Silylium ion-catalyzed challenging Diels-Alder reactions: The danger of hidden proton catalysis with strong Lewis acids

Article abstract of DOI:10.1021/ja211856m

The pronounced Lewis acidity of tricoordinate silicon cations brings about unusual reactivity in Lewis acid catalysis. The downside of catalysis with strong Lewis acids is, though, that these do have the potential to mediate the formation of protons by various mechanisms, and the thus released Bronsted acid might even outcompete the Lewis acid as the true catalyst. That is an often ignored point. One way of eliminating a hidden proton-catalyzed pathway is to add a proton scavenger. The low-temperature Diels-Alder reactions catalyzed by our ferrocene-stabilized silicon cation are such a case where the possibility of proton catalysis must be meticulously examined. Addition of the common hindered base 2,6-di-tert-butylpyridine resulted, however, in slow decomposition along with formation of the corresponding pyridinium ion. Quantitative deprotonation of the silicon cation was observed with more basic (Mes)₃P to yield the phosphonium ion. A deuterium-labeling experiment verified that the proton is abstracted from the ferrocene backbone. A reasonable mechanism of the proton formation is proposed on the basis of quantum-chemical calculations. This is, admittedly, a particular case but suggests that the use of proton scavengers must be carefully scrutinized, as proton formation might be provoked rather than prevented. Proton-catalyzed Diels-Alder reactions are not well-documented in the literature, and a representative survey employing TfOH is included here. The outcome of these catalyses is compared with our silylium ion-catalyzed Diels-Alder reactions, thereby clearly corroborating that hidden Bronsted acid catalysis is not operating with our Lewis acid. Several simple-looking but challenging Diels-Alder reactions with exceptionally rare dienophile/enophile combinations are reported. Another indication is obtained from the chemoselectivity of the catalyses. The silylium ion-catalyzed Diels-Alder reaction is general with regard to the oxidation level of the α,β-unsaturated dienophile (carbonyl and carboxyl), whereas proton catalysis is limited to carbonyl compounds.

Full text of DOI:10.1021/ja211856m

Article
pubs.acs.org/JACS
Silylium Ion-Catalyzed Challenging Diels−Alder Reactions: The
Danger of Hidden Proton Catalysis with Strong Lewis Acids
Ruth K. Schmidt,†,‡ Kristine Muther,†,‡ Christian Muck-Lichtenfeld,‡ Stefan Grimme,‡,§
̈
̈
and Martin Oestreich*,†,‡
†Institut fur Chemie, Technische Universitat Berlin, Strasse des 17. Juni 115, 10623 Berlin, Germany
̈
̈
‡Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, Corrensstrasse 40, 48149 Munster, Germany
̈
̈
̈
̈
§Mulliken Center for Theoretical Chemistry, Institut fur Physikalische und Theoretische Chemie, Rheinische
Friedrich-Wilhelms-Universitat Bonn, Beringstrasse 4, 53115 Bonn, Germany
̈
̈
S
* Supporting Information
ABSTRACT: The pronounced Lewis acidity of tricoordinate silicon cations brings about unusual reactivity in Lewis acid
catalysis. The downside of catalysis with strong Lewis acids is, though, that these do have the potential to mediate the formation
of protons by various mechanisms, and the thus released Brønsted acid might even outcompete the Lewis acid as the true
catalyst. That is an often ignored point. One way of eliminating a hidden proton-catalyzed pathway is to add a proton scavenger.
The low-temperature Diels−Alder reactions catalyzed by our ferrocene-stabilized silicon cation are such a case where the
possibility of proton catalysis must be meticulously examined. Addition of the common hindered base 2,6-di-tert-butylpyridine
resulted, however, in slow decomposition along with formation of the corresponding pyridinium ion. Quantitative deprotonation
of the silicon cation was observed with more basic (Mes)3P to yield the phosphonium ion. A deuterium-labeling experiment
verified that the proton is abstracted from the ferrocene backbone. A reasonable mechanism of the proton formation is proposed
on the basis of quantum-chemical calculations. This is, admittedly, a particular case but suggests that the use of proton scavengers
must be carefully scrutinized, as proton formation might be provoked rather than prevented. Proton-catalyzed Diels−Alder
reactions are not well-documented in the literature, and a representative survey employing TfOH is included here. The outcome
of these catalyses is compared with our silylium ion-catalyzed Diels−Alder reactions, thereby clearly corroborating that hidden
Brønsted acid catalysis is not operating with our Lewis acid. Several simple-looking but challenging Diels−Alder reactions with
exceptionally rare dienophile/enophile combinations are reported. Another indication is obtained from the chemoselectivity of
the catalyses. The silylium ion-catalyzed Diels−Alder reaction is general with regard to the oxidation level of the α,β-unsaturated
dienophile (carbonyl and carboxyl), whereas proton catalysis is limited to carbonyl compounds.
