Palladium(II)/Lewis acid synergistically catalyzed allylic C-H olefination

Article abstract of DOI:10.1021/ol501356z

The first allylic C-H olefination with α-diazo esters synergistically catalyzed by a palladium(II) complex and (salen)CrCl has been established to directly generate conjugated polyene derivatives in moderate to high yields and with excellent stereoselectivities.

Full text of DOI:10.1021/ol501356z

Letter
pubs.acs.org/OrgLett
Palladium(II)/Lewis Acid Synergistically Catalyzed Allylic C−H
Olefination
Pu-Sheng Wang, Hua-Chen Lin, Xiao-Le Zhou, and Liu-Zhu Gong*
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and
Technology of China, Hefei 230026, China
S
* Supporting Information
ABSTRACT: The first allylic C−H olefination with α-diazo
esters synergistically catalyzed by a palladium(II) complex and
(salen)CrCl has been established to directly generate
conjugated polyene derivatives in moderate to high yields
and with excellent stereoselectivities.
he allylic C−H functionalization has sparked great interest
T
in the development of new synthetic methods widely
applicable to the construction of structurally complex
architectures.1 Metal−carbenoids have been an active species
for the functionalization of allylic C−H bonds.2 In particular,
the C−H insertion reaction of rhodium carbenoid intermedia-
tes2a generated from α-diazo esters has rendered homoallylic
esters to be regiospecifically yielded (Scheme 1a). Recently,
Scheme 1. General Strategies for the Allylic C−H
Functionalization
Figure 1. Selected natural products containing a dienyl carboxylate or
carbinol moiety.
C−H olefination with α-diazo esters to directly produce
conjugated polyenes in excellent stereoselectivity (Scheme 1c).
Previously, Wang and co-workers established a palladium(0)-
catalyzed olefination of allylic halides with α-diazo esters,7
wherein π-allylic palladium complexes generated from oxidative
addition of Pd(0) onto allylic halides turned out to be key
intermediates participating in the carbon−carbon double bond
formation. Thus, we envisaged that a π-allylic palladium
intermediate A generated from the cleavage of allylic C−H
bond with Pd(II), would also be able to undergo a carbene
insertion reaction with diazo compounds to form a π-
allylpalladium carbenoid species B, which would undergo a
migratory insertion to afford intermediate C (Scheme 2).7 After
a subsequent β-H elimination occurs in the intermediate C, the
conjugated diene would be generated and the corresponding
palladium(0) would be released. Afterward, the oxidation of
Pd(0) with BQ in the presence of HOAc regenerated the
Pd(II) catalyst (Scheme 2). As such, an allylic C−H activation
based olefination would be accessed. On the other hand, an
alternative pathway involving allylic substitution and subse-
quent elimination (E1-type) of intermediate D to afford the
diene product is also possible.
a
b
Allylic C−H functionalization with α-diazo esters. Palladium(II)-
c
catalyzed allylic C−H functionalization. The allylic C−H olefination
(this work).
