Direct palladium-catalyzed carbonylative transformation of allylic alcohols and related derivatives

Article abstract of DOI:10.1021/acs.orglett.7b02801

A direct, palladium-catalyzed, carbonylative transformation of allylic alcohols for the synthesis of β,γ-unsaturated carboxylic acids has been developed. With formic acid as the CO source, various allylic alcohols were conveniently transformed into the corresponding β,γ-unsaturated carboxylic acids with excellent linear and (E)-selectivity. The reaction was performed under mild conditions; toxic CO gas manipulation and high-pressure equipment were avoided in this procedure.

Full text of DOI:10.1021/acs.orglett.7b02801

Letter
pubs.acs.org/OrgLett
Direct Palladium-Catalyzed Carbonylative Transformation of Allylic
Alcohols and Related Derivatives
Fu-Peng Wu,† Jin-Bao Peng,*,† Lu-Yang Fu,† Xinxin Qi,† and Xiao-Feng Wu*,†,‡
†Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, People’s Republic of China
‡Leibniz-Institut fur Katalyse e.V. an der, Institution Universitat Rostock, Albert-Einstein-Straße 29a, Rostock 18059, Germany
̈
̈
S
* Supporting Information
ABSTRACT: A direct, palladium-catalyzed, carbonylative
transformation of allylic alcohols for the synthesis of β,γ-
unsaturated carboxylic acids has been developed. With formic
acid as the CO source, various allylic alcohols were
conveniently transformed into the corresponding β,γ-unsatu-
rated carboxylic acids with excellent linear and (E)-selectivity.
The reaction was performed under mild conditions; toxic CO
gas manipulation and high-pressure equipment were avoided
in this procedure.
he transition-metal-catalyzed carbonylation reaction has
alcohols in the presence of phenols to afford the corresponding
Temerged as a versatile and powerful tool for the formation β,γ-unsaturated esters.5a Soon after, Alper and Xiao reported a
of various carbonyl compounds.1 A variety of efficient
carbonylation reactions have been developed during the past
novel thiocarbonylation reaction with thiols as nucleophiles to
afford β,γ-unsaturated thioesters.5b Recently, Beller and co-
workers developed an elegant carbonylation method of allylic
alcohols with aliphatic alcohols and aromatic amines to produce
β,γ-unsaturated esters5c and amides.5d However, these
procedures require the use of toxic carbon monoxide gas, and
special equipment is usually needed for handling high-pressure
gas, which make them not ideal for benchtop synthesis.
To circumvent the problem of carbon monoxide manipu-
lation and develop user-friendly carbonylation methods, several
research groups, including ours, have developed many efficient
carbonylation reactions based on CO surrogates.6 Recently, we
have reported a general carboxylation reaction of aryl halides
using formic acid as the CO source. Based on our continuous
interest in palladium-catalyzed carbonylation reactions with
formic acid as a green CO source, we recently became
interested in developing a direct carbonylation of allylic
compounds with formic acid. We assume that formic acid
would act in dual roles, both as a CO source and as a source of
the hydroxyl group.
Initially, cinnamyl alcohol was selected as a model substrate.
To our delight, after a solution of cinnamyl alcohol, formic acid,
and DCC was stirred in the presence of Pd(OAc)2 and
Xantphos in 1,4-dioxane at 50 °C, the hydroxylation reaction
proceeded successfully and the desired product (E)-4-phenyl-
but-3-enoic acid was isolated in 46% yield (Table 1, entry 1).
Notably, no (Z)-isomer was detected in this transformation.
Mechanistically, base was not required for this reaction, but the
acidity of the solution might have some important influence on
catalytic cycle. Thus, we also tested the effect of bases.
