Phospha-Michael additions to activated internal alkenes: Steric and electronic effects

Article abstract of DOI:10.1021/jo202183u

The addition of P(O)-H bonds to internal alkenes has been accomplished under solvent-free conditions without the addition of a catalyst or radical initiator. Using a prototypical secondary phosphine oxide, a range of substrates including cinnamates, crotonates, coumarins, sulfones, and chalcones were successfully functionalized. Highly activated acceptors such as isopropylidenemalononitrile and ethyl 2-cyano-3-methyl-2-butenoate underwent the phospha-Michael reaction upon simple trituration of the reagents at room temperature, whereas less activated substrates such as ethyl cinnamate and methyl crotonate required heating (>150 °C) in a microwave reactor to achieve significant consumption of the starting alkenes. For the latter alkenes, a competing reaction involving disproportionation of the ditolylphosphine oxide into ditolylphosphinic acid and ditolylphosphine was observed at the high temperatures needed to promote the addition reaction.

Full text of DOI:10.1021/jo202183u

Article
pubs.acs.org/joc
Phospha-Michael Additions to Activated Internal Alkenes: Steric and
Electronic Effects
Heather K. Lenker, Marcia E. Richard, Kyle P. Reese, Anthony F. Carter, Jason D. Zawisky, Eric F. Winter,
Timothy W. Bergeron, Krysta S. Guydon, and Robert A. Stockland, Jr.*
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania 17837, United States
S
* Supporting Information
ABSTRACT: The addition of P(O)−H bonds to internal alkenes has
been accomplished under solvent-free conditions without the addition of a
catalyst or radical initiator. Using a prototypical secondary phosphine
oxide, a range of substrates including cinnamates, crotonates, coumarins,
sulfones, and chalcones were successfully functionalized. Highly activated
acceptors such as isopropylidenemalononitrile and ethyl 2-cyano-3-methyl-2-butenoate underwent the phospha-Michael
reaction upon simple trituration of the reagents at room temperature, whereas less activated substrates such as ethyl
cinnamate and methyl crotonate required heating (>150 °C) in a microwave reactor to achieve significant consumption of
the starting alkenes. For the latter alkenes, a competing reaction involving disproportionation of the ditolylphosphine oxide
into ditolylphosphinic acid and ditolylphosphine was observed at the high temperatures needed to promote the addition
reaction.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
The addition of P−H bonds to alkenes and alkynes remains
one of the most effective methods for constructing organo-
phosphorus compounds.1−12 The resulting phosphonate,
phosphine oxide, and phosphonic acid containing compounds
are high-value targets with applications in medicine,13−22 mate-
rial science,23,24 and organic synthesis.25−28 Historically, this
reaction has been catalyzed by strong bases,29 radical
initiators,30 UV light,8 and transition metal catalysts.1−8
We recently reported the microwave-assisted addition of a
prototypical secondary phosphine oxide to terminal alkenes
under solvent-free conditions without the addition of a catalyst
or radical initiator (eq 1).31 A range of terminal alkenes were
To investigate whether or not conjugated internal alkenes
could be used in these phospha-Michael reactions, we screened
a model system comprised of ethyl cinnamate as the repre-
sentative alkene and ditolylphosphine oxide as the secondary
phosphine oxide. Ditolylphosphine oxide was selected as the
substrate for these reactions, as the methyl groups provided an
uncluttered resonance in the 1H NMR spectrum that was used
to monitor the consumption of the secondary phosphine oxide.
Using the same reaction conditions that were successful for the
phospha-Michael reactions involving terminal alkenes (solvent
free, 125 °C, 30 min), irradiating a 1:1 mixture of the model
substrates afforded low conversion. A temperature profile
revealed that heating the reaction mixture for 30 min at 180 °C
afforded moderate yields of the addition product.32 Analyzing
the 1H NMR spectra of the crude material revealed incomplete
consumption of the cinnamate, whereas the 31P NMR spectrum
showed the presence of ditolylphosphinic acid in addition to
what appeared to be unreacted ditolylphosphine oxide. The for-
mation of the phosphinic acid is likely due to disproportiona-
tion of ditolylphosphine oxide into ditolylphosphinic acid and
ditolylphosphine.33−35 The latter was rapidly oxidized to
ditolylphosphine oxide upon exposure to air, resulting in ap-
parently unreacted starting material. Performing the reaction at
lower temperatures to minimize this side reaction led to lower
yields of the phospha-Michael adduct. Increasing the temper-
ature above 200 °C afforded increased amounts of the
phosphinic acid. Heating the reaction at 190 °C for 35 min
generated the highest yield of the phospha-Michael adduct
and the smallest amount of the phosphinic acid. The Michael
employed in this chemistry, and moderate to excellent yields
were obtained for most substrates at 125 °C. In many cases,
the chemistry was remarkably clean, and near quantitative
conversions were observed by NMR before any purification.
Although a number of terminal alkenes worked well, only a
few internal alkenes with a single type of electron-
withdrawing group were screened. Although the phospha-
Michael additions were successful with these internal
alkenes, the substrate scope was extremely limited. To
address this issue, we have extended the chemistry to a wide
range of internal alkenes.
Received: October 21, 2011
Published: December 30, 2011
© 2011 American Chemical Society
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acceptor did not contribute to this process, as heating the
phosphine oxide (200 °C, 35 min) without the addition of the
Michael acceptor also consumed the ditolylphosphine oxide
and generated ditolylphosphinic acid and ditolylphosphine.
Once a successful system for the phospha-Michael addition
of ditolylphosphine oxide to ethyl cinnamate was identified, the
chemistry was extended to functionalized cinnamates and
related internal alkenes (Table 1). For cinnamates, the addition
nitro-substituted cinnamate, while similar yields of the addition
product were found when a methoxy group was incorporated
into ethyl cinnamate. Breaking the conjugation of the molecule
by exchanging the aromatic group on the alkene for an alkyl
group (Table 1, entry 8) did not change the outcome of the
reaction and high yields of the addition product were obtained.
Cyclic Michael acceptors, coumarin and 6-methyl coumarin,
were also successfully used in the phospha-Michael reaction.
Furthermore, adding a second electron-withdrawing group to
the β-position of the Michael acceptor (Table 1, entries 9, 10)
resulted in near quantitative yields (by NMR) of the Michael
adducts after irradiating the reagents at reduced temperatures
(110 °C, 35 min). While the addition reaction was moderately
tolerant of electron withdrawing or donating groups, the
addition reaction was completely suppressed when the steric
bulk of the substrate was increased by incorporating a second
substituent to the β-position of the internal alkene (Table 1,
entries 6, 7).
Table 1. Addition of Ditolylphosphine Oxide to Cinnamates,
a
Crotonates, and Related Internal Alkenes
The chemistry was extended to other internal alkenes
containing a single activating group such as chalcones and
cinnamonitriles (Table 2). For the chalcones, the lowest
effective reaction temperatures were between 120 and 130 °C
(20−35 min). Under these conditions, nearly quantitative
conversions into the addition products were observed with only
trace amounts of the phosphinic acid. Similar to the reactions
involving the cinnamates, substrates bearing either electron-
withdrawing or electron-donating groups were successfully
functionalized in these reactions. Of particular interest was the
use of an unprotected phenol in the chemistry. Historically,
protection/deprotection strategies were required when sub-
strates bearing phenols were used in phospha-Michael reactions
promoted by strong bases or transition metal catalysts. This was
not necessary in our microwave assisted chemistry as evidenced
by the high yields of the addition product obtained using a
representative phenol (Table 2, entry 1). Moving to nitrile-
functionalized substrates gave similar results. Both cinnamoni-
trile and 4-dimethylaminocinnamonitrile were successfully used
in these reactions. For these substrates, the reaction temper-
atures were similar to the cinnamates and methyl crotonate
(170−190 °C). While most of the internal alkenes screened
gave good to excellent yields of the addition products, using
phenyl trans-styryl sulfone as the Michael acceptor was less
successful (Table 2, entry 7). Although a range of conditions
was screened, a significant amount of secondary products was
1
observed in the H and 31P NMR spectra from reactions in-
volving this sulfone. Despite this complex mixture, the addition
product was able to be purified by column chromatography.
