3,5-Diphenyl-2-phosphafuran: Synthesis, structure, and thermally reversible [4 + 2] cycloaddition chemistry

Article abstract of DOI:10.1021/acs.joc.0c02025

Treatment of trans-chalcone with dibenzo-7-phosphanorbornadiene EtOPA (A = C₁₄H₁₀, anthracene), a source of ethoxyphosphinidene, followed by formal elimination of ethanol yields 3,5-diphenyl-2-phosphafuran (DPF) in 43% yield. We show that the phosphadiene moiety of DPF is a potent diene in the Diels?Alder reaction and reacts with dienophiles dimethyl acetylenedicarboxylate (DPF·DMAD, 68%), norbornene (DPF·norbornene, 73%), and ethylene (DPF·C₂H₄, 80%) under ambient conditions. Mild heating of DPF·C₂H₄ results in the corresponding retro-Diels?Alder reaction, establishing DPF as a molecule that is able to reversibly bind ethylene.

Full text of DOI:10.1021/acs.joc.0c02025

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3,5-Diphenyl-2-phosphafuran: Synthesis, Structure, and Thermally
Reversible [4 + 2] Cycloaddition Chemistry
Martin-Louis Y. Riu and Christopher C. Cummins*
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ABSTRACT: Treatment of trans-chalcone with dibenzo-7-phospha-
norbornadiene EtOPA (A = C14H10, anthracene), a source of ethoxy-
phosphinidene, followed by formal elimination of ethanol yields 3,5-
diphenyl-2-phosphafuran (DPF) in 43% yield. We show that the
phosphadiene moiety of DPF is a potent diene in the Diels−Alder reaction
and reacts with dienophiles dimethyl acetylenedicarboxylate (DPF·DMAD,
68%), norbornene (DPF·norbornene, 73%), and ethylene (DPF·C2H4, 80%)
under ambient conditions. Mild heating of DPF·C2H4 results in the
corresponding retro-Diels−Alder reaction, establishing DPF as a molecule
that is able to reversibly bind ethylene.
n recent years, main group elements have been exploited for
their “transition metal-like” properties and have been shown
Scheme 1. Preparation of DPF Proceeded in Two Steps
from EtOPA (1)
I
to react with catalytically relevant small molecules.1,2 In
particular, reversible complexation of unsaturated molecules by
main group species, previously thought to be the domain of
transition metals, is a flourishing field in the current literature.
Examples include ditetrelynes (RE≡ER, E = Ge, Sn),3−5
carbenes,6 tetrylenes (R2E, E = Si, Ge, Sn),7−10 digallenes,11
magnesium(I) dimers,12 and a number of boron13,14 and
aluminum15−18 species.
anion was then treated with trimethylsilyl chloride (Me3SiCl),
providing 3,5-diphenyl-2-phosphafuran (DPF) upon elimina-
tion of HN(SiMe3)2, NaCl, and Me3SiOEt (Scheme 1). In
agreement with a report of Mathey and co-workers,28 DPF
displays a notably deshielded 31P{1H} NMR resonance of δ
285.4 ppm in benzene. Regitz and co-workers have also
reported observation of a 2-phosphafuran by 31P NMR
spectroscopy; however, the authors found it to be too labile
for isolation.29 Crystallization from minimal pentane at −35 °C
provided DPF, as pale orange crystals, in 43% yield.
Crystals of DPF suitable for an X-ray diffraction study were
grown from minimal diethyl ether at −35 °C, and the
molecular stucture of DPF is shown in Figure 1A. The
experimental P−C bond length of 1.752(9) Å is between P−C
single and double bond lengths (1.86 and 1.69 Å,
respectively).30 This bond length is consistent with moderate
π-delocalization of the phosphaalkene double bond. A search
Considering that replacement of carbon by phosphorus in
unsaturated molecules yields energetically accessible frontier
orbitals, due to the poor π overlap between the carbon and
phosphorus centers,19 we targeted for synthesis a 2-
phosphafuran to be tested for the possible ability to undergo
low-barrier, thermally reversible cycloadditions. Such an ability
would call to mind the thermally reversible cycloadditions
between furan and maleimide moieties found in a number of
self-healing polymers.20,21 While there are a number of
reported phosphadienes that react with activated dienophiles,
such as maleimide,22−25 examples of low-coordinate phospho-
rus species reversibly binding unsaturated molecules are rare.26
Herein, we report the synthesis and characterization of a 2-
phosphafuran that reversibly binds ethylene.
