 Hz, 1.02H), 1.27 (t,
3JHH = 7.0 Hz, 4.98H). 13C NMR (125 MHz, CDCl3, ppm): δ 142.2
(d, 4JCP = 4.9 Hz), 141.5 (d, 4JCP = 3.7 Hz), 136.7 (d, 3JCP = 15.5 Hz),
O,O-Diethyl (5-Hydroxy-4-methylenehex-2-en-1-yl)-
phosphonothioate (3gb). Compounds 1g (147 mg, 0.75 mmol),
2b (43 mg, 0.25 mmol), and Ru3 (8 mg, 0.013 mmol) were used
following general procedure A (ca. 0.05 M). The catalyst was
quenched with methanolic potassium isocyanoacetate, which afforded
3gb after flash chromatography on silica gel (eluent: 5% ethyl acetate
in hexanes) as a mixture with the homodimer of 1g as a clear colorless
oil upon isolation. Analytical TLC: Rf = 0.17 (5% ethyl acetate in
hexanes).
The isolated mixture was added to a 25 mL rb flask and
subsequently dissolved in anhydrous methanol (5 mL, ca. 0.05M).
K2CO3 (53 mg, 0.38 mmol) was then added and the reaction mixture
was allowed to stir overnight (ca. 18 h). The reaction mixture was
then diluted with EtOAc (5 mL) and subsequently extracted with a
saturated aqueous solution of NH4Cl (5 mL). The organic layer was
removed and the aqueous layer was extracted with additional EtOAc
(3x, 10 mL). The organic layers were combined and were then
extracted with a saturated aqueous solution of K2CO3 (10 mL) and
3
2
2
134.2 (d, JCP = 15.8 Hz), 120.9 (d, JCP = 9.3 Hz), 119.3 (d, JCP
=
11.2 Hz), 117.4 (d, 5JCP = 4.5 Hz), 116.7 (d, 5JCP = 2.7 Hz), 62.9 (d,
2JCP = 7.0 Hz), 61.2, 60.7, 40.4 (d, JCP = 2.0 Hz), 39.7 (d, JCP
=
5
1
1
3
110.0 Hz), 35.6, 35.5 (d, JCP = 111.1 Hz), 16.31 (d, JCP = 6.7 Hz),
16.28 (d, 3JCP = 6.8 Hz). 31P{1H} NMR (121.5 MHz, CDCl3, ppm): δ
93.60 (s, minor), 92.83 (s, major). FT-IR (neat, cm−1): 3401, 2980,
2934, 2901, 2115, 1606, 1443, 1389, 1293, 1217, 1160, 1097, 1019,
954, 893, 864, 825, 763, 600. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C11H21O3PSNa 287.0841, found 287.0841.
(4E/Z,6E)-3-Methylene-7-phenylhepta-4,6-dien-2-yl benzoate
(4ab). Compounds 3ab (2:1 E/Z, 124 mg, 0.35 mmol) was added
to a 25 mL rb flask and was dissolved in THF (3 mL). The flask was
then cooled to −78 °C and a solution of KHMDS (66 mg, 0.33
mmol) in THF (1.5 mL), which was prepared in a glovebox, was
slowly added and allowed to stir for 1 h at −78 °C. Benzaldehyde (32
mg, 0.30 mmol) was dissolved in THF (1.5 mL) and then slowly
1381
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J. Org. Chem. 2021, 86, 1371−1384

The Journal of Organic Chemistry
pubs.acs.org/joc
Featured Article
added to the ylide of 3ab. The reaction mixture was then allowed to
stir and warm to room temperature overnight. A saturated aqueous
solution of NH4Cl (5 mL) was added and the organic layer was
removed. The aqueous layer was then extracted with Et2O (2x, 15
mL). The organic layers were then combined and extracted with
water (10 mL) and brine (10 mL). The organic layer was then dried
with MgSO4, which was subsequently removed via gravity filtration
through filter paper. The dried organic layer was then concentrated
via rotatory evaporation and the crude residue was purified by flash
column chromatography on silica gel (eluent: 0% to 2% ethyl acetate
in hexanes) to afford 4ab as a clear yellow oil with a 2:1 EE:ZE ratio
(43 mg, 47%). Only the E-isomer was observed from olefination,
whereas the E/Z isomer from metathesis was retained. Analytical
2.25H), 0.03 (s, 2.25H). 13C NMR (75 MHz, CDCl3, ppm) δ 168.5,
167.9, 153.5, 152.9, 151.2, 150.8, 141.9, 139.1, 135.9, 135.3, 131.50,
131.49, 131.4, 131.1, 129.2, 129.1, 129.0, 128.83, 128.75, 128.5, 128.3,
128.1, 128.04, 128.02, 127.9, 125.6, 125.4, 120.9, 120.6, 62.0, 61.8,
61.2, 60.8, 52.8, 52.0, 47.0, 46.5, 38.6, 37.8, 37.7, 30.5, 29.7, 25.9,
18.28, 18.26, 14.4, 13.8, −5.3. FT-IR (neat, cm−1): 2954, 2929, 2856,
2252, 1773, 1709, 1631, 1601, 1503, 1471, 1458, 1412, 1291, 1252,
1219, 1201, 1174, 1134, 1096, 1027, 1006, 974, 911, 835, 811, 775,
766, 731, 689, 663, 645, 617, 547, 506. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C32H42N3O5Si 576.2888, found 576.2902.