As mentioned above, the addition reaction between
ditolylphosphine oxide and coumarins was completely sup-
pressed when a second substituent was added to the β-position
of the alkene (Table 1). To investigate whether or not the
addition of a second electron-withdrawing group could
overcome this steric issue, a range of substrates incorporating
malonates and malononitriles was investigated. As shown in
Table 3, the addition of the second nitrile or ester group
strongly activated the alkene, and the phospha-Michael reaction
proceeded at reduced temperatures when compared to the
analogous reaction shown in Table 2. For example, cin-
namonitrile (Table 2 entry 8) required heating to 175 °C to
induce the phospha-Michael addition, whereas the same rea-
ction involving benzylidenemalononitrile (Table 3 entry 2)
proceeded at 65 °C. While this chemistry tolerated having two
alkyl substituents in the β-position of the Michael acceptor,
a
Reactions were carried out without solvent using 0.43 mmol of
b
ditolylphosphine oxide. Yields are based upon isolated material.
c
Initial microwave power levels.
chemistry was moderately tolerant of electronic changes to the
acceptor. Using ethyl cinnamate as the reference point, slightly
lower yields of the addition product were obtained using a
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Table 2. Addition of Ditolylphosphine Oxide to Chalcones
and Related Compounds
Table 3. Addition of Ditolylphosphine Oxide to Internal
Alkenes Containing Multiple Activating Groups
a
a
a
Reactions were carried out without solvent using 0.43 mmol of
b
ditolylphosphine oxide. Yields are based upon isolated material.
c
d
Initial microwave power levels. No irradiation.
To investigate whether or not the phospha-Michael
chemistry could be carried out using conventional heating,
the addition reactions were carried out using a preheated oil
bath. Heating benzylidenemalononitrile and dimethyl fuma-
rate with ditolylphosphine oxide at 65 °C (1 h) and 110 °C
(35 min) under solvent-free conditions afforded excellent yields
(91 and 85%) of the phospha-Michael adducts with minimal
amounts of secondary products.
a
Reactions were carried out without solvent using 0.43 mmol of
b
ditolylphosphine oxide. Yields are based upon isolated material.
c
Initial microwave power levels.
In addition to probing the effectiveness of the microwave-
assisted protocol with a range of Michael acceptors, the steric
and electronic limits of this reaction were also established from
the standpoint of the secondary phosphine oxide (Table 4). For
this set of experiments, 1,3-diphenyl-2-propenone was used as
the model Michael acceptor, and a range of HP(O)R2 donors
were screened. Irradiation of a 1:1 mixture of the Michael
acceptor and HP(O)(C6H4X)2 (X = OMe, H, CF3) species at
130 °C for 35 min afforded the Michael adducts in excellent
yields. No reduction in conversion was observed using either
analogous reactions with two aryl groups led to complete
recovery of the starting materials (Table 3, entry 8). Increasing
the temperature of the reaction simply resulted in high amounts
of phosphinic acid and no consumption of the alkene. In some
cases, the phospha-Michael reaction proceeded at ambient
temperature without irradiation. For example, simply triturating
isopropylidenemalononitrile or ethyl 2-cyano-3-methyl-2-bute-
noate with ditolylphosphine oxide at 25 °C for 12 h afforded
high yields of the adducts (Table 3, entries 3, 5).
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successful with a range of internal alkenes such as cinnamates,
coumarins, crotonates, sulfones, chalcones, and cinnamonitriles.
Furthermore, the presence of unprotected phenols did not
complicate the chemistry, and high yields of the phospha-
Michael adducts were obtained. For all of the reactions
described herein that require heating above 130 °C, developing
a successful phospha-Michael reaction for these internal alkenes
involved maximizing the addition chemistry while minimizing
the disproportionation of the secondary phosphine oxide.
Table 4. Addition of Functionalized Secondary Phosphine
Oxides to trans-Chalcone
a
EXPERIMENTAL SECTION
■
General Considerations. Unless specified, all solvents were dried
using a Grubbs-type solvent purification system. The phosphine oxi-
des were prepared according to literature procedures and purified
by column chromatography.36,37 The chalcones were prepared by con-
densation reactions and compared with literature 1H NMR
values.38−42 The remaining chemicals were obtained from commercial
1
sources and used as received. H and 13C{1H} chemical shifts were
determined by reference to residual nondeuterated solvent resonances.
All coupling constants are given in Hertz. 31P{1H} NMR spectra were
referenced to external H3PO4 (0 ppm). 19F NMR spectra were
referenced to C6F6 (−164.9). Microwave catalyzed reactions were car-
ried out in sealed vessels using a CEM Discover equipped with an
external IR (surface) temperature sensor. The temperatures reached and
maintained in these reactions are listed below as well as in Tables 1−4.
General Method for Phospha-Michael Reactions. Micro-
wave Heating (Method A). A reactor vial (10 mL) was charged with
the phosphine oxide, Michael acceptor, and a magnetic stirring bar.
After exchanging the air for nitrogen, the reagents were triturated and
irradiated (unless specified). The initial power setting listed for each
reaction was maintained until the desired temperature was reached.
The power was then reduced for the remainder of the reaction to
maintain the temperature. No ramping periods were used in these
reactions; thus, the reaction time listed is the total irradiation time
(not the time at the desired temperature). For reactions involving solid
reagents, the solids needed to melt before a significant temperature
increase was observed. For the reactions studied herein, this typically
occurred within 4 min. Care must be taken not to use initial high
levels of microwave power (to rapidly melt the solids), as significant
decomposition was observed under those conditions. Following
irradiation, the residue was cooled to room temperature and purified
by column chromatography. When liquid Michael acceptors were
used, they were injected into the reaction flask following the exchange
of air for nitrogen.
a
Reactions were carried out without solvent using 0.30−0.49 mmol of
b
the secondary phosphine oxide. Yields are based upon isolated material.
c
d
Initial microwave power levels. Determined by NMR spectroscopy.
Conventional Heating (Method B). A reactor vial (10 mL) was
charged with the phosphine oxide, Michael acceptor, and a magnetic
stirring bar. After exchanging the air for nitrogen, the reagents were
triturated and plunged into a preheated oil bath at the desired
temperature for the specified time.
electron-donating or electron-withdrawing groups. The steric
limits of this reaction were investigated by successively adding
methyl groups in the ortho positions of diphenylphosphine
oxide. Adding a single methyl group to each of the aromatic
rings in HP(O)Ph2 did not appreciably inhibit the reaction, and
high yields of the addition product were obtained. However,
adding a second methyl group (Table 4, entry 5) successfully
inhibited the reaction, and no addition product was observed
at 130 °C. Increasing the temperature of the reaction to 200 °C
for 35 min resulted in 15% conversion into the Michael adduct.
It was also noteworthy that no dimesitylphosphinic acid was
observed in these reactions. The incorporation of the sterically
imposing mesityl groups inhibited the disproportionation
reaction and mostly unreacted starting materials were observed
at the end of the reaction.
Ethyl 3-[Bis(4-methylphenyl)phosphinyl]-3-phenylpropa-
noate (1). The general procedure (method A) was followed with
ethyl cinnamate (73.5 μL g, 0.44 mmol) and ditolylphosphine oxide
(0.10 g, 0.43 mmol). Temperature = 180 °C; time = 30 min; initial
power level = 150 W. Chromatography: silica (19 g), hexane/THF
1:1. Rf = 0.35, yield = 0.16 g of a white powder (91%), mp = 155−
158 °C. Anal. Calcd for C25H27O3P: C, 73.87; H, 6.70. Found: C,
73.67; H, 6.90. Spectral data: 1H (CDCl3, 25 °C) δ 7.81 (m, 2H), 7.32
(m, 4H), 7.27 (m, 2H), 7.16 (m, 3H), 7.04 (m, 2H), 4.02 (ddd, 1H,
J = 11.4, 8.1, 3.3), 3.91 (q, 2H, J = 7.0), 3.06 (ddd, 1H, J = 16.8, 11.1,
5.9), 2.88 (ddd, 1H, J = 16.2, 9.0, 3.5), 2.41 (s, 3H), 2.26 (s, 3H), 1.02
(t, 3H, J = 7.2); 13C{1H} (CDCl3, 25 °C) δ 171.5 (d, J = 17.3), 142.4
(d, J = 2.3), 141.8 (d, J = 2.7), 135.4 (d, J = 5.6), 131.4 (d, J = 8.3),
131.1 (d, J = 9.0), 129.8 (d, J = 5.6), 129.6 (d, J = 11.8), 128.8 (d, J =
12.4), 128.3 (d, J = 102.7), 128.2 (d, J = 1.7), 128.1 (d, J = 97.1), 127.1
(d, J = 2.3), 60.7 (s), 43.1 (d, J = 67.9), 35.0 (s), 21.6 (d, J = 1.2), 21.5
(d, J = 1.2), 13.9 (s); 31P{1H}(CDCl3, 25 °C) δ 32.8 (s).