carbonyl12,15 hydrosilylation as well as in aliphatic C−F bond
INTRODUCTION
Silylium ions, tricoordinated silicon cations, are extremely
■
dehydrofluorination,9b,16 and it also includes silicon cation-
promoted polymerization reactions with diverse initiation
strategies.13,17 The use of silicon cations in transformations
where these are released unchanged after the catalytic event is
particularly attractive, as it holds significant potential in the
broad area of Lewis acid catalysis. While tetracoordinate silicon
Lewis acids, e.g., Me3SiOTf (4) and Me3SiNTf2 (5), are widely
applied in synthetic chemistry,18 these are either not able to
catalyze, e.g., “challenging” Diels−Alder reactions, or require
high loadings. A remarkable counteranion-dependent reactivity
difference between Me3SiOTf (4) and Me3SiNTf2 (5) was
demonstrated by Ghosez in the cycloaddition of cyclohexa-1,3-
diene (1) and methyl acrylate (2) (Scheme 1).19 To identify a
more reactive silicon Lewis acid, Sawamura20 introduced the
solvent-stabilized silicon cation [Et3Si(toluene)]+[B(C6F5)4]−
(6)5 to the above Diels−Alder reaction (Scheme 1). Recently,
our research group established the ferrocene-stabilized silylium
ion 721 as an even more effective catalyst for difficult Diels−
strong Lewis acids due to the electron sextet at the silicon
atom.1 Serious efforts had been invested into the isolation of a
“naked” three-coordinate silicon cation until a combination of
steric shielding of the empty orbital at the silicon atom and the
use of weakly coordinating anions finally allowed for the
crystallographic characterization2 of Lambertʼs “free” Mes3Si+
cation3 with Reedʼs [HCB11Me5Br6]− anion.4 During this long
quest and thereafter, many inter- and intramolecularly donor-
stabilized silylium ions were discovered; π basic solvents5 and
groups,6 weakly σ coordinating counteranions7 and halogen
atoms,8 as well as Si−H bonds9,10 were accidently found or
deliberately utilized to lend stabilization to the cationic silicon
atom.
Despite the progress in isolation and characterization of
silicon cations, it was only realized recently that these electron-
deficient compounds are promising reagents in catalysis.11
There are now several processes where the reactive silicon
cation is consumed in a bond formation but another molecule
of the silicon cation is then regenerated from a suitable
precursor in a subsequent step (self-regeneration,12 not self-
healing or self-repair13). That is found in alkene14 and
Received: December 20, 2011
Published: February 6, 2012
© 2012 American Chemical Society
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8 (Figure 1), prepared from the corresponding alcohol by
protonation followed by dehydration, was tested as a chiral
Scheme 1. Comparison of Different Silicon Lewis Acids 4−7
as Catalysts in the Diels−Alder Reaction of Cyclohexa-1,3-
diene (1) and Methyl Acrylate (2)
Figure 1. Planar chiral ferrocene-stabilized carbenium ion 8 used by
Sammakia.
Lewis acid catalyst in Diels−Alder reactions. As only racemic
material was obtained and the addition of the proton-scavenger
2,6-di-tert-butylpyridine inhibited the reaction, it was concluded
that it must be protons to promote the reaction.