White and co-workers established that Pd(II) complexes of
sulfoxides could efficiently accelerate allylic C−H oxidation of
terminal alkenes3 and, more significantly, had been general
catalyst systems for allylic C−H functionalizations, including
allylic esterification, amination, dehydrogenation, fluorination,
and alkylation as well4 (Scheme 1b). However, a direct allylic
C−H olefination,5 basically giving rise to polyenes, which have
been found in numerous natural products (Figure 1) and
therefore hold great potential in organic synthesis,6 has not
been described. Herein, we report a palladium-catalyzed allylic
Received: May 12, 2014
Published: June 12, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
Scheme 2. Pd(II)-Catalyzed Allylic C−H Olefination with
Diazo Compounds
Table 1. Evaluation of Lewis Acids and Optimization of
a
Reaction Conditions
a
b
c
entry
solvent
M
conv (%)
yield (%)
E/Z
1
2
3
4
5
6
7
toluene
toluene
toluene
toluene
THF
47
65
53
65
97
87
92
99
91
1
22
28
36
41
47
50
MnCl
FeCl
CrCl
CrCl
CrCl
CrCl
CrCl
CrCl
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
>15:1
DCE
dioxane
dioxane
dioxane
However, the proposed reaction was much more challenging
than anticipated because the Pd−carbenoid species E generated
rapidly from Pd(II) with the diazo compound, would undergo
allylic C−H insertion8 or cyclopropanation9 based on the
metal−carbenoid (Scheme 2, eq 1), either of which would
compete with the formation of π-allylic palladium intermediate
A via the allylic C−H activation by palladium(II). Indeed, the
initial experiment on the reaction of allylbenzene (1a) with
methyl phenyldiazoacetate (2a) in the presence of White
catalyst mostly gave C−H insertion based allylic alkylation and
cyclopropanation products, together with some other un-
identified molecules, whereas the desired olefination product
was isolated in a trace amount.10
The proposed reaction pathway (Scheme 2) indicates that if
the palladium(II) catalyzed allylic C−H activation is complete
to generate π-allylic palladium intermediate A prior to the
formation of palladium carbenoid E the desired catalytic cycle
might be realized. Thus, the allylic C−H olefination of
allylbenzene (1a) was examined using the White catalyst and
BQ/HOAc as an oxidant by slow addition of methyl
phenyldiazoacetate (2a) with syringe pump with a purpose to
diminish the side reaction promoted by palladium(0) (Table
1). Disappointingly, only trace amount of diene 3a was
detected (entry 1). We believed that the desired reaction failed
to occur probably because the π-allylic palladium carbene
intermediate B (Scheme 2) was unable to be efficiently
generated. Inspired by findings from White and co-workers that
the addition of Lewis acids as co-catalysts could facilitate the
functionalization of allylic C−H bonds,4a,11 we evaluated a
variety of metal−salen complexes (entries 2−4). To our
delight, the addition of 20 mol % of (salen)CrCl gave the
desired diene product 3a in a much enhanced 36% yield (entry
4). An evaluation of solvents suggested that ether-based
solvents were beneficial to the conversion of allylbenzene and
led to a considerable improvement in the yield (entries 5−7).
The diene 3a was isolated in a 54% yield in the presence of 15
mol % the White catalyst (entry 8). Importantly, the protocol
was scalable with maintained results (entry 9).
d
e
8
68 (54 )
d
,
f
e
9
77 (56 )
a
Determined by GC using benzophenone as an internal standard for
reactions carried out on a 0.1 mmol scale. 2a was dissolved in 0.5 mL
of solvent and added by syringe pump over 5 h, and then the reaction
was conducted for an additional 2 h. Combined GC yields of E and Z
isomers. Based on GC analysis of the crude reaction mixture, and
small response variations were uncorrected. 15 mol % of Pd of
catalyst was used. Isolated yield. The reaction was carried out on a
0.3 mmol scale.
b
c
d
e
f
Although the reaction was seemingly sensitive to the electron
feature of the aryl moiety of the olefin substrates, the presence
of either an electronically donating (3b−d) or withdrawing
(3e−f) substituent was allowed to give the desired products in
high yields (up to 83%). Notably, even simple alkyl olefins also
participated in the reaction to afford aliphatic conjugated dienes
in acceptable yield (3k−l). However, an alkyl bromide-
containing olefin was not well tolerated under the optimized
conditions but resulted in a debromination product (3m).
More significantly, for 1,4-diene-based allylic substrates, the C−
H olefination chemoselectively occurred to give triene
derivatives in good yields (3n−p). Moreover, the variation in
the steric and electronic elements of aryldiazoacetates 2 was
also well tolerated (3q−s). Interestingly, the subjection of ethyl
2-diazopropanoate to the identical conditions resulted in the
formation of a 1,4-diene 3t, a Hofmann-elimination like
product, rather than a 1,3-diene, suggesting that the E1-type
reaction is much less possible than β−H elimination (Scheme
2).
