Driving the Morita-Baylis-Hillman reaction to a multicomponent organic transformation

Article abstract of DOI:10.1002/ejoc.201301226

The combination of a trivalent phosphorus reagent with an aldehyde and a Michael olefin in the presence of water led to the formation of functionalized phosphine oxides. This approach turned the Lewis base organocatalyzed Morita-Baylis-Hillman reaction into a multicomponent organic transformation to provide rapid access to polyfunctionalized molecules.

Full text of DOI:10.1002/ejoc.201301226

FULL PAPER
DOI: 10.1002/ejoc.201301226
Driving the Morita–Baylis–Hillman Reaction to a Multicomponent Organic
Transformation
Anne-Françoise Guillouzic,[a] Sonia Montel,[a] Coralie Laborde,[a] Jean-Noël Volle,[a]
Jean-Luc Pirat,*[a] and David Virieux*[a]
Keywords: Multicomponent reactions / Domino reactions / Phosphorus / Alkenes / Aldehydes
The combination of a trivalent phosphorus reagent with an
aldehyde and a Michael olefin in the presence of water led
to the formation of functionalized phosphine oxides. This ap-
proach turned the Lewis base organocatalyzed Morita–
Baylis–Hillman reaction into a multicomponent organic
transformation to provide rapid access to polyfunctionalized
molecules.
formation of organophosphorus building blocks.[20] In the
early seventies, the Morita–Baylis–Hillman reaction (MBH
reaction) became the prototype of organocatalyzed trans-
formations.[21–29] Although the MBH reaction was for a
long time an isolated case, numerous examples emerged
during recent years, which deeply broaden the scope of the
success story of organocatalysis.[30–32] To date, the longest
organocatalyzed sequence was initiated by triphenylphos-
phine, which demonstrates the interest for trivalent phos-
phorus reagents in such processes.[33]
By careful examination of the structural characteristics
of the different partners, we envisioned that the course of
such an organocatalytic reaction could be deeply affected
by minor modifications to the trivalent phosphine catalyst
and transform it into a multicomponent procedure. The
Lewis base behavior of phosphines has been significantly
studied with regard to the development of catalytic reac-
tions.[34] More generally, the nucleophilic properties of tri-
valent phosphorus derivatives highly depend on the nature
of the substituents on the phosphorus atom along with their
leaving group character.[35,36] In this regard, heterophos-
phines such as aminophosphines and tricoordinate phos-
phorus esters appear to be model reactants to avoid the
elimination step of the phosphorus nucleophile in the cata-
lytic MBH process and develop a multicomponent reaction
to create both C–C and C–P bonds. Such a process should
benefit from the low stability of hetero- or pseudophos-
phonium intermediates compared to the phosphonium spe-
cies generally encountered in the MBH reaction.[37] More-
over, this one-step procedure could be advantageous com-
pared to the two- or three-step sequences that involve the
formation of the MBH adduct followed by the reaction of
the trivalent phosphorus reagent and then rearrange-
ment.[38–45]
Introduction
Organophosphorus compounds are attracting a lot of at-
tention from industrial and academic standpoints because
of their potent biological activities,[1] their ligand/catalyst
capabilities, and their specific behaviors with regard to ma-
terials science.[2] One striking area of interest can be attrib-
uted to the relative stability of the P–C bond, which remains
inert over a wide range of conditions and is formed in a
relatively straightforward manner compared to other car-
bon–heteroatom bonds. Short synthetic methods for the
preparation of highly functionalized compounds without
the need to incorporate protecting groups remain a chal-
lenge for organic chemists. In response to this, multicompo-
nent reactions (MCR) have attracted increasing interest be-
cause of the significant preparative advantages over step-
by-step procedures.[3–11] Often atom-economical, these
methods take advantage of simple or readily affordable re-
actants and increase their molecular complexity and struc-
tural diversity. With the exception of the widely used three-
component Kabachnik–Fields reaction for the preparation
of α-aminoalkylphosphorus derivatives, there are very few
reported MCR in the field of phosphorus chemistry.[12–19]
Recently, Smietana et al. introduced the Bestmann–Ohira
reagent for the regioselective synthesis of phosphonyl pyr-
azoles through a three-component reaction (i.e., 3-MCR),
which demonstrates the interest in this procedure for the
[a] Institut Charles Gerhardt – UMR 5253, Ecole Nationale
Supérieur de Chimie de Montpellier,
8, Rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France
E-mail: jean-luc.pirat@enscm.fr
david.virieux@enscm.fr
www.enscm.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301226.
788
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 788–796

Driving the Morita–Baylis–Hillman Reaction
(γ-hydroxyalkyl)phosphine oxides 4–12. The presence of
water appeared to have a deep influence on the course of
the reaction and drove the formation of the desired phos-
phine oxides. The reaction was general with non-enolizable
aromatic aldehydes and afforded the corresponding carbox-
ylic esters, cyanides, methyl ketones, and amides in isolated
yields of up to 86%. By contrast, phenylacetaldehyde gave
phosphine oxide 10 in 15% yield. Similarly, the reaction
with paraformaldehyde afforded the desired adduct 11 in
11% isolated yield. A synthesis on a 10 g scale was also
attempted using ethyl acrylate, (trifluoromethyl)benzalde-
hyde, and (diethylamino)diphenylphosphine to evaluate the
robustness of our process. Under such conditions, purifica-
tion by chromatography could be avoided, and the resulting
phosphine oxides were directly crystallized in the reaction
mixture to give pure 4 after filtration in 86% yield.
Results and Discussion
To achieve this goal, preliminary experiments were per-
formed using the highly nucleophilic (diethylamino)di-
phenylphosphine (i.e., 1; R1, R2 = Ph) in the presence of p-
(trifluoromethyl)benzaldehyde (i.e., 2; R3 = p-CF3C6H4)
and ethyl acrylate as the electron-deficient alkene 3 (see
Scheme 1). This attempt was quite disappointing and gave
an intriguing and highly complex reaction mixture. After 2
to 24 h of reaction time, more than 20 different phosphorus
products were observed as monitored by 31P NMR analysis
(see Figure 1). In the presence of stoichiometric amounts of
water and after the optimization of the reaction conditions,
we were pleased to observe the formation of the expected
In addition to the modification of Michael olefin 3 and
aldehyde 2, the four-component reaction was also carried
out with a tricoordinate phosphorus ester. The reaction of
diethyl phenylphosphonite afforded ethyl γ-hydroxyprop-
ylphosphinate 12 in 82% yield (by NMR analysis) and an
isolated yield of 50% after chromatography.
Another extension of the reaction involved electron-de-
ficient allenes 13 as the Michael olefin (see Scheme 2). The
reaction proceeded satisfactorily, but it required the use of
the Lewis acid ZrCl4 to activate the aldehyde and prevent
the polymerization of this highly reactive allene. Under
those conditions, vinylaminophosphonium chloride 14 was
formed in 76% yield. This compound was quite unstable
and was rapidly converted by air moisture at room tempera-
ture into phosphine oxide 15, which was finally isolated in
56% yield. No migration of the double bond was observed.
Scheme 1. Four-component synthesis of hydroxyalkylphosphine
oxides 4–12. The yields are given for the isolated product (EWG =
electron-withdrawing group).
Scheme 2. Extensions of the MCR reaction.
Another way to extend the scope of the present MCR
was to employ triphenylphosphine in the reaction. To cir-
cumvent the formation of the MBH adduct, the Michael
olefin should not have a proton at the α position, and we,
therefore, chose 2-chloroacrylonitrile (16) and allene 13 (see
Scheme 3). The reaction of the chloroacrylonitrile and tri-
phenylphosphine in the presence of ZrCl4 with various aro-
matic aldehydes gave the desired functionalized salts 17–
20 in isolated yields ranging from 54 to 81%. A second
experiment was conducted in the presence of allene 13.
Figure 1. 31P NMR spectra of the reaction of Ph2PNEt2, ethyl
acrylate, and trifluoromethylbenzaldehyde.
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J.-L. Pirat, D. Virieux et al.
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atom became more pronounced, and under these condi-
tions, we observed a competitive elimination that led mainly
to olefins 22 and 23.
These results and observations can be rationalized and
explained by the mechanism depicted in Scheme 5. Several
steps are commonly encountered during the MBH reaction.
The first one is the nucleophilic addition of the heterophos-
phine to electron-deficient alkene 24 to form phosphonio
enolate 25. As reported by McClure, the strong electrophilic
character of the pseudophosphonium function leads to the
formation of pentacoordinate oxaphosphoranes 26.[46–49]
The analysis of the reaction by 31P NMR clearly shows the
presence of the characteristic phosphorane signals at chemi-
cal shifts (δP) that ranged from –29.7 to –34.8 ppm (see Fig-
ure 1).[50,51] When phosphines are used as the organocata-
lyst, such intermediates are not observed in the MBH reac-
tion. In the second step, enolate 25 is trapped by the alde-
hyde to lead to alkoxide 27. Because 10 different pentacoor-
dinate phosphorus intermediates are observed in the reac-
tion mixture, it appears reasonable to postulate the forma-
tion of oxaphosphorane 28 at this stage too. The most
electrophilic phosphorus atom, with the two amino groups
attached, leads preferentially to acrylate 29 through an
E1cB mechanism, which is assisted by the formation of the
phosphoryl group. The presence of all these reactive inter-
mediates is also consistent with the Berry pseudorotation
mechanism, which can induce the formation of several dia-
stereomers of 26 and 28. Once water is added, the fully
equilibrated reaction system presumably shifts towards the
formation of phosphine oxide 34. For this to occur, an acid-
base reaction between alkoxide 27 and water leads to the
unstable hydroxyphosphorane 33, which readily collapses
upon elimination of diethylamine and forms of the stable
P=O bond, the effective driving force of the overall process.
Scheme 3. Reaction of phosphines Ϫ synthesis of polyfunction-
alized phosphonium salts.
Using the same conditions, we were pleased to observe the
formation of vinylphosphonium salt 21 in 80% yield, which
was finally isolated in 48% yield.
To complete this overview, the reactivity of bis(diethyl-
amino)phenylphosphine as a reagent was studied (see
Scheme 4). The electrophilic character of the phosphorus
Scheme 4. Bis(diethylamino)phenylphosphine reactivity.