Aware of these findings, we wished to secure that our
ferrocene-based silylium ion 7 indeed acts as a Lewis acid
catalyst in those unusual Diels−Alder reactions22 rather than a
proton source. Our concern was further fueled by the known
ring-opening protonolysis of sila[1]ferrocenophane 9, provid-
ing access to ether-stabilized analogue 10 of our silicon cation 7
(Scheme 2, upper).41 We, therefore, anticipated the reverse
Alder reactions, and excellent yields and endo/exo selectivities
were obtained at low temperatures.22−24
Scheme 2. Ring-Opening Protonolysis of Sila-
[1]ferrocenophane 9 (top) and Proposed Origin of Protons
Generated from Silylium Ion 7 (bottom) [ArF = 3,5-
Bis(trifluoromethyl)phenyl]
When dealing with Lewis acid catalysis, the possibility of
competing Brønsted acid catalysis (in part or as a whole) must
always be considered. It is, however, an issue that is rarely
alluded to, except for the actively explored current areas of
metal-catalyzed hydroamination and related transforma-
tions25−29 as well as transition metal-catalyzed carbophilic
activation.30−33 It is particularly the former catalyses where
proton-catalyzed pathways are now experimentally veri-
fied.26−28 Conversely, the role of protons in gold-catalyzed
reactions is not generally clarified.30 A recent quantum-
chemical comparison of gold- and proton-catalyzed alkene
hydroamination resulted in different (stepwise and concerted)
mechanisms;31 gold and proton catalysts might even produce
different constitutional isomers.32 It was also demonstrated for
a platinum-catalyzed skeletal rearrangement that the same
enyne metathesis is catalyzed by a Brønsted acid.33 There are
other individual investigations uncovering proton instead of
Lewis acid catalysis.34
With regard to Diels−Alder reactions, proton catalysis was
infrequently suspected to be operating.35 In fact, very little is
known about the use of achiral (inorganic) Brønsted acids as
promoters in simple Diels−Alder reactions,36 and that is
particularly noteworthy in view of the recent success in
asymmetric Brønsted acid catalysis.37 An early report by
Wassermann38 qualitatively showed the catalytic activity of
several Brønsted acids in Diels−Alder reactions of cyclo-
pentadiene with quinones. Six decades later (!), Yamamoto
observed a reversal of chemoselectivity in Diels−Alder
reactions with α,β-unsaturated aldehydes and ketones depend-
ing on the choice of catalyst.39 When an equimolar mixture of
acrolein and ethyl vinyl ketone was reacted with cyclo-
pentadiene, bulky Lewis acids selected the aldehyde whereas
Brønsted acids preferentially activated the more basic ketone.
Although Sawamura had ruled out proton catalysis in the
case of [Et3Si(toluene)]+[B(C6F5)4]− as the silylium ion
catalyst,20 a forgotten investigation by Sammakia40 attracted
our attention. The planar chiral ferrocene-based carbenium ion
reaction to be a conceivable origin of protons in our catalysis
(Scheme 2, lower). In this full account, we report a
spectroscopic and theoretical analysis of this hypothesis and
we also present a systematic comparison of silylium ion- and
Brønsted acid-catalyzed Diels−Alder reactions of simple-
looking but unusually difficult dienophile/enophile combina-
tions.
RESULTS AND DISCUSSION
■
Proton Release Mechanism or Provoking Proton
Abstraction: NMR Experiments. As an initial experiment,
we spectroscopically examined an equimolar mixture of our
silylium ion 7 and the proton-scavenger 2,6-di-tert-butylpyr-
idine.42 This hindered nitrogen donor was expected to not form
a Lewis pair with the electrophilic silicon atom but act as a base
instead. A small amount of the protonated pyridine was
observed in the 1H NMR spectrum immediately recorded after
mixing both compounds in 1,2-Cl2C6D4 at room temperature
(cf. the Supporting Information). Its quantity increased upon
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prolonged reaction time while the disappearance of the signals
corresponding to 7 indicated decomposition.
To further elucidate the origin of the proton(s), we decided
to employ (Mes)3P, a stronger and also hindered phosphorus
base (Scheme 3, upper). That would also allow for monitoring
observed (Scheme 3), thereby providing unambiguous evidence
for the proton to originate from the ferrocene group.43
Proton Release Mechanism or Provoking Proton
Abstraction: DFT Calculations. The deprotonation of
silylium ion 7 to the sila[1]ferrocenophane 11 using (Mes)3P
and 2,6-di-tert-butylpyridine as bases was modeled with DFT
calculations (TPSS-D3/dev2-TZVPP,44−46 cf. the Supporting
Information for details). We investigated the reaction in a
solvent, 1,2-dichlorobenzene, using a continuum solvation
model (COSMO).47
Scheme 3. Reaction of Silylium Ions 7 and d9-7 with (Mes)3P
a
(top ) and 1H and 2H NMR Spectra (middle) and 31P NMR
Spectra (bottom) of the Resulting Phosphonium Salts 12
and d1-12
The large dip angle of 7 (Figure 2, left) and the partly
covalent character of the Si−C′ipso bond21 are a first indication
Figure 2. Silylium ion 7 and sila[1]ferrocenophane 11 (TPSS-D3/
def2-TZVPP + COSMO). Selected bond lengths (Å): 7: Si−Fe, 2.440;
Fe−C′ipso, 2.063; Si−C′ipso, 2.621. 11: Si−Fe, 2.700; Fe−C′ipso, 2.007;
Si−C′ipso, 1.900.
