Palladium-catalyzed allylic esterification via C-C bond cleavage of a secondary homoallyl alcohol

Article abstract of DOI:10.1021/ol501887a

Palladium-catalyzed allylic esterifications of secondary homoallyl alcohols with acids via sequential retro-allylation and esterification are demonstrated, affording the corresponding allyl ester in up to 99% yield. The electron effect of the substituent of the secondary alcohol was found to be crucial to the selective C-C bond cleavage.

Full text of DOI:10.1021/ol501887a

Letter
pubs.acs.org/OrgLett
Palladium-Catalyzed Allylic Esterification via C−C Bond Cleavage of a
Secondary Homoallyl Alcohol
Yong Wang and Qiang Kang*
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences,
155 Yangqiao Road West, Fuzhou, 350002, China
S
* Supporting Information
ABSTRACT: Palladium-catalyzed allylic esterifications of
secondary homoallyl alcohols with acids via sequential retro-
allylation and esterification are demonstrated, affording the
corresponding allyl ester in up to 99% yield. The electron
effect of the substituent of the secondary alcohol was found to
be crucial to the selective C−C bond cleavage.
Scheme 1. π-Allyl Pd Formation and Esterification
ransition-metal-catalyzed C−C bond activation has been
Tan emerging area which provides new modes of chemical
reactivity to synthetic organic chemistry. The strategies mainly
involving three- or four-membered ring strain release,1
aromatization,2 and chelation assistance3 have been reported
to activate inert C−C bonds.4 However, activation of sp3C−
sp3C in unstrained molecules is less reported.5 Tertiary
homoallyl alcohols were successfully applied as substrates for
selective unstrained sp3C−sp3C bond cleavage via retro-
allylation,6,7 forming a stable π-allyl metal intermediate which
is suitable for subsequent transformation with aryl halides,8
aldehydes,9 cinnamyl acetate,10 and acrylate ester.11 In
comparison, secondary homoallyl alcohols have rarely been
employed in such transformations.9j There have been a few
reports with respect to C−C cleavage of secondary alcohols.12
For instance, Chiba’s group reported azide assisting the C−C
bond cleavage of cyclic secondary 2-azidoalcohols.5b Shi and co-
workers demonstrated some examples of C−C bond cleavage
of secondary alcohols through Rh(III)-catalyzed β-carbon
elimination with the pyridinyl group as a directing group.13
On the other hand, Pd-catalyzed allylic esterification has
always been a challenging research area due to the high
reactivity problem of the resulting allylic esters toward the
metal catalysts.14 Installation of a prefunctionalized group at the
allylic position for the generation of a key π-allyl Pd
intermediate is a prerequisite in traditional allylic esterification
(Tsuji−Trost reaction).15 The functionalized groups include
carbonate,14a,16 ester,14b,17 chlorine,14d,18 and phosphate19
(Scheme 1a). Oxidative allylic C−H bond esterification has
also been realized in recent years (Scheme 1b).20 However, to
the best of our knowledge, transition-metal-catalyzed allylic
esterification via selective C−C bond cleavage has not been
documented.
which is the typical transformation of secondary alcohols in
transition metal catalytic systems.21 This strategy would provide
a new model for allylic substitution reaction.
We initiated our studies by examining the reactivity of β-
phenylbut-3-en-1-ol (2a) with 4-methylbenzoic acid (1a) in the
presence of 10 mol % of Pd(OAc)2 and 1.2 equiv of Ag2CO3 in
toluene. To our delight, the reaction went smoothly at 100 °C
for 24 h to afford the desired allyl 4-methylbenzoate (3aa) in
44% GC yield (Table 1, entry 1). Other oxidants such as AgF,
AgOAc, Ag2O, and Cu(OAc)2 were found to be less efficient
for the reaction, and lower yields of 3aa were obtained (Table
1, entries 2−5, and Supporting Information Table S1). Then
we investigated various solvents including DMSO, DMF,
ODCB (1,2-dichlorobenzene), and PhCF3 (Table 1, entries
6−9). While all the tested solvents could be tolerated, the
reaction in ODCB gave the superior yield (57%) (Table 1,
Herein we report an unprecedented Pd(II)-catalyzed
sequential selective C−C bond cleavage of a secondary
homoallyl alcohol and esterification with acids as nucleophiles
(Scheme 1c). The major challenge in cleaving the C−C bond
adjacent to a secondary alcohol is to suppress β-H elimination
Received: June 30, 2014
Published: July 30, 2014
© 2014 American Chemical Society
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dx.doi.org/10.1021/ol501887a | Org. Lett. 2014, 16, 4190−4193