two decades. The majority of the previous works were focused
on the carbonylation of organic (pseudo)halides, which are of
great interest for both the academic and the industrial
community. However, the development of carbonylation of
alcohols, which are much more readily available, has attracted
less attention and remains a challenging goal. In this respect,
allylic alcohol has shown great potential due to its specialized
structure and reactivity. Compared to the flourishing develop-
ment of transition-metal-catalyzed nucleophilic substitution
reactions,2 there are only a few investigations of the
carbonylation reaction of allylic compounds. In addition,
carbonylation of allylic compounds represents a direct and
general method for the synthesis of the valuable synthetic
building blocks, β,γ-unsaturated carboxylic acids.3 Typically, an
activated allylic substrate with a good leaving group (i.e., allylic
sulfonates, acetates, carbonates, or halogens) is used in these
reactions.4 In spite of their good reactivity, these substrates
usually suffer two main drawbacks: first, multistep preinstalla-
tion of the leaving group was usually required for the
preparation of these substrates, thus reducing the general
efficiency. Second, stoichiometric amounts of wastes were
generated with the release of the leaving group, which also
might influence the subsequent reactions. The direct use of
unprotected allylic alcohol as the substrates turns out to be a
very economical and environmentally friendly method since it
gives water as the sole byproduct. Unfortunately, the high
activation barrier required for C−OH bond-breaking and the
nucleophilicity of the hydroxyl group have hindered allylic
alcohols from their application in carbonylation reactions. As a
result, there are very few reports on this subject.5 In 1997, the
Miura group demonstrated the direct carbonylation of allyl
Received: September 8, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02801
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
Table 2. Substrate Scope of the Carboxylation Reaction:
a
Primary Allylic Alcohols
b
entry
ligand
base
none
temp (°C)
yield (%)
1
2
3
4
Xantphos
Xantphos
Xantphos
Xantphos
PPh3
50
50
50
50
50
50
60
70
60
60
60
46
53
NaHCO3
HCO2Na
Et3N
35
trace
8
c
5
c
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
6
P(o-tolyl)3
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
trace
67
7
8
63
d
9
59
e
10
76
f
11
58
a
Reaction conditions: cinnamyl alcohol (0.5 mmol), formic acid (3.5
mmol), Pd(OAc)2 (3 mol %), Xantphos (3 mol %), base (1.0 mmol),
4 Å MS (80 mg). DCC (1.0 mmol), 1,4-dioxane (2 mL), 20 h.
b
c
d
e
Isolated yield. 6 mol %. 0.5 mmol of NaHCO3 was used. 1.5 mmol
f
of NaHCO3 was used. Xantphos (4.5 mol %).
Surprisingly, the addition of sodium bicarbonate increased the
yield to 53% (Table 1, entry 2), but sodium formate resulted in
lower yield (Table 1, entry 3). Organic base nearly stopped the
reaction, and only trace amount of the product was detected
(Table 1, entry 4). Subsequently, various phosphine ligands
were investigated. On the basis of our previous work on the
ligand-controlled carbonylation of aryl halides, bidentate
phosphine ligand with a large bite angle facilitated the
hydroxycarbonylation to give the acid product.6i Indeed,
triphenylphosphine showed much lower reactivity and gave a
poor yield of acid (Table 1, entry 5). Monodentate ligands such
as substituted triphenylphosphines and other bidentate ligands
with small bite angles like DPPP and DPPF were all ineffective
for this transformation (Table 1, entry 6 and also see details in
Supporting Information). It should be mentioned that when
monodentate phosphines were used as the ligand, formylation6i
product was not detected; instead, cinnamyl formate was
obtained in 10−30% yields, which indicates that the nature of
ligands has a significant influence in the oxidative addition step
of the palladium to the C−O bond. The reaction temperature
also played an important role. When the reaction was
performed at 60 °C, the yield was improved to 67% (Table
1, entry 7). However, increasing the temperature to 70 °C
resulted in a lower yield (Table 1, entry 8). Further screening of
the additives revealed that acid additives decreased the yield
(see details in the SI). The best result was obtained when 3
equiv of sodium bicarbonate was added, and the desired
product was isolated in 76% yield (Table 1, entry 10). Finally,
when we tested the influence of the ratio of palladium and
phosphine ligand, higher ligand loading reduced the yield
(Table 1, entry 11).
a
Reaction conditions: allylic alcohol (0.5 mmol), formic acid (3.5
mmol), Pd(OAc)2 (3 mol %), Xantphos (3 mol %), NaHCO3 (1.5
mmol), 4 Å MS (80 mg). DCC (1.0 mmol), 1,4-dioxane (2 mL), 60
°C, 20 h, isolated yield.
yields. All of the reactions proceeded regio- and stereo-
selectively. No branched or (Z)-isomers were detected in these
reactions. In addition, heteroaryl- and 2-naphthyl-substituted
allylic alcohols were also subjected to the carboxylation
reaction, and the corresponding products were conveniently
generated in good yields with excellent selectivity (Table 2,
entries 10−12). However, when alkyl substituted allylic alcohol
was used in this reaction, the desired product β,γ-unsaturated
carboxylic acid was obtained in moderate yield with a decreased
stereoselectivity (E/Z = 8:1, Table 2, entry 13).
