Carbocation catalysed ring closing aldehyde-olefin metathesis

Article abstract of DOI:10.1039/C8CC06734A

A highly efficient aldehyde-olefin metathesis catalysed by the carbocation, 4-phenylphenyl-diphenylmethylium ion, has been developed. This protocol is characterized by high yields, low catalyst loading (down to 2 mol%), good functional group compatibility and mild reaction conditions.

Full text of DOI:10.1039/C8CC06734A

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Carbocation catalysed ring closing
aldehyde–olefin metathesis†
Cite this: Chem. Commun., 2018,
54, 12982
Shengjun Ni
and Johan Franzen
*
´
Received 18th August 2018,
Accepted 24th October 2018
DOI: 10.1039/c8cc06734a
rsc.li/chemcomm
A highly efficient aldehyde–olefin metathesis catalysed by the
carbocation, 4-phenylphenyl-diphenylmethylium ion, has been
developed. This protocol is characterized by high yields, low catalyst
loading (down to 2 mol%), good functional group compatibility and
mild reaction conditions.
In contradiction to the well established transition metal catalysed
alkene–alkene metathesis,1 the direct catalytic carbonyl–olefin
metathesis is vastly underdeveloped despite its great potential
with respect to atom economy and substrate scope. In the
forefront of current research, a series of successful iron(III)-
catalysed ring closing ketone–olefin metathesis strategies have
been reported.2–6 However, the catalytic aldehyde–olefin meta-
thesis still remains elusive.7 As one of the few exceptions,
Lambert et al. reported the first aldehyde–olefin metathesis,
where they showed that a bicyclic hydrazine derivate could
catalyse the ring opening metathesis of cyclopropene derivatives
and aldehydes (Scheme 1, equiv. (a)).8 Unfortunately, this work
was limited to cyclopropene derivatives as the olefinic component.
Our group reported intermolecular aldehyde–olefin metathesis
by carbocation catalysis as an extension of the earlier report by
Bickelhaupt (Scheme 1, equiv. (b)).9–11 Although an important
proof of concept, from the synthetic point of view, this protocol
suffered from high catalyst loading and a rather limited
substrate scope. The main problem associated with aldehyde–
olefin metathesis is mainly due to the decomposition of both
the starting materials and the products in the presence of the
Lewis acid catalysts required for the reaction. Schindler et al.
reported a few specific examples of intramolecular aldehyde–
olefin metathesis in the formation of highly stable polycyclic
aromatic compounds (Scheme 1, equiv. (c)).3b
Scheme 1 Strategies toward aldehyde–olefin metathesis.
low catalyst loading with high yields (Scheme 1, equiv. (d)). It is
shown that the substituents on the olefin moiety as well as the
carbocation Lewis acidity are of crucial importance for mini-
mizing starting material and product decomposition.
The general mechanism for the Lewis acid mediated meta-
thesis is proposed to involve Lewis acid (LA) induced LUMO
activation of enal A through initial formation of oxonium ion B
(Scheme 2). The latter is now activated toward nucleophilic
attack from the pendant alkene moiety resulting in the forma-
tion of oxetane C. The formation of oxetane C can occur either
through a stepwise [2+2] mechanism involving a carbocationic
Here we show that 4-phenylphenyl-diphenylmethylium tetra-
fluoroborate efficiently catalyses the intramolecular aldehyde–
olefin metathesis of enals under mild reaction conditions and
Department of Chemistry, Organic Chemistry, Royal Institute of Technology (KTH),
Teknikringen 30, SE-100 44 Stockholm, Sweden. E-mail: jfranze@kth.se
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cc06734a
Scheme 2 Overview of the Lewis acid catalysed ring-closing metathesis.
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Table
1
Optimization of Lewis acid catalysed aldehyde–olefin ring
closing metathesisa
Yieldb (%)
Scheme 3 Comparison of aldehyde–olefin and ketone–olefin metatheses.