Heating a benzene solution of EtOPA (1)27 and trans-
chalcone to 80 °C for 4 h provided oxo-3-phospholene 2 as a
mixture of diastereomers (31P NMR δ 180.6 and δ 170.9 ppm;
syn/anti ratio 1.5:1; Scheme 1). The crude reaction mixture
also contains small amounts of 1 and a tentatively assigned
spirophosphorane byproduct (Figure S.1). Attempts to
separate 2 from this mixture by crystallization have been
unsuccessful. In order to eliminate HOEt from 2, compound 2
was first deprotonated with sodium bis(trimethylsilyl)amide
(Na[N(SiMe3)2]) and the resulting in situ generated, deep red
Special Issue: The New Golden Age of Organo-
phosphorus Chemistry
Received: August 21, 2020
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© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

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involving localized C−C and C−P π-bonds, suggesting
promise for Diels−Alder reactivity with dienophiles.
Quantum chemical calculations were employed to study the
energy landscape of formation of the major isomer of
compound 2 at the B3LYP-D3(BJ)/Def2-TZVPP level of
DFT (Figure 2). Calculations suggest that cheletropic addition
of trans-chalcone to EtOPA (1), resulting in the formation of
λ5-phosphorane I1, proceeds with an activation barrier of
+24.7 kcal/mol (TS1). It should be noted that attempts to
locate a local minimum for a possible zwitterionic product of
conjugate addition consistently resulted in the convergence to
I1. While formation of I1 is thermodynamically favorable, this
species was not observed by NMR spectroscopy. Our inability
to observe this species is consistent with the small barrier (+6.3
kcal/mol) to anthracene fragmentation from this species, a
process our computations suggest is a concerted cheletropic
extrusion pathway (TS2). Reductive elimination from λ5-
phosphoranes, yielding a phosphorus(III) product, has been
described previously.35−40
Treatment of DPF with dimethyl acetylenedicarboxylate
(DMAD) at 23 °C results in the formation of DPF·DMAD
(31P NMR δ 95.3 ppm), and this adduct was isolated in 68%
yield (Scheme 2). Colorless crystals of DPF·DMAD were
Figure 1. (A) Molecular structure of DPF shown with 50%
probability thermal ellipsoids. Hydrogen atoms are omitted for
clarity. Selected bond lengths: P1−C2:1.752(9) Å, C2−C1:1.406(10)
Å, C1−C3:1.370(10) Å, C3−O1:1.334(8) Å, O1−P1:1.6745(17) Å.
(B) Natural resonance theory (NRT) derived bond orders for DPF.
(C) Resonance weight calculated for the parent 2-phosphafuran using
NRT.
Scheme 2. Diels−Alder Adducts of DPF
of the Cambridge Structural Database returned no examples of
2-phosphafuran compounds with which to compare the
structural data we obtained for DPF.
Bonding in DPF was investigated using natural resonance
theory (NRT),31−33 a subroutine of natural bond orbital
methods.34 NRT-derived bond orders of 1.79 (C1−C3) and
1.80 (C2−P1) were found for DPF (Figure 1B), values that are
consistent with the intermediate bond lengths observed in the
crystal structure of DPF. The dominant natural Lewis
structures for the parent 2-phosphafuran were also determined,
as depicted in Figure 1C. The major resonance structure
(63.2% contributor) for the parent molecule resembles a diene,
grown from diethyl ether at −35 °C and structurally
characterized in a single-crystal X-ray diffraction study (Figure
3). Related 1-phosphanorbornadienes have been been accessed
Figure 2. Minimum energy pathway for the reaction of EtOPA (1) with trans-chalcone to give compound 2.
B
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by treating thermally generated 2H-phospholes with dien-
ophiles.22−25
Figure 4. Calculated stationary points and transition state (“TS”) and
their relative enthalpies (blue, kcal/mol) and free energies (pink,
kcal/mol, 298.15 K) involved in the Diels−Alder addition of DPF to
ethylene.
Figure 3. Molecular structure of cycloadducts DPF·DMAD (left) and
DPF·C2H4 (right) shown with ellipsoids at the 50% probability level.