that the abstraction of the proton at the C′ipso atom might be
facile; 11 (Figure 2, right) is indeed a stable energetic
minimum. Attempts to locate a C′ipso-protonated intermediate
(“σ-complex”) with a short Si−C′ipso bond yielded the silicon
cation 7 in all cases, indicating that its deprotonation is a one-
step process.
Location of transition structures (TSs) was achieved with
both (Mes)3P and 2,6-di-tert-butylpyridine as proton scav-
engers. Geometries and selected atom distances are given in
Figure 3. It is immediately notable from the shortened Si−C′ipso
a
Mes = mesityl (2,4,6-trimethylphenyl); counteranion [B(C6F5)4]− is
omitted for the sake of clarity.
the reaction by 31P NMR spectroscopy. An equimolar mixture
of 7 and (Mes)3P immediately showed quantitative formation
of the phosphonium salt 12 (= protonated phosphine), as
Figure 3. Transition structures of the deprotonation of silylium ion 7
with (Mes)3P (TS−P, left) and di-tert-butylpyridine (TS−N, right)
(TPSS-D3/def2-TZVPP + COSMO). Selected atom distances (Å):
1
indicated by a doublet in both the H NMR and 31P NMR
TS−P: C′ipso−H, 1.399; H−P, 1.841; Si−C′ipso, 2.023. TS−N: C′ipso
H, 1.372; H−N, 1.409; Si−C′ipso, 2.035.
−
1
spectra with a JP,H coupling constant of 477 Hz (Scheme 3).
The very broad ferrocene signals in the 1H NMR spectrum (cf.
1
the Supporting Information for the full H NMR spectrum)
distances that the structure of the silicon fragment is
significantly changed compared to that of the cation, largely
resembling that of the product. Si−C bond formation is
therefore the main structural change during the initial phase of
the deprotonation. The C′ipso−H distance in the TS is slightly
longer in TS−P (1.399 Å) than in TS−N (1.372 Å), but this is
a consequence of the larger H−base distance in the former.
suggested decomposition of 7. To prove the ferrocene
backbone's involvement in this, we repeated this NMR
experiment with silylium ion d9-7 containing a deuterated
ferrocenyl substituent (93% deuteration grade). As expected, a
2
1
doublet in the H NMR spectrum and a triplet with a JP,D
coupling constant of 72 Hz in the 31P NMR spectrum were
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The deprotonation is exothermic with both bases (Table 1);
under otherwise identical reaction conditions.49 The use of the
stronger Brønsted acid Tf2NH50 as the proton source also had
no effect. The situation with the most reactive carbonyl
compound 13 (Z = CHO) was similar. It had also performed
well in the Lewis acid-catalyzed reaction while the protic media
appeared to primarily promote oligomerization of aldehyde 13,
and isolation of the desired adduct 15 proved difficult. We
were, however, pleased to note that 14 (Z = C(O)Me) reacted
smoothly to afford 16 in both the silylium ion and the proton
catalysis; the isolated yield was lower in the latter though. It
must be noted that addition of (Mes)3P (1.1 equiv based on 7)
to silicon cation 7 completely thwarted the same low-
temperature Diels−Alder reaction, thereby indicating that
catalysis is not promoted by the phosphonium ion. Conversely,
less basic 2,6-di-tert-butylpyridine reacts only slowly with the
silicon cation (even at room temperature), and this silylium
ion-catalyzed Diels−Alder reaction proceeded nicely in its
presence. The outcome of this pair of catalyses is evidence
against hidden proton catalysis.
reaction with (Mes)3P is more favorable by 3.9 kcal·mol−1.
Table 1. Energies and Barriers for the Deprotonation of
Ferrocene-Stabilized Silicon Cation 7 by (Mes)3P and 2,6-
a
Di-tert-butylpyridine
energies and barriers
(kcal·mol−1
)
base
(Mes)3P
di-tert-butylpyridine
medium
ΔE
ΔE⧧
1,2-Cl2C6H4
1,2-Cl2C6H4
−6.7
−2.8
+13.4
+18.6
a
TPSS-D3/def2-TZVPP+COSMO.