Scheme 5. Proposed mechanism for synthesis of phosphine oxide 34 from (diethylamino)phosphines.
790
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Eur. J. Org. Chem. 2014, 788–796

Driving the Morita–Baylis–Hillman Reaction
NMR (250.13 MHz, CDCl3, major isomer): δ = 0.91 (t, 3J =
7.1 Hz, 3 H), 2.52 (ddd, 2J = 15.7 Hz, 3J = 7.6 Hz, 2JP,H = 14.7 Hz,
1 H), 2.75–2.82 (m, 1 H), 3.04–3.17 (m, 1 H), 3.69 and 3.77 (2 qd,
Conclusions
In summary, minor changes to the reaction conditions or
reagents with similar reactivity can have a significant im- 2J = 10.7 Hz, J = 7.1 Hz, J = 7.1 Hz, 2 H), 5.02 (d, J = 6.6 Hz,
pact on the course of chemical transformations. We have
demonstrated that the use of heterophosphines or phos-
3
3
3
1 H), 5.49 (d, 3J = 6.6 Hz, OH), 7.40–7.80 (m, 14 H) ppm. 1H
NMR (250.13 MHz, CDCl3, minor isomer): δ = 1.08 (t, 3J =
7.2 Hz, 3 H), 2.75–2.82 (m, 2 H), 3.28–3.36 (m, 1 H), 3.87 and 3.98
phine/zirconium tetrachloride under the MBH reaction
2
3
3
(2 qd, J = 10.8 Hz, J = 7.1 Hz, J = 7.1 Hz, 2 H), 5.33 (m, 1 H),
conditions can lead to regioselective four- or three-compo-
nent reactions instead of an organocatalyzed process. The
characteristics of this new reaction allow the creation of
multifunctional organophosphorus building blocks in a sin-
gle operation and present a relatively large tolerance for the
starting reagents. From a conceptual point of view, this
5.40 (m, OH), 7.40–7.80 (m, 14 H) ppm. 13C NMR (50.32 MHz,
1
CDCl3, major isomer): δ = 13.49 (s), 28.91 (d, JP.C = 70.7 Hz),
47.97 (d, 2JP,C = 2.6 Hz), 60.94 (s), 74.64 (d, 3JP,C = 7.8 Hz), 124.07
1
3
(q, JF,C = 272.2 Hz), 125.07 (q, JF,C = 3.6 Hz), 127.00 (s), 128.66
(d, JP,C = 11.9 Hz), 128.72 (d, JP,C = 11.9 Hz), 130.29 (q, JF,C
32.1 Hz), 130.59 (d, JP,C = 9.7 Hz), 131.06 (d, JP,C = 9.3 Hz),
3
3
2
=
2
2
4
1
methodology could be extended to any reaction in which 132.08 (d, JP,C = 2.4 Hz), 132.60 (d, JP,C = 101.2 Hz), 132.75 (d,
1JP,C = 102.2 Hz), 145.67 (m), 172.46 (d, JP,C = 6.7 Hz) ppm. 13C
3
phosphines have been implemented as Lewis base organo-
catalysts and provide rapid access to polyfunctionalized
NMR (50.32 MHz, CDCl3, minor isomer): δ = 13.74 (s), 27.60 (d,
3
1JP,C = 71.1 Hz), 46.54 (s), 61.25 (s), 73.52 (d, JP,C = 6.3 Hz),
molecules of interest.
1
3
124.07 (q, JF,C = 272.2 Hz), 125.07 (q, JF,C = 3.6 Hz), 126.62 (s),
3
2
128.79 (d, JP,C = 11.9 Hz), 130.10 (q, JF,C = 32.1 Hz), 130.49 (d,
2JP,C = 9.7 Hz), 131.13 (d, JP,C = 9.3 Hz), 131.15 (d, JP, C
=
2
1
Experimental Section
1
4
99.8 Hz), 131.59 (d, JP,C = 100.3 Hz), 132.20 (d, JP,C = 2.4 Hz),
145.28 (m), 172.14 (d, JP,C = 9.7 Hz) ppm. IR (solid, KBr): ν =
3
General Methods: Anhydrous reactions were carried out in glass-
ware that was dried under vacuum in anhydrous solvents under
nitrogen. TLC plates were made from silica gel 60 F254 on alumi-
num sheets (Merck). The 1H NMR spectroscopic data were re-
˜
3350, 3206, 3061, 2978, 2956, 2955, 2919, 2879, 1727, 1619, 1590,
1475, 1437, 1376, 1323, 1273, 1182, 1163, 1133, 1116, 1066, 1016,
996, 982, 946, 889, 857, 839, 810, 784, 758, 746, 723, 696, 657, 607,
555, 520 cm–1. MS (FAB+): m/z (%) = 499 (10) [M + Na]+, 477
(100) [M + H]+, 459 (8) [M – OH]+, 413 (10), 387 (4) [M – OH –
CO2Et]+, 257 (10) [M – H2O – Ph2PO]+, 215 (20) [Ph2POCH2]+,
201 (70) [Ph2PO]+. HRMS (FAB+): calcd. for [C25H25F3O4P]+
477.1443; found 477.1445.
corded with
a Bruker AC-200 (200.13 MHz), Avance 250
(250.13 MHz), or Avance 400 (400.13 MHz) spectrometer. Chemi-
cal shifts are reported in δ (ppm). Residual peaks of the deuterated
solvents were used as internal standards. The abbreviations used to
characterize the multiplicity of the signals are s (singlet), br. s
(broad singlet), d (doublet), t (triplet), and m (multiplet). The spec-
tra were interpreted as first-order spectra. Coupling constants (J)
are given in Hertz (Hz). The 13C NMR spectroscopic data were
[2-Cyano-3-hydroxy-3-(4Ј-trifluoromethylphenyl)]propyldiphenyl-
phosphine Oxide (5): According to the general procedure, 5 was
obtained from the reaction between acrylonitrile (196 mg,
1.0 equiv.), Ph2PNEt2 (950 mg, 1 equiv.), and p-trifluorobenzal-
dehyde (642 mg, 1.0 equiv.) for 30 h. The resulting solid was dis-
solved in CH2Cl2 (60 mL), and the organic layer was washed with
an aqueous solution of HCl (10%, 3ϫ 20 mL) and then dried with
Na2SO4. After filtration and evaporation under reduced pressure,
5 (650 mg, 43% yield, 62%de) was isolated as a white solid; m.p.
169 °C. 31P NMR (101.25 MHz, CDCl3, major isomer): δ = 33.09
(81%) ppm. 31P NMR (101.25 MHz, CDCl3, minor isomer): δ =
33.47 (19%) ppm. 19F NMR (188.31 MHz, CDCl3, major isomer):
δ = –62.94 ppm. 19F NMR (188.31 MHz, CDCl3, minor isomer): δ
recorded with
a Bruker AC-200 (50.32 MHz), Avance 250
(62.90 MHz), or Avance 400 (101.61 MHz) spectrometer. The 31P
NMR spectroscopic data were recorded with Bruker AC-200
(81.01 MHz) and Avance 250 (101.25 MHz) spectrometers. The 19
F
NMR spectroscopic data were recorded with a Bruker AC-200
(188.31 MHz) spectrometer. Mass spectra were recorded with a
JEOL JMS DX-300 mass spectrometer in the positive FAB ioniza-
tion mode with the p-nitrobenzyl alcohol. Elemental analyses were
determined with a Thermofinnigan Flash EA 1112 apparatus.
General Procedure for the Synthesis of Compounds 4–12: To a mix-
ture of the electron-deficient alkene (1 m solution, from 1.0 to
1.5 equiv.) and (diethylamino)diphenylphosphine (1.0 equiv.) in an-
hydrous CH2Cl2 was added dropwise at 20 °C over 20 min a solu-
tion of the aldehyde (1 m solution, from 1.0 to 1.4 equiv.) in anhy-
drous CH2Cl2 followed by the addition of water (1.0 equiv.). The
reaction was monitored by 31P NMR spectroscopy. Upon comple-
tion, the reaction mixture was poured into hexane. The resulting
precipitate was removed by filtration, washed with hexane, and
dried under reduced pressure in presence of P2O5 to give the desired
compound as a mixture of two diastereomers.
1
= –62.97 ppm. H NMR (250.13 MHz, CDCl3, major isomer): δ =
2.54–2.83 (m, 1 H), 2.92–3.11 (m, 1 H), 3.20–3.31 (m, 1 H), 5.38
(m, 1 H), 6.16 (br. d, 1 H, OH), 7.40–7.62 (m, 14 H) ppm. 1H NMR
(250.13 MHz, CDCl3, minor isomer): δ = 2.54–2.83 (m, 2 H), 3.39
2
3
3
3
(dtd, JP,H = 13.8 Hz, J = 6.7 Hz, J = 6.7 Hz, 1 H), 5.16 (d, J =
6.7 Hz, 1 H), 7.40–7.62 (m, 14 H) ppm. 13C NMR (62.89 MHz,
CDCl3, major isomer): δ = 29.44 (d, JP,C = 69.6 Hz), 35.44 (s),
1
3
3
71.72 (d, JP,C = 3.8 Hz), 118.74 (d, JP,C = 13.0 Hz), 124.40 (q,
1JF,C = 272.1 Hz), 125.87 (q, JF,C = 3.8 Hz), 126.99 (s), 129.46 (d,
3
3JP,C = 12.0 Hz), 129.67 (d, JP,C = 12.0 Hz), 130.14 (q, JF,C
=
3
2
2
1
[2-Ethoxycarbonyl-3-hydroxy-3-(4Ј-trifluoromethylphenyl)]propyl- 32.6 Hz), 130.80 (d, JP,C = 10.1 Hz), 131.01 (d, JP,C = 97.4 Hz),
2
4
diphenylphosphine Oxide (4): According to the general procedure,
the reaction between ethyl acrylate (406 mg, 1.1 equiv.), Ph2PNEt2
(642 mg, 1.0 equiv.), and p-trifluorobenzaldehyde (950 mg,
1.0 equiv.) for 7 h gave compound 4 (1.49 g, 86% yield, 14%de) as
131.46 (d, JP,C = 9.6 Hz), 133.13 (d, JP,C = 2.9 Hz), 133.21 (d,
4JP,C = 2.4 Hz), 144.92 (s) ppm. 13C NMR (62.89 MHz, CDCl3,
1
2
minor isomer): δ = 28.98 (d, JP,C = 69.6 Hz), 34.77 (d, JP,C
=
2.9 Hz), 73.52 (d, 3JP,C = 6.2 Hz), 119.18 (d, 3JP,C = 8.2 Hz), 124.40
a white solid; m.p. 199–201 °C. 31P NMR (81.01 MHz, CDCl3, (q, JF,C = 272.1 Hz), 125.87 (q, JF,C = 3.8 Hz), 127.74 (s), 129.48
1
3
3
3
2
major and minor isomer): δ = 33.72 ppm. 19F NMR (188.31 MHz,
CDCl3, major isomer): δ = –62.94 (s, 57 %) ppm. 19F NMR
(188.31 MHz, CDCl3, minor isomer): δ = –62.91 (s, 43%) ppm. H
(d, JP,C = 12.0 Hz), 129.50 (d, JP,C = 12.0 Hz), 130.50 (q, JF,C =
2
1
32.6 Hz), 131.00 (d, JP,C = 10.1 Hz), 131.36 (d, JP,C = 103.2 Hz),
131.37 (d, 2JP,C = 9.6 Hz), 133.14(d, 4JP,C = 2.9 Hz), 133.31 (d, 4JP,C
1
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791

J.-L. Pirat, D. Virieux et al.