CONCLUSION
■
In summary, we have developed a protocol for the addition of
P(O)−H bonds to internal alkenes without using a radical
initiator, strong base, or metal catalyst. This methodology was
Ethyl 3-[Bis(4-methylphenyl)phosphinyl]-3-(4-nitrophenyl)-
propanoate (2). The general procedure (method A) was followed with
ethyl 4-nitrocinnamate (0.096 g, 0.43 mmol) and ditolylphosphine
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oxide (0.10 g, 0.43 mmol). Temperature = 170 °C; time = 35 min;
initial power level = 130 W. Chromatography: silica (19.0 g), EtOAc/
hexane (gradient 30:70−80:20). Rf = 0.84 (EtOAc/hexane = 80:20).
Yield = 0.13 g of a white powder (66%), mp = 211−214 °C. Anal.
Calcd For C25H26NO5P: C, 66.51; H, 5.80. Found: C, 66.24; H, 5.74.
Spectral data: 1H (CDCl3, 25 °C) δ 8.03 (m, 2H), 7.81 (m, 2H), 7.47
(m, 2H), 7.35 (m, 4H), 7.09 (m, 2H), 4.14 (ddd, 1H, J = 11.4, 8.1,
3.3), 3.93 (m, 2H), 3.09 (ddd, 1H, J = 17.1, 11.4, 5.7), 2.89 (ddd, 1H, J =
16.8, 9.0, 3.0), 2.43 (s, 3H), 2.29 (s, 3H), 1.05 (t, 3H, J = 7.2);
13C{1H} (CDCl3, 25 °C) δ 170.9 (d, J = 16.9), 147.0 (d, J = 2.7),
143.7 (d, J = 5.6), 142.9 (d, J = 2.7), 142.5 (d, J = 2.9), 131.2 (d, J =
9.0), 130.8 (d, J = 9.7), 130.6 (d, J = 5.0), 129.8 (d, J = 11.8), 129.2 (d,
J = 12.4), 127.6 (d, J = 103.3), 127.3 (d, J = 99.4), 123.3 (d, J = 1.7),
61.1 (s), 43.2 (d, J = 65.8), 34.8 (s), 21.6 (s), 21.5 (s), 14.0 (s);
31P{1H}(CDCl3, 25 °C) δ 31.8 (s).
3-[Bis(4-methylphenyl)phosphinyl]-3-(4-ethoxyphenyl)-
propanoate (3). The general procedure (method A) was followed
with ethyl 4-ethoxycinnamate (0.095 g, 0.43 mmol) and ditolylphos-
phine oxide (0.10 g, 0.43 mmol). Temperature = 180 °C; time = 30
min; initial power level = 75 W. Chromatography: (silica) 19.0 g;
hexane/THF 1:1. Rf = 0.26 (hexane/THF = 50:50). Yield = 0.16 g of a
white powder (82%), mp = 121−124 °C. Anal. Calcd for C27H31O4P:
C, 71.98; H, 6.94. Found: C, 72.20; H, 6.65. Spectral data: 1H (CDCl3,
25 °C) δ 7.77 (m, 2H), 7.31 (m, 4H), 7.16 (m, 2H), 7.05 (m, 2H),
6.69 (m, 2H), 3.92 (m, 5H), 3.00 (ddd, 1H, J = 16.3, 11.3, 6.1), 2.83
(ddd, 1H, J = 16.3, 8.7, 3.4), 2.39 (s, 3H), 2.26 (s, 3H), 1.35 (t, 3H, J =
7.0), 1.03 (t, 3H, J = 7.1); 13C{1H} (CDCl3, 25 °C) δ 171.6 (d, J =
17.6), 158.1 (d, J = 2.3), 142.3 (d, J = 2.7), 141.7 (d, J = 2.8), 131.4 (d,
J = 8.9), 131.1 (d, J = 9.2), 130.8 (d, J = 5.4), 129.5 (d, J = 11.6), 128.9
(d, J = 12.1), 128.4 (d, J = 102.5), 128.3 (d, J = 96.6), 127.0 (d, J =
5.5), 114.3 (d, J = 1.6), 63.3 (s), 60.7 (s), 42.2 (d, J = 69.2), 35.2 (s),
21.6 (d, J = 0.9), 21.5 (d, J = 1.0), 14.8 (s), 14.0 (s); 31P{1H}(CDCl3,
25 °C) δ 32.5 (s).
4-[Bis(4-methylphenyl)phosphinyl]-3,4-dihydro-2H-1-ben-
zopyran-2-one (4). The general procedure (method A) was followed
with coumarin (0.064 g, 0.44 mmol) and ditolylphosphine oxide
(0.1 g, 0.43 mmol). Temperature = 130 °C; time = 35 min; initial
power level = 100 W. Chromatography: (silica) 19.0 g; hexane/THF
(gradient 20:80−0:100). Rf = 0.47 (hexane/THF = 20:80). Yield =
0.12 g (73%) of a white powder, mp = 268−272 °C. Anal. Calcd for
C23H21O3P: C, 73.39; H, 5.62. Found: C, 73.40; H, 5.96. Spectral data:
1H (CDCl3, 25 °C) δ 7.69 (m, 2H), 7.41 (m, 2H), 7.32 (m, 2H),
7.25−7.19 (m, 3H), 6.99 (d, 1H, J = 8.1), 6.87 (t, 1H, J = 7.5), 6.67
(dt, 1H, J = 7.7, 2.0), 3.88 (ddd, 1H, J = 9.9, 8.0, 1.8), 3.21 (ddd, 1H,
J = 16.8, 9.5, 1.8), 2.95 (ddd, 1H, J = 29.7, 16.7, 8.0), 2.42 (s, 3H), 2.38
(s, 3H); 13C{1H} (CDCl3, 25 °C) δ 165.6 (d, J = 3.0), 152.6 (d, J =
4.6), 143.12 (d, J = 2.7), 143.10 (d, J = 2.7), 131.8 (d, J = 9.1), 131.6
(d, J = 9.3), 129.7 (d, J = 12.0), 129.5 (d, J = 4.0), 129.3 (d, J = 12.1),
129.2 (d, J = 3.0), 126.6 (d, J = 99.9), 125.5 (d, J = 100.5), 123.9 (d,
J = 2.6), 117.6 (d, J = 2.5), 117.5 (d, J = 5.6), 37.9 (d, J = 66.0), 28.8
(d, J = 2.1), 21.66 (d, J = 1.3), 21.65 (d, J = 1.3); 31P{1H} (CDCl3,
25 °C) δ 31.3 (s).
28.8 (d, J = 2.1), 21.64 (d, J = 1.2), 21.62 (d, J = 1.3), 20.5 (s);
31P{1H} (CDCl3, 25 °C) δ 31.1(s).
Methyl 3-[Bis(4-methylphenyl)phosphinyl]butanoate (8).
The general procedure (method A) was followed with methyl
crotonate (46.0 μL, 0.43 mmol) and ditolylphosphine oxide (0.10 g,
0.43 mmol). Temperature = 170 °C; time = 35 min; initial power level =
50 W. Chromatography: (silica) 19.0 g; ETOAc. Rf = 0.37 (EtOAc).
Yield = 0.10 g of a colorless waxy solid (70%). Anal. Calcd for
C19H23O3P: C, 69.08; H, 7.02. Found: C, 69.35; H, 6.91. Spectral data:
1H (CDCl3, 25 °C) δ 7.68 (m, 4H), 7.27 (m, 4H), 3.62 (s, 3H), 2.92
(m, 1H), 2.62 (ddd, 1H, J = 16.4, 10.1, 3.0), 2.43 (ddd, 1H, J = 16.5,
10.9, 5.5), 2.38 (s, 3H), 2.37 (s, 3H), 1.18 (dd, 3H, J = 16.0, 7.0);
13C{1H} (CDCl3, 25 °C) δ 172.7 (d, J = 17.8), 142.24 (d, J = 2.7),
142.18 (d, J = 2.8), 131.1 (d, J = 9.1), 131.0 (d, J = 9.1), 129.5 (d, J =
12.2), 129.4 (d, J = 12.3), 128.4 (d, J = 98.2), 128.3 (d, J = 99.6), 51.9
(s), 34.3 (s), 29.4 (d, J = 73.3), 21.55 (d, J = 1.2), 21.54 (d, J = 1.2),
12.9 (d, J = 2.7); 31P{1H} (CDCl3, 25 °C) δ 36.0(s).
