Radical-chain isomerisation of allyl silyl ethers to silyl enol ethers in the presence of thiols as polarity reversal catalysts

Article abstract of DOI:10.1016/S0040-4039(01)00630-X

The radical-chain isomerisation of allyl silyl ethers to silyl enol ethers takes place on heating in the presence of an initiator and an arenethiol as a protic polarity reversal catalyst; pentafluorothiophenol is particularly effective in this role. The reaction complements the transition-metal-catalysed isomerisation and could be useful for the preparation of silyl enol ethers from readily available allylic alcohols.

Full text of DOI:10.1016/S0040-4039(01)00630-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4061–4064
Radical-chain isomerisation of allyl silyl ethers to silyl enol
ethers in the presence of thiols as polarity reversal catalysts
Alistair J. Fielding and Brian P. Roberts*
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK
Received 12 March 2001; accepted 11 April 2001
Abstract—The radical-chain isomerisation of allyl silyl ethers to silyl enol ethers takes place on heating in the presence of an
initiator and an arenethiol as a protic polarity reversal catalyst; pentafluorothiophenol is particularly effective in this role. The
reaction complements the transition-metal-catalysed isomerisation and could be useful for the preparation of silyl enol ethers from
readily available allylic alcohols. © 2001 Elsevier Science Ltd. All rights reserved.
Silyl enol ethers are important reagents for organic
synthesis, when they provide a source of nucleophilic
2
b) has been obtained recently under conditions of
4
kinetic control. We reasoned that allyl silyl ethers should
also undergo this type of rearrangement by a radical-
chain mechanism, in the presence of an appropriate thiol
1
carbon for CꢀC bond formation, for example in their
reactions with carbonyl electrophiles in the presence of
2
5
Lewis acid catalysts. The most common preparative
which would act as a protic polarity reversal catalyst to
methods for silyl enol ethers involve O-silylation of an
enolate ion or hydrosilylation of an a,b-unsaturated
carbonyl compound in the presence of a transition metal
catalyst. A third route involves the rearrangement of an
allyl silyl ether 1, generalised in Scheme 1, again under
the influence of a transition metal catalyst (usually Ru
promote the overall abstraction of hydrogen from the
electron-rich allylic HꢀCO bond in 1 by the chain-carry-
ing nucleophilic allylic radical. In this paper we report
that such rearrangements do indeed take place under
relatively mild, metal-free conditions and could provide
a useful route to silyl enol ethers 2 when the starting
allylic alcohol is readily available.
3
or Ir based), and a degree of stereoselectivity (2a versus
R3
R3
R3
R1
R1
R1
R4
OSiR3
OSiR3
R2 R4
R2 R4
R2 OSiR3
1
2a
2b
Scheme 1.
t
OSiPh But
2
OSiPh Bu
2
3
4
t
OSiPh But
OSiPh But
OSiPh Bu
2
2
2
5
6E
6Z
Scheme 2.
Keywords: radicals and radical reactions; catalysis; thiols; isomerisation; silicon and compounds.
*
0
Corresponding author.
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00630-X

4
062
A. J. Fielding, B. P. Roberts / Tetrahedron Letters 42 (2001) 4061–4064
Initial experiments were carried out with the 2-methyl-
1:2.8 in both cases. Simple distillation afforded 6 in
85% isolated yield and chromatography on silica gel
yielded pure 6Z, a sample of which was then heated
under reflux in octane for 2.5 h in the presence of PFTP
and DBPB (10 mol% of each). Isomerisation of the silyl
enol ether took place to give a final E:Z ratio of 1:2.8,
indicating that thermodynamic equilibrium between 6E
and 6Z is established under the conditions used to
convert 5 to 6. The radical-chain mechanism for the
isomerisation of allyl silyl ethers to silyl enol ethers is
illustrated in Scheme 3 and the function of the thiol is
to act as a protic polarity reversal catalyst to promote
the overall abstraction of allylic hydrogen from the
allyloxysilane by the allylic radical 7, a reaction that is
slow in the absence of thiol because of the lack of
favourable charge-transfer stabilisation of the transition
6
allyloxysilane 3 and conversion to the silyl enol ether 4
1
(
Scheme 2) was monitored by H NMR spectroscopy.