FULL PAPER
= 2.9 Hz), 144.21 (s) ppm. IR (solid, KBr): ν = 3257, 3058, 2919,
minor isomer): δ = 1.08 (t, 3J = 7.1 Hz, 3 H), 2.48 (ddd, 2J =
15.5 Hz, 2JP,H = 13.9 Hz, 3J = 6.6 Hz, 1 H), 2.78 (ddd, 2J = 15.5 Hz,
2JP,H = 8.5 Hz, 3J = 6.7 Hz, 1 H), 3.30 (m, 3J = 6.6 Hz, 3J = 6.7 Hz,
˜
2850, 2242, 1733, 1618, 1588, 1485, 1440, 1419, 1324, 1246, 1176,
1119, 1067, 1014, 998, 932, 907, 855, 805, 780, 745, 721, 696, 657,
616, 602, 546, 520, 509 cm–1. MS (FAB+): m/z (%) = 430 (100) [M 3JP,H = 11.9 Hz, 3J = 5.0 Hz, 1 H), 3.84 (qd, 2J = 10.7 Hz, 3J =
+ H]+, 412 (20) [M – OH]+, 215 (14) [M – Ph2POCH2 + H]+, 201 7.1 Hz, 1 H), 3.96 (qd, J = 10.7 Hz, J = 7.1 Hz, 1 H), 4.81 (dl,
2
3
(25) [Ph2PO]+. C23H19F3NO2P (429.36): calcd. C 64.34, H 4.46, N 3J = 8.0 Hz, OH), 5.18 (dd, J = 8.0 Hz, J = 3.8 Hz, 1 H), 7.31–
3
3
3.26; found C 64.08, H 4.40, N 3.44.
7.79 (m, 15 H) ppm. 13C NMR (100.61 MHz, CDCl3, major iso-
1
2
mer): δ = 13.61 (s), 28.67 (d, JP,C = 71.1 Hz), 47.98 (d, JP,C
=
[2-(Dimethylamino)carbonyl-3-hydroxy-3-(4Ј-trifluoromethyl-
phenyl)]propyldiphenylphosphine Oxide (7): According to the gene-
ral procedure, 7 was obtained from the reaction between N,N-di-
methylacrylamide (446 mg, 1.5 equiv.), Ph2PNEt2 (772 mg,
1.0 equiv.), and p-trifluorobenzaldehyde (522 mg, 1.0 equiv.), which
was heated at reflux in tetrahydrofuran (THF) for 4 d. After fil-
tration, the mother liquor was concentrated, and the residue dis-
solved in a mixture of hexane/CH2Cl2 (90:10). The resulting pre-
cipitate was filtered. Both fractions of the solid were combined and
dried with P2O5 under reduced pressure to give 7 (340 mg, 26%
yield, 74 % de) as a white solid; m.p. 253 °C. 3 1 P NMR
(101.25 MHz, CDCl3, major isomer): δ = 32.76 (87%) ppm. 31P
NMR (101.25 MHz, CDCl3, minor isomer): δ = 31.31 (13%) ppm.
19F NMR (188.31 MHz, CDCl3): δ = –62.83 ppm. 1H NMR
(250.13 MHz, CDCl3, major isomer): δ = 2.44–2.57 (m, 1 H), 2.52
(s, 3 H), 2.77 (s, 3 H), 2.89–3.05 (m, 1 H), 3.39–3.50 (m, 1 H), 4.99
(d, 3J = 4.3 Hz, 1 H) 5.32 (br. s, OH), 7.35–7.85 (m, 14 H) ppm.
1H NMR (250.13 MHz, CDCl3, minor isomer): δ = 2.25 (s, 3 H),
2.46 (s, 3 H), 2.89–3.05 (m, 1 H), 3.13–3.26 (m, 1 H), 3.60–3.80 (m,
3
2.4 Hz), 60.77 (s), 75.23 (d, JP,C = 8.6 Hz), 126.58 (s), 127.77 (s),
128.22 (s), 128.68 (d, JP,C = 11.6 Hz), 131.11 (d, JP,C = 9.8 Hz),
3
2
2
4
131.16 (d, JP,C = 9.8 Hz), 131.89 (d, JP,C = 3.1 Hz), 132.63 (d,
1JP,C = 74.8 Hz), 132.68 (d, JP,C = 80.9 Hz), 141.46 (s), 172.82 (d,
1
3JP,C = 5.5 Hz) ppm. 13C NMR (100.61 MHz, CDCl3, minor iso-
1
2
mer): δ = 13.83 (s), 27.93 (d, JP,C = 71.1 Hz), 46.66 (d, JP,C
=
3
1.8 Hz), 61.10 (s), 74.69 (d, JP,C = 8.0 Hz), 126.34 (s), 127.72 (s),
128.30 (s), 128.58 (d, JP,C = 11.6 Hz), 128.72 (d, JP,C = 12.3 Hz),
3
3
2
2
130.63 (d, JP,C = 8.6 Hz), 130.72 (d, JP,C = 8.6 Hz), 131.30 (d,
1JP,C = 99.3 Hz), 131.77 (d, JP,C = 99.3 Hz), 132.01 (d, JP,C
=
1
4
2.4 Hz), 141.00 (s), 172.73 (d, 3JP,C = 8.6 Hz) ppm. IR (solid, KBr):
ν = 3239, 3057, 2973, 1726, 1654, 1438, 1396, 1317, 1181, 1166,
˜
1145, 1116, 1099, 1056, 1025, 834, 781, 747, 723, 696, 668, 560,
533, 518 cm–1. MS (FAB+): m/z (%) = 409 (90) [M + H]+, 391 (20)
[M – OH]+, 345 (18) [M – OH – OC2H5]+, 201 (18) [Ph2PO]+.
HRMS (FAB+): calcd. for [C24H26O4P]+ 409.1569; found 409.1563.
(2-Cyano-3-hydroxy-3-phenyl)propyldiphenylphosphine Oxide (9):
According to the general procedure, 9 was obtained in 4 d from the
reaction between acrylonitrile (2.14 g, 1.1 equiv.), Ph2PNEt2
(9.42 g, 1.0 equiv.), and benzaldehyde (3.88 g, 1.0 equiv.). The crude
product was purified by flash column chromatography on silica gel
(hexane/ethyl acetate, 30:70 then CH2Cl2/EtOH, 60:40) to afford 9
(4.04 g, 30% yield, 76%de) as a white solid; m.p. 202 °C. 31P NMR
{161.97 MHz, [D6]DMSO (deuterated dimethyl sulfoxide), major
isomer}: δ = 27.99 (88 %) ppm. 31P NMR (161.97 MHz, [D6]-
DMSO, minor isomer): δ = 28.13 (12 %) ppm. 1 H NMR
(400.13 MHz, [D6]DMSO, major isomer): δ = 2.58 (ddd, 2J =
15.4 Hz, 2JP,H = 13.1 Hz, 3J = 3.9 Hz, 1 H), 2.71 (ddd, 2J = 15.4 Hz,
2JP,H = 8.3 Hz, 3J = 10.3 Hz, 1 H), 3.25 (m, 3J = 3.9 Hz, 3J =
3
3
1 H), 4.85 (dl, J = 8.5 Hz, 1 H), 5.62 (d, J = 8.5 Hz, OH), 7.35–
7.85 (m, 14 H) ppm. 13C NMR (100.61 MHz, CDCl3, major iso-
1
mer): δ = 27.22 (d, JP,C = 71.9 Hz), 35.48 (s), 37.67 (s), 41.09 (d,
2JP,C = 2.7 Hz), 74.02 (d, JP,C = 10.3 Hz), 124.10 (q, JF,C
=
=
3
1
3
3
272.0 Hz), 125.26 (q, JF,C = 3.9 Hz), 126.48 (s), 128.50 (d, JP,C
12.2 Hz), 128.75 (d, JP,C = 12.2 Hz), 129.83 (q, JF,C = 32.6 Hz),
3
2
2
2
130.22 (d, JP,C = 9.4 Hz), 130.85 (d, JP,C = 9.4 Hz), 131.70 (d,
1JP,C = 98.4 Hz), 131.90 (d, JP,C = 2.8 Hz), 131.97 (d, JP, C
=
4
4
1
3
2.8 Hz), 132.92 (d, JP,C = 100.6 Hz), 145.06 (m), 173.34 (d, JP,C
= 2.8 Hz) ppm. 13C NMR (100.61 MHz, CDCl3, minor isomer): δ
1
2
= 31.46 (d, JP,C = 70.8 Hz), 34.89 (s), 37.37 (s), 39.67 (d, JP,C
2.2 Hz), 76.24 (d, JP,C = 11.6 Hz), 124.10 (q, JF,C = 272.0 Hz),
125.17 (q, JF,C = 3.9 Hz), 125.72 (s), 128.44 (d, JP,C = 11.6 Hz),
=
3
1
3
3
3
10.3 Hz, J = 5.2 Hz, JP,H = 11.2 Hz, 1 H), 4.95 (dd, J = 5.2 Hz,
3
3
3J = 4.6 Hz, 1 H), 6.25 (d, 3J = 4.6 Hz, OH), 7.26–7.90 (m, 15
3
2
128.88 (d, JP,C = 11.6 Hz), 129.83 (q, JF,C = 32.6 Hz), 130.24 (d,
1
H) ppm. H NMR (400.13 MHz, [D6]DMSO, minor isomer): δ =
2JP,C = 9.4 Hz), 130.96 (d, JP,C = 9.4 Hz), 132.03 (d, JP, C
=
2
4
2
2
3
2.80 (ddd, J = 15.4 Hz, JP,H = 12.8 Hz, J = 5.2 Hz, 1 H), 3.02
4
1
2.8 Hz), 132.09 (d, JP, C = 3.3 Hz), 132.30 (d, JP, C = 99.0 Hz),
133.47 (d, JP,C = 100.1 Hz), 146.64 (sl), 172.61 (d, JP, C
2
2
3
3
(ddd, J = 15.4 Hz, JP,H = 8.5 Hz, J = 8.5 Hz, 1 H), 3.12 (m, J
= 5.2 Hz, 3J = 8.5 Hz, 3J = 4.3 Hz, 3JP,H = 10.6 Hz, 1 H), 4.96 (dd,
3J = 4.3 Hz, 3J = 4.7 Hz, 1 H), 6.25 (d, 3J = 4.7 Hz, OH), 7.26–
7.90 (m, 15 H) ppm. 13C NMR (100.61 MHz, [D6]DMSO, major
isomer): δ = 27.53 (d, JP,C = 70.3 Hz), 33.94 (d, JP,C = 3.7 Hz),
72.71 (d, JP,C = 10.2 Hz), 119.69 (d, JP,C = 4.4 Hz), 127.30 (s),
1
3
=
2.2 Hz) ppm. IR (solid, KBr): ν = 3406, 3214, 3062, 2946, 1634,
˜
1487, 1438, 1418, 1399, 1384, 1326, 1161, 1119, 1068, 1016, 881,
853, 809, 744, 724, 697, 658, 603, 556, 524 cm–1. MS (FAB+): m/z
(%) = 476 (100) [M + H]+, 431 (16) [M – Me2N]+, 413 (14) [M –
Me2N – H2O]+, 201 (28) [Ph2PO]+. C25H25F3NO3P (475.45): calcd.
