One-pot combination of the Wittig olefination with oxidation, hydrogenation, bromination, and photocyclization reactions

Article abstract of DOI:10.1016/j.tetlet.2006.11.021

Co-polycondensation of tetramethoxysilane, 2-diphenyl(phosphino)ethyltri(ethoxy)silane, and N-2-(aminoethyl)-3-aminopropyltri(methoxy)silane forms a heterogenized tertiary phosphine reagent (HPR) that reacts with benzyl chlorides and aldehydes to give alkenes. This Wittig condensation can be coupled, as a one-pot process, with hydrogenation, oxidation, bromination or photocyclization.

Full text of DOI:10.1016/j.tetlet.2006.11.021

Tetrahedron Letters 48 (2007) 293–295
One-pot combination of the Wittig olefination
with oxidation, hydrogenation, bromination,
and photocyclization reactions
Khalil Hamza and Jochanan Blum*
Department of Organic Chemistry, The Hebrew University, Jerusalem 91904, Israel
Received 27 September 2006; accepted 2 November 2006
Available online 27 November 2006
Abstract—Co-polycondensation of tetramethoxysilane, 2-diphenyl(phosphino)ethyltri(ethoxy)silane, and N-2-(aminoethyl)-3-
aminopropyltri(methoxy)silane forms a heterogenized tertiary phosphine reagent (HPR) that reacts with benzyl chlorides and alde-
hydes to give alkenes. This Wittig condensation can be coupled, as a one-pot process, with hydrogenation, oxidation, bromination
or photocyclization.
ꢀ
2006 Elsevier Ltd. All rights reserved.
In the framework of our studies on the conversion of
multi-step reactions into economically and environmen-
bination of the Wittig olefination with other processes
based on separate entrapment of some of the reacting
components within silica sol–gel matrices.
1
–3
8
tally favored one-pot processes, we found that Wittig
reactions with a sol–gel entrapped tertiary phosphine
can be combined in the same vessel with several other
processes. Since the alkenes are fundamental building
blocks for numerous chemicals, several attempts have
already been made to develop special technologies for
The polycondensation of tetramethoxysilane (TMOS),
2-diphenyl(phosphino)ethyltri(ethoxy)silane, Ph P(CH ) -
2
2 2
Si(OEt) , and N-(2-aminoethyl)-3-aminopropyltri(meth-
3
oxy)silane, H N(CH ) NH(CH ) Si(OMe) , affords het-
2
2 2
2 3
3
4
9
such combinations. Notable are the reactions per-
erogenized phosphorus containing reagents (HPR) that
can be applied in the condensation of aldehydes and
benzyl halides. Some representative examples for the
applications of this reagent to the Wittig olefination
reaction are listed in Table 1. The diamine may be
5
formed under solid-state synthesis conditions which in
6
a few cases proceed in a highly selective fashion, but
7
more often form a complex mixture of products. In this
letter, we report an alternative system for one-pot com-
a
Table 1. Condensation of some aldehydes and benzyl chlorides in the presence of HPR
b
Entry
Aldehyde
CHO
4-CH
4-ClC
4-O NC
2-ClC
Halide
Reaction time, h
Products (yield in the first run, %)
E-C CH@CHC (80)
E-4-CH CH@CHC
E-4-ClC CH@CHC
E-4-O NC
E-2-ClC
1
2
3
4
5
6
7
8
C
6
H
5
C
6
C
6
C
6
C
6
C
6
H
5
H
5
H
5
H
5
H
5
CH
CH
CH
CH
CH
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
12
12
12
16
12
12
12
16
6
H
5
6 5
H
3
C
6
H
4
CHO
3
C
6
H
4
6
H
5
(91)
6 5
H (84)
6
H
4
CHO
6
H
4
2
6
H
4
CHO
2
6
H
4
CH@CHC
CH@CHC
6
H
5
(53)
6
H
4
CHO
6
H
4
6
H
5
(72)
C
6
H
5
CHO
4-CH
4-O NC
4-CH
4-CH
3
C
C
6
6
H
H
4
CH
CH
2
Cl
Cl
E-4-CH
E-4-CH
3
C
C
6
H
H
4
CH@CHC
CH@CHC
6
6
H
5
(90)
–4-CH
–4-NO
3
C
6
H
4
CHO
CHO
3
4
2
3
6
4
H
4
3
(81)
(36)
2
6
H
4
4-O
2
NC
6
H
4
CH
(CH
aldehyde (0.5 mmol), and dry toluene (7 ml), stirring under N
2
Cl
E-4-O
2
NC
6
H
4
6
CH@CHC H
4
2
a
Reaction conditions: HPR [generated from 0.66 mmol Ph
2
2
)
2
Si(OEt)
3
and 0.83 mmol H
2
N(CH
2
)
2
NH(CH
2
)
3
Si(OMe)
3
], chloride (0.5 mmol),
at 110 ꢁC. The filtered solution was concentrated and the product was separated by
2
13
1
chromatography and analyzed by GC, GCMS, and H and C NMR by comparing with authentic samples.