Dimethyl-2-[bis(4-methylphenyl)phosphinyl]succinate (9).
The general procedure (method A) was followed with methyl fu-
marate (0.062 g, 0.43 mmol) and ditolylphosphine oxide (0.10 g, 0.43
mmol). Temperature = 110 °C; time = 35 min; initial power level
setting 50 W. Chromatography: silica (5.0 g), ETOAc. Rf = 0.41
(EtOAc). Yield = 0.145 g of a white powder (89%), mp = 94−95 °C.
Anal. Calcd for C20H23O5P: C, 64.17; H, 6.19. Found: C, 64.41; H,
6.03. Spectral data: 1H (CDCl3, 25 °C) δ 7.71 (m, 4H), 7.29 (m, 4H),
4.00 (ddd, 1H, J = 14.5, 11.3, 3.1), 3.64 (s, 3H), 3.44 (s, 3H), 3.13
(ddd, 1H, J = 17.5, 11.8, 5.8), 2.77 (ddd, 1H, J = 17.6, 8.50, 3.14), 2.41
(s, 3H), 2.40 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 172.0 (d, J = 15.7),
169.3 (d, J = 3.3), 143.0 (d, J = 2.7), 142.9 (d, J = 2.7), 131.6 (d, J =
9.7), 131.4 (d, J = 9.7), 129.5 (d, J = 12.8), 129.2 (d, J = 12.4), 127.6
(d, J = 104.9), 126.8 (d, J = 104.9), 52.3 (s), 52.2 (s), 44.8 (d, J =
58.4), 30.8 (s), 21.63 (d, J = 1.1), 21.61 (d, J = 1.1); 31P{1H} (CDCl3,
25 °C) δ 29.9 (s). The title compound was also prepared using
dimethyl maleate (54.4 μL, 0.43 mmol): Temperature = 110 °C;
time = 35 min; power = 50 W. Yield = 0.12 g (74%). The title com-
pound was also prepared using method B. Triturating methyl fumarate
(0.062 g, 0.43 mmol) and ditolylphosphine oxide (0.10 g, 0.43 mmol)
at 110 °C for 35 min afforded 85% of the phospha-Michael adduct as
1
determined by H NMR spectroscopy using anisole as an internal
standard.
4-[Bis(4-methylphenyl)phosphinyl]-4-[4-hydroxy-3-
methoxyphenyl]butan-2-one (10). The general procedure (meth-
od A) was followed with 3-methoxy-4-hydroxybenzalacetone (0.083 g,
0.43 mmol) and ditolylphosphine oxide (0.10 g, 0.43 mmol).
Temperature = 130 °C; time = 35 min; power = 50 W. Chro-
matography: silica (19.0 g), THF/hexane (70:30). Rf = 0.28 (THF/
hexane 70:30). Yield = 0.15 g of a white powder (82%), mp = 158−
161 °C. Anal. Calcd for C25H27O4P: C, 71.08; H, 6.44. Found: C,
71.11; H, 6.23. Spectral data: 1H (CDCl3, 25 °C) δ 7.78 (m, 2H), 7.33
(m, 4H), 7.06 (m, 2H), 6.85 (m, 1H), 6.74 (m, 2H), 5.65 (s, 1H), 4.09
(ddd, 1H, J = 10.4, 7.7, 2.8), 3.75 (s, 3H), 3.24 (ddd, 1H, J = 17.8,
10.3, 5.1), 2.89 (ddd, 1H, J = 17.8, 10.9, 2.8), 2.41 (s, 3H), 2.28 (s,
3H), 1.96 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 205.8 (d, J = 13.0),
146.6 (d, J = 1.9), 145.0 (d, J = 2.4), 142.4 (d, J = 2.7), 141.8 (d, J =
2.7), 131.3 (d, J = 8.9), 131.1 (d, J = 9.2), 129.6 (d, J = 11.6), 128.8 (d,
J = 12.1), 128.4 (d, J = 102.7), 128.3 (d, J = 96.7), 127.4 (d, J = 5.6),
122.7 (d, J = 6.4), 114.5 (d, J = 1.7), 112.4 (d, J = 5.1), 55.8 (s), 43.7
(s), 40.8 (d, J = 69.7), 30.7 (s), 21.6 (d, J = 0.9), 21.4 (d, J = 1.0);
31P{1H} (CDCl3, 25 °C) δ 34.4 (s).
3-[Bis(4-methylphenyl)phosphinyl]-1,3-diphenylpropan-1-
one (11). The general procedure (method A) was followed with (E)-
1,3-diphenyl-2-propenone (0.090 g, 0.43 mmol) and ditolylphosphine
oxide (0.10 g, 0.43 mmol). Temperature = 135 °C; time = 35 min;
power = 100 W. Chromatography: silica (19.0 g), hexane/THF (1:1).
Rf = 0.27 (hexane/THF 1:1). Yield = 0.16 g of a white powder (84%),
mp = 187−189 °C. Anal. Calcd for C29H27O2P: C, 79.43; H, 6.21.
Found: C, 79.08; H, 6.53. Spectral data: 1H (CDCl3, 25 °C) δ 7.85 (m,
4H), 7.47 (m, 1H), 7.40 (m, 2H), 7.35 (m, 4H), 7.30 (m, 2H), 7.15
(m, 2H), 7.09 (m, 1H), 7.04 (m, 2H), 4.43 (ddd, 1H, J = 9.9, 7.2, 2.6),
3.99 (ddd, 1H, J = 18.0, 10.8, 4.2), 3.38 (ddd, 1H, J = 18.0, 11.4, 2.4),
6-Methyl-4-[bis(4-methylphenyl)phosphinyl]-3,4-dihydro-
2H-1-benzopyran-2-one (5). The general procedure (method A)
was followed with 6-methyl coumarin (0.069 g, 0.43 mmol) and
ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 130 °C;
time = 35 min; initial power level = 100 W. Chromatography: (silica)
19.0 g; hexane/THF (gradient 50:50−0:100). Rf = 0.79 (hexane/
THF = 20:80). Yield = 0.12 g (71%) of a white powder, mp = 275−
277 °C. Anal. Calcd for C24H23O3P: C, 73.83; H, 5.94. Found: C,
73.53; H, 6.01. Spectral data: 1H (CDCl3, 25 °C) δ 7.68 (m, 2H), 7.41
(m, 2H), 7.33 (m, 2H), 7.21 (m, 2H), 7.02 (m, 1H), 6.87 (m, 1H),
6.41 (s, 1H), 3.79 (ddd, 1H, J = 12.1, 8.0, 2.0), 3.19 (ddd, 1H, J = 16.8,
9.5, 1.8), 2.94 (ddd, 1H, J = 30.0, 16.8, 8.2), 2.43 (s, 3H), 2.40 (s, 3H),
2.09 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 165.8 (d, J = 3.1), 150.4 (d,
J = 4.6), 143.07 (d, J = 2.8), 143.04 (d, J = 2.8), 133.3 (d, J = 2.7),
131.9 (d, J = 9.1), 131.6 (d, J = 9.2), 130.0 (d, J = 4.0), 129.7 (d, J =
3.0), 129.6 (d, J = 12.0), 129.2 (d, J = 12.1), 126.6 (d, J = 99.7), 125.6
(d, J = 100.4), 117.2 (d, J = 2.5), 117.0 (d, J = 4.8), 38.1 (d, J = 66.0),
1382
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2.36 (s, 3H), 2.25 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 196.8 (d, J =
13.4), 142.4 (d, J = 2.7), 141.7 (d, J = 2.9), 136.5 (s), 136.3 (d, J =
5.6), 133.2 (s), 131.3 (d, J = 8.9), 131.0 (d, J = 9.5), 129.9 (d, J = 6.2),
129.6 (d, J = 11.8), 128.8 (d, J = 11.8), 128.7 (d, J = 102.7), 128.5 (s),
128.4 (d, J = 97.0), 128.2 (d, J = 2.3), 128.1 (s), 126.9 (d, J = 2.3), 41.2
(d, J = 69.1), 39.2 (s), 21.5 (s), 21.4 (s); 31P{1H} (CDCl3, 25 °C) δ
34.5 (s).
