A direct synthesis of vinylphosphonium salts from α-trimethylsilyl ylides and non-enolizable aldehydes

Article abstract of DOI:10.1002/chem.200801358

A direct synthesis of vinylphosphonium salts from α-trimethylsilyl ylides and non-enolizable aldehydes was reported. The vinylphosphonium salt was isolated in 90% yield and with high stereoselectivity favoring the (E)-olefin. High chemoselectivity observed favoring Peterson elimination over Wittig-type elimination and general stereoselectivity favoring (E)-vinylphosphonium salts require free-rotation about the central C-C bond of a betaine intermediate. The results show that the clean synthesis of the stable silylphosphonium iodide salt, subsequent generation of its yield derivative, and stoichiometric reaction with aldehydes at low temperature allows highly selective vinylphosphonium salt formation. It is also seen that the (E)-vinylphosphonium stereoselectivity is due to kinetic control involving Peterson syn-elimination from the erythro betaine.

Full text of DOI:10.1002/chem.200801358

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DOI: 10.1002/chem.200801358
A Direct Synthesis of Vinylphosphonium Salts from a-Trimethylsilyl Ylides
and Non-Enolizable Aldehydes
James McNulty* and Priyabrata Das[a]
Although the first reported synthesis of a vinylphosphoni-
um salt 4 appeared almost 1.5 centuries ago,[1] their utility as
synthetic intermediates awaited a flurry of publications in
the mid-1960s.[2–4] The electrophilic nature of the olefin in
such species was demonstrated through the conjugate addi-
tion of phenyllithium[2] and a range of simple nucleophiles
derived from enolizable precursors and amines.[3] Conjugate
addition to vinylphosphonium salts leads to an initial phos-
phorane (ylide) which may be subsequently trapped through
an intra- or intermolecular olefination reaction. Schweizer
and co-workers expanded the scope of vinylphosphonium
salts to a range of conjugate addition-trapping reactions.[4]
The use of this electron deficient olefin as a dienophile in
Diels–Alder and other cycloaddition reactions has also been
demonstrated.[3] Surprisingly, few reports on synthetic appli-
cations of vinylphosphonium salts have appeared in the liter-
ature since.[5] The synthesis of vinylphosphonium salts is usu-
ally accomplished through quaternization of a trialkyl- or
triarylphosphane with a bromoethane derivative containing
a b-leaving group, the olefin being introduced through a
subsequent elimination step. The tetravinylphosphonium[6]
cation was recently reported through a similar pathway
from phosphine (PH3). Triarylvinylphosphonium salts have
also been reported via Pd-mediated phosphination of vinyl
bromides and triflates,[7] Pd-mediated alkyne addition[8] and
via an electrochemical oxidation process.[9] Thus, synthesis
of vinylphosphonium salts requires the prior assembly of a
corresponding vinyl bromide or vinyl triflate, an alkylating
agent containing an appropriate b-leaving group or a func-
tionalized alkyne. The limitation in routes available for the
synthesis of vinylphosphonium salts is arguably the major
hindrance to their more widespread use, given the range of
valuable synthetic interconversions that have been demon-
strated.
We have recently become interested in the synthesis and
reactivity of 1,1-bis-heteroatom substituted methylenes[10]
and methines[11] as a route to useful synthetic intermediates
through olefination reactions with readily available carbonyl
compounds. An alternative route towards the synthesis of
vinylphosphonium salts might potentially be the reaction be-
tween an a-silylated ylide and carbonyl compound, as out-
lined in Scheme 1. The intermediate, here shown as the silyl
betaine, could potentially eliminate in Peterson fashion
through O-silyl migration yielding a vinylphosphonium salt,
or alternatively through Wittig-type elimination of phos-
phane oxide from the betaine (or oxaphosphetane) yielding
a
vinylsilane. While a-trimethylsilyl ylides are well
known,[12] their reactions with carbonyl compounds are re-
ported to be complex,[13] yielding allenes[12a,13b] and many
side products. Furthermore, the one example[13a] of
a
straightforward olefination with an a-silyl ylide reacting
with benzaldehyde is reported to give the vinylsilane prod-
uct in good yield, a result that has been claimed to be gener-
al.[13c] On the basis of these reports, the direct synthesis of
vinylphosphonium salts from a-silyl ylides and carbonyl
compounds would not appear promising. Nonetheless, these
results appeared unusual to us for several reasons. First of
all, high chemoselectivity has previously been documented
favouring Peterson-type elimination over Horner–Emmons
phosphonate elimination with a-silyl phosphonate/aldehyde
intermediates.[11] Secondly, Gilman initially postulated a vi-
nylphosphonium intermediate in such a reaction (although it
was not isolated) and showed that vinylphosphonium salts
[a] Prof. Dr. J. McNulty, P. Das
Department of Chemistry, McMaster University
1280Main Street West
Hamilton, Ontario, L8S 4M1 (Canada)
Fax : (+1)905-522-2509
E-mail: jmcnult@mcmaster.ca
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801358.