The yields are the average of at least two reactions that did not differ by more than 5%.
b
Keywords: Catalysis; One-pot synthesis; Silica sol–gel; Wittig reaction.
*
Corresponding author. Tel.: +972 2 6585329; fax: +972 2 6513832; e-mail: jblum@chem.ch.huji.ac.il
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.11.021

294
K. Hamza, J. Blum / Tetrahedron Letters 48 (2007) 293–295
Table 2. Combined multi-step one-pot reactions with HPR
a
Entry
Non-entrapped reaction components
Sol–gel entrapped components
Temp (ꢁC)
Time (h)
Products (yield, %)
(PhCH (77)
E-PhCH@CHPh (68)
(PhCH (52)
PhCHBrCHBrPh (54),
E-PhCH@CHPh (18)
PhCHBrCHBrPh (40),
1
2
3
4
PhCH
PhCH
PhCH
PhCH
2
2
2
2
Cl, PhCHO, H
2
HPR, RhCl(PPh
3
)
3
110
98
110
80
20
12
20
2 2
)
b
Cl, PhCH
Cl, PhCH
2
OH
OH, H
HPR, PyCr
b
2
2
HPR, PyCr, RhCl(PPh
3
)
3
2 2
)
þ
ꢀ
c
Cl, PhCHO
Cl, PhCHO
Cl, PhCHO, O
HPR, Py HBr
20
3
þ
ꢀ
5
6
PhCH
PhCH
2
2
HPR, Py HBr
80
78
12
3
E-PhCH@CHPh (28)
d
e
2
, I
2
(hv)
HPR
20
C
14
H
10 (55), E- and
f
Z-PhCH@CHPh (20)
a
b
c
d
e
f
In separated sol–gel matrices.
A 1:1.05 molar mixture of 2-(trimethoxysilylethyl)pyridine and chromium trioxide was used.
The Wittig condensation was conducted for 12 h followed by treatment with the entrapped bromination reagent for 8 h.
The Wittig condensation was conducted for 12 h followed by UV irradiation for 8 h.
Phenanthrene.
Minute changes in the irradiation conditions caused significant differences in the ratio of the Z:E isomers, but the total yield remained the same.
omitted from the HPR and added, instead, to the solu-
tion of the aldehyde and the halide. Reactions con-
ducted with entrapped or free diamine give essentially
the same results. Surprisingly, unlike the Wittig reaction
phosphine oxide, which in the absence of the diamine
could be reduced to the active P(III) reagent by HSiCl
3
1
3
and Me NPh and recycled in a second run. Thus when
2
benzyl chloride was reacted with benzaldehydes and
H N(CH ) NH(CH ) Si(OMe) in the presence of the
1
0
under conventional conditions, the experiments listed
2
2 3
2 3
3
in Table 1 afford solely products with an E configuration
entrapped phosphine, and the latter was recovered by
(
see Table 2).
HSiCl reduction, we obtained in the first four runs,
3
under the conditions of Table 1, 80%, 68%, 68%, and
65% of E-stilbene, respectively.
Solid-state P NMR studies11 suggest that in the
absence of entrapped diamine, the heterogenized tertiary
phosphine, and benzyl chloride form, after heating in
toluene for 6.5 h at 50 ꢁC, a sol–gel entrapped phospho-
nium salt. The resulting ceramic material has a broad
3
1
The main advantage of performing the Wittig reaction
with sol–gel entrapped components is the ability to com-
bine this process with other reactions in one pot. For
example, it is possible to perform the condensation de-
scribed in entry 1 together with a hydrogenation process
3
1
11
P NMR peak centered at 30.25 ppm, which resem-
bles that of soluble [Ph P(CH Ph)(CH ) Si(OEt) ] Cl
at 29.44 obtained by interaction of Ph P(CH ) Si(OEt)
+
ꢀ
2
2
2 2
3
1
4
in the presence of the heterogenized Wilkinson catalyst
2
2 2
3
and PhCH Cl under homogeneous conditions. The
to give 77% of bibenzyl after 20 h. This combined
one-pot process has been further extended by the addi-
tion of an oxidation step. Instead of starting the conden-
sation with benzaldehyde, this reagent was generated by
in situ oxidation of benzyl alcohol with sol–gel en-
2
3
1
solid-state P NMR signal of the product of benzyl
chloride and HPR (that contains immobilized diamine)
appears at ꢀ9.62 ppm. This suggests the formation of
3
1
a heterogenized ylide. It resembles the P signal of
the ylide generated from [Ph P(CH Ph)(CH ) -
1
5,16
trapped pyridinium dichromate.
