Lewis Acid-Mediated Decarboxylative Allylation of Enol Carbonates

Article abstract of DOI:10.1002/hlca.202100065

A homoallylic ketone can be transformed and functionalized by various synthetic reactions, and thus, is regarded as one of the representative building blocks in organic chemistry. An additional route to access homoallylic ketones, namely, a Lewis acid-mediated decarboxylative allylation of cyclic enol carbonates, prepared by fixation of carbon dioxide onto propargyl alcohols, was developed in this work. The treatment of a cyclic enol carbonate with a Lewis acid in the presence of an allylsilane resulted in the formation of a homoallylic ketone. It was found that the title reaction proceeded well by the combined use of zirconium tetrachloride with allyltrimethylsilane. The allylation occurred with high regioselectivity and the corresponding homoallylic ketones were obtained in good-to-high yields. A reaction mechanism involving the decarboxylative formation of an oxyallyl cation equivalent is proposed.

Full text of DOI:10.1002/hlca.202100065

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Accepted Article
Title: Lewis Acid-Mediated Decarboxylative Allylation of Enol
Carbonates
Authors: Tohru Yamada, Kodai Saito, Yoichi Dokai, and Takuma
Nishizawa
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10.1002/hlca.202100065
Helvetica Chimica Acta
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Lewis Acid-Mediated Decarboxylative Allylation of Enol Carbonates
Yoichi Dokai,a Takuma Nishizawa,a Kodai Saito,a and Tohru Yamada*,a
a Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, e-mail: Yamada@chem.keio.ac.jp
Dedicated to Prof. Peter Kündig on the occasion of his 75th birthday
A homoallylic ketone can be transformed and functionalized by various synthetic reactions, and thus, is regarded as one of the representative
building blocks in organic chemistry. An additional route to access homoallylic ketones, namely, a Lewis acid-mediated decarboxylative
allylation of cyclic enol carbonates, prepared by fixation of carbon dioxide onto propargyl alcohols, was developed in this work. The treatment
of a cyclic enol carbonate with a Lewis acid in the presence of an allylsilane resulted in the formation of a homoallylic ketone. It was found that
the title reaction proceeded well by the combined use of zirconium tetrachloride with allyltrimethylsilane. The allylation occurred with high
regioselectivity and the corresponding homoallylic ketones were obtained in good-to-high yields. A reaction mechanism involving the
decarboxylative formation of an oxyallyl cation equivalent is proposed.
Keywords: allylation • Lewis acid • decarboxylation • homoallylic ketone • carbon-carbon bond formation
This strategy is based on the reaction of an allyl electrophile with an
Introduction
enolate equivalent. In its original iteration, the formation of an
Homoallylic ketones (γ,δ-unsaturated ketones) have been employed
as versatile building blocks in synthetic organic chemistry because
they contain useful functional groups, such as carbonyl and alkenyl
groups. Representative approaches to access these compounds
include a nucleophilic addition of an enolate or its equivalent onto π-
allylpalladium complexes,[1-4] 1,4-addition of vinyl anion equivalents
to α,β-unsaturated ketones,[5-7] Claisen rearrangements,[8-10] etc.[11-14]
electrophilic π-allylpalladium complex from an allyl derivative having
a leaving group with a palladium complex triggered the addition of
an enolate equivalent as a carbon nucleophile (Scheme 1 (a)). In one
variant of the Pd-catalyzed allylic alkylation, a decarboxylative
alkylation of an allyl enol carbonate catalyzed by palladium
complexes, established by Tsuji, also supplied a homoallylic ketone
(Scheme 1 (b)).[20-21] The decarboxylation of the allyl enol carbonate
generates the π-allylpalladium intermediate, followed by the addition
of the enolate, to afford the homoallylic ketone. An asymmetric
version of this process was developed and applied to the synthesis of
complex molecular structures.[22] An acid-catalyzed allylic alkylation of
allyl acetate also affords the corresponding homoallylic ketone. At
first, this allylic alkylation was reported as an intramolecular reaction
by the Nozaki group.[23] An allylic acetate bearing a silyl enol ether
was treated by a catalytic amount of MeAl(OCOCF3)2 to give a seven-
membered homoallylic ketone. This methodology was applied to an
intermolecular reaction by Saigo et al. (Scheme 1 (c)).[24] They
introduced a directing group on the allylic acetate and achieved
regioselective alkylation using a silyl enol ether, an enamine, and an
allylsilane as nucleophiles.
Recently, Lewis acid-catalyzed decarboxylative transformations
of cyclic enol carbonates, which became easily available from
propargylic alcohols by silver-catalyzed reactions,[25-27] have been
reported by our group.[28-30] In our proposed reaction mechanism, the
decarboxylation of the cyclic enol carbonate is promoted by a Lewis
acid, resulting in the formation of an oxyallyl cation intermediate or
Scheme 1. Homoallylic alcohol synthesis by allylic alkylation.
Among these methods, the allylic alkylation has been most
actively studied and numerous variants have been developed.[1-4,15-19]
1
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10.1002/hlca.202100065
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its equivalent. It was elucidated that the intermediate could be
utilized for intramolecular carbon-carbon bond formation reactions,
such as the Nazarov cyclization. Treatment of a cyclic enol carbonate
bearing an alkene moiety with a catalytic amount of Lewis acid
induces the decarboxylative ring closure to afford a cyclopentenone