3 -[Bis( 4-methy lphenyl)phosphin yl]-1, 3 -bis(4-
methylphenyl)propan-1-one (12). The general procedure (method
A) was followed with trans-4,4′-dimethylchalcone (0.105 g, 0.44 mmol)
and ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 135 °C;
time = 35 min; power = 100 W. Chromatography: silica (5.5 g), hexane/
THF (gradient 90:10−20:80). Rf = 0.35 (hexane/THF 50:50). Yield =
0.19 g of a white powder (94%), mp = 191−193 °C. Anal. Calcd for
C31H31O2P: C, 79.81; H, 6.70. Found: C, 79.58; H, 6.33. Spectral data:
1H (CDCl3, 25 °C) δ 7.82 (m, 2H), 7.72 (m, 2H), 7.37 (m, 2H), 7.27
(m, 4H), 7.15 (m, 2H), 7.05 (m, 2H), 6.95 (m, 2H), 4.40 (ddd, 1H, J =
9.9, 7.2, 2.6), 3.93 (ddd, 1H, J = 17.7, 10.5, 4.2), 3.31 (ddd, 1H, J = 18.0,
11.1, 2.3), 2.36 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H), 2.19 (s, 3H); 13C{1H}
(CDCl3, 25 °C) δ 196.5 (d, J = 13.4), 144.0 (s), 142.2 (d, J = 2.9), 141.6
(d, J = 2.9), 136.4 (d, J = 2.1), 134.1 (s), 133.2 (d, J = 5.7), 131.3 (d, J =
9.0), 131.1 (d, J = 9.0), 129.7 (d, J = 5.6), 129.6 (d, J = 11.8), 129.1 (s),
129.0 (d, J = 1.7), 128.9 (d, J = 102.7), 128.8 (d, J = 11.8), 128.7 (d, J =
96.5), 128.2 (s), 40.7 (d, J = 69.5), 39.1 (s), 21.57 (s), 21.53 (s), 21.47
(s), 21.0 (s); 31P{1H} (CDCl3, 25 °C) δ 34.5 (s).
Found: C, 70.28; H, 5.40. Spectral data: 1H (CDCl3, 25 °C) δ 8.21 (m,
2H), 7.96 (m, 2H), 7.81 (m, 2H), 7.34−7.27 (m, 6H), 7.07 (m, 2H), 6.70
(m, 2H), 4.31 (ddd, 1H, J = 10.3, 7.3, 2.9), 3.92 (ddd, 1H, J = 18.0, 10.4,
5.0), 3.71 (s, 3H), 3.39 (ddd, 1H, J = 17.9, 10.3, 2.8), 2.38 (s, 3H), 2.29
(s, 3H); 13C{1H} (CDCl3, 25 °C) δ 196.0 (d, J = 13.7), 158.7 (d, J = 2.3),
150.4 (s), 142.6 (d, J = 2.7), 141.9 (d, J = 2.7), 140.9 (s), 131.2 (d, J =
9.0), 131.0 (d, J = 9.0), 130.8 (d, J = 5.4), 129.7 (d, J = 11.8), 129.1 (s),
129.0 (d, J = 11.7), 128.3 (d, J = 101.0), 128.3 (d, J = 99.5), 127.7 (d, J =
5.6), 123.7 (s), 113.9 (d, J = 1.5), 55.1 (s), 40.6 (d, J = 69.4), 39.9 (s),
21.6 (d, J = 1.2), 21.5 (d, J = 1.2); 31P{1H} (CDCl3, 25 °C) δ 33.0 (s).
Bis(4-methylphenyl)[1-phenyl-2-(phenylsulfonyl)ethane]-
phosphine Oxide (16). The general procedure (method A) was
followed with phenyl trans-styryl sulfone (0.11 g, 0.45 mmol) and
ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 125 °C;
time = 35 min; power = 50 W. Chromatography: silica (19.0 g),
hexane/THF (4:6). Rf = 0.39. Yield = 0.10 g of a white powder (49%),
mp = 284−286 °C. Anal. Calcd for C28H27O3PS: C, 70.87; H, 5.73.
Found: C, 70.94; H, 5.79. Spectral data: 1H (CDCl3, 25 °C) δ 7.82 (m,
2H), 7.44 (m, 2H), 7.38 (m, 3H), 7.22 (m, 2H), 7.16 (m, 2H), 7.02−
6.94 (m, 7H), 4.09 (ddd, 1H, J = 11.3, 9.1, 1.9), 4.01 (ddd, 1H, J =
14.9, 12.6, 2.6), 3.56 (ddd, 1H, J = 14.9, 9.8, 1.7), 2.46 (s, 3H), 2.24 (s,
3H); 13C{1H} (CDCl3, 25 °C) δ 143.1 (d, J = 2.8), 142.2 (d, J = 2.9),
139.6 (s), 133.1 (s), 132.2 (d, J = 6.0), 131.4 (d, J = 8.9), 131.0 (d, J =
9.5), 130.0 (d, J = 11.8), 129.8 (d, J = 5.2), 128.8 (d, J = 12.4), 128.8
(s), 128.1 (d, J = 2.1), 127.7 (s), 127.4 (d, J = 2.6), 127.4 (d, J =
104.5), 126.7 (d, J = 98.1), 56.3 (s), 42.5 (d, J = 63.0), 21.7 (d, J =
1.1), 21.5 (d, J = 1.2); 31P{1H} (CDCl3, 25 °C) δ 33.0 (s).
3-[Bis(4-methylphenyl)phosphinyl]-3-phenylpropanenitrile
(17). The general procedure (method A) was followed with
cinnamonitrile (54.0 μL, 0.43 mmol) and ditolylphosphine oxide (0.10
g, 0.43 mmol). Temperature = 175 °C; time = 35 min; power = 50 W.
Chromatography: silica (19.0 g), hexane/THF (gradient 90:10−30:70).
Rf = 0.27 (hexane/THF 50:50). Yield = 0.11 g of a white powder (70%),
mp = 225−228 °C. Anal. Calcd for C23H22NOP: C, 76.86; H, 6.17. Found:
C, 76.90; H, 6.55. Spectral data: 1H (CDCl3, 25 °C) δ 7.78 (m, 2H), 7.37
(m, 2H), 7.29−7.24 (m, 7H), 7.06 (m, 2H), 3.70 (ddd, 1H, J = 11.8, 7.8,
3.9), 3.11 (ddd, 1H, J = 17.2, 12.0, 6.9), 2.87 (ddd, 1H, J = 17.3, 6.5, 3.7),
2.44 (s, 3H), 2.28 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 143.2 (d, J = 2.8),
142.5 (d, J = 2.9), 133.5 (d, J = 5.2), 131.2 (d, J = 9.0), 131.1 (d, J = 9.4),
129.9 (d, J = 11.8), 129.4 (d, J = 5.3), 129.0 (d, J = 12.5), 128.8 (d, J = 1.7),
128.2 (d, J = 2.2), 127.1 (d, J = 98.2), 127.0 (d, J = 105.0), 117.8 (d, J =
19.0), 43.8 (d, J = 66.0), 21.6 (d, J = 1.1), 21.5 (d, J = 1.2), 19.5 (d, J =
2.3); 31P{1H} (CDCl3, 25 °C) δ 31.3 (s)
3 -[Bis( 4-methy lphenyl)phosphin yl]-1, 3 -bis(4-
methoxyphenyl)propan-1-one (13). The general procedure (meth-
od A) was followed with trans-4,4′-dimethoxychalcone (0.116 g, 0.43
mmol) and ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature =
135 °C; time = 35 min; power = 100 W. Chromatography: silica (5.0 g),
hexane/THF (gradient 90:10−10:90). Rf = 0.45 (hexane/THF 40:60).