We then turned our attention to test the generality of the
carboxylation reaction with different secondary and tertiary
allylic alcohols. As demonstrated in Table 3, various aryl- and
heteroaryl-substituted secondary allylic alcohols were subjected
to the optimized reaction conditions, and the carboxylation
With the optimized reaction conditions in hand (Table 1,
entry 10), we investigated the substrates scope of the reaction
with various substituted allylic alcohols. First, as summarized in
Table 2, a series of primary allylic alcohols was successfully
applied to the carboxylation reaction. The steric and electronic
property of the substitution on the benzene ring does not affect
the yield and selectivity of the reaction. Both electron-donating
group (Table 2, entries 2−5) and electron-withdrawing group
(Table 2, entries 6−9) substituted cinnamyl alcohols were all
well tolerated and delivered the corresponding acids in 64−76%
B
DOI: 10.1021/acs.orglett.7b02801
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
were delivered in moderate yield with lower E/Z selectivity
(Table 3, entries 13 and 14). It should be mentioned that the
secondary and tertiary allylic alcohols can be easily prepared
from the nucleophilic addition of alkenyl metal reagent to
aldehydes and ketones. Thus, this procedure provides a two-
step alternative method for the synthesis of β,γ-unsaturated
carboxylic acids from aldehydes and ketones by introducing a
C3 unit.
Table 3. Substrate Scope of the Carboxylation Reaction:
Secondary and Tertiary Allylic Alcohols
a
We further investigated the carboxylation of other allylic
substrates, as shown in Table 4. When activated cinnamyl
a
Table 4. Investigation of Other Leaving Groups
entry
X
yield (%)
E/Z
1
2
3
4
5
OAc
OBoc
OMe
Cl
75
66
18
79
14
>99:1
>99:1
>99:1
>99:1
>99:1
NMe2
a
Reaction conditions: allylic compounds (0.5 mmol), formic acid (3.5
mmol), Pd(OAc)2 (3 mol %), Xantphos (3 mol %), NaHCO3 (1.5
mmol), 4 Å MS (80 mg). DCC (1.0 mmol), 1,4-dioxane (2 mL), 60
°C, 20 h, isolated yield.
acetate and carbonate were employed as the substrate, the
carboxylation reaction proceeded effectively and gave yields and
selectivity similar to those of the unprotected alcohol (Table 4,
entries 1 and 2). However, when cinnamyl methyl ether was
applied in this reaction, owing to the poor leaving ability of the
methoxyl group, only 18% yield of product was generated
(Table 4, entry 3). This also indicates that formic acid did play
an activating rule by converting the hydroxyl group to its
formate. Although cinnamyl chloride gave a slightly higher yield
than cinnamyl alcohol, as stated above, its availability might be
a problem which restricts the substrate scope. Interestingly,
when cinnamyl amine was subjected to the optimized
condition, the carboxylation reaction proceeded as well, albeit
with a low yield, and no aminocarbonylation product was
observed.
On the basis of these results and previous reports, a possible
reaction mechanism is proposed in Scheme 1. First, allylic
Scheme 1. Plausible Reaction Mechanism
a
Reaction conditions: allylic alcohol (0.5 mmol), formic acid (3.5
mmol), Pd(OAc)2 (3 mol %), Xantphos (3 mol %), NaHCO3 (1.5
mmol), 4 Å MS (80 mg). DCC (1.0 mmol), 1,4-dioxane (2 mL), 60
°C, 20 h, isolated yield.
reaction proceeded smoothly. Interestingly, in all of these
reactions, the double bond had migrated and linear (E)-β,γ-
unsaturated carboxylic acids were isolated in moderate to good
yields (Table 3, entries 1−11). No branched isomer was
observed. This might be caused by the stereoisomerization of
the allylic palladium complex after the oxidative addition of Pd0
to the C−O bond. Similar to the primary allylic alcohol,
cyclohexyl-substituted allylic alcohol gave a lower yield and
decreased E/Z selectivity (Table 3, entry 12). In addition,
tertiary allylic alcohols were also tolerated in this trans-
formation, and trisubstituted β,γ-unsaturated carboxylic acids
C
DOI: 10.1021/acs.orglett.7b02801
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
alcohol and relative derivatives 1 or 1′ reacted with Pd0 to give
an allylic palladium complex 4, which thermodynamically favors
the linear configuration 5 owing to the tremendous steric effect
of the bisphosphine ligated palladium structure. Subsequently,
coordination and insertion of 5 with CO, which was generated
in situ from the reaction of formic acid with DCC, and X ligand
exchange of Pd−X with formic acid afforded the acylpalladium
formic acid complex 7. Reductive elimination delivered the
formic anhydride 8 and regenerated Pd0 for the next catalyst
cycle. The formic anhydride 8 then decomposed to generate
the product 2 and release CO at the same time.