C 63.16, H 5.30, N 2.95; found C 63.16, H 5.59, N 3.00.
1
2
3
3
3
3
128.50 (s), 128.59 (s), 129.17 (d, JP,C = 11.7 Hz), 129.32 (d, JP,C
= 11.0 Hz), 130.74 (d, JP,C = 9.5 Hz), 131.12 (d, JP,C = 9.5 Hz),
2
2
4
1
(2-Ethoxycarbonyl-3-hydroxy-3-phenyl)propyldiphenylphosphine 132.50 (d, JP,C = 2.2 Hz), 132.84 (d, JP,C = 98.1 Hz), 133.48 (d,
Oxide (8): According to the general procedure, 8 was obtained from
the reaction between ethyl acrylate (3.30 g, 1.1 equiv.), Ph2PNEt2
(7.98 g, 1.0 equiv.), and benzaldehyde (3.29 g, 1.0 equiv.) for 24 h.
The crude product was purified by flash column chromatography
on silica gel (hexane/ethyl acetate, 20:80 then CH2Cl2/EtOH, 90:10)
to afford 8 (4.28 g, 35% yield, 14%de); m.p. 141 °C. 31P NMR
1JP,C = 99.5 Hz), 140.93 (s) ppm. 13C NMR (100.61 MHz, [D6]-
1
DMSO, minor isomer): δ = 29.02 (d, JP,C = 69.5 Hz), 35.29 (d,
2JP,C = 3.7 Hz), 72.50 (d, 3JP,C = 8.8 Hz), 119.11 (d, 3JP,C = 6.6 Hz),
126.34 (s), 128.23 (s), 128.65 (s), 129.21 (d, 3JP,C = 12.4 Hz), 129.32
3
2
2
(d, JP,C = 11.0 Hz), 130.77 (d, JP,C = 8.8 Hz), 131.14 (d, JP,C
=
4
1
9.5 Hz), 132.47 (d, JP, C = 2.2 Hz), 132.41 (d, JP, C = 82.7 Hz),
(101.25 MHz, CDCl3, major isomer): δ = 33.79 (57%) ppm. 31P 133.80 (d, JP,C = 84.2 Hz), 142.25 (s) ppm. IR (solid, KBr): ν =
1
˜
NMR (101.25 MHz, CDCl3, minor isomer): δ = 34.00 (43%) ppm. 3244, 3080, 3059, 3026, 2960, 2917, 2243, 1590, 1487, 1449, 1435,
1H NMR (250.13 MHz, CDCl3, major isomer): δ = 0.90 (t, 3J =
1410, 1334, 1230, 1193, 1180, 1154, 1124, 1089, 1069, 1040, 1026,
2
7.1 Hz, 3 H), 2.78–2.85 (m, 2 H), 3.06–3.19 (m, 1 H), 3.67 (qd, J 998, 872, 836, 811, 799, 758, 747, 740, 721, 693, 528, 510 cm–1. MS
3
2
3
= 10.7 Hz, J = 7.1 Hz, 1 H), 3.76 (qd, J = 10.7 Hz, J = 7.1 Hz, (FAB+): m/z (%) = 723 (5) [2M + H]+, 362 (100) [M + H]+, 344
1 H), 4.75 (dl, 3J = 3.8 Hz, OH), 4.95 (dd, 3J = 6.8 Hz, 3J = 3.8 Hz,
(40) [M – OH]+, 201 (15) [Ph2PO]+. HRMS (FAB+): calcd. for
[C22H21O2NP]+ 362.1310; found 362.1314.
1 H), 7.31–7.79 (m, 15 H) ppm. 1H NMR (250.13 MHz, CDCl3,
792
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 788–796

Driving the Morita–Baylis–Hillman Reaction
(2-Cyano-3-hydroxy-3-benzyl)propyldiphenylphosphine Oxide (10): 2.89–3.33 (m, 1 H), 3.50–4.19 (m, 4 H), 4.77–5.26 (m, 2 H), 7.25–
According to the general procedure, 10 was obtained from the reac-
tion between acrylonitrile (265 mg, 1.0 equiv.), Ph2PNEt2 (1.28 g,
1.0 equiv.), and phenylacetaldehyde (841 mg, 1.0 equiv.) for 43 h. = 101.6 Hz), 28.09 (d, JP,C = 101.2 Hz), 28.23 (d, JP, C
7.65 (m, 9 H) ppm. 13C NMR (100.61 MHz, CDCl3): δ = 13.50,
13.61, 13.65, 13.81, 14.02, 14.08, 16.13, 16.27, 16.40, 27.92 (d, 1JP,C
1
1
=
After removal of solvent, the residual oil was purified by flash col-
umn chromatography on silica gel (hexane/ethyl acetate, from 50:50
to 30:70) to afford 10 (300 mg, 15% yield, 14%de) as a viscous oil.
31P NMR (81.02 MHz, CDCl3, major isomer): δ = 31.91
(57%) ppm. 31P NMR (81.02 MHz, CDCl3, minor isomer): δ =
101.2 Hz), 46.57, 47.70, 47.76, 47.90, 60.32, 60.71, 61.03, 61.07,
73.97, 74.20, 74.41, 125.84 (q, JF,C = 3.3 Hz), 126.70, 126.84,
3
126.87, 128.36, 128.80, 129.46, 130.11, 130.75, 130.80, 131.03,
131.23 (m), 131.38, 131.85 (m), 132.42, 132.86, 145.38, 145.72,
172.07, 172.44 (m) ppm. MS (FAB+): m/z (%) = 445 (100) [M +
H]+, 428 (25) [M – OH]+, 399 (30) [M – OEt]+, 353 (38) [M –
CO2Et – H2O]+, 271 (10) [M – F3CPhCHO + 1]+. HRMS (FAB+):
1
31.77 (43%) ppm. H NMR (250.13 MHz, CDCl3): δ = 2.38–3.45
(m, 5 H), 4.02–4.19 (m, 1 H, major), 4.19–4.40 (m, 1 H, minor),
4.80 (sl, OH), 7.05–7.95 (m, 15 H) ppm. 13C NMR (62.89 MHz, calcd. for [C21H25F3O5P]+ 445.1392; found 445.1402.
1
1
CDCl3): δ = 29.13 (d, JP,C = 70.1 Hz, minor), 29.26 (d, JP,C
=
Methyl 2-[(4Ј-Trifluoromethylphenyl)hydroxymethyl]-3-dieth-
ylamino-diphenylphosphoniobut-3-enoate Chloride (14): To a mix-
ture of p-trifluoromethylbenzaldehyde (835 μL, 1.0 equiv.,
6.11 mmol) and Ph2PNEt2 (1.57 g, 1.0 equiv.) in dry dichlorometh-
ane (15 mL) at –40 °C under nitrogen was added ZrCl4 (1.42 g,
1.0 equiv.) in a suspension. A solution of methyl 2,3-butadienoate
(594 mg, 1.0 equiv.) in dry dichloromethane (5 mL) was then added
dropwise at –40 °C over 15 min. The reaction mixture was stirred
at –40 °C for 4 h and then warmed to room temperature overnight.