Organic Letters
Letter
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Palladium(II)-Catalyzed Retro-Allylation and
a
,b
Esterification of 2a with Acids
b
entry
oxidant
solvent
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
Ag2CO3
AgF
toluene
toluene
toluene
toluene
toluene
DMSO
DMF
24
24
24
28
29
33
33
50
50
50
24
44
12
15
20
9
AgOAc
Ag2O
Cu(OAc)2
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
32
19
57
56
f
ODCB
PhCF3
ODCB
ODCB
c
e
10
80(77)
d
e
11
91(88)
a
Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), Pd(OAc)2 (10
b
mol %), oxidant (0.36 mmol), solvent (2 mL). GC yield using
dodecane as internal standard. Oxidant (0.9 mmol). 2a (0.9 mmol),
oxidant (0.9 mmol). Isolated yield in parentheses. ODCB = 1,2-
dichlorobenzene.
c
d
e
f
entry 8). Further investigation revealed that increasing the
amount of Ag2CO3 (3 equiv) and 2a (3 equiv) could deliver the
best yield of 3aa (88% isolated yield) (Table 1, entry 11).
Under the optimal reaction conditions (10 mol % of
Pd(OAc)2, 3 equiv of Ag2CO3, 3 equiv of 2a, ODCB (0.15
M), 100 °C) (Table 1, entry 11), a variety of acids 1 were
examined to evaluate the generality of the reaction. The results
were summarized in Scheme 2. First, different substituted
benzoic acids were tested. In general, benzoic acids bearing an
alkyl group on different positions of the phenyl ring could be
tolerated in reaction conditions (58%−88%, 3aa−3ae). For the
substrates with an electron-withdrawing (3ag, 3ah) and
electron-donating group (3ai, 3an and 3ao) on the phenyl
ring, the reaction went smoothly to afford the desired products
in good yields. It is worth noting that various functionalities
including acetyl (3aj), acetoxyl (3ak), nitrile (3al), and formyl
(3am) groups were tolerated in optimal reaction conditions.
Moreover, benzoylformic acid worked well, affording allyl
benzoylformate 3ap in 83% yield. This procedure also
proceeded smoothly with naphthoic acid 3ar and 3as as
substrates. We further examined aliphatic acid as substrates and
found all of them deliver corresponding products in good yields
(3at−3ay). Heterocyclic carboxylic acid gave product 3aq in a
lower yield (33%) due to part of the substrate decomposing
under the reaction conditions.
The reactivities of a variety of homoallyl alcohols were
further surveyed (Table 2). Our studies indicated an electron-
rich aromatic substituent improved the reactivity of the C−C
bond cleavage.22 Under the optimal reaction conditions, by
employing 2,4-dimethoxy substituent 2b as a substrate, 3aa was
obtained in 99% GC yield. In light of this observation, we
attempted to reduce the consumption of 2 and Ag2CO3. The
reaction of 1a with 1.2 equiv of 2b afforded the corresponding
product 3aa in 99% yield (Ag2CO3, 2.0 equiv) and 93% yield
(Ag2CO3, 1.4 equiv), respectively (Table 2, entry 1). These
findings revealed that β-H elimination was well suppressed
when the substrate with an electron-rich aromatic ring adjacent
to the hydroxyl group was employed. Further substrate
investigation was conducted under these reaction conditions:
a
Reaction conditions: 1 (0.3 mmol), 2a (0.9 mmol), Pd(OAc)2 (10
b
mol %), Ag2CO3 (0.9 mmol), ODCB (2 mL), 24 h. Isolated yield.
Table 2. Palladium(II)-Catalyzed Retro-Allylation and
Esterification of 2 with Acid 1a
a
b
entry
2/R
yield (%)
c
1
2
3
4
5
6
2b/2,4-(OMe)2-C6H3
2c/4-OMe-C6H4
99 (93)
71
72
59
9
2d/2,3,4-(OMe)3-C6H2
2e/3,4,5-(OMe)3-C6H2
2f/2,4,6-(OMe)3-C6H2
2g/4-NO2-C6H4
8
a
Reaction conditions: 1a (0.3 mmol), 2 (0.36 mmol), Pd(OAc)2 (10
b
mol %), Ag2CO3 (0.42 mmol), ODCB (2 mL), 24 h. GC yield using
dodecane as internal standard. Ag2CO3 (0.6 mmol).
c
10 mol % of Pd(OAc)2, 1.4 equiv of Ag2CO3, 1.2 equiv of 2,
ODCB (0.15 M), 100 °C. When the phenyl ring was p-
methoxy substituted (2c), 2,3,4-trimethoxy substituted (2d),
and 3,4,5-trimethoxy substituted (2e), slightly decreased yields
were afforded (Table 2, entries 2−4). The substrate 2f with a
2,4,6-trimethoxy substituent on the phenyl ring only gave a 9%
GC yield mainly due to the steric hindrance effect (Table 2,
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Organic Letters
Letter
entry 5). Substrate 2g with a nitro group barely provided
product in 8% yield (Table 2, entry 6).
intermediate via C−C bond cleavage for the allylic substitution
reaction. Further studies on other transformations based on this
concept are ongoing in our laboratory, and the results will be
reported in due course.
A controlled experiment was conducted with allyl ketone 4
instead of allyl alcohol 2a to investigate whether the oxidation
product 4 via β-H elimination from a secondary homoallyl
alcohol could be transferred to desired product 3aa. The result
showed no desired product was obtained under such reaction
conditions, which ruled out the possibility of generating desired
product 3aa from the byproduct 4 (Scheme 3).
ASSOCIATED CONTENT
* Supporting Information
■
S
Procedures and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
Scheme 3. Reaction between 1a and 4 under the Optimal
Reaction Conditions
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: kangq@fjirsm.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Based on the above studies, a plausible mechanism has been
proposed for this Pd(II)-catalyzed sequential C−C bond
cleavage of a secondary homoallyl alcohol and esterification
reaction (Scheme 4). Before the Pd(II) catalyst coordinates
We thank the National Natural Science Foundation of China
(21302183) and the “Strategic Priority Research Program” of
the Chinese Academy of Sciences (Grant No. XDA09030102)
for financial support. We thank Prof. Weiping Su from Fujian
Institute of Research on the Structure of Matter, Chinese
Academy of Sciences for providing GC support.
Scheme 4. Plausible Mechanism
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