Hydrogen atoms are omitted for clarity.
protecting group via the Diels−Alder reaction, a methodology
that is largely absent from the literature due to the typically
high temperatures required for cycloaddition and cyclo-
reversion, especially in the case of an unactivated alkene as
the dienophile.42−44
Encouraged by the facile cycloaddition of DPF to DMAD,
DPF was treated with ethylene. In contrast to the high
temperatures and pressures often required for Diels−Alder
addition of dienes to unactivated alkenes,41 complete
conversion of DPF to DPF·C2H4 (31P NMR δ 94.5 ppm)
was observed 12 h after exposure to ethylene (1 atm) at 23 °C
(Scheme 2). Colorless crystals of DPF·C2H4 were grown from
pentane at −35 °C in 80% yield. DPF·C2H4 was structurally
characterized by X-ray crystallography, and its molecular
structure is shown in Figure 3.
We also found that treatment of DPF with an excess of 1-
hexene (10 equiv) led to partial conversion (ca. 64%) of DPF
to the corresponding cycloadduct, as a mixture of diaster-
eomers in a 3:8:25:62 molar ratio, after 12 h at 23 °C.
However, no reaction was observed between DPF and
unactivated internal olefins, such as cyclohexene and cis-4-
octene, under similar conditions. Furthermore, no reaction was
observed after heating a toluene solution of DPF and cis-4-
octene (5 equiv) to 110 °C for 12 h.
EXPERIMENTAL SECTION
■
General Considerations. Except as otherwise noted, all
manipulations were performed in a Vacuum Atmospheres model
MO-40M glovebox under an inert atmosphere of purified N2. All
solvents were obtained anhydrous and oxygen-free by bubble
degassing (Ar), purification by passage through columns of alumina
using a solvent purification system (Pure Process Technology,
Nashua, NH),45 and storage over 4 Å molecular sieves.46 Deuterated
solvents were purchased from Cambridge Isotope Laboratories, then
degassed, and stored over molecular sieves for at least 48 h prior to
use. Celite (EM Science), 4 Å molecular sieves, silica, acidic alumina,
and charcoal were dried by heating above 200 °C under dynamic
vacuum (50 mTorr) for at least 48 h prior to use. All glassware was
dried in an oven for at least 2 h at temperatures greater than 150 °C.
127 was prepared according to a literature procedure. trans-
Chalcone (Sigma-Aldrich), sodium bis(trimethylsilyl)amide (Sigma-
Aldrich), norbornene (Alfa-Aesar), trimethylsilyl chloride (Fluka),
ethylene (Airgas), and triphenylphosphine (Strem) were used as
received. Dimethyl acetylenedicarboxylate (Alfa-Aesar), cis-4-octene
(Sigma-Aldrich), 1-hexene (Sigma-Aldrich), and cyclohexene (Sigma-
Aldrich) were distilled, degassed three times by the freeze−pump−
thaw method, and stored over 4 Å molecular sieves for 48 h prior to
use.
Remarkably, when DPF·C2H4 was heated to 65 °C in
tetrahydrofuran, formation of ethylene and DPF was observed
by NMR spectroscopy. When this experiment was repeated at
75 °C in the presence of norbornene, clean formation of DPF·
norbornene was observed after 15 h. To confirm the identity of
the product, DPF·norbornene was prepared independently and
obtained in 73% isolated yield (Scheme 2).
NMR spectra were obtained on a Jeol ECZ-500 instrument
equipped with an Oxford Instruments superconducting magnet, on a
Bruker Avance 400 instrument equipped with a Magnex Scientific or
with a SpectroSpin superconducting magnet, or on a Bruker Avance
500 instrument equipped with a Magnex Scientific or with a
SpectroSpin superconducting magnet. 1H and 13C NMR spectra
were referenced internally to residual solvent signals.47 31P NMR
spectra were externally referenced to 85% H3PO4 (0 ppm). Structural
assignments were made with additional information from gCOSY,
gHSQC, gHMBC, and gNOESY experiments. Elemental combustion
analyses were performed by Midwest Micro Laboratories (Indian-
apolis, IN, USA).
High resolution mass spectral (HRMS) data were collected using a
Jeol AccuTOF 4G LC-Plus mass spectrometer equipped with an Ion-
Sense DART source. Data were calibrated to a sample of PEG-600
and were collected in positive-ion mode. Samples were prepared in
THF (10 μM concentration) and were briefly exposed to air (<5 s)
before being placed in front of the DART source.