After hydrolysis with water (15 mL), the aqueous phase was washed
with CH2Cl2 (2 ϫ 10 mL). The combined organic layers were
washed with water (10 mL), dried with Na2SO4, and then filtered,
and the solvent was removed under reduced pressure. The resulting
oil was triturated with pentane until there was crystallization. The
2
70.1 Hz, major), 32.19 (s, major), 32.40 (d, JP,C = 3.4 Hz, minor),
3
40.93 (s, minor), 41.96 (s, major), 71.86 (d, JP,C = 4.8 Hz, major),
73.01 (d, 3JP,C = 7.7 Hz, minor), 119.30 (d, 3JP,C = 12.5 Hz, major),
3
119.96 (d, JP,C = 5.8 Hz, minor), 127.04, 127.08, 128.87, 129.06,
129.31, 129.35, 129.50, 129.54, 129.60, 130.03, 130.89, 131.06,
131.12, 131.21, 131.31, 131.41, 131.47, 131.56, 132.91, 133.05,
1
1
130.95 (d, JP,C = 101.2 Hz, major), 131.93 (d, JP,C = 102.2 Hz,
minor), 137.55 (s, major), 137.87 (s, minor) ppm. IR (film, KBr): ν
˜
= 3281, 3054, 2986, 2305, 1592, 1495, 1438, 1422, 1265, 1177, 1121,
1074, 1046, 998, 896, 703, 704, 544, 513 cm–1. MS (FAB+): m/z (%)
= 376 (100) [M + H]+, 358 (16) [M – H2O]+, 284 (14) [M –
PhCH2]+, 201 (25) [Ph2PO]+. HRMS (FAB+): calcd. for
[C23H23O2NP]+ 376.1466; found 376.1458.
(2-Ethoxycarbonyl-3-hydroxy)propyldiphenylphosphine Oxide (11): product was filtered, washed with pentane, and dried under re-
According to the general procedure, 11 was obtained from the reac-
tion between ethyl acrylate (370 mg, 1.0 equiv.), Ph2PNEt2 (950 mg,
1.0 equiv.), and paraformaldehyde (139 mg, 1.2 equiv.). After stir-
ring at 20 °C for 48 h, EtOH (10 mL) was added, and the mixture
was stirred and heated at reflux for 24 h. The solvents were re-
moved in vacuo to give an oil that was purified by flash column
chromatography on silica gel (CH2Cl2/EtOH, 99:1 then 98:2) to
afford 11 (124 mg, 11 % yield) as a colorless oil. 31P NMR
duced pressure in the presence of P2O5 to afford 14 (1.07 g, 31%
yield, 63 % purity, 40 % de) as an unstable white solid that was
rapidly hydrolyzed by air. 31P NMR (81.02 MHz, CDCl3, major
isomer): δ = 49.85 (70 %) ppm. 31P NMR (81.02 MHz, CDCl3,
minor isomer): δ = 50.02 (30 %) ppm. 19F NMR (188.31 MHz,
CDCl3, major isomer): δ = –62.89 (s, 70 %) ppm. 19F NMR
1
(188.31 MHz, CDCl3, minor isomer): δ = –62.84 (s, 30%) ppm. H
NMR (200.13 MHz, CDCl3): δ = 1.07 (t, 3J = 7.1 Hz, 6 H, major),
3
(81.02 MHz, CDCl3): δ = 33.69 ppm. 1H NMR (250.13 MHz, 1.34 (t, J = 7.2 Hz, 6 H, minor), 3.19 (s, 3 H, major), 3.33 (s, 3 H,
CDCl3): δ = 1.16 (t, 3J = 7.2 Hz, 3 H), 2.59–3.0 (m, 3 H), 3.97 (dq,
2J = 10.8 Hz, 3J = 7.2 Hz, 1 H), 4.04 (dq, 2J = 10.8 Hz, 3J = 7.2 Hz,
minor), 3.19–4.15 (m, 5 H), 5.16–5.57 (m, 1 H), 6.12–6.53 (m, 1
H), 6.91–7.95 (m, 15 H) ppm.
1 H), 4.03 (m, 2 H), 4.68 (sl, OH), 7.42–7.76 (m, 10 H) ppm. 13C
Methyl 2-[(4Ј-Trifluoromethylphenyl)hydroxy]-3-diphenyloxyphos-
phinobut-3-enoate (15): Compound 14, which was sensitive to air
moisture, was readily hydrolyzed to give compound 15. The re-
sulting crude product was purified by flash column chromatog-
raphy on silica gel (hexane/ethyl acetate, 70:30 to 20:80) to separate
both diastereomers of 15 (major isomer, 1.0 g, m.p. 135 °C; minor
isomer, 260 mg, 56 % yield, 58 % de) as white solids. 31P NMR
(81.02 MHz, CDCl3, major isomer): δ = 37.09 ppm. 31P NMR
(81.02 MHz, CDCl3, minor isomer): δ = 34.23 ppm. 19F NMR
(188.31 MHz, CDCl3): δ = –62.85 (s) ppm. 1H NMR (200.13 MHz,
CDCl3, major isomer): δ = 3.34 (s, 3 H), 3.87 (dd, 3J = 8.2 Hz,
1
NMR (50.32 MHz, CDCl3): δ = 13.95 (s), 28.65 (d, JP, C
=
=
2
3
71.8 Hz), 42.37 (d, JP,C = 2.6 Hz), 61.00 (s), 63.49 (d, JP, C
3
2
6.3 Hz), 128.70 (d, JP, C = 11.9 Hz), 130.52 (d, JP,C = 9.3 Hz),
2
1
131.03 (d, JP,C = 9.3 Hz), 131.21 (d, JP,C = 99.4 Hz), 132.82 (d,
1JP,C = 101.2 Hz), 173.04 (d, 3JP,C = 10.8 Hz) ppm. IR (film, KBr):
ν = 3440, 3078, 3058, 2981, 2939, 2904, 2873, 1736, 1717, 1647,
˜
1590, 1540, 1483, 1471, 1438, 1406, 1376, 1346, 1300, 1190, 1123,
1101, 1058, 1028, 996, 923, 901, 837, 784, 748, 723, 698, 552,
552 cm–1. MS (FAB+): m/z (%) = 355 (49) [M + Na]+, 333 (100)
[M + H]+, 287 (10) [M – EtO]+, 269 (34) [M – H2O – EtO]+, 201
[Ph2PO]+. HRMS (FAB+): calcd. for [C18H22O4P]+ 333.1256;
found 333.1259.
3
3
3JP,H = 13.5 Hz, 1 H), 5.20 (d, J = 8.2 Hz, 1 H), 5.54 (d, JP,H
=
3
20.1 Hz, 1 H), 6.27 (sl, OH), 6.38 (d, JP,H = 42.1 Hz, 1 H), 7.25–
Ethyl [2-Ethoxycarbonyl-3-hydroxy-3-(4Ј-trifluoromethylphenyl)]- 7.70 (m, 14 H) ppm. 1H NMR (400.13 MHz, CDCl3, minor iso-
3
3
propylphenylphosphinate (12): According to the general procedure,
12 was obtained from the reaction between ethyl acrylate (370 mg,
1.0 equiv.), PhP(OEt)2 (731 mg, 1.0 equiv.), and p-trifluoromethyl-
benzaldehyde (642 mg, 1.0 equiv.), which was heated at reflux for
2 d. After removal of solvent, the residual oil was purified by flash
column chromatography on silica gel (hexane/ethyl acetate, 25:75)
mer): δ = 3.55 (s, 3 H), 4.16 (dd, J = 4.9 Hz, JP,H = 12.7 Hz, 1
3
3
H), 5.36 (d, J = 5.1 Hz, 1 H), 5.58 (d, JP,H = 20.3 Hz, 1 H), 5.65
3
(sl, OH), 5.97 (d, JP,H = 42.1 Hz, 1 H), 7.42–7.80 (m, 14 H) ppm.
13C NMR (62.89 MHz, CDCl3, major isomer): δ = 51.79 (s), 55.54
2
1
(d, JP,C = 9.7 Hz), 74.82 (s), 124.13 (q, JF,C = 272.1 Hz), 124.93
(q, JF,C = 3.7 Hz), 127.12 (s), 128.51 (d, JP,C = 12.7 Hz), 128.60
(d, JP,C = 12.3 Hz), 129.49 (q, JF,C = 32.0 Hz), 129.89 (d, JP,C =
3
3
to afford 12 (890 mg, 50% yield, ratio of 27:26:25:21) as an oil. 31
P
3
2
1
NMR (81.02 MHz, CDCl3): δ = 39.22 (s, 21%), 39.58 (s, 25%), 104.9 Hz), 129.90 (d, 1JP,C = 106.1 Hz), 131.86 (d, 2JP,C = 10.0 Hz),
39.75 (s, 26 %), 39.90 (s, 27 %) ppm. 19F NMR (188.31 MHz, 131.92 (d, JP,C = 10.0 Hz), 132.39 (d, JP,C = 3.7 Hz), 132.46 (d,
2
4
CDCl3): δ = –62.86, –62.91, –62.96, –62.98 ppm. 1H NMR 4JP,C = 3.0 Hz), 134.08 (d, JP,C = 9.7 Hz), 138.27 (d, JP, C
=
2
1
(200.13 MHz, CDCl3): δ = 0.82–1.34 (m, 6 H), 1.91–2.58 (m, 2 H),
94.2 Hz), 146.61 (d, 5JF,C = 1.1 Hz), 170.50 (d, 3JP,C = 6.3 Hz) ppm.
Eur. J. Org. Chem. 2014, 788–796
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
793

J.-L. Pirat, D. Virieux et al.