Thus, all three
2
2
2 2
+
ꢀ
Si(OEt) ] Cl and H N(CH ) NH(CH ) Si(OMe) in
toluene, which appears at ꢀ9.44 ppm.
stages, the oxidation of the carbinol, the olefination of
the aldehyde, and the hydrogenation of the Wittig
product have been performed as a one-pot process (see
Scheme 1). The overall yield of bibenzyl from benzyl
alcohol was after 20 h in boiling n-heptane 52%. In the
absence of the immobilized hydrogenation catalyst, only
E-stilbene was formed in 68% yield.
3
2
2 2
2 3
3
1
1
The electronic nature of the reagents affects the hetero-
genic Wittig reaction in a rather unexpected way. Unlike
1
0
the effect in the conventional process, electron donat-
ing methyl substituents (Table 1, entries 2 and 7) en-
hance the rate, while electron attracting groups (entries
4
and 8) cause it to slow down. The effect of the steric
Two further one-pot multi-step reactions with HPR
have been performed. One is the combination of the
Wittig condensation with a bromination process, and
the second one combines the Wittig reaction with photo-
cyclization (Scheme 1). Stilbene dibromide was obtained
by two methods. The first one consisted of a one-pot
consecutive process where benzyl chloride, benzaldehyde,
and HPR were first heated in n-heptane at 80 ꢁC for
12 h followed by the addition of sol–gel-bound pyridi-
constraints can be deduced from comparison of the
reactions of the isomeric 2- and 4-chlorobenzaldehydes
listed as entries 3 and 5.
Although it has been reported that strong guanidine
bases smoothly transform phosphonium salts to
ylides, it seems that the weaker diamine H N(CH ) -
1
2
2
2 2
NH(CH ) Si(OMe) requires the activation by the silica
2
3
3
4
3
in the matrix. While the reaction described in entry 1
gives 80% of E-stilbene, the analogous homogeneous
process gives (in two steps) only 37% of the product.
nium hydrobromide perbromide and further heating
of the mixture at the same temperature for 8 h. meso-
Dibromobibenzyl was obtained in 54% yield along with
1
8% of E-stilbene and 25% of each of the unreacted
During the Wittig condensation the entrapped
Ph P(CH ) Si(O) is converted into the corresponding
starting compounds. Alternatively, the various reac-
tion components were heated together in n-heptane at
2
2 2
3

K. Hamza, J. Blum / Tetrahedron Letters 48 (2007) 293–295
295
O
OH py Cr O @s.g.
H
2
2
7
H2
HPR C H CH Cl
RhCl(PPh
) @s.g.
3 3
6
5
2
Br
+
py HBr3-@s.g.
O , hν
2
Br
Si(O)3
NH
Si(O)
3
HPR:
PPh2
+
@s.g.
H N
2
Scheme 1. Some one-pot reactions combined with the Wittig olefination.
8
0 ꢁC and afforded after 12 h a mixture of 40% of the
7. Regen, S. L.; Kodomari, M. J. Chem. Soc., Chem.
Commun. 1987, 1428–1429.
dibromide, 16% of E-stilbene and 30–32% of unreacted
starting reagents. In analogy to the combination of the
Heck coupling with photocyclization, we combined a
photochemical process with the heterogeneous Wittig
condensation. Irradiation of a mixture of HPR, benzyl
chloride, benzaldehydes, and benzene at 78 ꢁC in a
quartz well with a 150 W medium pressure mercury
lamp afforded under an ambient atmosphere after
8
. We recall that a few phosphorans have already been
bound to silica surfaces but have not been entrapped
within porous matrices: (a) Feher, F. J.; Phillips, S. H. J.
Organomet. Chem. 1996, 521, 401–403; (b) Outran, H. S.;
Raw, S. A.; Taylor, J. K. Tetrahedron Lett. 2002, 43,
2
6
185–6187.