When a solution of 3 (1 mol) and azobis(isobutyro-
3
nitrile) (AIBN, 10 mol%) in dry benzene (1.5 cm ) was
heated under reflux under nitrogen for 2.5 h, the allyl
silyl ether was unchanged and no silyl enol ether was
detectable. However, when the experiment was repeated
in the additional presence of pentafluorothiophenol
(
PFTP, 10 mol%), clean and complete conversion of 3
to 4 took place. The same result was obtained when the
AIBN was replaced by dilauroyl peroxide (DLP, 10
mol%), whereas without any initiator but in the pres-
ence of thiol, no conversion to silyl enol ether was
observed. Choice of the thiol catalyst proved to be
critical since, under otherwise identical conditions, thio-
phenol, tert-dodecanethiol and tri-tert-butoxysilane-
thiol gave conversions to 4 of 21, 5 and 17%, respec-
5
state. The allylic radical 7 exists in syn and anti forms,
that can be detected separately by EPR spectroscopy at
7
11
tively.
low temperature, and trapping of 7-anti by the thiol
presumably gives the E-isomer of the silyl enol ether,
while trapping of 7-syn will give the Z-isomer.
Although these results point strongly to a radical-chain
mechanism for the isomerisation of 3 to 4, in principle,
some form of acid-catalysed process might be involved,
In order for effective thiol-catalysed conversion of an
allylic molecule to a more stable vinylic isomer (Scheme
4, D=electron-donating substituent), both reactions a
and c must be rapid. Furthermore, removal of thiol by
radical addition to the double bonds in the reactant or
8
the acid being generated in situ during the reaction. In
order to exclude this possibility, two identical reactions
A and B (10 mol% each of PFTP and AIBN) were run
side by side and samples were withdrawn from both for
NMR analysis after 15 min. At the same time, the
isolable aryloxyl radical galvinoxyl (10 mol%) was
’
product must be minimised, by making addition of XS
to the CꢁC bonds highly reversible and/or retarded by
the steric bulk of the thiyl radical. Both reactions a and
c will be favoured for more electrophilic thiyl radicals
but, since the activation energy for a reaction cannot be
less than its endothermicity, the strength of the SꢀH
bond should be such that neither reaction is signifi-
cantly endothermic. Although reaction a will be very
rapid with alkane- or silane-thiols as catalysts, reaction
c (and reaction b) is likely to be appreciably endother-
mic and relatively slow, with the equilibrium favouring
the allylic radical. Because of the weaker SꢀH bond in
thiophenol, reaction c will be faster and this thiol is a
more efficient catalyst. The SꢀH bond in PFTP is likely
9
added to flask B. After 15 min heating, conversion of
3
to 4 was 48% in reaction A and 45% in reaction B,
while after 2.5 h heating conversion was complete in
reaction A but still only 45% in the inhibited reaction
B. These results strongly support a radical-chain mech-
anism for the isomerisation process.
After 2.5 h in refluxing benzene under the usual condi-
tions, using PFTP as catalyst and DLP as initiator, 90%
of the allyl silyl ether 5 was converted to silyl enol ether
1
0
6
with an E:Z ratio of 1:3.0. However, isomerisation
was complete in refluxing toluene with 1,1-di-tert-
butylperoxycyclohexane (DBPC, 10 mol%) as initiator
or in refluxing octane with 2,2-di-tert-butylperoxy-
butane (DBPB, 10 mol%) as initiator; the E:Z ratio was
12
to be stronger than that in thiophenol, leading to a
still more favourable balance between reactions a and c,
and the presence of the ring-fluorine atoms in PFTP
will also maximise favourable polar effects for the
abstraction of hydrogen by the especially electrophilic
XS
OSiR3
OSiR3
-anti
OSiR3
7-syn
’
thiyl radical C F S , to give the nucleophilic siloxyallyl
XSH
6 5
radical (reaction a), as well as for abstraction of hydro-
gen from the thiol by the latter radical (reaction c).
7
XS XSH
XS XSH
The secondary allyl silyl ether 8 underwent isomerisa-
tion somewhat less readily than the primary analogue 5.
Thus, in refluxing benzene with AIBN and PFTP (both
OSiR3
OSiR3
1
0 mol%), conversion was 77% after 2.5 h (9E:9Z=
13
E
Z
1:1.9), although the conversion was increased to 86%
when the AIBN was replaced by DLP (Scheme 5). In
refluxing toluene (DBPC initiator) or refluxing octane
Scheme 3.
a
b
c
D
D
D
XS
XSH
XS
d
Scheme 4.