The reversible Diels−Alder reaction of DPF with ethylene
prompted us to investigate the energy landscape of this
reaction using quantum chemical calculations (Figure 4).
Calculations performed using DFT, at the ωB97X-D3/Def2-
TZVPP level of theory, suggest that the cycloaddition is a
concerted process, proceeding with an activiation barrier of
+26.5 kcal/mol (TS). These calculations also reveal that the
reaction is enthalpically favorable (ΔH = −18.1 kcal/mol) but
is downhill by only −4.8 kcal/mol, consistent with the
experimental observation of retrocyclization at elevated
temperatures.
This work introduces 3,5-diphenyl-2-phosphafuran as a
potent diene in the Diels−Alder reaction. DPF not only
forms a cycloadduct with ethylene, but additionally, mild
heating of DPF·C2H4 results in the retro-Diels−Alder reaction.
Future work will involve the application of DPF as an olefin
C
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Synthesis of 2-Ethoxy-3,5-diphenyl-3-hydro-1,2-oxaphosphole
(2). A solution of 1 (2.50 g, 9.84 mmol, 1.00 equiv) and trans-
chalcone (2.05 g, 9.84 mmol, 1.00 equiv) in benzene (10 mL) was
prepared in a 25 mL Schlenk tube containing a stir bar. The tube was
removed from the glovebox and placed in an oil bath preheated to 80
°C. After 4 h, the flask was removed from the oil bath and allowed to
cool for 30 min, during which time flakes of anthracene crystallized.
The sealed tube was returned to the glovebox, where all volatile
materials were removed in vacuo. To the residue was added Et2O (15
mL), and the resulting slurry was filtered through a coarse sintered frit
(15 mL) containing a one-inch plug of charcoal. The plug was washed
with Et2O (15 mL), and the combined filtrates were concentrated to
ca. 5 mL under reduced pressure. The solution was then cooled to
−35 °C in the glovebox freezer. After 24 h, the supernatant was
decanted away from the white solids that had formed and all volatile
materials were removed from the supernatant under reduced pressure.
A pale yellow oil (2.41 g) comprising a mixture of 1, anti-2, syn-2, and
a tentatively assigned spirophosphorane byproduct (Figure S.1), in a
ca. 2:35:52:11 molar ratio, was obtained. The ratio of 1, 2, and
spirophosphorane was determined by 31P{1H} NMR spectroscopy.
Attempts to remove EtOPA and the spirophosphorane byproduct
from the mixture by crystallization have been unsuccessful. anti-2:
DART HRMS(Q-TOF) m/z: [M + H]+ Calcd for C17H18O2P
(0.200 g, 0.840 mmol, 1.00 equiv) in THF (5 mL). After vigorous
stirring for 20 min, all volatile materials were removed in vacuo from
the reaction mixture. A white heterogeneous mixture was obtained
after adding pentane (10 mL) to the resulting colorless residue and
stirring the solution for 20 min. The white precipitate was collected by
vacuum filtration using a 15 mL coarse sintered frit, and the solids
were washed with minimal pentane (ca. 2 × 5 mL) and dried to
constant mass under reduced pressure. Crystallization from minimal
diethyl ether at −35 °C provided colorless crystals of DPF·DMAD
(0.217 g, 0.571 mmol, 68%). Melting point: 95−96 °C dec. DART
HRMS(Q-TOF) m/z: [M + H]+ Calcd for C21H18O5P 381.0892;
1
Found 381.0897. H NMR (500 MHz, chloroform-d, 25 °C): δ 7.84
(d, J = 9.0 Hz, 1H), 7.64−7.61 (m, 3H), 7.55 (d, J = 8.0 Hz, 2H),
7.45 (t, J = 7.2 Hz, 2H), 7.43−7.38 (m, 3H), 7.35 (t, J = 7.3 Hz, 1H),
3.79 (s, 3H), 3.61 (s, 3H) ppm. 13C{1H} NMR (126 MHz,
chloroform-d, 25 °C): δ 166.7 (d, J = 35.3 Hz), 166.2 (d, J = 2.9 Hz),
163.9 (d, J = 17.8 Hz) 163.9 (d, J = 3.2 Hz), 153.3 (d, J = 41.7 Hz),
139.1 (d, J = 2.0 Hz), 134.9, 134.1 (d, J = 17.8 Hz), 129.4, 129.3,
129.2, 128.9, 126.7, 126.4, 108.0 (d, J = 12.1 Hz), 52.7, 52.6 ppm.