. A typical procedure for the formation of HPR was as
follows: solution of tetramethoxysilane (3 ml,
9
A
2
0 h, 41% of phenanthrene and 10% of isomeric stilb-
20.34 mmol) in MeOH (4 ml, 101 mmol) was treated for
20 min at room temperature with water (4 ml, 101 mmol).
A mixture of N-(2-aminoethyl)-3-aminopropyltri(meth-
oxy)silane (0.54 ml, 2.5 mmol) 2-(diphenylphosphino)eth-
yltri(ethoxy)silane (0.752 ml, 2 mmol) and MeOH (4 ml,
enes. The yield of the cyclization product could be in-
creased to 55% by performing the processes stepwise,
that is, by initial interaction of the HPR with benzyl
chloride and benzaldehydes for 12 h under an N atmo-
sphere followed by the UV irradiation in the presence of
air for 8 h.
2
1
01 mmol) was added. The gel which was formed within a
few minutes was aged for 16 h and dried at 1 mm for 12 h.
The resulting xerogel was washed with CH Cl (10 ml),
2
2
sonicated twice for 15 min and redried for 3 h.
0. Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–
In summary, we have shown that the application of the
sol–gel technology to the Wittig reaction enables to
combine it with other processes as a one-pot process
and save the need of isolation and purification of the
reaction intermediates.
1
927, and references cited therein.
3
1
11. The solid-state P NMR was recorded on a Bruker DMX
500 NMR spectrometer equipped with a solids BL-4
4 2 4
probe. The spectral reference was external (NH )H PO
and the chemical shifts were calculated to fit the standard
scale of 0.00 for 85% orthophosphoric acid: Jasinski, A.;
Sulek, Z. Phys. Status Solidi B 1976, 74, K5–K8.
Acknowledgements
1
2. For example, (a) Simoni, D.; Rossi, M.; Rondanin, R.;
Mazzali, A.; Barucello, R.; Malagutti, C.; Roberti, M.;
Invidiata, F. P. Org. Lett. 2000, 2, 3765–3768; (b)
Blackburn, L.; Pei, C.; Taylor, J. K. Synlett 2002, 215–218.
3. Bernard, M.; Ford, W. T. J. Org. Chem. 1983, 48, 326–
We gratefully acknowledge the support of this study by
the Israel Science Foundation (ISF) through Grant No.
1
77/03.
1
1
1
3
32.
4. Gelman, F.; Blum, J.; Avnir, D. J. Am. Chem. Soc. 2000,
122, 11999–12000.
5. Gelman, F.; Blum, J.; Avnir, D. New J. Chem. 2003, 27,
205–207.
References and notes
. Blum, J.; Avnir, D. In Handbook of Sol–Gel Science and
1
Technology; Sakka, S., Ed.; Kluwer: Boston, 2005; Vol. 3,
pp 507–526, and references therein.
. Hamza, K.; Abu-Reziq, R.; Avnir, D.; Blum, J. J. Org.
Lett. 2004, 6, 925–927.
. Levin, Y.; Hamza, K.; Abu-Reziq, R.; Blum, J. Eur. J.
Org. Chem. 2006, 1396–1399.
. See, for example, Kelly, S. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Schreiber, S. L., Eds.;
Pergamon: Oxford, 1991; Vol. 1, pp 730–817, and refer-
ences cited therein.
16. In a typical combination of the Wittig condensation with
oxidation and hydrogenation processes, a mixture of
benzyl alcohol (0.5 mmol), benzyl chloride (0.5 mmol),
HPR (0.83 g containing 0.66 mmol of the tertiary phos-
phine and 0.83 mmol of the diamine), sol–gel entrapped
silylated pyridinium dichromate (prepared from
2.28 mmol 2-(trimethoxysilylethyl)pyridine, and 2.4 mmol
2
3
4
of CrO ), sol–gel encaged RhCl(PPh ) (prepared from
3 3 3
ꢀ
2
15
2.5 · 10 mmol of the free rhodium complex) and n-
heptane (15 ml) was stirred under N in an autoclave for
2
5
6
. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.;
Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.;
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1
12 h at 98 ꢁC. The N was replaced by H and the vessel
2
2
was pressurized to 13 bar and the heating was continued
for another 8 h. The sol–gel material was filtered off, and
the filtrate was concentrated and chromatographed on
silica gel. GC, GCMS and NMR analyses indicated the
presence of 52% of bibenzyl.
2
000, 3815–4195.
. Bolli, M. H.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1
998, 2243–2246.
1