Entry
Catalyst
5
2a
6a
86
74
78
100
83
17
1
2
3
4
5
6
TrBF4
FeCl3
InCl3
BF3ÁEt2O
HBF4ÁEt2O
AlCl3
0
0
0
0
0
71
0
14
20
0
intermediate, or through a concerted [2+2] cycloaddition.
Recent mechanistic studies by Schindler et al. for FeCl3 cata-
lysed ketone–olefin metathesis show strong support for a Lewis
acid induced concerted, asynchronous [2+2]-cycloaddition.3c
A subsequent fragmentation of oxetane C, either a stepwise or
concerted retro-[2+2] cycloaddition, leads to the formation of
the cycloalkene adduct D and the carbonyl by-product E.
In line with our previous work9,11a–e and inspired by the
elegant work of Schindler3 and Li,4 we sought to overcome the
difficulties associated with the catalytic aldehyde–olefin meta-
thesis and turned our attention towards the trityl ion catalysed
ring closing metathesis of enal 1. After extensive optimization,
the best yield of indene 2a was 60% after full conversion of 1a
in only 5 minutes (Scheme 3). This indicates that enal 1 decom-
poses or undergoes side reactions in the presence of TrBF4.
Furthermore, as outlined in the mechanistic proposal of the
carbonyl–olefin metathesis (see Scheme 2), the metathesis
adduct D and a new carbonyl compound E are formed in a
1 : 1 ratio. Thus, a comparison of the yield of 2a with the yield of
the formed acetone (60% and 76%, respectively) indicates that
product 2a decomposes under these reaction conditions, most
likely through Lewis acid initiated polymerization. In compar-
ison, the metathesis of the corresponding ketone 3 under the
same reaction conditions gave a very high yield, almost the
same as that of 4 and acetone, indicating minor decomposition/
side reactions of starting material 1b and negligible trityl ion
induced decomposition of methyl-indene 4 (Scheme 3).
64
3
a
Reaction conditions: TrBF4 was added to 5a in DCM (0.01 M) for
4 hours at room temperature. Yields were determined by 1H NMR
b
spectroscopy.
Table 2 Evaluation of the influence of olefin substitution and carbocation
Lewis acidity on aldehyde–olefin metathesisa
Yieldb (%)
Entry
S. M.
R
Catalyst
t (h)
S. M.
2a
6
1
2
3
4
5
6
7
8c
7
8
p-NO2
p-MeO
o-Me
p-Me
o-Me
o-Me
o-Me
o-Me
TrBF4
TrBF4
TrBF4
TrBF4
Cat A
Cat B
Cat C
Cat C
2.5
5 min
40 min
15 min
29
4
3
100
0
0
0
8
0
0
0
0
22
75
60
17
76
80
80
0
26
84
74
78
85
86
86
9a
10
9a
9a
9a
9a
8
a
Reaction conditions: TrBF4 (10 mol%) was added to 7–10 in DCM
b
Inspired by Li’s work4 we instead investigated the trityl ion
catalysed ring closing metathesis of enals. Gratifyingly, indene
2a and benzaldehyde 6a were obtained in 71% and 86% yields,
(0.01 M) for the indicated time at room temperature. Yields were
determined by 1H NMR spectroscopy. 5 mol% of Cat C was used.