(Scheme 2). Since the Lewis acid-catalyzed decarboxylative Nazarov
cyclization overcame problematic issues that have been difficult to
solve in the conventional Nazarov cyclization, such as stoichiometric
loading of the acid catalyst and control of the stereoselectivity, we
hypothesized that the decarboxylation process plays a key role in the
efficient bond formation. In order to investigate applications of the
decarboxylation-initiated reaction using cyclic enol carbonates, it was
envisioned that intermolecular carbon-carbon bond formation could
be realized by the use of a suitable carbon nucleophile. Here we wish
to report the zirconium-mediated decarboxylative allylation of cyclic
enol carbonates using an allylsilane as an allyl nucleophile.
An initial attempt was carried out with the cyclic enol carbonate 1a in
the presence of an excess amount of Lewis acid in dichloromethane
(Table 1). When 1a was treated with (CH3)3SiOTf, allylation products
.
were not obtained (entry 1). The use of BF3 OEt2, which was the
optimal catalyst in the decarboxylative Nazarov cyclization,[25]
resulted in no conversion (entry 2). Next, group 13 metals, such as
AlCl3 and GaCl3, were employed for the reaction; however, only
moderate conversions of 1a were observed (entries 3 and 4). TiCl4,
which was used in intramolecular allylic alkylations,[23] showed
moderate activity to give the allylated product 2a and its isomer 3a
in 56% yield with 2a/3a = 85:15 (entry 5). When the catalysts of
group 4 were investigated, it was found that ZrCl4 could efficiently
convert 1a into 2a and 3a in 80% yield with the regioselectivity of
2a/3a = 70/30 (entry 6). In contrast, the employment of HfCl4 did not
mediate the allylation reaction at all (entry 7). The effect of
Cp2Zr(OTf)2 was also examined, and low catalytic activity was
confirmed (entry 8). It was found that efficient conversion was also
realized by a lower ZrCl4 loading (entry 9). Finally, the optimum
reaction conditions were established as follows: 1.2 equivalents of
ZrCl4 in CH2Cl2 at 0 oC - room temperature.
Table 1. Examination of reaction conditions.
Entrya
Lewis acid
[equiv]
Time
[h]
Yield of
Ratio of
2a/3ac
2a and 3a [%]b
1
2
3
4
5
6
7
8
9
(CH3)3SiOTf [2.0]
BF3⋅OEt2 [2.0]
AlCl3 [2.0]
24
0
-
24
0
-
1
56
64/36
42/58
85/15
70/30
-
GaCl3 [2.0]
12
48
TiCl4 [2.0]
24
56
ZrCl4 [2.0]
30 min
24
80 (73)d
0
HfCl4 [2.0]
Cp2Zr(OTf)2 [1.5]
ZrCl4 [1.2]
21
trace
82(71)d
-
1.2
73:27
[a] Reaction conditions: 1a (0.10 mmol), Lewis acid, and allyltrimethylsilane
(0.30 mmol) were stirred in CH2Cl2 (1 mL). [b] Yield was estimated as mixture
of 2a and 3a after the purification of the crude mixture. [c] Ratio was
determined by 1H NMR of the crude mixture. [d] Isolated yield. [e]
Allyltrimethylsilane (0.20 mmol) was used.
Scheme 2. Background and representative concepts of the present work.
Results and Discussion
2
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10.1002/hlca.202100065
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Scheme 4. Plausible reaction mechanism.
The proposed mechanism for the formation of allylated products
2 and 3 is shown in Scheme 4. Activation of the carbonyl group of
the substrate 1 and sequential decarboxylation occurs by ZrCl4, which
leads to the formation of the oxyallyl cation equivalents 4 and 5.
Next, nucleophilic attack of the allylsilane on the intermediates
proceeds, which results in the generation of zirconium enolates 6 and
7. Finally, protonation of 6 and 7 proceed to give products 2 and 3.
The allylation preferentially occurs on the less-steric site α of 4,
affording 2 as the major product.
Conclusions
Scheme 3. Substrate scope.
Next, we explored the substrate scope of the decarboxylation
allylation reaction. Substrates 1b and 1c bearing ethyl or n-propyl
groups at R2 and R3 were converted into the desired products 2b/3b
and 2c/3c in 71% (2b/3b = 74/26) and 82% (2c/3c = 91/9) yields,
respectively. Substrates containing a cyclic alkyl moiety at R2-R3, such
as a cyclopentane (1d), cyclohexane (1e), and cycloheptane (1f), were
also tolerated to give 2d/3d (69% yield, 2d/3d = 100:0), 2e/3e (70%
yield, 2e/3e = 68/32), and 2f/3f (65% yield, 2f/3f = 88/12). Then, the
effect of the substituent at R1 was investigated. The reaction of 1g,
1h and 1i having a phenethyl group at R1 proceeded to afford 2g/3g
(71% yield, 2g/3g = 60/40), 2h/3h (70% yield, 2h/3h = 100/0), and
2i/3i (69% yield, 2i/3i = 42/58). The substitution of R1 by p-tolyl and
We have developed a zirconium-mediated decarboxylative allylation
reaction using cyclic enol carbonates. It was demonstrated that this
system could be applied to various substrates and the corresponding
homoallylic ketones were obtained in good-to-high yields with
good-to-high regioselectivities. Further investigation of the
mechanism of and application to the synthesis of more complex
molecules is underway in our laboratory.
Supplementary Material
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/MS-number.
p-methoxyphenyl (PMP) resulted in efficient allylation to furnish 2j/3j Acknowledgements
and 2k/3k in 70% and 79% yields in ratios of 2j/2j = 83/17 and
We would like to thank DAIICHI KIGENSO KAGAKU KOGYO CO., LTD.
2k/3k = 81/19. A methallyltrimethylsilane was also applicable as an
allylating agent for the reaction of 1d to afford 2l/3l in 74% yield
with 2l/3l = 100/0.
for financial support.
Author Contribution Statement
3
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Lewis acid-mediated decarboxylative allylation of enol carbonates was developed. Treatment of an enol carbonate with a Lewis
acid in the presence of an allylsilane resulted in the formation of a homoallylic ketone.
5
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