FULL PAPER
13C NMR (100.61 MHz, CDCl3, minor isomer): δ = 52.18 (s), 53.62
major isomer): δ = 18.99 (s, 78%) ppm. 31P NMR (81.01 MHz,
CD3OD, minor isomer): δ = 19.19 (s, 22 %) ppm. 1H NMR
(400.13 MHz, CD3OD, major isomer): δ = 4.72 (d, 2JP,H = 12.9 Hz,
2 H, PCH2), 5.30 (s, 1 H, CH), 7.71–7.80 (m, 19 H, CHAr) ppm.
2
3
1
(d, JP,C = 10.2 Hz), 73.58 (d, JP,C = 2.2 Hz), 124.14 (q, JF,C
271.5 Hz), 124.96 (q, JF,C = 3.7 Hz), 127.31 (s), 128.62 (d, JP,C
=
=
3
3
3
2
11.7 Hz), 128.74 (d, JP,C = 12.4 Hz), 129.77 (q, JF,C = 32.9 Hz),
130.07 (d, JP,C = 99.5 Hz), 130.10 (d, 1JP,C = 101.7 Hz), 131.94 (d,
1H NMR (400.13 MHz, CD3OD, minor isomer): δ = 4.87 (d, JP,H
1
2
2JP,C = 10.2 Hz), 131.95 (d, JP,C = 9.5 Hz), 132.43 (d, JP, C
=
= 13.1 Hz, 2 H, PCH2), 5.40 (s, 1 H, CH), 7.71–7.80 (m, 19 H,
2
4
4
2
3.7 Hz), 132.43 (d, JP,C = 2.9 Hz), 134.71 (d, JP,C = 8.8 Hz),
CHAr) ppm. 13C NMR (100.61 MHz, CD3OD, major isomer): δ =
1
3
1
3
137.58 (d, JP,C = 95.1 Hz), 145.11 (s), 170.70 (d, JP, C
=
31.66 (d, JP,C = 57.6 Hz, PCH2), 78.94 (d, JP,C = 9.2 Hz, CH),
116.95 (d, 3JP,C = 2.4 Hz, C), 119.13 (d, 1JP,C = 87.6 Hz, C), 126.13
(q, 3JF,C = 3.7 Hz, CH), 130.77 (s, CH), 131.58 (d, 3JP,C = 13.5 Hz,
7.3 Hz) ppm. IR (solid, KBr, major isomer): ν = 3222, 3075, 2954,
˜
2885, 2846, 1738, 1619, 1590, 1485, 1437, 1415, 1324, 1302, 1275,
1247, 1202, 1165, 1118, 1094, 1084, 1066, 1041, 1014, 968, 937,
846, 811, 780, 748, 728, 694, 647, 555, 520, 503 cm–1. MS (FAB+,
2
4
CH), 135.60 (d, JP,C = 10.4 Hz, CH), 136.86 (d, JP,C = 3.1 Hz,
CH), 142.09 (s, C) ppm. 13C NMR (100.61 MHz, CD3OD, minor
major isomer): m/z (%) = 497 (34) [M + Na]+, 475 (100) [M + isomer): δ = 32.53 (d, JP,C = 55.8 Hz, PCH2), 80.10 (d, JP,C
=
=
=
=
1
3
H]+, 457 (30) [M – H2O]+, 425 (10) [M – H2O – OCH3]+, 397 (8)
[M – H2O – CO2Me]+, 300 (15) [M – F3C – C6H4OH]+, 269 (30)
8.6 Hz, CH), 116.35 (d, JP,C = 2.4 Hz, C), 119.33 (d, JP, C
87.6 Hz, C), 126.60 (m, CH), 130.63 (s, CH), 131.58 (d, JP,C
3
1
3
[M – F3C – C6H4OH – OCH3]+, 201 (85) [Ph2PO]+. MS (FAB+, 13.5 Hz, CH), 135.55 (d, JP,C = 10.4 Hz, CH), 136.83 (d, JP,C
2
4
minor isomer): m/z (%) = 497 (15) [M + Na]+, 475 (100) [M +
H]+, 457 (24) [M – H2O]+, 425 (7) [M – H2O – OCH3]+, 397 (7)
[M – H2O – CO2Me]+, 300 (12) [M – F3C – C6H4OH]+, 269 (32)
[M – F3C – C6H4OH – OCH3]+, 201 (77) [Ph2PO]+. HRMS
(FAB+): calcd. for [C25H23O4F3P]+ 475.1286; found 475.1290.
3.1 Hz, CH), 142.39 (s, C) ppm. IR (solid, KBr): ν = 3147, 2847,
˜
2216, 1619, 1589, 1487, 1439, 1326, 1161, 1115, 1066, 996, 745,
719, 689, 516, 506, 490 cm–1. MS (FAB+): m/z (%) = 524 (100)
[M]+, 488 (15) [M – Cl]+, 262 (37) [Ph3P]+. HRMS (FAB+): calcd.
for [C29H23F3ClNOP]+ 524.1158; found 524.1124.
1-{[2-Chloro-2-cyano-3-(4Ј-nitrophenyl)-3-hydroxy]propyl}-
triphenylphosphonium Chloride (19): Compound 19 (1.01 g, 81%)
was obtained as a white solid. 31P NMR (81.01 MHz, CD3OD,
major isomer): δ = 19.00 (s, 70%) ppm. 31P NMR (81.01 MHz,
General Procedure for the Synthesis of Compounds 17–20: To a solu-
tion of aromatic aldehyde (2.50 mmol, 1.0 equiv.) were added tri-
phenylphosphine (656 mg, 2.50 mmol, 1.0 equiv.) in anhydrous
CH2Cl2 (10 mL) and zirconium tetrachloride (582 mg, 2.50 mmol,
1.0 equiv.) under nitrogen. Then, a solution of 2-chloroacrylonitrile
(200 μL, 2.50 mmol, 1 equiv.) in CH2Cl2 (4 mL) was added drop-
wise over 40 min. The reaction mixture was left at 18 °C for 21 h
and then hydrolyzed by the addition of water (15 mL). The water
phase was extracted with CH2Cl2 (3ϫ 15 mL), and the combined
organic layers were dried with Na2SO4 and evaporated under vac-
uum. The solid residue was washed with acetone (50 mL) and then
filtered.
CD3OD, minor isomer): δ = 19.18 (s, 30 %) ppm. 1H NMR
2
(250.13 MHz, CD3OD, major isomer): δ = 4.74 (d, JP, H
=
–13.1 Hz, 2 H, PCH2), 5.37 (s, 1 H, CH), 7.75–8.09 (m, 19 H,
1
CHAr) ppm. H NMR (250.13 MHz, CD3OD, minor isomer): δ =
4.74 (d, 2JP,H = –13.1 Hz, 2 H, PCH2), 5.46 (s, 1 H, CH), 7.75–8.09
(m, 19 H, CHAr) ppm. 13C NMR (100.61 MHz, CD3OD, major
1
2
isomer): δ = 32.35 (d, JP,C = 57.6 Hz, PCH2), 61.22 (d, JP,C
=
8.3 Hz, C), 79.37 (d, 3JP,C = 9.2 Hz, CH), 117.55 (d, 3JP,C = 3.7 Hz,
C), 119.79 (d, JP,C = 87.9 Hz, C), 124.92 (s, CH), 131.99 (s, CH),
132.31 (d, JP,C = 12.9 Hz, CH), 137.32 (d, JP,C = 10.7 Hz, CH),
137.61 (d, 4JP,C = 3.1 Hz, CH), 145.45 (d, 4JP,C = 0.9 Hz, C), 150.92
(s, C) ppm. 13C NMR (100.61 MHz, CD3OD, minor isomer): δ =
33.24 (d, 1JP,C = 56.7 Hz, PCH2), 60.15 (d, 2JP,C = 8.0 Hz, C), 80.49
1
3
2
1-[(2-Chloro-2-cyano-3-phenyl-3-hydroxy)propyl]triphenylphos-
phonium Chloride (17): Compound 17 (900 mg, 54%) was obtained
as a white solid. 31P NMR (81.01 MHz, CD3OD, major isomer): δ
= 20.51 (s, 71%) ppm. 31P NMR (81.01 MHz, CD3OD, minor iso-
mer): δ = 20.75 (s, 29%) ppm. 1H NMR (400.13 MHz, CD3OD,
3
3
(d, JP,C = 8.3 Hz, CH), 116.95 (d, JP,C = 3.4 Hz, C), 119.98 (d,
2
major isomer): δ = 4.57 and 4.66 (2 dd, 2J = 16.2 Hz, JP, H
=
1JP,C = 87.9 Hz, C), 125.95 (s, CH), 130.10 (s, CH), 132.75 (d, 3JP,C
12.9 Hz, 2JP,H = 12.6 Hz, 2 H, PCH2), 5.17 (s, 1 H, CH), 7.40–7.75
2
4
= 13.5 Hz, CH), 136.27 (d, JP,C = 10.4 Hz, CH), 137.57 (d, JP,C
= 3.4 Hz, CH), 145.76 (d, 4JP,C = 0.9 Hz, C), 150.88 (s, C) ppm. IR
(m, 20 H, CHAr) ppm. 1H NMR (400.13 MHz, CD3OD, minor iso-
2
mer): δ = 4.79 (d, JP,H = 12.6 Hz, 2 H, PCH2), 5.26 (s, H, CH),
(solid, KBr): ν = 3060, 2857, 2202, 1830, 1710, 1605, 1588, 1517,
˜
7.40–7.75 (m, 20 H, CHAr) ppm. 13C NMR (100.61 MHz, CD3OD,
1485, 1438, 1347, 1225, 1193, 1114, 1074, 995, 932, 896, 860, 840,
748, 689, 516, 507 cm–1. MS (FAB+): m/z (%) = 501 (100) [M]+,
465 (18) [M – Cl]+, 262 (100) [Ph3P]+. HRMS (FAB+): calcd. for
[C28H23O3N2PCl]+ 501.1135; found 501.1090.
