Triflimide-catalyzed allyl-allyl cross-coupling: A metal-free allylic alkylation

Article abstract of DOI:10.1039/c2cc33641c

A highly efficient metal-free intermolecular C(sp3)-C(sp3) allyl-allyl cross-coupling protocol between allyl acetates and allyltrimethylsilanes, which proceeded smoothly in the presence of catalytic triflimide to form 1,5-dienes with good to excellent regioselectivity, has been developed.

Full text of DOI:10.1039/c2cc33641c

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COMMUNICATION
Triflimide-catalyzed allyl–allyl cross-coupling: a metal-free allylic
alkylationw
Feiqing Ding, Ronny William, Fei Wang and Xue-Wei Liu*
Received 21st May 2012, Accepted 9th July 2012
DOI: 10.1039/c2cc33641c
A highly efficient metal-free intermolecular C(sp3)–C(sp3) allyl–
allyl cross-coupling protocol between allyl acetates and allyltri-
methylsilanes, which proceeded smoothly in the presence of
catalytic triflimide to form 1,5-dienes with good to excellent
regioselectivity, has been developed.
synthesis of valuable 1.5-dienes. These dienes are not only
ubiquitous in naturally occurring terpenes but also serve as
highly versatile intermediates and building blocks in organic
synthesis.3,4 Despite rapid advances in the transition metal-
catalyzed allylic alkylation, the intermolecular C(sp3)–C(sp3)
allyl–allyl coupling remains a challenging task.5 To date,
several transition-metal catalysts such as copper, nickel and
palladium have been developed to enable allylation of organo-
metallic compounds, including magnesium, aluminum, boron,
and zinc reagents (eqn (2)).6 The use of palladium catalysts, in
particular, has seen considerable success in the past due to a high
and predictable level of regio- and stereoselectivity. Although it
represents a highly valuable synthetic tool, the presence of heavy
transition-metal impurities complicates the purification step, and
thus results in an increase in the cost involved throughout the
process. In addition, most reactions employ an excess of toxic or
harmful reagents and require harsh conditions.
Allylic alkylation reactions are among the most versatile
and efficient carbon–carbon and carbon–heteroatom bond
formation methods in organic synthesis because allyl moieties
can serve as a powerful handle for further transformation to
access a wide array of functional groups.1 Early work reported
by Trost and Tsuji on the metal-catalyzed allylic alkylation of
a variety of soft and hard nucleophiles with allylic compounds
has attracted a great deal of attention (Scheme 1, eqn (1)).2 Of
particular significance, the metal-mediated allyl–allyl cross-
coupling between allyl metal compounds and allylic electro-
philes possessing functional groups that exhibit good leaving
group ability such as halides, carboxylates, carbonates,
triflates or phosphates provides a reliable method for the
The development of metal-free allylic alkylation, on the
other hand, constitutes a significant challenge in organic
synthesis, and in spite of the exciting developments in the field
of Brønsted acid catalysis, metal-free allylic alkylations invol-
ving allylic p ion pairs have remained elusive.7,8 Inspired by
our previous work in carbohydrate chemistry, whereby
Brønsted acids were used to catalyze the Ferrier rearrange-
ment reaction through generation of a carbocation inter-
mediate (eqn (3)), we are encouraged to pursue a different
highly challenging strategy for the Brønsted acid-catalyzed
allyl–allyl cross-coupling.9 To the best of our knowledge, this
is the first report concerning such direct intermolecular allylic
coupling reaction of cinnamyl acetate with allyltrimethylsilane
using Brønsted acid (eqn (4)).
We began our investigation using readily available cinnamyl
acetate (1a) and allyltrimethylsilane (2a) for reaction develop-
ment (Table 1). Unexpectedly, however, the results demon-
strated that the reaction between 1a and 2a was not successful
in the presence of common Brønsted acids such as TsOH, HCl,
AcOH, H3PO4, MeSO3H (Table 1, entry 1). After a series of
trials, we found that triflimide10 (Tf2NH) afforded the desired
allyl–allyl coupling products 1,5-hexadienes 3a and 4a in 39%
total yield with a linear to branched diene ratio of 69/31
(Table 1, entry 2).11 Encouraged by these results, both solvents
and reaction temperatures were evaluated to identify the
optimal conditions (Table 1, entries 2–4, for details see ESIw).
Subsequently, slight increase or decrease in Tf2NH catalyst
Scheme 1 Earlier studies and the concept of the present work.
Division of Chemistry and Biological Chemistry, School of Physical
and Mathematical Sciences, Nanyang Technological University,
637371, Singapore. E-mail: xuewei@ntu.edu.sg; Fax: +65 6791 1961
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization, 1H and 13C NMR spectra of all new
compounds. See DOI: 10.1039/c2cc33641c
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 8709–8711 8709