Yield = 0.17 g of a white powder (79%), mp = 198−200 °C. Anal. Calcd
for C31H31O4P: C, 74.68; H, 6.27. Found: C, 74.94; H, 6.25. Spectral
1
data: H (CDCl3, 25 °C) δ 7.82 (m, 4H), 7.32 (m, 6H), 7.05 (m, 2H),
6.82 (m, 2H), 6.69 (m, 2H), 4.38 (ddd, 1H, 9.7, 7.1, 2.2), 3.90 (ddd, 1H,
J = 17.4, 10.4, 4.2), 3.26 (ddd, 1H, J = 17.7, 11.1, 2.0), 3.79 (s, 3H), 3.68
(s, 3H), 2.36 (s, 3H), 2.26 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 195.4 (d,
J = 13.4), 163.6 (s), 158.4 (d, J = 2.3), 142.2 (d, J = 2.7), 141.6 (d, J =
2.9), 131.2 (d, J = 8.9), 131.0 (d, J = 9.5), 130.9 (d, J = 6.2), 130.4 (s),
129.7 (s), 129.6 (d, J = 11.2), 128.9 (d, J = 102.6), 128.8 (d, J = 11.8),
128.6 (d, J = 96.4), 128.3 (d, J = 5.6), 113.7 (d, J = 1.2), 113.6 (s), 55.4
(s), 55.1 (s), 40.3 (d, J = 70.1), 38.8 (s), 21.5 (s), 21.4(s); 31P{1H}
(CDCl3, 25 °C) δ 34.7 (s).
3-[Bis(4-methylphenyl)phosphinyl]-1-(4-methoxyphenyl)-3-
(3-nitrophenyl)propan-1-one (14). The general procedure (meth-
od A) was followed with trans-4′-methoxy-3-nitrochalcone (0.125 g, 0.44
mmol) and ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature =
130 °C; time = 20 min; power = 150 W. Chromatography: silica (19.0 g),
gradient EtOAc/hexane (30:70−80:20). Rf = 0.54 (EtOAc/hexane =
80:20). Yield = 0.20 g of a white powder (90%), mp = 202−204 °C. Anal.
Calcd for C30H28NO5P: C, 70.17; H, 5.50. Found: C, 69.83; H, 5.48.
Spectral data: 1H (CDCl3, 25 °C) δ 8.13 (m, 1H), 7.95 (m, 1H), 7.86 -
7.78 (m, 5H), 7.38−7.31 (m, 5H), 7.06 (m, 2H), 6.84 (m, 2H), 4.51
(ddd, 1H, J = 10.8, 7.0, 2.4), 3.96 (ddd, 1H, J = 18.1, 10.7, 4.3), 3.81 (s,
3H), 3.35 (ddd, 1H, J = 18.1, 10.5, 2.4), 2.38 (s, 3H), 2.26 (s, 3H);
13C{1H} (CDCl3, 25 °C) δ 194.6 (d, J = 13.0), 163.9 (s), 147.8 (d, J =
1.9), 142.8 (d, J = 2.8), 142.3 (d, J = 2.8), 138.8 (d, J = 5.4), 135.5 (d, J =
5.0), 131.1 (d, J = 9.0), 130.6 (d, J = 9.3), 130.4 (s), 129.8 (d, J = 11.8),
129.2 (d, J = 1.2), 129.1 (d, J = 12.1), 129.1 (d, J = 2.0), 127.9 (d, J =
103.2), 127.5 (d, J = 98.8), 125.1 (d, J = 5.8), 121.9 (d, J = 2.2), 113.8 (s),
55.5 (s), 41.3 (d, J = 67.6), 38.3 (s), 21.6 (d, J = 1.1), 21.4 (d, J = 1.1);
31P{1H} (CDCl3, 25 °C) δ 34.6 (s).
3-[Bis(4-methylphenyl)phosphinyl]-3-(4-methoxyphenyl)-1-
(4-nitrophenyl)propan-1-one (15). The general procedure (meth-
od A) was followed with trans-4′-nitro-4-methoxychalcone (0.125 g,
0.44 mmol) and ditolylphosphine oxide (0.10 g, 0.43 mmol).
Temperature = 130 °C; time = 20 min; power = 140 W. Chroma-
tography: silica (19.0 g), EtOAc/hexane (gradient 10:90−80:20). Rf =
0.74 (EtOAc/hexane = 80:20). Yield = 0.17 g of a white powder (76%),
mp = 210−215 °C. Anal. Calcd for C30H28NO5P: C, 70.17; H, 5.50.
3-[Bis(4-methylphenyl)phosphinyl]-3-[(4-dimethylamino)-
phenyl]propanenitrile (18). The general procedure (method A)
was followed with (4-dimethylamino)cinnamonitrile (0.074 g, 0.43
mmol) and ditolylphosphine oxide (0.10 g, 0.43 mmol). Tempera-
ture = 200 °C; time = 35 min; power = 150 W. Chromatography: silica
(19.0 g), hexane/THF (1:1). Rf = 0.26. Yield = 0.15 g of a white
powder (87%), mp = 204−208 °C. Anal. Calcd for C25H27N2OP: C,
1
74.61; H, 6.76. Found: C, 74.90; H, 7.06. Spectral data: H (CDCl3,
25 °C) δ 7.74 (m, 2H), 7.34 (m, 4H), 7.13 (m, 2H), 7.08 (m, 2H),
6.60 (m, 2H), 3.63 (ddd, 1H, J = 12.0, 8.4, 3.6), 3.02 (ddd, 1H, J =
18.9, 12.0, 6.9), 2.91 (s, 6H), 2.85 (ddd, 1H, J = 17.4, 6.6, 3.8), 2.43 (s,
3H), 2.29 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 150.2 (d, J = 1.8), 142.9
(d, J = 2.9), 142.2 (d, J = 2.9), 131.3 (d, J = 8.9), 131.2 (d, J = 9.7),
130.1 (d, J = 5.0), 129.8 (d, J = 11.5), 129.0 (d, J = 12.4), 127.7 (d, J =
96.8), 127.5 (d, J = 104.5), 120.4 (d, J = 5.0), 118.2 (d, J = 19.3), 112.6
(d, J = 1.5), 42.9 (d, J = 68.2), 40.4 (s), 21.6 (d, J = 1.2), 21.5 (d, J =
1.4), 19.7 (d, J = 3.3); 31P{1H} (CDCl3, 25 °C) δ 31.5 (s)
(2-Nitro-1-phenylethyl)-bis(4-methylphenyl)phosphine
Oxide (19). The general procedure (method A) was followed with β-
nitrostyrene (0.064 g, 0.43 mmol) and ditolylphosphine oxide (0.10 g,
0.43 mmol). Temperature = 130 °C; time = 35 min; power = 100 W.