To understand the mechanism for this direct allylic C−H
olefination, we investigated the π-allylic palladium intermediate
forming step in the proposed catalytic cycle. The π-allyl
palladium dimer 4 was prepared in a good yield from allylic C−
H bond cleavage reaction between the palladium acetate and
the allylbenzene 1a.4h Then, we explored the effect of either
ligand or Lewis acid on the olefination reaction of π-allyl Pd
intermediate 4 with methyl phenyldiazoacetate 2a (Table 2). As
indicated previously, the allylic substitution of π-allyl palladium
acetate dimer with nucleophiles could be accelerated by
sulfoxide ligand and BQ.4f,h,12 However, neither the sulfoxide
ligand nor BQ was able to exert apparent impact on the
performance of olefination reaction, which implied that this
Under the optimized conditions, structurally different olefin
substrates were examined to demonstrate the generality
(Scheme 3). A wide scope of either commercially available or
easily accessible terminal olefins was able to be tolerated and
smoothly underwent the allylic C−H olefination reaction to
generate conjugated olefins in moderate to high yields.
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Organic Letters
Letter
a
accelerated effect was observed (entries 1−3). This conclusion
was also indicated by the fact that a 4-diene 3t rather than 1,3-
diene product was formed as shown in Scheme 3. A much-
enhanced yield was obtained when the olefination was
conducted in the presence of BQ and (salen)CrCl, but with
a poor stereoselectivity (entry 4). Interestingly, the use of
(salen)CrCl alone as the cocatalyst rendered the reaction to
give an excellent conversion, but still with a poor stereo-
selectivity (entry 5). In addition, the addition of disulfoxide
ligand led to an enhanced stereoselectivity (entry 6). On the
basis of these preliminary results, we identified that disulfoxide
ligand not only served as a promoter to the allylic C−H
cleavage, but also contributed to the control of stereoselectivity.
The (salen)CrCl might act as a Lewis acid to enhance the
nucleophility of the α-diazo esters by coordinating to the
nitrogen and thereby would facilitate the formation of π-allylic
palladium carbenoid (Scheme 4),13 rather than the activation of
the π-allylPd species by coordination to BQ.12
Scheme 3. Substrate Scope
Scheme 4. Proposed Pathway for the Chromium(III) Lewis
Acid Accelerated Carbenoid Transfer
In conclusion, we have developed the first C−H activation
based olefination reaction between allyl hydrocarbons and α-
diazo esters. The use of the palladium(II) complex and
(salen)CrCl as a binary catalyst system efficiently promoted the
olefination reaction for a wide scope of allyl compounds and α-
diazo esters to directly generate conjugated polyene derivatives
in moderate to high yields and with excellent stereoselectivities.
An obvious synergistic effect between palladium(II) and
[(salen)CrCl] was observed in the catalysis, probably because
the [(salen)CrCl] acted as a Lewis acid to facilitate the
formation of π-allylic palladium carbenoid. This finding might
be amenable to improve the efficiency of other reactions
involving metal carbene intermediates.
a
The reactions was carried out on a 0.3 mmol scale. 2 was dissolved in
1 mL of solvent and added by a syringe pump over 5 or 8 h, and then
the reaction was conducted for additional 2 h. The isolated yields were
obtained after flash chromatography. In some cases, the products were
mixed with byproducts and isolable after the reduction of NaBH4.
b
c
The starting terminal olefin was 5-bromopent-1-ene. The E/Z ratio
points to the double bond adjacent to the aryl group
ASSOCIATED CONTENT
* Supporting Information
Complete experimental procedures and characterization data
for the prepared compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
Table 2. Effects of Ligand and Lewis Acid on the Olefination
of a π-Allyl Palladium Dimer
AUTHOR INFORMATION
Corresponding Author
■
a
b
entry
ligand
yield (%)
E/Z
1
2
3
4
5
6
9
11
7
*E-mail: gonglz@ustc.edu.cn.
Notes
1,2-bis(phenylsulfinyl)ethane
BQ
The authors declare no competing financial interest.
BQ + (R,R)-(Salen)CrCl
(R,R)-(Salen)CrCl
46
93
85
1.6:1
1.3:1
2.7:1
ACKNOWLEDGMENTS
We are grateful for financial support from NSFC (21302177),
Ministry of Education, and CAS.
■
1,2-bis(phenylsulfinyl)ethane +
(R,R)-(Salen)CrCl
a
Determined by GC using 1,3,5-tri-tert-butylbenzene as an internal
standard for reactions. Based on GC analysis of the crude reaction
mixture, and small response variations were uncorrected.
b
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Letter
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