c
respectively (Table 1, entry 1). Surprisingly, FeCl3, which was decomposition and metathesis and only starting materials
successfully used for intramolecular ketone–olefin metathesis could be recovered (Table 2, entry 1). In contrast, increasing
both by Schindler and Li,3,4 rapidly consumed enal 5 without any the electron density/nucleophilicity of the alkene by introducing
observable formation of indene 2a (Table 1, entry 2). However, an electron donating para-methoxy-group greatly accelerated
the formation of benzaldehyde 6a in 74% yield shows that the the decomposition of enal 8 in the presence of TrBF4, enabling
metathesis do occur although indene 2a rapidly decomposes in full conversion in only 5 minutes with a low yield of indene 2a
the presence of FeCl3. The same outcome was observed for InCl3, (Table 2, entry 2). Additional tuning of the electronic properties
BF3ÁEt2O and HBF4ÁEt2O that gave benzaldehyde 6a in high of the alkene moiety revealed that the weak electron donating
yields and with low or no observable formation of indene 2a groups o-methyl 9a and p-methyl 10 shorten the reaction time,
(Table 1, entries 3–5). AlCl3 was the least efficient catalyst with leading to a somewhat reduced product decomposition and
only 36% conversion and 3% yield (Table 1, entry 6).12
only a minor increased enal decomposition (Table 2, entries 3
In order to gain further insight into the metathesis process, and 4). Among the latter, o-methyl substituted enal 9a was the most
in terms of reactivity and Lewis acid induced decomposition, efficient, affording indene 2a in 75% yield (Table 2, entry 3).13
we turned our attention to the styryl moiety. Decreasing the
After identifying the o-tolyl-group in enal 9a as the best
electron density/nucleophilicity through an electron with- alkene-leaving group, we investigated the influence of carboca-
drawing para-nitro group (enal 7) completely stopped both enal tion Lewis acidity on the aldehyde–olefin metathesis. The trityl
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ion constitutes a rather unique mode of carbon-centered Lewis The 5-methoxy-substituted enal 9d also had an accelerating
acidity with extensive possibilities for relatively easy tuning effect on the metathesis and gave 5-methoxy-indene 2d in 68%
through variation of the electronic properties of the surrounding isolated yield (Table 3, entry 4). In contrast, the 4-methyl-group
aromatic groups.11a–e,14 The trityl ions Cat A–C were screened as in enal 9e and the 2-benzyloxy-group in 9f gave the corres-
catalysts for the metathesis of enal 9a. The mono-methoxy ponding indenes 2e and 2f in low yields (Table 3, entries 5
substituted trityl ion, Cat A, is the least Lewis acidic carbocation and 6). This is most likely due to the increased product decom-
screened, due to the strong electron donating properties of the position as a result of the higher reactivity of 6-methyl-indene
p-methoxy-phenyl group to the carbocationic center. Unfortu- 2e and 4-benzyloxy-indene 2f caused by the electron donating
nately, the lower Lewis acidity of Cat A resulted in a drastically properties of the methyl- and benzyloxy-groups in the para- and
prolonged reaction time and low yield of indene 2a and did ortho-positions, respectively, to the indene double bond. Different
not prevent starting material/product decomposition (Table 2, halogenated enals were also screened and fluorinated enals
entry 5). The mono-methyl substituted trityl ion, Cat B, is a 9g–i gave indenes 2g–i in good yields. However, the 5-chloro-
considerably stronger Lewis acid compared to Cat A although it substituent in enal 9j had a negative effect on the metathesis
is less Lewis acidic compared to TrBF4 and gave full conversion and 5-chloro-indene 2j was isolated in 45% yield.
after 4 h (Table 2, entry 6). Interestingly, despite the increased
We next evaluated functionalization at the benzylic position
reaction time, the yield was virtually the same as for TrBF4, of enals 11 that would allow for easy access to 1-functionalized
indicating that product decomposition was considerably slower indenes 12 (Table 4). To our delight, functionalization at this
with Cat B (Table 2, entry 6). However, after extensive screening, position had a remarkable effect on the reactivity and for the
we found that with the mono-p-phenyl substituted trityl ion, Cat C catalysed metathesis of enals 11a–h, the catalyst loading
Cat C, the yield of indene 2a could be increased up to 80% within could be reduced down to 2.0 mol% without any loss in the
3 h (Table 2, entry 7). Notably, reducing the catalyst loading to efficiency. Under these conditions, the corresponding products
only 5 mol% prolonged the reaction time to 8 h without any loss 12a–h were isolated in 78–84% yields within less then one hour.
in the yield (Table 2, entry 8). Thus, the p-phenyl substituted This drastic increase in the reactivity is most likely due to
trityl ion, Cat C, almost completely diminished product decom- the Thorpe–Ingold effect favouring cyclization. However, the
position, giving essentially the same yields of metathesis adduct 3-benzyloxypropyl functionalized enal 11i reacted considerably
2a and 2-methylbenzaldehyde 6.