31P{1H} NMR (203 MHz, chloroform-d, 25 °C): δ 95.4 ppm.
Synthesis of 2,4-Diphenyl-7-oxa-1-phosphabicyclo[2.2.1]hept-2-
ene (DPF·C2H4). A solution of DPF (100 mg, 0.42 mmol, 1 equiv) in
THF (3 mL) was prepared in the glovebox and transferred to a sealed
25 mL Schlenk tube containing a stir bar. The tube was removed from
the glovebox, degassed by three freeze−pump−thaw cycles, and
backfilled with ethylene (1.0 atm, 1.1 mmol, 0.031 g). After vigorously
stirring for 12 h, the sealed tube was returned to the glovebox, where
all volatile materials were removed in vacuo. Pentane (10 mL) was
added to the pale brown residue, and the resulting solution was
filtered through a 15 mL coarse-sintered frit containing a one-inch
plug of Celite. The plug was washed with additional pentane (5 mL),
and all volatile materials were removed from the combined filtrates
under reduced pressure. Crystallization from minimal diethyl ether at
−35 °C provided colorless crystals of DPF·C2H4 (0.089 g, 0.33 mmol,
80%). Melting point 74−75 °C. Anal. Calcd for C17H15OP: C, 76.75;
1
285.1044; Found 285.1063. H NMR (400 MHz, chloroform-d, 25
°C): δ 7.81−7.09 (aryl, 10H), 5.94 (dd, J = 9.3, 3.7 Hz, 1H), 4.13 (t, J
= 3.6 Hz, 1H), 4.01 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H). 13C{1H} NMR
2
(101 MHz, chloroform-d, 25 °C): δ 157.6 (d, JPC = 7.3 Hz), 138−
1
2
123 (aryl), 102.2, 64.7 (d, JPC = 19.3 Hz), 57.8 (d, JPC = 26.7 Hz),
17.4 (d, 3JPC = 5.3 Hz) ppm. 31P{1H} NMR (162 MHz, chloroform-d,
25 °C): δ 180.3 ppm. syn-2: DART HRMS(Q-TOF) m/z: [M + H]+
Calcd for C17H18O2P 285.1044; Found 285.1063. 1H NMR (400
MHz, chloroform-d, 25 °C): δ 7.81−7.09 (aryl, 10H), 5.85 (dd, J =
8.6, 2.5 Hz, 1H), 4.45 (dd, J = 31.9, 2.5 Hz, 1H), 3.88−3.59 (m, 2H),
0.88 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (101 MHz, chloroform-d, 25
°C): δ 157.7 (d, 2JPC = 6.8 Hz), 138−123 (aryl), 101.6, 64.3 (d, 1JPC
=
2
3
11.8 Hz), 58.9 (d, JPC = 26.0 Hz), 16.8 (d, JPC = 5.2 Hz) ppm.
31P{1H} NMR (162 MHz, chloroform-d, 25 °C): δ 170.5 ppm.
Synthesis of 3,5-Diphenyl-2-phosphafuran (DPF). To a thawing
solution of crude 2 (0.500 g, 1.76 mmol, 1.00 equiv; the amount
weighed out depends on the composition of the crude starting
material) in 1,2-dimethoxyethane (20 mL) was added sodium
bis(trimethylsilyl)amide (0.323 g, 1.76 mmol, 1.00 equiv) portion-
wise. After vigorously stirring for 15 min, the deep red solution was
frozen in the glovebox coldwell. To the thawing solution was added
trimethylsilyl chloride (0.192 g, 1.76 mmol, 1.00 equiv) dropwise.
Following the addition, the mixture was stirred as it warmed to 23 °C
over 1 h. During this period the reaction mixture became cloudy and
bright orange. All volatile materials were removed in vacuo, and the
resulting bright orange solids were taken up in pentane (10 mL). The
solution was then filtered through a 15 mL coarse sintered frit
containing a two-inch plug of Celite. The Celite plug was washed with
additional pentane (10 mL) and all volatile materials were removed
from the combined filtrates in vacuo, yielding a deep orange residue.