major isomer): δ = 32.57 (d, 1JP,C = 57.0 Hz, PCH2), 61.65 (d, 2JP,C
3
3
= 8.0 Hz, C), 80.64 (d, JP,C = 8.0 Hz, CH), 117.82 (d, JP,C
=
3.7 Hz, C), 119.83 (d, 1JP,C = 88.2 Hz, C), 130.01 (s, 6 CH), 130.68
(s, CH), 131.46 (s, CH), 132.29 (d, 3JP,C = 13.5 Hz, CH), 136.28 (d,
1-{[2-Chloro-2-cyano-3-(4Ј-tolyl)-3-hydroxy]propyl}triphenyl-
phosphonium Chloride (20): Compound 20 (632 mg, 54%) was ob-
tained as a white solid. 31P NMR (81.01 MHz, CD3OD, major iso-
mer): δ = 20.15 (s, 69%) ppm. 31P NMR (81.01 MHz, CD3OD,
minor isomer): δ = 19.88 (s, 31%) ppm. 1H NMR (400.13 MHz,
CD3OD, major isomer): δ = 2.30 (s, 3 H, CH3), 5.06 (dd, 2J =
2JP,C = 10.4 Hz, CH), 137.55 (d, JP,C = 3.1 Hz, CH), 138.40 (s,
4
C) ppm. 13C NMR (100.61 MHz, CD3OD, minor isomer): δ =
33.24 (d, 1JP,C = 57.0 Hz, PCH2), 60.71 (d, 2JP,C = 8.0 Hz, C), 81.59
3
3
(d, JP,C = 9.2 Hz, CH), 117.42 (d, JP,C = 3.7 Hz, C), 120.08 (d,
1JP,C = 87.6 Hz, C), 130.00 (s, CH), 130.54 (s, CH), 131.44 (s, CH),
3
2
132.28 (d, JP,C = 12.9 Hz, CH), 136.24 (d, JP,C = 10.4 Hz, CH),
137.49 (d, 4JP,C = 3.1 Hz, CH), 138.70 (s, C) ppm. IR (solid, KBr):
2
2
–12.1 Hz, JP,H = –16.8 Hz, 1 H, PCH2), 5.36 (dd, J = –12.1 Hz,
2JP,H = –16.6 Hz, 1 H, PCH2), 5.63 (s, 1 H, CH), 7.10 (d, 3J =
ν = 3060, 2852, 2202, 1977, 1709, 1587, 1487, 1437, 1344, 1260,
˜
3
8.0 Hz, 2 H, CH), 7.45 (d, J = 8.0 Hz, 2 H, CH), 7.68–8.08 (2 m,
1109, 1059, 996, 746, 686, 606, 516, 506, 487 cm–1. MS (FAB+):
m/z (%) = 456 (55) [M]+, 420 (20) [M – Cl]+, 262 (30) [Ph3P]+.
HRMS (FAB+): calcd. for [C28H24ClNOP]+ 456.1284; found
456.1319.
15 H, CHAr) ppm. 1H NMR (400.13 MHz, CD3OD, minor iso-
mer): δ = 2.33 (s, 3 H, CH3), 4.89 (dd, 2J = –12.4 Hz, JP,H
=
2
2
2
–16.8 Hz, 1 H, PCH2), 5.69 (dd, J = –12.4 Hz, JP,H = –16.8 Hz,
1 H, PCH2), 5.43 (s, 1 H, CH), 7.10 (d, 3J = 8.0 Hz, 2 H, CH),
3
1-{[2-Chloro-2-cyano-3-(4Ј-trifluomethylphenyl)-3-hydroxy]propyl}-
triphenylphosphonium Chloride (18): Compound 18 (750 mg, 58%)
was obtained as a white solid. 31P NMR (81.01 MHz, CD3OD,
7.45 (d, J = 8.0 Hz, 2 H, CH) 7.68–8.08 (2m, 15 H, CHAr) ppm.
13C NMR (100.61 MHz, CD3OD, major isomer): δ = 21.29 (s,
1
2
CH3), 31.61 (d, JP,C = 57.5 Hz, PCH2), 60.93 (d, JP,C = 8.3 Hz,
794
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 788–796

Driving the Morita–Baylis–Hillman Reaction
3
3
C), 79.79 (d, JP,C = 8.8 Hz, CH), 117.03 (d, JP,C = 3.9 Hz, C),
tion mixture was concentrated under vacuum, and the resulting
1
119.07 (d, JP,C = 87.9 Hz, C), 129.76 (s, CH), 129.92 (s, CH), residue was purified by silica gel chromatography (hexane/AcOEt,
131.46 (d, JP,C = 13.3 Hz, CH), 134.58 (s, C), 135.46 (d, JP,C
3
2
=
from 50:50 to 30:70) to give (Z)-22 (480 mg) and (E)-22 (110 mg)
as colorless oils. Data for (Z)-22: 31P NMR (81.01 MHz, CDCl3):
δ = 34.33 (s) ppm. 19F NMR (188.31 MHz, CDCl3): δ = –63.14
4
10.5 Hz, CH), 136.72 (d, JP,C = 3.3 Hz, CH), 140.80 (s, C) ppm.
13C NMR (100.61 MHz, CD3OD, minor isomer): δ = 21.28 (s,
1
2
1
3
CH3), 32.21 (d, JP,C = 56.4 Hz, PCH2), 60.02 (d, JP,C = 7.7 Hz, (s) ppm. H NMR (200.13 MHz, CDCl3): δ = 1.06 (t, J = 7.1 Hz,
3
3
C), 80.05 (d, JP,C = 7.7 Hz, CH), 116.66 (d, JP,C = 3.9 Hz, C),
6 H, CH3), 1.12 (t, 3J = 7.1 Hz, 3 H, CH3), 2.95–3.15 (m, 4 H,
119.32 (d, JP,C = 87.9 Hz, C), 129.61 (s, CH), 129.80 (s, CH), NCH2), 3.33 and 3.47 (m, ABX system, 2J = 14.1 Hz, JP, H
=
1
2
3
2
2
3
3
131.44 (d, JP,C = 12.7 Hz, CH), 134.90 (s, C), 135.43 (d, JP,C
10.5 Hz, CH), 136.65 (d, JP,C = 2.8 Hz, CH), 140.76 (s, C) ppm.
=
13.6 Hz, JP,H = 19.3 Hz, 2 H, PCH2), 3.98 (2 qd, J = 7.0 Hz, J
4
2
3
3
= 7.2 Hz, J = 10.8 Hz, 4 H, CH2), 4.03 (2 qd, J = 7.0 Hz, J =
IR (solid, KBr): ν = 3662, 3059, 2863, 2202, 1823, 1614, 1587,
7.2 Hz, 2J = 10.8 Hz, 2 H, CH2), 7.30–7.73 (m, 10 H, =CH,
˜
1485, 1438, 1347, 1225, 1193, 1109, 1070, 996, 743, 687, 513 cm–1. CHAr) ppm. 13C NMR (62.89 MHz, CDCl3): δ = 14.44 (s, CH3),
MS (FAB+): m/z (%) = 470 (100) [M]+, 434 (22) [M – Cl]+, 262
15.01 (d, JP,C = 3.4 Hz, CH3), 28.64 (d, JP,C = 87.3 Hz, PCH2),
3
1
(30) [Ph3P]+. HRMS (FAB+): calcd. for [C29H26ONClP]+ 470.1441; 40.19 (d, JP,C = 2.4 Hz, NCH2), 61.67 (s, OCH2), 124.40 (q, JF,C
2
1
3
2
found 470.1427.
= 272.1 Hz, C), 125.70 (q, JF,C = 3.7 Hz, CH), 127.56 (d, JP,C
=
=
=
=
3
5
7.4 Hz, C), 128.55 (d, JP,C = 12.5 Hz, CH), 129.75 (d, JP, C
1.4 Hz, CH), 130.54 (q, JF,C = 32.6 Hz, C), 132.01 (d, JP, C
Methyl 2-[(4Ј-Trifluoromethylphenyl)hydroxymethyl]-3-triphenyl-
phosphoniobut-3-enoate (21): To a solution of p-trifluoromethylben-
zaldehyde (477 μL, 3.49 mmol, 1.1 equiv.) and PPh3 (917 mg,
3.49 mmol, 1.1 equiv.) in anhydrous CH2Cl2 (15 mL) at –20 °C un-
der N2 was added ZrCl4 (814 mg, 3.49 mmol, 1.1 equiv.). After
10 min, methyl 2,3-butadienoate (308 mg, 3.17 mmol, 1.0 equiv.) in
anhydrous CH2Cl2 (3 mL) was added dropwise at –25 °C over
10 min. The reaction mixture was left, as it was stirred at –25 °C
for 20 h and at room temp. for 24 h. Water (15 mL) was added to
the reaction mixture, and the resulting solution was extracted with
CH2Cl2 (3ϫ 15 mL). The combined organic layers were washed
with water (10 mL) and dried with Na2SO4, and the solvents were
evaporated under vacuum. The resulting solid was dissolved in
CH2Cl2 (2 mL), and diethyl ether (50 mL) was added. After fil-
tration and drying under vacuum, compound 21 (860 mg, 48%
yield, Ͼ90% purity) was obtained as a white powder. 31P NMR
(81.01 MHz, CDCl3, major and minor isomers): δ = 27.27 (s) ppm.
19F NMR (188.31 MHz, CDCl3, major isomer): δ = –62.78 (s,
86%) ppm. 19F NMR (188.31 MHz, CDCl3, minor isomer): δ =
2
4
2
1
2.4 Hz, CH), 132.59 (d, JP,C = 9.1 Hz, CH), 132.62 (d, JP,C
124.3 Hz, C), 138.99 (qd, 4JP,C = 3.1 Hz, 5JF,C = 1.5 Hz, C), 139.96
3
3
(d, JP,C = 9.6 Hz, CH), 176.68 (d, JP,C = 1.9 Hz, C) ppm. IR (so-
lid, KBr): ν = 3052, 2976, 2868, 1711, 1631, 1613, 1588, 1570, 1465,
˜
1437, 1413, 1380, 1367, 1329, 1301, 1260, 1215, 1162, 1110, 1067,
1019, 937, 917, 834, 789, 732, 698, 673, 637, 602, 564, 511 cm–1.