ASSOCIATED CONTENT
■
sı
1
* Supporting Information
TLC: Rf = 0.19 (1% ethyl acetate in hexanes). H NMR (500 MHz,
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02886.
CDCl3, ppm): δ 8.11−8.07 (m, 1H), 8.05−8.01 (m, 0.65H), 7.59−
7.52 (m, 1H), 7.49−7.38 (m, 3.35H), 7.36−7.28 (m, 2.65H), 7.25−
7.20 (m, 1H), 7.01 (dd, 3JHH = 15.8, 11.2 Hz, 0.35H), 6.83 (dd, 3JHH
3
NMR spectra for new compounds (PDF)
= 15.5, 10.4 Hz, 0.65H), 6.62 (d, JHH = 15.5 Hz, 0.65H), 6.61 (dd,
3
3JHH = 15.6, 10.1 Hz, 0.65H), 6.49 (d, JHH = 11.4 Hz, 0.35H), 6.39
FAIR data, including the primary NMR FID files, for
compounds 1g, 2h, 3aa−al, 3bf, 3bj, 3cb, 3cd, 3ch, 3df,
3dh, 3ec, 3ef, 3ff, 3fh, 3gb, 3gf, 4ab, and 4ef (ZIP)
3
3
(d, JHH = 15.9 Hz, 0.65H), 6.37 (d, JHH = 15.9 Hz, 0.35H), 6.28
3
3
(dd, JHH = 11.4, 11.4 Hz, 0.35H), 5.89 (q, JHH = 6.5 Hz, 0.65H),
5.80 (q, JHH = 6.6 Hz, 0.35), 5.36 (s, 0.65H), 5.36 (s, 0.35H), 5.25
3
3
(s, 0.65H), 5.25 (s, 0.35H), 1.58 (d, JHH = 6.6 Hz, 1.95H), 1.55 (d,
3JHH = 6.5 Hz, 1.05H). 13C NMR (125 MHz, CDCl3, ppm): δ 165.9,
AUTHOR INFORMATION
■
165.8, 146.5, 146.4, 137.5, 137.4, 133.8, 133.5, 133.11, 133.06, 131.8,
131.0, 130.6, 130.4, 130.1, 129.79, 129.77, 129.75, 129.3, 129.0, 128.8,
128.53, 128.50, 128.47, 127.8, 127.3, 126.6, 126.3, 115.8, 114.9, 70.9,
70.5, 20.8, 20.5. FT-IR (neat, cm−1): 3025, 2983, 2932, 1715, 1601,
1584, 1491, 1450, 1373, 1314, 1271, 1176, 1107, 1081, 1069, 1026,
987, 948, 900, 805, 777, 749, 711, 690, 618, 505. HRMS (ESI-TOF)
m/z: [M + Na]+ calcd for C21H20O2Na 327.1355, found 327.1343.
( )-Ethyl (E/Z)-2-((7-(2-((tert-Butyldimethylsilyl)oxy)ethyl)-1,3-
dioxo-2-phenyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]-
pyridazin-5-yl)methyl)-3-phenylacrylate (4ef). Compound 3ef (107
mg, 0.24 mmol) was added to a 25 mL rb flask and was subsequently
dissolved in CH2Cl2 (ca. 0.05 M). 4-Phenyl-1,2,4-triazole-3,5-dione
(41 mg, 0.24 mmol) was freshly prepared following the literature
procedure51 and was added to the rb flask, which formed a dark red
solution. The reaction mixture was then allowed to stir for 2 h, which
afforded a light pink solution. TLC analysis showed consumption of
the diene.