Both reaction barriers are in a range suitable for reaction at
ambient temperatures. Proton abstraction is, however, expected
to be significantly slower with the hindered pyridine than that
with the phosphine, as the energy difference of the transition
states is 5.2 kcal·mol−1. Assuming similar activation entropies,
this difference should result in rate constants differing by a
factor of 1.5 × 10−4. This agrees nicely with the different rates
observed in the NMR experiments.
Survey of Silylium Ion- and Proton-Catalyzed Diels−
Alder Reactions. To compare our silicon Lewis acid 7 and the
Brønsted acid TfOH (generated from Tf2O and H2O) as
catalysts in low-temperature Diels−Alder reactions (Scheme
4),48 we tested representative dienophiles at various oxidation
As expected, on the basis of the chemoselectivity reported by
the Yamamoto group,39 we found α,β-unsaturated ketones to
be the preferred dienophiles for the Brønsted acid-catalyzed
Diels−Alder reaction. We therefore decided to investigate the
application of both our silicon cation 7 and TfOH as catalysts
in Diels−Alder reactions in more detail.
Silylium Ion-Catalyzed Diels−Alder Reactions of α,β-
Unsaturated Ketones. We began exploring the scope of our
silylium ion catalysis in the reaction of relatively unreactive
cyclohexa-1,3-diene (1) [approximately 500 times less reactive
than cyclopentadiene (34)] with a challenging selection of
acyclic and cyclic dienophiles 14 and 17−21 (Table 2). We
note here that there are hardly any examples reported for the
seemingly simple Diels−Alder reaction of 1 and 18−21.
As methyl vinyl ketone (14) had undergone the reaction in
high yield (Scheme 4 and Table 2, entry 1), we also examined
commonly employed ethyl vinyl ketone (17) with success
(Table 2, entry 2). We next turned our attention to the β-aryl-
substituted dienophiles 4-phenyl-butenone (18) and chalcone
(19) with E configuration (Table 2, entries 3 and 4). To the
best of our knowledge, only two reports of their Diels−Alder
reactions with cyclohexa-1,3-diene (1) exist, requiring either
high pressure51a or microwave heating.51b We were therefore
delighted to find that, with 5.0 mol % of 7 at a reaction
temperature of −40 °C, we obtained both adducts 23 and 24 in
good yield and with superb endo/exo selectivity. As reported
before,22 cyclic ketones 20 and 21, which are equally delicate
dienophiles in Diels−Alder reactions, reacted particularly well,
and adducts 25 and 26 were formed with excellent endo/exo
ratios (Table 2, entries 5 and 6).
Scheme 4. Comparison of Lewis and Brønsted Acid-
Catalyzed Diels−Alder Reactions of Cyclohexa-1,3-diene (1)
and Representative Dienophiles 2, 13, and 14 (Si = tert-
Butylferrocenylmethylsilyl)
We also examined the same series of dienophiles 14 and 17−
21 in the silylium ion-catalyzed Diels−Alder reaction with
slightly more reactive 2,3-dimethyl-1,3-butadiene (27) [approx-
imately 250 times less reactive than cyclopentadiene (34)]
(Table 3).
Alkyl-substituted acyclic 14 and 17 again performed well,
yielding the desired adducts 28 and 29 in good yields after just
1 h at −78 °C (Table 3, entries 1 and 2). The uncommon β-
aryl-substituted dienophiles 18 and 19 reacted at slightly
elevated temperature of −40 °C, affording adducts 30 and 31 in
good yields (Table 3, entries 3 and 4). For cyclic 20, we
detected full conversion to 32 (GC-MS analysis) after only
minutes, but we were not able to isolate the product 32 in pure
form, assuming decomposition upon workup. In turn, cyclic 21
levels (2, 13, and 14) in the cycloaddition with cylohexa-1,3-
diene (1). Reaction rates for the 5.0 mol % of Brønsted acid
employed here are likely to be much higher than that
potentially released from 5.0 mol % of our silicon cation, but
reaction rates with a more realistic amount of 0.50 mol %
TfOH were significantly slower; essentially the same results
were obtained.