Scheme 1. Synthesis of vinylsilanes and/or vinylphosphonium salts via the
reaction of an aldehyde with an a-silyl ylide.
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Table 1. Reaction of (TMS)CHPBu3 with aldehydes.
could independently be converted to allenes, the main prod-
ucts of Gilmanꢁs investigation.[12a] We have reinvestigated
this chemistry, as shown in Scheme 2. Herein we report the
finding that a-silyl ylides react with aldehydes to provide vi-
nylphosphonium salts in high yield. Commercially avail-
able[14] iodomethyltrimethylsilane (1) selectively reacts with
tributylphosphane (2) yielding the a-trimethylsilylphospho-
nium salt 3. The ylide derived from 3 enters into Peterson-
type olefination reactions with aldehydes with high selectivi-
Entry Aldehyde
4
E/Z Yield [%]
1
49:1 90
2
3
49:1 95
49:1 92
ty providing
a direct, general synthesis of tributyl-
ACHTREUNG(vinyl)phosphonium salts 4.
4
5
6
49:1 91
49:1 85
49:1 90
49:1 90
Scheme 2. Synthesis of vinylphosphonium salts via the ylide derived from
3.
The reaction of chloromethyltrimethylsilane with triphe-
nylphosphane or tributylphosphane 2 proceeded in THF to
provide a mixture of the phosphonium chloride correspond-
7
8
ing to 3 and triphenyl- or tributylACHTRE(UNG methyl)phosphonium
chloride.[15] Desilylation reactions are characteristic in many
of the a-silyl ylide preparations described above,[12a,b,d] pro-
duced via chloride mediated desilylation and protonation of
the intermediate ylide. We first found that the correspond-
ing iodide salt 3 can be formed (ICH2TMS, Bu3P, THF,
208C, 13 h) and that this salt is stable in solid form and in
CDCl3 solution for at least two months. The stability of the
5:1
3:1
85
99
9
À
iodide salt is most likely due to the lesser propensity for Si
10
11
3:1
1:3
1:3
90
78
75
I bond formation in comparison to the chloride analogue. A
general procedure was then developed for the selective Pe-
terson reaction through ylide formation from 3, generated
under kinetically controlled conditions, reacting with a
range of aldehydes. Thus, a THF solution of 3 was cooled to
À788C and one equivalent of sBuLi added providing a
yellow solution of the ylide to which was added one equiva-
lent of 4-chlorobenzaldehyde. The dry-ice bath was removed
after 2 h and the reaction allowed to warm to room temper-
ature. The desired vinylphosphonium salt 4a was isolated in
90% yield and with high stereoselectivity favouring the (E)-
olefin.
12
13
1.1:1 77
The reaction proved to be very general for a range of
both electron-rich and electron-deficient aromatic alde-
hydes, all of which yielded the desired phosphonium salts in
excellent yield and high stereoselectivity (Table 1, entries 1
to 7). In addition, heterocyclic derivatives could be prepared
from 3-substituted furan, indole and pyridine derivatives in
high yields but with slightly lower stereocontrol (Table 1, en-
tries 8 to 10).
The synthetic utility of this novel reaction as a route to
conjugated 1,3-dienylphosphonium salts was also investigat-
ed with a range of unsaturated aldehydes (Table 1, entries
11–13). The isolated yields were invariably good in all of the
cases investigated, however, the reactions proceeded with
lower stereoselectivity. The reaction was also investigated
with hexanal, which provided a 60% yield of a 3:1 Z/E mix-
ture of the corresponding vinyl phosphonium salts. In this
case
a
significant amount (35%) of the tributyl-
AHCTRE(UNG methyl)phosphonium salt was also formed which we attri-
bute to protonation and enolate-induced desilylation of the
ylide derivative of 3. High stereoselectivity appears to be re-
stricted to non-enolizable aldehydes at present, although the
chemoselectivity favouring vinylphosphonium over vinylsi-
lane formation remains completely dominant.