slower and required 5 mol% catalyst loading to give indene 12i
With these optimal conditions in hand (Cat C (5 mol%), in 80% yield. The terminal alkene moiety in enal 11j had a
DCM, RT), the aldehyde–olefin metathesis of enal 9a gave negative influence on the metathesis with an increased reaction
indene 2a in 81% isolated yield (Table 3, entry 1). Introducing time and side reactions to give 12j in only 37% yield.
a methyl-substituent in the 5-position of enal 9b gave the corre-
In conclusion, we have developed a direct organocatalytic
sponding 7-methyl-indene 2b in 71% yield (Table 3, entry 2). aldehyde–olefin ring closing metathesis. The reaction is oper-
In contrast, the 3-methyl-group in enal 9c greatly accelerated ationally simple and enables direct coupling of aldehydes and
the metathesis and afforded 7-methyl-indene 2c in 78% yield pendant olefins in the presence of the easily available 4-phenyl-
within 30 minutes of reaction time (Table 3, entry 3). The phenyl-diphenylmethylium ion as the Lewis acid catalyst. The
increased reactivity is most likely a result of 1,3-allylic strain catalyst loadings can be reduced as low as 2 mol% and the
induced by the 3-methyl-group that locks the conformation with
the olefin side chain in closer proximity to the aldehyde moiety.
Table 4 Substrate scope of carbocation catalysed aldehyde–olefin ring
closing metathesisa
Table 3 Substrate scope of carbocation catalysed aldehyde–olefin ring
closing metathesisa
Entry
S. M.
R
Product
t (h)
Yieldb (%)
Entry
S. M.
R
Product
t (h)
Yieldb (%)
1
2
3
4
5
6
7
11a
11b
11c
11d
11e
11f
11g
11h
11i
Me
n-Butyl
Cyclopentyl
Phenylethyl
Phenylpropyl
3-Chlorophenylethyl
2-Fluorophenylethyl
4-Methylphenylethyl
3-Benzyloxypropyl
3-Butenyl
12a
12b
12c
12d
12e
12f
12g
12h
12i
0.5
1
0.5
1
0.75
1
1
1
1
4
78
83
84
84
80
83
81
81
80
37
1
2
3
4
5
6
7
8
9
10
9a
9b
9c
9d
9e
9f
9g
9h
9i
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
8
4
0.5
0.75
6
1.75
4
0.5
4
5
81
71
78
68
40
26
80
60
73
45
5-Methyl
3-Methyl
5-Methoxyl
4-Methyl
2-BnO
4-Fluro
6-Fluro
8
9c
10c
4,5-Difluro
5-Chloro
11j
12j
9j
2j
a
Reaction conditions: Cat C (2 mol%) was added to 11 in DCM (0.01 M)
a
b
c
Reaction conditions: Cat C (5 mol%) was added to 9 in DCM (0.01 M) for the indicated time at RT. Isolated yield. 5 mol% catalyst loading
b
for the indicated time at room temperature. Isolated yield.
was used.
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7 During the preparation of this manuscript, Schindler et al. reported
on the GaCl3 catalyzed aldehyde–olefin ring opening metathesis
with low to moderate yields. H. Albright, H. L. Vonesh, M. R. Becker,
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products are isolated in good yields, often in a very clean and
selective manner. With the developed procedure, a variety of
functionalized indene derivatives could be easily prepared. This
protocol represents a rare example of a catalytic aldehyde–
olefin metathesis and efforts to extend this process to a broader
array of substrates are currently on going in our laboratory.
These results will be reported in due course.
´
9 V. R. Naidu, J. Bah and J. Franzen, Eur. J. Org. Chem., 2015, 1834.
S. N. gratefully acknowledges the Chinese Scholarship Council
(CSC) for a grant.
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S. Ni and J. Franzen, ChemCatChem, 2015, 7, 13; (b) J. Bah,
´
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357, 148; (c) J. Bah and J. Franzen, Chem. – Eur. J., 2014, 20, 1066;
´
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(d) M. A. A. El Remaily, V. R. Naidu, S. Ni and J. Franzen, Eur. J. Org.
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