As to least reactive α,β-unsaturated carboxyl compound 2 (Z
= C(O)OMe), the outcome of the silicon cation and Brønsted
acid catalyses was dramatically different. Our previously
reported silylium ion-catalyzed procedure yielded adduct 3
almost quantitatively whereas no reaction occurred with TfOH
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Table 2. Silylium Ion-Catalyzed Diels−Alder Reactions of
α,β-Unsaturated Ketones 14 and 17−21 with Cyclohexa-1,3-
Table 3. Silylium Ion-Catalyzed Diels−Alder Reactions of
α,β-Unsaturated Ketones 14 and 17−21 with 2,3-Dimethyl-
a
a
diene (1)
1,3-butadiene (27)
a
All reactions were performed according to General Procedure 2 (GP
2 in the Supporting Information) at a concentration of 0.5 M of the
b
dienophile. Determined by GLC analysis of the reaction mixture
c
d
prior to purification. trans/cis ratio. Analytically pure product after
a
All reactions were performed according to General Procedure 2 (GP
flash column chromatography on silica gel.
2 in the Supporting Information) at a concentration of 0.5 M of the
b
c
dienophile. trans/cis ratio. Analytically pure product after flash
yielded analytically pure 33 in moderate isolated yield (Table 3,
entries 5 and 6).
d
column chromatography on silica gel. Full conversion; decomposition
upon isolation.
Proton-Catalyzed Diels−Alder Reactions of α,β-Un-
saturated Ketones. We next turned our attention to Brønsted
acid-catalyzed Diels−Alder reactions, applying our straightfor-
ward protocol to the previous selection of α,β-unsaturated
ketones as dienophiles and three representative dienes (Tables
4−6).
As shown in our comparative survey (Scheme 4), methyl
vinyl ketone (14) reacted with cyclohexa-1,3-diene (1) in high
yield (Table 4, entry 1). We also examined ethyl vinyl ketone
(17) and found that after only half an hour full conversion had
occurred, and 22 was isolated in moderate yield (Table 4, entry
2). Challenging substrate 18 underwent the Diels−Alder
reaction with 1 to form 23 in decent yield (Table 4, entry
3); even at a reaction temperature of 0 °C, full conversion was
not reached though. Not surprisingly, more challenging
chalcone (19) was not sufficiently reactive in the Brønsted
acid catalysis (Table 4, entry 4). No conversion of the
dienophile was seen at ambient temperature and after
prolonged reaction times. Cyclic 20 and 21 were equally
unreactive, but the former decomposed after three days at room
temperature (Table 4, entries 5 and 6).
at −78 °C to form adducts 28 and 29, respectively, in decent
yields (Table 5, entries 1 and 2). Again, β-aryl-substituted 18
performed well to yield 30 (Table 5, entry 3). We next
examined the reaction of chalcone (19) with 27. There had
been only one previous example of a catalytic Diels−Alder
reaction of these reaction partners reported,52 and we were
therefore delighted to find that our TfOH catalysis yielded
significant amounts of 31 (Table 5, entry 4). Conversely, cyclic
20 and 21 were still too unreactive in the proton catalysis
(Table 5, entries 5 and 6), and only decomposed material was
detected with 10 mol % TfOH after several days at 0 °C or
room temperature.
We decided to also investigate the Brønsted acid-catalyzed
Diels−Alder reaction of cyclopentadiene (34), arguably the
most commonly used diene. Alkyl-substituted 14 and 17 again
reacted smoothly at low temperature to form 35 and 36 in
good yields and with excellent endo/exo selectivities (Table 6,
entries 1 and 2). 18 with an aryl substituent in the β-position
afforded 37 at −40 °C in good yield (Table 6, entry 3).
Remarkably, the scarcely reported53,54 Diels−Alder reaction of
chalcone (19) also proceeded cleanly to yield 38 with high
endo/exo selectivity (Table 6, entry 4). With diene 34, cyclic 20
Similar results were obtained in the TfOH-catalyzed Diels−
Alder reaction with 2,3-dimethyl-1,3-butadiene (27). The
reactions of alkyl vinyl ketones 14 and 17 proceeded rapidly
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Table 4. Proton-Catalyzed Diels−Alder Reactions of α,β-
Unsaturated Ketones 14 and 17−21 with Cyclohexa-1,3-
Table 5. Proton-Catalyzed Diels−Alder Reactions of α,β-
Unsaturated Ketones 14 and 17−21 with 2,3-Dimethyl-1,3-
a
a
diene (1)
butadiene (27)
a
All reactions were performed according to General Procedure 3 (GP
3 in the Supporting Information) at a concentration of 0.5 M of the
b
dienophile. Determined by GLC analysis of the reaction mixture
c
d
a
prior to purification. trans/cis ratio. Analytically pure product after
All reactions were performed according to General Procedure 3 (GP
e
f
flash column chromatography on silica gel. 68% conversion. No
3 in the Supporting Information) at a concentration of 0.5 M of the
g
b
c
conversion. Traces due to decomposition under reaction conditions.
dienophile. trans/cis ratio. Analytically pure product after flash
d
n.d. = not determined.
column chromatography on silica gel. 5.0 and 10 mol % of TfOH.