The high chemoselectivity observed favouring Peterson
elimination over Wittig-type elimination and general stereo-
selectivity favouring (E)-vinylphosphonium salts also offers
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Vinylphosphonium Salts
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some interesting insights into the mechanism of the Wittig
reaction itself. Although the initial formation of oxaphos-
phetanes is now accepted,[16] a clear, stepwise account of the
reaction mechanism is still debated[16a] and much discussion
has been made over the relative importance of oxaphosphe-
tane versus betaine intermediates in the Wittig reaction.[16b]
In the present case, the ob-
tween the TMS group and aldehyde substituents and of 1,3-
steric effects between the alkyl groups on phosphorus and
the aryl substituent of the aldehyde are both expected to
favour the puckered cis transition state, leading to the eryth-
ro oxaphosphetane, as shown in Scheme 3. Oxaphosphetane
opening, bond rotation and Peterson-type elimination then
served Peterson elimination is
revealing as it requires free-ro-
À
tation about the central C C
bond of a betaine intermedi-
ate, prior to O-silyl transfer
and elimination. If an oxaphos-
phetane is the kinetic inter-
mediate in the present case,
this is evidence that it readily
ionizes to the betaine inter-
Scheme 3. Stereoselectivity favouring (E)-vinylphosphonium salts via the kinetic erythro betaine.
mediate, under kinetically controlled conditions, in contrast
to a direct elimination of tributylphosphane oxide, which
would yield the corresponding vinylsilane.
provides the (E)-vinylphosphonium salt. The overall results
appear to indicate that the predominantly (E)-vinylphospho-
nium stereoselectivity is due to kinetic control involving Pe-
terson syn-elimination from the erythro betaine. The transi-
tion state leading to the diastereomeric oxaphosphetane
(and hence threo betaine) intermediate may be slightly
more favourable on the basis of electronic effects. 1,3-Sec-
ondary orbital interactions between the electron rich p-mo-
lecular orbital system in entry 8 or 9, or the lone pair in the
case of entry 10, and empty d orbital on phosphorus would
be expected to stabilize the planar trans transition state and
explaining the lower stereoselectivities that are observed in
those cases.
It is difficult to rationalize the prior report on the synthe-
sis of a vinylsilane from an a-silyl ylide,[13a] although this
previous result employed an entirely salt-free ylide. The re-
action of silylated ylides is reported to be complex, however,
we note that many of the earlier methods[12,13] employ an
excess of base or carbonyl component, use less reactive ke-
tones such as benzophenone and often contain excess of co-
ordinating halide, particularly chloride, which is prone to de-
silylate the necessary intermediates.[12] The clean synthesis
of the stable silylphosphonium iodide salt 3, subsequent gen-
eration of its ylide derivative and stoichiometric reaction
with aldehydes at low temperature nonethelss allows highly
selective vinylphosphonium salt formation. The present re-
action may of course proceed kinetically via the betaine-
type intermediate, and proceed to an oxaphosphetane only
in the complete absence of lithium salts,[13a] followed by
Wittig-type elimination providing the vinylsilane. Thus, we
have also investigated the reaction of the ylide derived from
3 with piperonal (Table 1, entry 5) under salt-free conditions.
The original process gave high yield of essentially the pure
(E)-vinylphosphonium salt. When a solution of the ylide
was prepared under identical conditions and the resulting
lithium iodide (93% calculated mass of LiI recovered) fil-
tered off through canula, addition to piperonal gave the vi-
nylphosphonium salt with lower stereoselectivity (3:2 E/Z).
Importantly, no vinylsilane formation or phosphane oxide
was formed, indicating that the preferred mode of reaction
remains Peterson-like. This result may indicate that a cata-
lytic amount of lithium salt may be all that is required to
favour the Peterson elimination via oxaphosphetane open-
ing.
In conclusion, we have shown that a-trimethylsilyl-
AHCTRE(UNG methyl)phosphonium iodide may be prepared from the re-
action of tributylphosphane and iodomethyltrimethylsilane
and that its ylide derivative adds cleanly to aromatic and un-
saturated aldehydes, eliminating selectively in Peterson fash-
ion to yield vinylphosphonium salts in excellent yield and
(E)-stereoselectivity. Further extension and application of
this unprecedented and chemoselective method for vinyl-
phosphonium salt synthesis is currently under investigation.
