Mendeleev Commun., 2002, 12(5), 176–177
Synthesis of α,β-unsaturated esters from dialkoxyphosphoryl esters and aldehydes
in the ionic liquid [bmim][PF6]
Galina V. Kryshtal, Galina M. Zhdankina and Sergei G. Zlotin*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
1
0.1070/MC2002v012n05ABEH001623
α,β-Unsaturated esters were synthesised by LiOH·H O-promoted reactions of triethyl phosphonoacetate 1 and triethyl 3-methyl-
2
4
-phosphono-2-butenoate 2 with aldehydes in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF ]).
6
The base-promoted reactions of carbonyl compounds with
phosphonic esters containing electron-accepting groups at the
α-position (Horner–Emmons reaction) are widely used for
propanecarbaldehyde 3d, picolinaldehyde 3e and citronellal 3f
in [bmim][PF ] afforded olefination products 4b–f in 68–81%
6
†
yields (Table 1, rows 4–9). Reactions between triethyl 3-methyl-
1
the synthesis of di- and tri-substituted alkenes including those
4-phosphono-2-butenoate 2 and 3-methylbutanal 3a or 3,7-di-
methyloctanal 3g gave 3,7-dimethyloctadienic ester 5 and
hydroprene 6 in 48% and 75% yields, respectively (Table 1,
2
with a required configuration of the double bond. This reaction
1
is usually performed in polar organic solvents or in nonpolar
3
(a)–(d)
†
solvents under phase-transfer catalysis conditions.
rows 10–11). To the best of our knowledge, the synthesis of
Recently, a base-promoted synthesis of α-fluoro-α,β-un-
saturated esters by the reaction of triethyl 2-fluoro-2-phos-
phonoacetate with aldehydes in a solution of 8-alkyl-1,8-
diazabicyclo[5,4,0]-7-undecenium and 1,3-dialkylimidazolium
compounds 5 and 6 is the first example of the preparation of
biologically active compounds by the Horner–Emmons reaction
performed in an ionic liquid. Ester 5 is an effective sterilising
agent for spider mite (Tetranychidae); hydroprene 6 is an
analogue of the insect juvenile hormone.6
4
triflates was reported. These liquid triflates belong to organic
ionic liquids, which attract interest as an alternative to common
organic solvents. Ionic liquids consisting of an onium organic
The reactions were completed within 2–10 h depending on
the structure of starting compounds (TLC monitoring). The
reactions of phosphonoester 2 with aldehydes take longer times
than the corresponding reactions of compound 1. The reaction
time usually increased with the chain length of substituent R in
the aldehyde component (Table 1).
5
cation and a poorly coordinating (often fluorine-containing)
5
(c)
anion are thermally stable, non-volatile and recyclable.
Here, we report the synthesis of biologically active compounds
by the base-promoted Horner–Emmons reaction performed in
an ionic liquid. As the starting compounds, we used triethyl
phosphonoacetate 1 and triethyl 3-methyl-4-phosphono-2-
butenoate 2, which are known as building blocks for the
The reactions are stereoselective. According to 1H NMR
spectra, the newly formed double bond in compounds 4a–f, 5
3
and 6 has the E-configuration ( J
~ 16 Hz, which is
H–C=C–H
6
1(c),9
synthesis of biologically active isoprenoid compounds. 1-Butyl-
typical of E-olefins
). Isomerization takes place in com-
2
3
2
3
-methylimidazolium hexafluorophosphate ([bmim][PF ]), which
pounds 5 and 6 regarding to the C =C (∆ ) double bond pre-
6
was applied previously as a reaction medium in C–C coupling
viously existing in starting phosphonoester 2. The 2E,4E/2Z,4E
reactions,7
(a)–(f)
, was chosen as the ionic solvent.
isomer ratio determined by the ratio of Me protons at C and
3
2
1
To find optimum reaction conditions, we investigated a
reaction between the compound 1 and 3-methylbutanal 3a in
olefinic protons at C in the H NMR spectra of the compounds
5 and 6, as well as by GLC, is 60/40 or 75/25, respectively. It is
comparable with the isomer distribution in compounds 5 and 6
obtained under phase-transfer catalysis conditions.2
[
bmim][PF ] in the presence of various deprotonating agents.