Crystallization from minimal pentane at −35 °C provided DPF as a
pale orange crystalline material (0.180 g, 1.51 mmol, 43%). Melting
point: 82−83 °C. DART HRMS(Q-TOF) m/z: [M + H]+ Calcd for
C15H12OP 239.0626; Found 239.0620. Anal. Calcd for C15H11OP: C,
1
H, 5.68; N, 0. Found: C, 76.68; H, 5.12; N, 0. H NMR (500 MHz,
chloroform-d, 25 °C): δ 7.60 (d, J = 7.3 Hz, 2H), 7.49 (d, J = 7.8 Hz,
2H), 7.44 (t, J = 7.6 Hz, 2H), 7.38−7.32 (m, 3H), 7.32−7.24 (m,
1H), 6.90 (d, J = 9.1 Hz, 1H), 2.21 (qd, J = 11.4, 2.3 Hz, 1H), 1.97−
1.87 (m, 1H), 1.88−1.76 (m, 1H), 1.44−1.32 (m, 1H) ppm. 13C{1H}
NMR (126 MHz, chloroform-d, 25 °C): δ 153.3 (d, J = 29.3 Hz),
140.6, 137.8, 134.1 (d, J = 16.8 Hz), 129.0, 128.7, 128.4, 128.0, 126.9
(d, J = 8.9 Hz), 125.8, 100.8 (d, J = 11.7 Hz), 28.4, 25.7 (d, J = 21.0
Hz). 31P{1H} NMR (202 MHz, chloroform-d, 25 °C): δ 95.6 ppm.
Synthesis of ( )-(1R,2R,3S,6R,7R,8S)-8,10-Diphenyl-11-oxa-1-
phosphatetracyclo[6.2.1.13,6.02,7]dodec-9-ene (DPF·Norbornene).
Norbornene (0.040 g, 0.42 mmol, 1.0 equiv) was added to a solution
of DPF (0.100 g, 0.420 mmol, 1.00 equiv) in THF (4 mL)
portionwise. After vigorous stirring for 5 h, all volatile materials were
removed in vacuo, resulting in a colorless residue. Pentane (10 mL)
was added to this residue, and the resulting solution was filtered
through a 15 mL coarse sintered frit containing a one-inch plug of
Celite. The plug was washed with additional pentane (5 mL), and all
volatile materials were removed from the combined filtrates in vacuo.
Crystallization from minimal pentane at −35 °C provided colorless
crystals of DPF·norbornene (0.102 g, 0.31 mmol, 73%). Melting point
110−111 °C. Anal. Calcd for C22H21OP: C, 79.88; H, 6.19; N, 0.
1
75.21; H, 4.77; N, 0. Found: C, 75.63; H 4.65; N, 0. H NMR (400
1
Found: C, 79.50; H, 6.37; N, 0. H NMR (500 MHz, chloroform-d,
MHz, chloroform-d, 25 °C): δ 7.84 (d, J = 7.8 Hz, 2H), 7.61 (d, J =
7.6 Hz, 2H), 7.49 (d, 3JPH = 8.8 Hz, 1H), 7.44 (m, 4H), 7.35 (m, 2H)
ppm. 13C{1H} NMR (101 MHz, chloroform-d, 25 °C): δ 180.6 (d, J
= 52.0 Hz), 167.5, 134.2 (d, J = 14.2 Hz), 132.2 (d, J = 5.0 Hz),
129.3, 129.0 (d, J = 1.2 Hz), 128.7 (d, J = 2.6 Hz), 128.7 (d, J = 3.0
Hz), 126.1 (d, J = 11.8 Hz), 125.1 (d, J = 1.9 Hz), 110.7 (d, J = 2.8
Hz) ppm. 31P{1H} NMR (162 MHz, chloroform-d, 25 °C): δ 284.6
25 °C): δ 7.55 (d, J = 7.4 Hz, 2H), 7.45 (t, J = 7.4 Hz, 2H), 7.43 (d, J
= 6.3 Hz, 2H), 7.34 (t, J = 7.4 Hz, 3H), 7.29−7.24 (m, 1H), 6.96 (d, J
= 9.2 Hz, 1H), 2.63 (br, 1H), 1.92 (dd, J = 6.3, 1.7 Hz, 1H), 1.86 (d, J
= 9.9 Hz, 1H), 1.81−1.76 (m, 2H), 1.61−1.49 (m, 1H), 1.44−1.34
(m, 1H), 1.24−1.15 (m, 1H), 1.09−1.00 (m, 1H), 0.82 (d, J = 9.8 Hz,
1H) ppm. 13C{1H} NMR (126 MHz, chloroform-d, 25 °C): δ 152.4
(d, J = 28.4 Hz), 140.4, 139.6, 134.4 (d, J = 16.9 Hz), 128.9, 128.5,
128.3, 127.3, 126.8 (d, J = 8.7 Hz), 125.7, 102.8 (d, J = 10.2 Hz) 51.1
(d, J = 22.5 Hz), 50.3 (d, J = 2.4 Hz), 39.5 (d, J = 13.3 Hz), 37.1,
34.1, 30.8 (d, J = 10.1 Hz), 30.2 ppm. 31P{1H} NMR (202 MHz,
chloroform-d, 25 °C): δ 101.7 ppm.