Experimental Section
TrimethylsilylACTHRE(UNG methyl)tributylphosphonium iodide 3: Into a flame-dried
flask, containing a magnetic stirring bar, was weighed iodomethyltrime-
thylsilane (200 mL, 1.346 mmol) under argon and dry THF (2.7 mL) was
added to make a 0.5m solution. The flask was stirred for 15 min. at room
temperature whereupon tributylphosphane (353 mL, 1.413 mmol) was
added slowly to the reaction flask. The flask was maintained at room
temperature for 13 h. Solvent was removed under vacuum to yield the
title compound (0.555 g, 99%) as colourless crystals. M.p. 101–1028C;
1H NMR (600 MHz, CDCl3): d=0.30 (s, 9H); 0.95 (m, 9H); 1.53 (m,
12H), 1.87 (d,
J
P, H =17.0Hz, 2H); 2.36 ppm (m, 6H); 13C NMR
Although speculative, stereochemical arguments can also
be made for the intermediacy of oxaphosphetane intermedi-
ates in the reaction. The high (E)-stereoselectivity observed
can be rationalized in terms of the currently accepted transi-
tion states leading to the oxaphosphetane intermediates.[16a]
Relief of torsional and 1,2-non-bonding interactions be-
(150MHz, CDCl 3): d=1.0, 6.9 (d, J=42.3 Hz), 13.6, 22.2 (d, J=49.2 Hz),
23.9 (d, J=12.1 Hz), 24.1 ppm; 31P NMR (80MHz, CDCl 3): d=34.9 ppm;
HRES MS: m/z: calcd for C16H38PSi: 289.2468, found: 289.2480[ M]+.
(E)-2-(3’,4’-Methylenedioxyphenyl)vinyl-1-tributylphosphonium
(Table 1, entry 5): Into a flame-dried flask, containing a magnetic stirring
bar, was weighed trimethylsilyl(methyl)tributylphosphonium iodide
iodide
AHCTREUNG
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8471

J. McNulty and P. Das
(200 mg, 0.481 mmol) under argon and dry THF (1 mL) was added to
make a 0.5m solution. The flask was stirred for 15 min. at À788C where-
upon sBuLi (360 mL, 0.505 mmol, 1.4m stock, C6H12) was added slowly.
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After 40min,
a 0.5 m solution (in THF) of piperonal (75.8 mg,
0.505 mmol) was added slowly to the reaction flask maintained at À788C.
The flask was kept at À788C for 2 h and then slowly warmed to room
temperature where it was stirred for a further 2 h. The resulting mixture
was concentrated to remove solvent. Water was added (5 mL) to the resi-
due, and the resulting mixture was extracted with dichloromethane (3ꢂ
15 mL). The combined organic layers were dried over MgSO4, filtered,
and concentrated. Hexane was added (5 mL) to the flask which was
stirred, vacuum filtered and dried to yield the title compound (195 mg,
85%) as a yellow solid. 1H NMR (600 MHz, CDCl3): d=0.92 (m, 9H),
[6] U. V. Monkowius, S. D. Nogai, H. Schmidbaur, J. Am. Chem. Soc.
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1.50(m, 12H), 2.55 (m, 6H), 5.90(s, 2H); 6.71 (dd,
17.5 Hz, 1H), 6.84 (d, JHH =8.5 Hz, 2H), 7.22 (s, 1H), 7.59 ppm (dd,
H,H =17.5, JP, H =20.9 Hz, 1H); 13C NMR (150MHz, CDCl 3): d=13.6,
JH,H =17.5, JP, H =
[8] M. Arisawa, M. Yamaguchi, J. Am. Chem. Soc. 2000, 122, 2287–
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J
20.1 (d, J=47.2 Hz), 23.8, 23.9 (d, J=19.3 Hz), 101.7 (d, J=64.8 Hz),
102.0, 107.0, 108.6, 125.8, 128.6 (d, 18.8 Hz), 148.6, 150.8, 152.5 ppm (d,
J=3 Hz); 31P NMR (80MHz, CDCl 3): d=27.7 ppm; HRES MS: m/z:
calcd for C21H34O2P: 349.2282, found: 349.2296 [M]+.
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Acknowledgements
We thank Cytec Canada Inc. and NSERC for financial support of this
work.
Keywords: alkenes
compounds · ylides
·
betaines
·
carbanions
·
vinylic
mixture of a-trimethylsilylACHTRE(UGN methyl)triphenylphosphonium and tri-
phenylmethylphosphonium salts.
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Received: July 4, 2008
Published online: August 7, 2008
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