6
,6
We found that phosphonoester 1 containing less acidic α-hydrogen
atoms than the α-hydrogen atom in triethyl 2-fluoro-2-phos-
phonoacetate does not react with aldehyde 3a in the ionic
solvent in the presence of K CO or 1,8-diazabicyclo[5.4.0]-
undec-7-ene (DBU) (i.e., under conditions described previously ).
The use of stronger bases, such as NaOH or KOH, led to
hydrolysis of the ester group in compound 1.
The stereoselectivity of C=C bond formation distinguishes
the studied reaction from the appropriate reactions between
4
aldehydes and α-fluorophosphonoesters or α-substituted phos-
2
3
4
10
phoranes in the ionic liquids that afforded the mixtures of E-
and Z-isomers in various proportions. A synthetic advantage of
the method compared to the Wittig olefination reaction10 is that
We were able to direct the reaction to the formation of alkene
there is no need to separate the reaction products from Ph PO.
3
4
a by performing it in the presence of LiOH·H O. The reaction
As a whole, the reaction of phosphonoesters 1, 2 with alde-
2
of equimolar amounts of compounds 1 and 3a with an excess of
hydes and LiOH·H O in [bmim][PF ] resembles those per-
2
6
LiOH·H O (4–5 equiv.) in [bmim][PF ] (2–3 equiv.) at 20 °C
2
6
†
General procedure. The ionic solvent was synthesised according to the
afforded 5-methyl-2-hexenoic acid ester 4a in 70% yield (Table 1).†
An excess of the base is necessary for the reaction to be com-
pleted: the yield of 4a was reduced to 20% in the presence of
7
(b)
1
31
19
reported method.
The H, P and F NMR spectra of the melt
2
recorded in [ H ]acetone contained only signals of the ionic liquid.
6
1
H NMR, d: 0.93 (t, 3H, J 7.2 Hz), 1.36 (sep, 2H, J 7.5 Hz), 1.89 (pent,
1
equiv. of LiOH·H O added to the reaction mixture. The
2
2H, J 7.6 Hz), 4.0 (s, 3H), 4.3 (t, 2H, J 4.0 Hz), 7.62 (t, 1H, J 1.8 Hz),
reaction is heterogeneous (LiOH·H O is poorly soluble in
31
2
7.68 (t, 1H, J 1.8 Hz), 8.82 (s, 1H). P NMR, d: –142.4 relative to H PO
3 4
[
bmim][PF ]); therefore, it is influenced by the particle size of
(heptet, : –71.0 relative to CFCl (d, JP–F 708 Hz).
To [bmim][PF ] (11–15 mmol) was added LiOH·H O (22–25 mmol)
1
JP–F 708 Hz). 19F NMR,
d
1
6
3
the base. The highest reproducible yields of compound 4a were
obtained when the reaction was carried out in a suspension of
LiOH·H O in [bmim][PF ].
6
2
and the mixture was vigorously stirred at 20 °C for 0.5–1.0 h. To the
resulting suspension were added successively 1 or 2 (5 mmol) and 3a–g
5 mmol). The reaction mixture was stirred at 20 °C for 2–10 h (TLC
2
6
(
The different behaviour of LiOH·H O, as compared to other
2
monitoring) and extracted with Et O (4×10 ml). The combined ether
alkali metal hydroxides, in the reaction can probably be ex-
plained by the more effective ion–dipole interaction between
Li cations and water formed during deprotonation that moves
it out of the reaction area and prevents hydrolysis of the ester
group.
The found conditions were applied to the synthesis of
α,β-unsaturated esters from phosphonoester 1, 2 and aliphatic,
aromatic and heteroaromatic aldehydes. The reactions of com-
pound 1 with benzaldehyde 3b, cinnamaldehyde 3c, cyclo-
2
extracts were dried with anhydrous MgSO . The solvent was evaporated,
4
and remaining products 4a–f, 5 and 6 were distilled in vacuo. Compound
+
8
4
d was also isolated by direct distillation from the reaction mixture. The
20
1
boiling points, nD and H NMR spectra of the compounds 4a–f, 5 and 6
were in accordance with reported data. The remaining ionic liquid was
filtered from inorganic salts, washed with water (3×10 ml) and kept at
1
31
4
0–60 °C (2 Torr) for 2 h to afford 89–94% of [bmim][PF ]. The H, P
6
and 19F NMR spectra of thus recovered melt were identical to the spectra
of freshly prepared [bmim][PF6].
–
176 –