Chromatography: silica (19.0 g), hexane/THF (gradient 90:10−
10:90). Rf = 0.37 (hexane/THF 50:50). Yield = 0.11 g of a white
powder (68%), mp = 192−194 °C. Anal. Calcd for C22H22NO3P: C,
69.65; H, 5.84. Found: C, 69.39; H, 5.92. Spectral data: 1H (CDCl3, 25
°C) δ 7.85 (m, 2H), 7.39 (m, 2H), 7.29 (m, 4H), 7.21 (m, 3H), 7.06
(m, 2H), 5.07 (ddd, 1H, J = 13.8, 11.8, 3.8), 4.75 (ddd, 1H, J = 13.8,
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6.0, 3.3), 4.36 (ddd, 1H, J = 11.9, 10.4, 3.4), 2.44 (s, 3H), 2.28 (s, 3H);
13C{1H} (CDCl3, 25 °C) δ 143.3 (d, J = 2.9), 142.6 (d, J = 2.9), 132.0
(d, J = 5.6), 131.2 (d, J = 9.7), 131.1 (d, J = 9.5), 130.0 (d, J = 11.9),
129.5 (d, J = 5.1), 129.1 (d, J = 12.4), 128.7 (d, J = 1.7), 128.2 (d, J =
2.3), 127.0 (d, J = 104.4), 127.0 (d, J = 98.8), 76.0 (d, J = 5.6), 46.1 (d,
J = 63.9), 21.6 (d, J = 1.2), 21.5 (d, J = 1.1); 31P{1H} (CDCl3, 25 °C)
δ 30.2
Dimethyl 2-(1-[Bis(4-methylphenyl)phosphinyl]ethyl)-
malonate (20). The general procedure (method A) was followed
with dimethyl ethylidenemalonate (61.0 μL, 0.43 mmol) and
ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 150 °C;
time = 25 min, 100 W. Chromatography: silica (5.6 g), EtOAc. Rf =
0.57. Yield = 0.15 g of a colorless gel (90%). Anal. Calcd for
C21H25O5P: C, 64.94; H, 6.49. Found: C, 64.67; H, 6.73. Spectral data:
1H (CDCl3, 25 °C) δ 7.69 (m, 4H), 7.29 (m, 4H), 3.81 (dd, 1H, J =
9.6, 6.6), 3.69 (s, 3H), 3.48 (s, 3H), 3.29 (m, 1H), 2.39 (s, 3H), 2.37
(s, 3H), 1.24 (dd, 3H, J = 15.6, 7.2); 13C{1H} (CDCl3, 25 °C) δ 168.6
(d, J = 9.7), 168.1 (d, J = 8.9), 142.4 (d, J = 2.7), 142.3 (d, J = 2.9),
131.4 (d, J = 9.0), 131.3 (d, J = 9.5), 129.4 (d, J = 11.8), 129.3 (d, J =
11.8), 128.4 (d, J = 98.6), 127.7 (d, J = 99.8), 52.6 (s), 52.5 (s), 50.4
(s), 33.0 (d, J = 71.1), 21.6 (d, J = 1.2), 21.5 (d, J = 1.1), 11.1 (d, J =
1.7); 31P{1H} (CDCl3, 25 °C) δ 34.2 (s).
132.5 (d, J = 8.3), 129.0 (d, J = 11.5), 127.4 (d, J = 94.0), 61.2 (s), 54.4
(d, J = 2.4), 40.1 (d, J = 69.4), 21.5 (d, J = 0.8), 20.4 (s), 13.9 (s);
31P{1H} (CDCl3, 25 °C) δ 35.3 (s).
2-(2-[Bis(4-methylphenyl)phosphinyl]propan-2-yl)-
propanedinitrile (24). The general procedure (method A) was
followed with isopropylidenemalononitrile (48.0 μL, 0.43 mmol) and
ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 25 °C;
time = 12 h; no irradiation. Chromatography: silica (19.0 g), hexane/
THF (gradient 90:10−40:60). Rf = 0.39 (50:50). Yield = 0.12 g of a
white powder (82%), mp = 134−138 °C. Anal. Calcd for
C20H21N2OP: C, 71.41; H, 6.29. Found: C, 71.76; H, 6.23. Spectral
data: 1H (CDCl3, 25 °C) δ 7.90 (m, 4H), 7.35 (m, 4H), 4.49 (d, 1H,
J = 7.0), 2.42 (s, 6H), 1.52 (d, 6H J = 13.9); 13C{1H} (CDCl3, 25 °C)
δ 143.5 (d, J = 2.9), 132.1 (d, J = 8.7), 129.7 (d, J = 12.0), 125.5 (d, J =
98.2), 111.1 (d, J = 8.4), 40.3 (d, J = 67.5), 30.6 (d, J = 4.3), 21.6 (d,
J = 1.0), 21.3 (s); 31P{1H} (CDCl3, 25 °C) δ 31.7 (s).
2-([Bis(4-methylphenyl)phosphinyl](furan-2-yl)methyl)-
propanedinitrile (25). The general procedure (method A) was
followed with (2-furanylmethylene)malononitrile (0.062 g, 0.43 mmol)
and ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 90 °C;
time = 35 min; power = 50 W. Chromatography: silica (5.6 g), hexane/
THF (50:50). Rf = 0.50 (hexane/EtOAc 50:50). Yield = 0.14 g of a white
powder (87%), mp = 161−163 °C. Anal. Calcd for C212H19N2O2P: C,
70.58; H, 5.12. Found: C, 70.34; H, 5.43. Spectral data: H (CDCl3, 25
°C) δ 7.71 (m, 2H), 7.41 (m, 2H), 7.36 (m, 3H), 7.20 (m, 2H), 6.34 (m,
1H), 6.32 (m, 1H), 4.82 (dd, 1H, J = 4.1, 4.1), 4.35 (dd, 1H, J = 12.8,
4.1), 2.43 (s, 3H), 2.36 (s, 3H); 13C{1H} (CDCl3, 25 °C) δ 143.9 (d, J =
2.9), 143.7 (d, J = 3.9), 143.6 (d, J = 2.3), 143.6 (d, J = 2.7), 131.9 (d, J =
10.1), 131.2 (d, J = 9.7), 129.9 (d, J = 12.2), 129.2 (d, J = 13.0), 126.6 (d,
J = 103.2), 124.7 (d, J = 106.6), 111.9 (d, J = 5.1), 111.5 (d, J = 10.0),
111.4 (d, J = 2.3), 110.9 (d, J = 5.9), 42.4 (d, J = 64.0), 23.1 (d, J = 2.3),
21.71 (s), 21.66 (s); 31P{1H} (CDCl3, 25 °C) δ 28.2 (s).
3-[Bis(4-methoxyphenyl)phosphinyl]-1,3-diphenyl-1-propa-
none (28).43 The general procedure (method A) was followed with
(E)-1,3-diphenyl-2-propenone (0.079 g, 0.38 mmol) and bis(4-
methoxyphenyl)phosphine oxide (0.10 g, 0.38 mmol). Temperature =
130 °C; time = 35 min; power = 100 W. Chromatography: silica
(19.0 g), hexane/THF (gradient 40:60−100:0). Rf = 0.43 (hexane/
THF 20:80). Yield = 0.17 g of a white powder (95%). mp = 180−
183 °C. Anal. Calcd for C29H27O4P: C, 74.03; H, 5.78. Found: C,
74.29; H, 5.49.
3-(Diphenylphosphinyl)-1,3-diphenyl-1-propanone
(29).43,44 The general procedure (method A) was followed with (E)-
1,3-diphenyl-2-propenone (0.105 g, 0.50 mmol) and diphenylphos-
phine oxide (0.10 g, 0.49 mmol). Temperature = 130 °C; time =
35 min; power = 100 W. Chromatography: silica (19.0 g), EtOAc. Rf =
0.49 (EtOAc). Yield = 0.18 g of a white powder (89%). mp = 239−
241 °C (lit. = 238 °C).44
2-([Bis(4-methylphenyl)phosphinyl]phenylmethyl)-
propanedinitrile (21). The general procedure (method A) was
followed with benzylidenemalononitrile (0.067 g, 0.43 mmol) and
ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 65 °C;
time = 45 min; power = 50 W. Chromatography: silica (19.0 g),
hexane/THF (1:1). Rf = 0.21 (hexane/THF 1:1). Yield = 0.12 g of a
white powder (72%), mp = 196−198 °C. Anal. Calcd for
C24H21N2OP: C, 74.99; H, 5.51. Found: C, 75.16; H, 5.30. Spectral
1
data: H (CDCl3, 25 °C) δ 7.81 (m, 2H), 7.39−7.28 (m, 9H), 7.07
(m, 2H), 4.69 (t, 1H, J = 7.5), 3.95 (t, 1H, J = 7.8), 2.44 (s, 3H), 2.28
(s, 3H); 13C{1H} (CDCl3, 25 °C) δ 143.8 (d, J = 2.9), 143.0 (d, J =
2.9), 131.4 (d, J = 9.6), 131.3 (d, J = 9.4), 131.0 (d, J = 4.0), 130.0 (d,
J = 12.3), 129.8 (d, J = 5.2), 129.3 (d, J = 1.8), 129.2 (d, J = 1.0), 129.1
(d, J = 12.8), 126.8 (d, J = 100.6), 126.1 (d, J = 107.4), 111.5 (d, J =
8.5), 111.3 (d, J = 8.6), 47.3 (d, J = 63.2), 24.8 (d, J = 1.7), 21.7 (d, J =
1.2), 21.5 (d, J = 1.2); 31P{1H} (CDCl3, 25 °C) δ 28.8 (s). The title
compound was also prepared following method B. Trituration of
benzylidenemalononitrile (0.067 g, 0.43 mmol) and ditolylphosphine
oxide (0.10 g, 0.43 mmol) at 65 °C for 1 h afforded 91% of the
phospha-Michael adduct as determined by 1H NMR spectroscopy
using anisole as an internal standard.