Decomposition under reaction conditions.
e
and 21 reacted well under proton catalysis; 39 and 40 were
isolated in decent yields (Table 6, entries 5 and 6).
(ΔΔE⧧ = 5.2 kcal·mol−1) and thermodynamically (ΔΔE = 3.9
kcal·mol−1) favored for the hindered phosphine.
CONCLUSION
That indirect evidence for protons (through pyridinium and
phosphonium ions when adding proton scavengers) in the
silylium ion-catalyzed Diels−Alder reactions called for a
systematic comparison of these with the same set of reactions
potentially catalyzed by protons using TfOH and Tf2NH. One
immediate difference between silyium ion and proton catalysis
is its chemoselectivity in the reaction with α,β-unsaturated
dienophiles; catalysis with 7 is equally efficient with any
oxidation level whereas the Brønsted acids cannot promote the
reaction of α,β-unsaturated esters, and α,β-unsaturated
aldehydes are even oligomerized. Moreover, the silicon cation
7 catalyzes several simple-looking but delicate Diels−Alder
reactions with exceptionally rare dienophile/enophile combi-
nations at low temperature. Conversely, proton catalysis fails in
almost all of these cases.
■
Doubts about whether the unique reactivities seen in our
silylium ion-catalyzed Diels−Alder reactions are due to protons
rather than the ferrocene-stabilized silicon cation 7 marked the
beginning of the present investigation. The experimental
observation that 2,6-di-tert-butylpyridine is slowly protonated
under the above reaction setup further increased these doubts.
Proton catalysis is a serious but often ignored twist with strong
Lewis acids.
As verified by deuterium-labeling of the ferrocene backbone
of silicon cation 7 (= d9-7), hindered bases that will not form a
Lewis pair with the electrophilic silicon atom do abstract a
proton from the lower Cp ring with concomitant (assumed)
ring closure to yield the correponding sila[1]ferrocenophane
11; the reverse reaction, the ring-opening protonolysis with
[H(OEt2)2]+[B(ArF)4]−, is well-documented.41 The ring-open-
ing and, likewise, ring-closing events were found to be one-step
processes by quantum-chemical calculations. The deprotona-
tion was examined spectroscopically and theoretically with 2,6-
di-tert-butylpyridine and with (Mes)3P, and the data are in
excellent qualitative agreement. Proton abstraction is kinetically
All experimental data clearly support silylium ion catalysis
not blurred by proton catalysis, but in turn, it also suggests that
the use of proton scavengers must be carefully scrutinized, as
proton formation might be provoked rather than prevented.
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Journal of the American Chemical Society
Article
We thank Dr. Klaus Bergander (Universitat Munster) for
expert advice with nuclear magnetic resonance measurements.
̈
̈
Table 6. Proton-Catalyzed Diels−Alder Reactions of α,β-
Unsaturated Ketones 14 and 17−21 with Cyclopentadiene
a
(34)
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
2
Experimental details, characterization data, as well as H, H,
11B, 13C, 19F, 29Si, and 31P NMR spectra and quantum-chemical
calculation data. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
martin.oestreich@tu-berlin.de
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This research was supported by the Sonderforschungsbereich
858 of the Deutsche Forschungsgemeinschaft (Projects A3 and
Z1). R.K.S. is a member of the Integrated Research Training
Group within the Sonderforschungsbereich 858. K.M. thanks
the Studienstiftung des Deutschen Volkes for a predoctoral
fellowship (2009−2012). K.M. is a member of the International
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(16 h) was also sufficient: Klare, H. F. T. Ph.D. Thesis, Westfalische
̈
Wilhelms-Universitat Munster, Germany, 2011.
̈
̈
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Research Training Group Munster-Nagoya (GRK 1143 of the
̈
Deutsche Forschungsgemeinschaft). M.O. is indebted to the
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