3
(d, JPH = 8.8 Hz) ppm.
Synthesis of Dimethyl 4,6-Diphenyl-7-oxa-1-phosphabicyclo-
[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (DPF·DMAD). A solution
of dimethyl acetylenedicarboxylate (0.119 g, 0.840 mmol, 1.00 equiv)
in THF (2 mL) was added dropwise to a stirring solution of DPF
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Air Stability of DPF. A 0.02 M solution of DPF in benzene-d6 was
prepared and transferred to an NMR tube. To this tube was added a
glass capillary containing a 0.67 M solution of triphenylphosphine in
benzene-d6, and initial NMR spectra were collected (Figures S.36 and
S.37). The cap of the tube was removed outside of the glovebox, and
after 1 h the solution became pale yellow. NMR spectra of this sample
were collected, and the spectra are depicted in Figures S.38 and S.39.
Complete consumption of DPF and no new resonances were
observed by 31P{1H} NMR spectroscopy. The fate of DPF under
these conditions is not yet known.
asymmetric unit. The molecule exhibits no disorder. Similarity and
rigid bond restraints for anisotropic displacement parameters were
applied to all non-hydrogen atoms.
Single crystals of DPF·C2H4 were grown from −35 °C diethyl
ether. The structure was solved in the monoclinic space group P21/n
with one molecule of DPF·C2H4 and no solvent molecules in the
asymmetric unit. The molecule exhibits no disorder. Similarity and
rigid bond restraints for anisotropic displacement parameters were
applied to all non-hydrogen atoms.
Computational Studies. All calculations were performed with
the ORCA 4.0.1 quantum chemistry package from the development
team at the University of Bonn.51,52 Initial geometries were
constructed in Avogadro.53,54 Geometry optimizations were per-
formed at the ωB97X-D3/Def2-TZVPP level of theory using
keywords wB97X-D3 def2-TZVPP def2/J TightSCF
RIJCOSX Grid4 FinalGrid5 Opt for the geometries listed
in Supporting Information S.4.1−S.4.7 and at the B3LYP-D3(BJ)/
Def2-TZVPP level using keywords B3LYP D3BJ Def2-TZVPP
TightSCF RIJCOSX Grid4 FinalGrid5 Opt for the
geometries listed in Supporting Information S.4.8−S.4.12. For
transition states, the keyword Opt was replaced by OptTS.
Vibrational frequency calculations were carried out on the optimized
geometries using the keyword NumFreq. Intermediate and transition
state geometries were found to have zero and one imaginary
frequency, respectively. Natural bond orbital (NBO) calculations
were performed using NBO634 within the ORCA program. The
natural resonance theory (NRT) keyword was specified to generate
natural resonance structures of the parent 2-phosphafuran molecule.
Lower contributing resonance structures (all below 5%) were not
included in the main text.
Thermal Stability of DPF·C2H4. A 0.03 M solution of DPF·C2H4
in THF was prepared in the glovebox and transferred to a J Young
tube containing a flame-sealed glass capillary charged with a 0.67 M
benzene-d6 solution of triphenylphosphine. An initial 31P{1H} NMR
spectrum of the solution was collected (Figure S.40). The tube was
then placed in a preheated 65 °C oil bath, and NMR spectra of the
solution were collected after 4 h (Figure S.41). Partial conversion of
DPF·C2H4 to DPF was observed, as assessed by 31P{1H} NMR
spectroscopy, and a resonance assigned to ethylene (δ 5.34 ppm) was
1
present in the H NMR spectrum (Figure S.42).