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Table 2 Scope for allyl acetates and allyltrimethylsilanesa
Table 1 Optimization studies
Entry Catalysts (mol%) Solvent
Temp. (1C) 3a/4aa Yieldb (%)
1
2
3
4
BA (1)c
DCMd
DCMd
rt
rt
—
nrf
69/31 39
Tf2NH (1)
Tf2NH (1)
Tf2NH (1)
Tf2NH (0.5)
Tf2NH (0.5)
d
CH3NO2 rt
—
Trace
DCMe
DCMe
DCMe
0
rt
À20
76/24 45
78/22 57
91/9
5
6g
89h (85)i
a
b
The ratio determined by crude NMR. Isolated yield after purifica-
c
tion. BA = Brønsted acid (TsOH, H3PO4, HCl, AcOH, MeSO3H).
d
e
[M] = 0.5 M. [M] = 0.1 M. nr = no reaction. Using 3.0 equiv.
f
g
h
i
of 2a. Reaction was performed on a 0.2 mmol scale. Performed on
a 5.0 mmol scale.
loading has no significant detrimental effect on the reaction
yield and regioselectivity (Table 1, entry 5). Finally, under the
optimized conditions, the total yield of coupling reaction was
enhanced to 89% and the ratio of the linear product to the
branched product improved to 91/9 when 3 equiv. of 2a was
used. Moreover, when the reaction was performed on a
5.0 mmol scale, a similar result was obtained (Table 1, entry 6).
In the absence of the triflimide catalyst, however, formation of
desired 1,5-diene was not observed at all. Moreover, examina-
tion of a set of simple allylic electrophiles bearing a potential
leaving group revealed that the reaction is well tolerated with
various leaving groups (see ESIw).
a
All reactions are performed as described in Table 1 (entry 6) on a
Having established the optimal reaction conditions (Table 1,
entry 6), we next explored the scope and limitation of the
reaction with a variety of allylic acetates and allyltrimethyl-
silanes (Table 2). The reaction occurred smoothly with ortho-,
para-, and meta-substituted aromatic cinnamyl acetates afford-
ing the desired 1,5-dienes in moderate to good yields and
regioselectivities (Table 2, products 3a–3f). Notably, reaction
of the cinnamyl acetate bearing substituents at both ortho
positions with allyltrimethylsilane also furnished dienes in good
yields with excellent regioselectivities, suggesting that substitu-
tion leading to a branched product is sterically disfavored
(Table 2, products 3g–3i). The naphthylallylic acetate and
biphenyl allylic acetate were also suitable substrates for this
reaction (Table 2, products 3j–3k).12a Substitution at the double
bond of cinnamyl acetate was well-tolerated as demonstrated
by the facile stereoselective formation of methyl-substituted
1,5-diene 3n and 3o when treated with the allylsilane reagent
under the present reaction conditions (Table 2).12 Weak electron-
withdrawing groups such as Br were tolerated on the aromatic
ring of cinnamyl acetate (Table 2, product 3m), the resulting
bromide group in the corresponding product is synthetically
useful for further transformation.13 Interestingly, we found that
analogous reaction of phenyldienyl acetate14 also proceeded in
the same manner to afford the corresponding 1,5,7-triene in
65% yield with high regioselectivity (Table 2, product 3p).15
Unfortunately, strong electron-withdrawing groups such as
–NO2, ketone, and ÀCF3 groups on the aromatic ring did not
lead to the formation of a coupling product but instead starting
materials were recovered at the end of the reaction. Next, we
examined the substrate generality of the cross-coupling reaction
0.2 mmol scale, unless otherwise noted. Yields are given for isolated
products after column chromatography. New C–C bonds are shown in
bold. The ratio of the linear product and the branched product (L/B) is
1
determined by crude H NMR.
with respect to allyltrimethylsilane derivatives as coupling
partners. We found that b-methallyltrimethylsilane is also a
viable coupling partner giving good yield of the product, albeit
with low selectivity of linear over branched diene 3q.10b,11b,16
Under the same reaction conditions, cinnamyl-trimethylsilane
reacted smoothly to give the corresponding diene 3r in 70%
yield with moderate regioselectivity. Interestingly, a highly
sterically hindered vinylcyclohexyl trimethylsilane also reacted
with cinnamyl acetate albeit with low conversion. Finally, cyclic
allylsilane compounds such as trimethylsilyl-cyclopentadiene
efficiently coupled to provide cinnamyl-substituted cyclopenta-
diene 3t.
Although detailed studies are required, we would like to
propose a plausible mechanism for the allyl–allyl cross-
coupling reaction as depicted in Scheme 2.17 Activation of
the acetate moiety of the allylic acetate derivative by the
triflimide leads to the formation of ion pairs between the
benzylic p carbocation intermediate and the triflimide anion.
Nucleophilic attack of the allyltrimethyl silane moiety followed
by desilylation of the b-silyl carbocation intermediate by the
triflimide anion affords the corresponding coupling products.
Depending on the position attacked by allyltrimethylsilane,
either the linear or branched product is obtained. Coupling at
the terminal end of the allylic acetate derivative affords the
c
8710 Chem. Commun., 2012, 48, 8709–8711
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Scheme 2 Proposed reaction mechanism.
corresponding linear product via path a. On the other hand, an
alternative attack via path b affords the corresponding branched
product as a minor product because of steric hindrance.
In conclusion, we have uncovered a new protocol for direct
catalytic allylic alkylation of acetates using a Brønsted acid
catalyst. Traditionally, allylic alkylation was promoted by
transition metal catalysts that are associated with limitations
like the presence of heavy metal impurities in the final product
and harsh reaction conditions. In contrast, this new method
is operationally simple and proceeds under remarkably mild
reaction conditions. It is noteworthy that use of just 0.5 mol%
of a simple, cheap, and easily accessible organic substance is
sufficient to catalyze intermolecular allyl–allyl cross-coupling.
The only waste produced in this new protocol for allylic
coupling reaction is acetic acid which is not harmful and
environmentally benign. The transformations occur with
excellent regioselectivity and yield. Further studies of asym-
metric ally–allyl cross coupling are ongoing in our lab and
would be reported in due course.
We thank Prof. Narasaka Koichi for invaluable suggestion
on reaction mechanisms. We gratefully acknowledge Nanyang
Technological University (RG50/08) and the Ministry of
Education, Singapore (MOE 2009-T2-1-030) for the financial
support of this research.
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c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 8709–8711 8711