MS (FAB+): m/z (%) = 476 (4) [M + Na]+, 454 (28) [M + H]+,
408 (7) [M – OEt]+. HRMS (FAB+): calcd. for [C23H28F3O3NP]+
454.1759; found 454.1750. Data for (E)-22: 31P NMR (81.01 MHz,
CDCl3): 34.87 (s) ppm. 19F NMR (188.31 MHz, CDCl3): δ =
1
3
–63.05 (s) ppm. H NMR (200.13 MHz, CDCl3): δ = 0.87 (t, J =
3
7.1 Hz, 3 H, CH3), 1.10 (t, J = 7.1 Hz, 6 H, CH3), 3.01–3.14 (m,
4 H, CH2), 3.19 and 3.30 (m, ABMX, 2J = –14.2 Hz, JP, H
=
2
21.4 Hz, 2JP,H = –17.9 Hz, 4J = 1.12 Hz, 2 H, PCH2), 3.78 and 4.03
3
3
2
(2 qd, J = 7.2 Hz, J = 7.1 Hz, J = –10.8 Hz, 2 H, CH2), 6.84–
4
6.87 (d, JP,H = 4.7 Hz, 1 H, CH), 7.12–7.16, 7.36–7.53, and 7.69–
7.79 (m, 9 H, CHAr) ppm. 13C NMR (50.32 MHz, CDCl3): δ =
3
1
13.32 (s, CH3), 14.39 (d, JP,C = 3.35 Hz, CH3), 33.89 (d, JP,C
86.7 Hz, PCH2), 39.47 (d, JP,C = 3.0 Hz, CH2), 60.86 (s, CH2),
124.02 (q, JF,C = 272.0 Hz, C), 124.63 (q, JF,C = 3.7 Hz, CH),
127.00 (d, JP,C = 7.4 Hz, C), 128.22 (d, JP,C = 12.3 Hz, CH),
128.32 (s, JP,C = 2.6 Hz, CH), 129.48 (q, JF,C = 32.75 Hz, C),
131.65 (d, JP,C = 2.6 Hz, CH), 131.79 (d, JP,C = 124.3 Hz, C),
131.85 (d, JP,C = 9.3 Hz, CH), 138.13 (d, JP,C = 9.3 Hz, CH),
140.04 (qd, JP,C = 3.0 Hz, JF,C = 1.5 Hz, C), 167.39 (d, JP,C
=
1
–62.86 (s, 14%) ppm. H NMR (400.13 MHz, CD3OD, major iso-
2
mer): δ = 3.38 (s, 3 H, CH3), 3.69 (dd, 3J = 5.1 Hz, 3JP,H = 12.3 Hz,
1 H, CH), 5.15 (d, 3J = 5.1 Hz, 1 H, CH), 6.30 (d, 3JP,H = 23.3 Hz,
1 H, =CH2), 6.91–7.95 (m, 20 H, =CH2, CHAr) ppm. 1H NMR
1
3
2
3
5
2
(400.13 MHz, CD3OD, minor isomer): δ = 3.31 (s, 3 H, CH3) 3.69
4
1
(m, 1 H, CH), 5.43 (d, 3J = 8.2 Hz, 1 H, CH), 6.28 (d, JP,H
=
3
2
3
23.3 Hz, 1 H, =CH2), 6.91–7.95 (m, 20 H, =CH2, CHAr) ppm. 13C
4
5
3
=
NMR (100.61 MHz, CD3OD, major isomer): δ = 52.65 (s, CH3),
53.39 (d, JP,C = 11.0 Hz, CH), 73.03 (d, JP, C = 4.3 Hz, CH),
116.65 (d, JP,C = 88.3 Hz, C), 124.41 (d, JF,C = 272.1 Hz, C),
125.10 (m, CH), 125.41 (d, JP,C = 102.2 Hz, C), 127.29 (s, CH),
129.45 (q, JF,C = 32.6 Hz, C), 130.97 (d, JP,C = 12.9 Hz, CH),
135.06 (d, JP,C = 10.1 Hz, CH), 136.05 (d, JP,C = 2.9 Hz, CH),
4.1 Hz, C) ppm. IR (solid, KBr): ν = 2979, 2936, 2873, 1706, 1615,
˜
2
3
1465, 1438, 1379, 1324, 1246, 1215, 1167, 1132, 1112, 1066, 1019,
928, 910, 897, 862 830, 794, 755, 743, 732, 666, 670, 646, 532,
502 cm–1. MS (FAB+): m/z (%) = 476 (15) [M + Na]+, 454 (100)
[M + H]+, 408 (7) [M – OEt]+. HRMS (FAB+): calcd. for
[C23H28F3O3NP]+ 454.1759; found 454.1750.
1
1
1
2
3
2
4
2
3
146.47 (s, C), 147.46 (d, JP,C = 6.2 Hz, CH2), 169.42 (d, JP,C
=
7.2 Hz, C) ppm. 13C NMR (100.61 MHz, CD3OD, minor isomer):
(E)-1-{[2-Cyano-3-(4Ј-trifluoromethylphenyl)]prop-2-enyl}phenyl-
N,N-diethylphosphinamide (23): To a solution of p-trifluoromethyl-
benzaldehyde (504 μL, 3.69 mmol, 1.0 equiv.) and bis(diethylamino)-
phenylphosphine (904 μL, 3.69 mmol, 1 equiv.) in anhydrous
CH2Cl2 (4 mL) was added dropwise a solution of acrylonitrile
(267 μL, 4.04 mmol, 1.1 equiv.) in CH2Cl2 (4 mL) at room tempera-
ture under nitrogen. After 3 d, the reaction mixture was concen-
trated under vacuum, and the resulting residue was purified by sil-
ica gel chromatography (hexane/AcOEt, from 50:50 to 30:70).
Compound 23 (430 mg, 30%) was obtained as a white solid. 31P
NMR (161.97 MHz, CDCl3 ): 32.97 (s) ppm. 1 9 F NMR
(188.31 MHz, CDCl3): δ = –63.38 (s) ppm. 1H NMR (200.13 MHz,
CDCl3): δ = 1.13 (t, 3J = 7.2 Hz, 6 H, CH3), 3.12–3.16 (m, 5 H,
NCH2, CH2P), 3.26 (dd, 2J = 16.6 Hz, 2JP,H = 16.5 Hz, 1 H, CH2P),
7.17 (d, 4JP,H = 4.4 Hz, 1 H, =CH), 7.46–7.58 (m, 3 H, CHAr), 7.61
2
3
δ = 52.74 (s, CH3), 55.33 (d, JP,C = 9.6 Hz, CH), 73.83 (d, JP,C
=
3.8 Hz, CH), 117.08 (d, 1JP,C = 88.3 Hz, C), 125.27 (m, CH), 127.29
2
3
(s, CH), 129.77 (q, JF,C = 32.2 Hz, C), 130.94 (d, JP,C = 12.5 Hz,
2
4
CH), 134.79 (d, JP,C = 10.1 Hz, CH), 136.05 (d, JP,C = 2.9 Hz,
CH), 145.42 (d, 2JP,C = 3.3 Hz, CH2), 146.47 (s, C), 170.21 (d, 3JP,C
= 5.3 Hz, C) ppm. MS (FAB+): m/z (%) = 1105 (35) [2M + Cl]+,
535 (100) [M]+, 361 (50) [M – CF3C6H4CHO]+, 262 (30) [Ph3P]+.
(Z,E)-1-{[2-Ethoxycarbonyl-3-(4Ј-trifluoromethylphenyl)]prop-2-
enyl}phenyl-N,N-diethylphosphinamide (22): To a solution of ethyl
acrylate (519 μL, 4.79 mmol, 1.3 equiv.) and bis(diethylamino)-
phenylphosphine (959 μL, 3.69 mmol, 1.0 equiv.) in anhydrous
CH2Cl2 (4 mL) was added dropwise a solution of p-trifluoro-
methylbenzaldehyde (504 μL, 3.69 mmol, 1.0 equiv.) in CH2Cl2
(4.0 mL) at room temperature under nitrogen. After 3 d, the reac-
Eur. J. Org. Chem. 2014, 788–796
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
795

J.-L. Pirat, D. Virieux et al.
FULL PAPER
(d, 3J = 8.5 Hz, 2 H, CHAr), 7.70 (d, 3J = 8.5 Hz, 2 H, CHAr),
[21] D. Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003,
103, 811–891.
7.74–7.80 (m, 2 H, CHAr) ppm. 13C NMR (100.61 MHz, CDCl3):
[22] D. Basavaiah, B. S. Reddy, S. S. Badsara, Chem. Rev. 2010, 110,
3
1
δ = 14.36 (d, JP,C = 3.1 Hz, CH3), 35.06 (d, JP,C = 84.6 Hz,
5447–5674.
2
2
PCH2), 39.44 (d, JP,C = 3.1 Hz, NCH2), 104.17 (d, JP,C = 9.2 Hz,
=C), 118.00 (d, JP,C = 5.5 Hz, CN), 123.69 (q, JF,C = 272.7 Hz,
CF3), 125.68 (q, JF,C = 3.7 Hz, CH), 128.76 (d, JP,C = 12.2 Hz,
[23] V. Singh, S. Batra, Tetrahedron 2008, 64, 4511–4574.
[24] V. Declerck, J. Martinez, F. Lamaty, Chem. Rev. 2009, 109, 1–
48.
[25] E. Ciganek, in: Organic Reactions (Ed.: L. A. Paquette), John
Wiley & Sons, New York, 1997, vol. 51, p. 201–350.
[26] J. N. Kim, K. Y. Lee, Curr. Org. Chem. 2002, 6, 627–645.
[27] K. Y. Lee, S. Gowrisankar, J. N. Kim, Bull. Korean Chem. Soc.
2005, 26, 1481–1490.
2
1
3
3
5
2
CH), 128.91 (d, JP,C = 1.8 Hz, CH), 131.62 (q, JF,C = 32.5 Hz,
2
4
C), 132.01 (d, JP,C = 9.8 Hz, CH), 132.38 (d, JP,C = 3.1 Hz, CH),
3
136.72 (m, 4 C), 146.41 (d, JP,C = 8.6 Hz, =CH) ppm. IR (solid,
KBr): ν = 3057, 2977, 2954, 2917, 2876, 2213, 1618, 1466, 1437,
˜
1420, 1387, 1325, 1215, 1189, 1168, 1126, 1069, 1017, 950, 914,
882, 832, 797, 783, 746, 722, 695, 670, 626, 598, 528, 500 cm–1. MS
(FAB+): m/z (%) = 407 (100) [M + H]+, 334 (5) [M – NEt2]+, 196
(30) [PhP(O)NEt2]+. HRMS (FAB+): calcd. for [C21H23N2OF3P]+
407.1500; found 407.1497.
[28]
S. Gowrisankar, H. S. Lee, S. H. Kim, K. Y. Lee, J. N. Kim,
Tetrahedron 2009, 65, 8769–8780.
[29] M. Shi, F.-J. Wang, M.-X. Zhao, Y. Wei, The Chemistry of the
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The authors gratefully thank the Ministère de l’Enseignement Sup-
érieur et de la Recherche (MESR) for a grant to A.-F. G.
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Received: August 14, 2013
Published Online: November 26, 2013
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