Thermolysis of DPF·C2H4 in the Presence of Norbornene. A
solution of DPF·C2H4 (10 mg, 0.038 mmol, 1.0 equiv) and
norbornene (4 mg, 0.04 mmol, 1 equiv) in THF (0.7 mL) was
prepared in the glovebox and transferred to a J Young tube containing
a flame-sealed glass capillary charged with a 0.67 M benzene-d6
solution of triphenylphosphine. An initial 31P{1H} NMR spectrum of
the solution was collected (Figure S.43). The tube was then placed in
a preheated 75 °C oil bath, and 31P{1H} NMR spectra of the solution
were collected after 3 and 15 h (Figures S.44 and S.45). Clean
formation of DPF·norbornene was observed.
Treatment of DPF with 1-Hexene. A solution of DPF (10 mg,
0.038 mmol, 1.0 equiv) and 1-hexene (32 mg, 0.38 mmol, 10 equiv)
in benzene-d6 (0.7 mL) was prepared in the glovebox and transferred
to an NMR tube containing a flame-sealed glass capillary charged with
a 0.67 M benzene-d6 solution of triphenylphosphine. A 31P{1H} NMR
spectrum of the solution was collected after 12 h (Figure S.46). Partial
conversion (ca. 64%) of DPF to the corresponding cycloadduct, as a
mixture of diastereomers in a 3:8:25:62 molar ratio, was observed.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02025.
NMR spectra of new compounds and reactivity studies,
X-ray crystallograpic data, and computational details
(PDF)
1
Due to overlapping signals in H NMR spectrum, we are unable to
assign the stereochemistry of the cycloadducts. Attempts to separate
the cycloadducts by crystallization have been unsuccessful.
FAIR data, including the primary NMR FID files, for
compounds 2, DPF, DPF·DMAD, DPF·C2H4, and DPF·
norbornene (ZIP)
X-ray Diffraction Studies. Low-temperature diffraction data were
collected on a Bruker-AXS X8 Kappa Duo diffractometer with IμS
microsources, coupled to a Photon 3 CPAD detector using Mo Kα
radiation (λ = 0.71073 Å) for the structure of DPF·DMAD and a
Smart APEX2 CCD detector using Mo Kα radiation (λ = 0.71073 Å)
for the structures of DPF and DPF·C2H4, performing ϕ- and ω-scans.
The structures were solved by dual-space methods using SHELXT48
and refined against F2 on all data by full-matrix least-squares with
SHELXL-201748 following established refinement strategies.49,50 All
non-hydrogen atoms were refined anisotropically. All hydrogen atoms
were included into the model at geometrically calculated positions
and refined using a riding model. The isotropic displacement
parameters of all hydrogen atoms were fixed to 1.2 times the U-
value of the atoms they are linked to (1.5 times for methyl groups).
Descriptions of the individual refinements follow below, and details of
the data quality and a summary of the residual values of the
refinements for all structures are given in Tables S.1 and S.2. Further
details can be found in the form of .cif files available from the CCDC.
Single crystals of DPF were grown from −35 °C pentane. The
structure was solved in the orthorhombic space group Pnma with half
a molecule of DPF and no solvent molecules in the asymmetric unit.
The structure exhibits whole molecule disorder about a crystallo-
graphic inversion center. Disorders were refined with the help of the
FLAT restraint in SHELXL and similarity restraints on 1,2 and 1,3
distances. Similarity and rigid bond restraints for anisotropic
displacement parameters were applied to all non-hydrogen atoms.
Single crystals of DPF·DMAD were grown from −35 °C diethyl
ether. The structure was solved in the monoclinic space group P21/c
with one molecule of DPF·DMAD and no solvent molecules in the
Accession Codes
CCDC 1912975, 1912977, and 1913045 contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
Christopher C. Cummins − Department of Chemistry,
Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139; orcid.org/0000-0003-2568-3269;
Email: ccummins@mit.edu
Author
Martin-Louis Y. Riu − Department of Chemistry, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139;
orcid.org/0000-0002-0900-3545
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02025
E
https://dx.doi.org/10.1021/acs.joc.0c02025
J. Org. Chem. XXXX, XXX, XXX−XXX

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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Michael B. Geeson, Wesley J. Transue, and Scott M.
Shepard for thoughtful discussions and suggestions. This
material is based on research supported by the National
Science Foundation under CHE-1955612.
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