Ethyl 2-Cyano-3-[bis(4-methylphenyl)phosphinyl]-3-methyl-
buanoate (22). The general procedure (method A) was followed
with ethyl 2-cyano-3-methyl-2-butenoate (0.066 g, 0.43 mmol) and
ditolylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 25 °C;
time = 12 h; no irradiation. Chromatography: silica (19.0 g), hexane/
THF (gradient 90:10−50:50). Rf = 0.36 (hexane/THF 50:50). Yield =
0.15 g of a white powder (90%), mp = 191−193 °C. Anal. Calcd for
C22H26NO3P: C, 68.92; H, 6.83. Found: C, 69.28; H, 6.63. Spectral
data: 1H (CDCl3, 25 °C) δ 7.90 (m, 4H), 7.32 (m, 4H), 4.14 (m, 1H),
4.03 (m, 1H), 3.99 (d, 1H, J = 7.8), 2.41 (s, 3H), 2.40 (s, 3H), 1.53 (d,
3H, J = 15.0), 1.42 (d, 3H, J = 14.4), 1.26 (t, 3H, J = 7.2); 13C{1H}
(CDCl3, 25 °C) δ 164.5 (d, J = 7.9), 143.0 (d, J = 2.8), 142.8 (d, J =
2.8), 132.4 (d, J = 8.6), 132.3 (d, J = 8.6), 129.4 (d, J = 9.0), 129.3 (d,
J = 9.0), 126.5 (d, J = 97.0), 126.3 (d, J = 95.6), 114.8 (d, J = 9.5), 62.7
(s), 43.2 (d, J = 3.6), 40.0 (d, J = 68.8), 22.1 (s), 21.6 (s), 21.5 (s),
20.2 (s), 13.8 (s); 31P{1H} (CDCl3, 25 °C) δ 33.5 (s).
Diethyl 2-(2-[Bis(4-methylphenyl)phosphinyl]propan-2-yl)-
malonate (23). The general procedure (method A) was followed
with diethyl isopropylidenemalonate (86.0 μL, 0.44 mmol) and
ditolylphosphine oxide (0.100 g, 0.43 mmol). Temperature = 130 °C;
time = 35 min; power = 50 W. Chromatography: silica (5.6 g);
hexane/EtOAc (30:70). Rf = 0.18 (hexane/EtOAc 30:70). Yield = 0.18
g of a white powder (96%), mp = 92−94 °C. Anal. Calcd for
C24H31O5P: C, 66.96; H, 7.26. Found: C, 67.24; H, 7.40. Spectral data:
1H (CDCl3, 25 °C) δ 7.89 (m, 4H), 7.28 (m, 4H), 3.99 (m, 4H), 3.85
3-[Bis[(4-trifluoromethyl)phenyl]phosphinyl]-1,3-diphenyl-
1-propanone (30). The general procedure (method A) was followed
with (E)-1,3-diphenyl-2-propenone (0.062 g, 0.30 mmol) and bis[(4-
trifluoromethyl) phenyl]phosphine oxide (0.10 g, 0.30 mmol). Tem-
perature = 130 °C; time = 35 min; power = 100 W. Chromatography:
silica (19.0 g), hexane/THF (gradient 40:60−50:50). Rf = 0.46
(hexane/THF 60:40). Yield = 0.13 g of a white powder (80%), mp =
234−237 °C. Anal. Calcd for C29H21F6O2P: C, 63.74; H, 3.87. Found:
1
C, 63.65; H, 3.85. Spectral data: H (CDCl3, 25 °C) δ 8.12 (m, 2H),
7.84 (m, 2H), 7.78 (m, 2H), 7.63 (m, 2H), 7.53 (m, 3H), 7.39 (m,
4H), 7.16 (m, 3H), 4.58 (ddd, 1H, J = 9.3, 6.6, 2.7), 3.98 (ddd, 1H, J =
15.0, 9.6, 5.4), 3.40 (ddd, 1H, J = 15.0, 12.0, 2.8); 13C{1H} (CDCl3, 25
°C) δ 196.1 (d, J = 12.2), 136.1 (s), 135.5 (d, J = 98.2), 135.4 (d, J =
92.5), 135.1 (d, J = 5.6), 134.2 (qd, J = 33.1, 2.8), 133.7 (s), 133.6 (qd,
J = 32.6, 2.7), 131.8 (d, J = 8.9), 131.4 (d, J = 8.9), 129.8 (d, J = 6.2),
128.7 (d, J = 2.7), 128.7 (s), 128.1 (s), 127.6 (d, J = 2.3), 126.0 (dq,
J = 11.3, 3.7), 125.2 (dq, J = 11.8, 3.9), 123.4 (q, J = 272.5), 40.7 (d,
J = 70.1), 38.9 (s); 31P{1H} (CDCl3, 25 °C) δ 32.5 (s)
3-[Bis(2-methylphenyl)phosphinyl]-1,3-diphenyl-1-propa-
none (31). The general procedure (method A) was followed with
(E)-1,3-diphenyl-2-propenone (0.091 g, 0.44 mmol) and bis(2-methyl
phenylphosphine oxide (0.10 g, 0.43 mmol). Temperature = 130 °C;
(d, 1H, J = 7.5), 2.39 (s, 6H), 1.49 (d, 6H, J = 15.5), 1.19 (d, 6H, J =
7.2); 13C{1H} (CDCl3, 25 °C) δ 167.1 (d, J = 10.4), 142.1 (d, J = 2.7),
1384
dx.doi.org/10.1021/jo202183u | J. Org. Chem. 2012, 77, 1378−1385

The Journal of Organic Chemistry
Article
time = 35 min; power = 100 W. Chromatography: silica (19.0 g),
hexane/THF (50:50). Rf = 0.69 (hexane/THF 50:50). Yield = 0.17 g
of a white powder (89%), mp = 140−142 °C. Anal. Calcd for
C29H27O2P: C, 79.43; H, 6.21. Found: C, 79.16; H, 6.32. Spectral data:
1H (CDCl3, 25 °C) δ 7.92 (m, 2H), 7.82 (m, 1H), 7.51 (m, 2H), 7.39
(m, 5H), 7.29 (m, 1H), 7.20 (m, 2H), 7.11−7.01 (m, 4H), 6.93 (m,
1H), 4.69 (ddd, 1H, J = 10.5, 6.9, 1.9), 4.18 (ddd, 1H, J = 18.6, 10.8,
3.8), 3.71 (ddd, 1H, J = 18.6, 10.8, 2.0), 2.39 (s, 3H), 2.15 (s, 3H);
13C{1H} (CDCl3, 25 °C) δ 197.0 (d, J = 13.0), 143.3 (d, J = 7.4),
141.8 (d, J = 8.5), 136.6 (d, J = 4.5), 136.5 (s), 133.4 (s), 132.7 (d, J =
10.7), 132.5 (d, J = 10.1), 131.8 (d, J = 2.7), 131.2 (s), 131.2 (d, J =
13.0), 131.1 (d, J = 92.0), 131.0 (d, J = 10.1), 130.1 (d, J = 96.5), 129.7
(d, J = 5.6), 128.6 (s), 128.2 (s), 127.0 (d, J = 2.9), 125.6 (d, J = 11.2),
125.0 (d, J = 12.4), 39.9 (s), 39.5 (d, J = 69.5), 21.4 (d, J = 3.9), 21.0
(d, J = 3.5); 31P{1H} (CDCl3, 25 °C) δ 37.8 (s).
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H, 13C{1H}, and 31P{1H} NMR spectra for all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: rstockla@bucknell.edu.
ACKNOWLEDGMENTS
■
The authors thank the Petroleum Research Fund (43494-B10),
the Camille and Henry Dreyfus Foundation (New Faculty
Award: SU-00-020), NSF (NMR spectrometers; CHE-
0521108), and Bucknell University (HKL, AFC, MER
(Gebhardt Fellowship), and KPR; and a scholarly development
grant to RASJ) for support of this work.
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Shen, S.; Varsolona, R.; Wei, X.; Senanayake, C. H. Org. Lett. 2005, 7,
4277−4280.
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