A. J. Fielding, B. P. Roberts / Tetrahedron Letters 42 (2001) 4061–4064
4063
t
t
t
OSiPh Bu
OSiPh Bu
OSiPh Bu
2
2
2
8
9E
9Z
OSiR3
OSiR3
R SiO
3
1
0 R Si = Me Si
11E R Si = Me Si
11Z R Si = Me Si
3 3
3
3
3
3
t
t
t
1
2 R Si = Ph Bu Si
13E R Si = Ph Bu Si
13Z R Si = Ph Bu Si
3 2
3
2
3
2
Scheme 5.
(
DBPB initiator) conversion was >98% (9E:9Z=1:1.6 in
the silyl enol ether could be isolated easily by simple
distillation of the reaction mixture. Density functional
calculations at the (U)B3LYP/6-31G(d,p) level of the-
both cases). The lower reactivity of secondary allyl-
oxysilanes seems likely to be mainly a stereoelectronic
effect, arising from the fact that the single allylic CH
bond is positioned close to the nodal plane of the double
bond in the preferred conformation of the starting
material, such that the allylic hydrogen atom is
abstracted relatively slowly by a thiyl radical; steric
effects may also play a role. A number of other allyl silyl
ethers were isomerised to silyl enol ethers under similar
conditions and the results are summarised in Table 1.
ory predict that the E- and Z-isomers of Me SiOCHꢁ
3
CHMe are lower in energy than the most stable confor-
14
mation of allyloxytrimethylsilane by 29.7 and 33.0 kJ
−
1
mol (DG at 25°C), respectively, while the syn-isomer
of the allylic radical 7 (R=Me) is more stable than the
−
1
anti-isomer by 1.4 kJ mol (compare Ref. 11). The
appreciably greater stability of the silyl enol ether com-
pared with the allyl silyl ether accords with the effec-
tively complete isomerisation of the latter observed
experimentally and the predicted equilibrium E:Z ratio
is ca. 1:2.8 at 115°C, in excellent agreement with the result
obtained in refluxing toluene (1:2.2).
Isomerisation of the prototypical allyloxytrimethylsilane
took place readily either in refluxing toluene or in the
neat silane as solvent (entries 2 and 3). In the latter case,
a
Table 1. Isomerisation of allyl silyl ethers to silyl enol ethers catalysed by pentafluorothiophenol
Entry
Allyl silyl ether
Silyl enol ether
Solvent
Initiator
Conversion
E:Z
ratioc
b
(%)
OSiMe2But
OSiMe3
OSiMe2But
OSiMe3
1
2
3
4
Toluene
Toluene
Neatd
DBPC
DBPC
DBPC
DBPB
95
1:2.6
1:2.2
1:2.2
1:2.0
>98
OSiMe3
OSiMe3
>98 (82)
>98
OSiMe2But
OSiMe2But
Octane
OSiMe2But
OSiMe2But
5
Toluene
DBPC
96e
1:13.0
Ph
Ph
OSiMe2But
OSiMe2But
6
7
8
9
Octane
Octane
DBPB
DBPB
>98
87
1:14.0
1:1.3
Ph
Ph
OSiPh2But
OSiPh2But
OSiMe2But
OSiMe2But
Octane
Benzene
Neatd
DBPB
AIBN
DBPC
AIBN
91
1:1.3
4.2:1
4.4:1
4.6:1
10
10
12
11
11
13
96
1
0
1
95 (78)
f
1
Benzene
96 (81)
a
3
Unless stated otherwise, reactions were carried out on the 1 mmol scale in 1.5 cm of solvent under reflux for 2.5 h, in the presence of PFTP
b
1
c
and initiator (both 10 mol%). Determined by H NMR spectroscopy; isolated yields of E/Z mixtures in parentheses. Isomers identified on the
basis of the magnitudes of the vicinal vinylic-proton coupling constants or of NOE experiments. Large scale (10-20 mmol); bath temperature
20°C. Conversions using tert-dodecanethiol or 4-fluorothiophenol (both 10 mol%) as catalysts were 2% and 11%, respectively. In refluxing
d
e
f
1
octane with DBPB as initiator, the conversion was >98% (E:Z=4.8:1).