Corresponding Author
Steven T. Diver − Department of Chemistry, University at
Buffalo, the State University of New York, Buffalo, New York
14260, United States; orcid.org/0000-0003-2840-6726;
Email: diver@buffalo.edu
Authors
Laurence N. Rohde, Jr. − Department of Chemistry,
University at Buffalo, the State University of New York,
Buffalo, New York 14260, United States; orcid.org/
0000-0003-3908-5104
́
̀
Therese H. Wild − Department of Chemistry, University at
Buffalo, the State University of New York, Buffalo, New York
14260, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02886
The reaction mixture was then concentrated and dissolved in THF
(5 mL). NaH (60% dispersion in mineral oil; 10 mg, 0.26 mmol) was
then added and the mixture was allowed to stir for one hour; This
afforded a yellow solution upon formation of the ylide. Benzaldehyde
(27 mg, 0.26 mmol) was dissolved in THF (1.5 mL) and was slowly
added to the ylide. The reaction mixture was then allowed to stir
overnight, which afforded a pale orange solution. A saturated aqueous
solution of NH4Cl (5 mL) was added and the organic layer was
removed. The aqueous layer was then extracted with Et2O (2×, 10
mL). The organic layers were then combined and extracted with
water (10 mL) and brine (10 mL). The organic layer was then dried
with MgSO4, which was subsequently removed via gravity filtration
through filter paper. The dried organic layer was then concentrated
via rotatory evaporation and the crude residue was purified by flash
column chromatography on silica gel to afford 4ef after flash
chromatography on silica gel (eluent: 15% to 20% ethyl acetate in
hexanes) as a clear light orange oil with a 3:1 E/Z ratio (102 mg, 75%
over two steps). Analytical TLC: Rf = 0.55 (25% ethyl acetate in
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors gratefully acknowledge the NSF (CHE-1900392
and CHE-1566162) for financial support of this work. The
authors wish to thank Dr. Adam Johns (Materia) and Umicore
Precious Metals for supplying the Ru carbenes used in this
work.
REFERENCES
■
(1) Wadsworth, W. S.; Emmons, W. D. The Utility of Phosphonate
Carbanions in Olefin Synthesis. J. Am. Chem. Soc. 1961, 83, 1733.
(2) For reviews on the Horner−Wadsworth−Emmons reaction used
in natural product synthesis, see refs 3 and 4.
1
hexanes). H NMR (500 MHz, CDCl3, ppm): δ 7.79 (s, 0.75H),
7.51−7.17 (m, 10H), 6.77 (s, 0.25H), 5.77−5.72 (m, 0.25H), 5.59−
3
(3) Wadsworth, W. S., Jr. Synthetic Applications of Phosphoryl-
5.55 (m, 0.75H), 4.90−4.81 (m, 1H), 4.26 (q, JHH = 7.1 Hz, 1.5H),
3
3
Stabilized Anions. Organic Reactions 1977, 25, 73−253.
4.24 (d, JHH = 16.0 Hz, 0.25H), 4.19 (d, JHH = 16.4 Hz, 0.75H),
3
4
(4) Mulzer, J.; Sieg, A.; Brucher, C.; Muller, D.; Martin, H. J.
̈ ̈
4.11−4.03 (m, 0.5H), 3.99 (dt, JHH = 16.2 Hz, JHH = 2.2 Hz,
0.25H), 3.90 (dt, 3JHH = 16.3 Hz, 4JHH = 2.2 Hz, 0.75H), 3.73 (t, 3JHH
= 6.4 Hz, 0.5H), 3.65 (t, 3JHH = 6.4 Hz, 1.5H), 3.23 (dd, 2JHH = 13.9
Horner-Wadsworth-Emmons Reactions as a Facile Entry to
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5
2
5
Hz, JHH = 6.6 Hz, 0.75H), 3.00 (dd, JHH = 13.7 Hz, JHH = 6.5 Hz,
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3
0.75H), 2.98−2.91 (m, 0.5H), 2.39−2.27 (m, 0.5H), 2.24 (t, JHH
=
6.3 Hz, 1.5H), 1.33 (t, 3JHH = 7.1 Hz, 2.25H), 1.06 (t, 3JHH = 7.1 Hz,
0.75H), 0.89 (s, 2.25H), 0.88 (s, 6.75H), 0.05 (s, 1.5H), 0.04 (s,
1382
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J. Org. Chem. 2021, 86, 1371−1384