4
064
A. J. Fielding, B. P. Roberts / Tetrahedron Letters 42 (2001) 4061–4064
t
The quantitative conversion of Bu Me SiOCHPh-
2,2-di-tert-butylperoxybutane (DBPB: 54 mL of a 50%
w/w solution in mineral oil, 0.1 mmol) in dry octane (1.5
cm ) was stirred and heated under reflux under nitrogen
2
CHꢁCH to the corresponding silyl enol ether (entry 5)
2
3
was reduced to almost zero when the PFTP was
replaced by tert-dodecanethiol, again emphasising the
importance of the choice of thiol catalyst. The low
efficiency of the alkanethiol is presumably a conse-
quence of the low rate of reaction c (Scheme 4), because
of the effective stabilisation of the phenyl-substituted
allylic radical intermediate involved in this isomerisa-
tion.
for 2.5 h. The solvent was removed under reduced pres-
sure and the silyl enol ether 4 (0.27 g, 87%) was isolated
by chromatography on silica gel (petroleum, bp 40–60°C,
eluent) as a colourless oil that solidified on standing (mp
ca. 30°C). (Found: C, 77.3; H, 8.2. C H OSi requires C,
20
26
7
7.4; H, 8.4%). NMR data for compound 4 (400 MHz
1
13
for H, 100 MHz for C, CDCl solvent, J in Hz). l
3
H
t
1
.09 (9H, s, Bu ), 1.35 (3H, s, Me), 1.66 (3H, s, Me), 6.07
1H, apparent septet, J ca.1.4, vinyl-H), 7.24–7.43 (6H,
m, aryl-H), 7.68–7.72 (4H, m, aryl-H); l 15.0, 19.2, 26.6,
The PFTP-catalysed isomerisation of primary allyl silyl
ethers could provide a very convenient source of silyl
enol ethers that might be less accessible from the appro-
priate aldehydes by O-silylation of their enolates. Thus,
the terpenoid (1R)-(−)-myrtenol, a primary allylic alco-
hol that is readily available from the chiral pool, can be
silylated under standard conditions to give the silyl
ethers 10 and 12 (Scheme 5). Isomerisation of both
compounds took place readily in refluxing benzene (or
in the neat state for ease of product isolation), to give
the silyl enol ethers 11 and 13 as predominantly the
E-isomers, presumably because of steric destabilisation
of the Z-isomers (entries 9–11).
(
C
29.7, 113.0, 127.7, 129.9, 133.3, 133.7 and 135.4. Satisfac-
tory spectroscopic data and elemental analyses were
obtained for all other new compounds.
. Pentafluorothiophenol is itself a relatively strong acid
8
(
pK ca. 2.7) because of the presence of the electronega-
a
tive ring-fluorine atoms, see: Jencks, W. P.; Salvesen, K.
J. Am. Chem. Soc. 1971, 93, 4433.
9
. As evidenced by the rapid colour change of the solution
from dark brown to pale yellow, galvinoxyl reacts imme-
diately with PFTP, presumably by abstraction of hydro-
gen to give the phenol monohydrogalvinoxyl that must
also act as a radical scavenger to inhibit the radical-chain
process. 2-6-Di-tert-butyl-4-methylphenol also inhibited
the isomerisation, although less effectively.
References
1
0. The E- and Z-isomers were readily distinguished on the
basis of the coupling constants between the vinylic pro-
tons.
1
. (a) Gennari, C. In Comprehensive Organic Synthesis;
Heathcock, C. H., Ed.; Pergamon Press: Oxford, 1991;
Vol. 2, Chapter 2.4; (b) Fleming, I.; Barbero, A.; Walter,
D. Chem. Rev. 1997, 97, 2063.
1
1
1. Elford, P. E.; Roberts, B. P. J. Chem. Soc., Perkin Trans.
2
1996, 2247.
2
3
4
. (a) Rasmussen, J. K. Synthesis 1977, 91; (b) Mukaiyama,
2. The presence of electronegative substituents on the ring
would be expected to strengthen the SH bond, compared
with that in thiophenol, see: Nau, W. M. J. Org. Chem.
1996, 61, 8312; J. Phys. Org. Chem. 1997, 10, 445.
T. Pure Appl. Chem. 1983, 55, 1749.
. Suzuki, H.; Koyama, Y.; Moro-oka, Y.; Ikawa, T. Tetra-
hedron Lett. 1979, 1415.
. Ohmura, T.; Shirai, Y.; Yamamoto, Y.; Miyaura, N.
Chem. Commun. 1998, 1337.
. Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25.
. Weigand, S.; Br u¨ ckner, R. Synthesis 1996, 475.
. Typical procedure: A solution of the allyl silyl ether 3
13. Geometrical isomers were identified on the basis of NOE
wexperiments.
5
6
7
14. The SiꢀO bond eclipses the CꢁC bond in the preferred
conformation; the conformation in which an allylic CꢀH
6
−
1
(0.31 g, 1.0 mmol), PFTP (13.3 mL, 0.1 mmol) and
bond eclipses the CꢁC bond is less stable by 3.1 kJ mol .
.