In conclusion, a palladium-catalyzed direct carbonylative
transformation of unactivated allylic alcohol with formic acid
has been established. With formic acid as the CO source, a wide
range of primary, secondary, and tertiary allylic alcohols were
transformed into the corresponding β,γ-unsaturated carboxylic
acids in good yields. The reaction was conducted in a user-
friendly manner in which no gas manipulations were required,
and excellent regio- and stereoselectivity was obtained.
(4) (a) Loh, T.-P.; Cao, G.-Q.; Yin, Z. Tetrahedron Lett. 1999, 40,
2649−2652. (b) Miyazawa, M.; Yamamoto, K. Chem. Lett. 1994, 23,
491−494. (c) Troisi, L.; Granito, C.; Rosato, F.; Videtta, V.
Tetrahedron Lett. 2010, 51, 371−373. (d) Imada, Y.; Shibata, O.;
Murahashi, S. I. J. Organomet. Chem. 1993, 451, 183−194.
(e) Tommasi, S.; Perrone, S.; Rosato, F.; Salomone, A.; Troisi, L.
Synthesis 2012, 44, 423−430.
(5) (a) Satoh, T.; Ikeda, M.; Kushino, Y.; Miura, M.; Nomura, M. J.
Org. Chem. 1997, 62, 2662−2664. (b) Xiao, W.-J.; Alper, H. J. Org.
Chem. 1998, 63, 7939−7944. (c) Liu, Q.; Wu, L.; Jiao, H.; Fang, X.;
Jackstell, R.; Beller, M. Angew. Chem., Int. Ed. 2013, 52, 8064−8068.
(d) Li, H.; Neumann, H.; Beller, M. Chem. - Eur. J. 2016, 22, 10050−
10056. (e) Fu, M.-C.; Shang, R.; Cheng, W.-M.; Fu, Y. Chem. - Eur. J.
2017, 23, 8818−8822.
(6) (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A. Org. Lett. 2003, 5,
4269−4272. (b) Korsager, S.; Taaning, R. H.; Skrydstrup, T. J. Am.
Chem. Soc. 2013, 135, 2891−2894. (c) Morimoto, T.; Kakiuchi, K.
Angew. Chem., Int. Ed. 2004, 43, 5580−5588. (d) Wu, L.; Liu, Q.;
Jackstell, R.; Beller, M. Angew. Chem., Int. Ed. 2014, 53, 6310−6320.
(e) Gautam, P.; Bhanage, B. M. Catal. Sci. Technol. 2015, 5, 4663−
4702. (f) Qi, X.; Jiang, L.-B.; Li, C.-L.; Li, R.; Wu, X.-F. Chem. - Asian J.
2015, 10, 1870−1873. (g) Qi, X.; Li, C.-L.; Jiang, L.-B.; Zhang, W.-Q.;
Wu, X.-F. Catal. Sci. Technol. 2016, 6, 3099−3107. (h) Peng, J.-B.; Wu,
F.-P.; Li, C.-L.; Qi, X.; Wu, X.-F. Eur. J. Org. Chem. 2017, 2017, 1434−
1437. (i) Wu, F.-P.; Peng, J.-B.; Meng, L.-S.; Qi, X.; Wu, X.-F.
ChemCatChem 2017, 9, 3121−3124. (j) Seo, Y.-S.; Kim, D.-S.; Jun, C.-
H. Chem. - Asian J. 2016, 11, 3508−3512.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b02801.
Experimental details and characterization data (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: pengjb_05@zstu.edu.cn.
*E-mail: xiao-feng.wu@catalysis.de.
ORCID
Xiao-Feng Wu: 0000-0001-6622-3328
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are thankful for financial support from NSFC (21472174,
21602201, 21602204), the Education Department of Zhejiang
Province (Y201636555), Zhejiang Sci-Tech University
(16062095-Y), and Zhejiang Natural Science Fund for
Distinguished Young Scholars (LR16B020002)
REFERENCES
■
(1) (a) Beller, M. Applied Homogeneous Catalysis with Organometallic
Compounds, 2nd ed.; Wiley-VCH: Weinheim, 2002; Vol. 1, pp 145−
156. (b) Brennfuhrer, A.; Neumann, H.; Beller, M. Angew. Chem., Int.
̈
Ed. 2009, 48, 4114−4133. (c) Gabriele, B.; Mancuso, R.; Salerno, G.
Eur. J. Org. Chem. 2012, 2012, 6825−6839. (d) Peng, J.-B.; Qi, X.; Wu,
X.-F. Synlett 2017, 28, 175−194. (e) Wu, X.-F. RSC Adv. 2016, 6,
83831−83837. (f) Peng, J.-B.; Qi, X.; Wu, X.-F. ChemSusChem 2016,
9, 2279−2283.
(2) For selected reviews, see: (a) Sundararaju, B.; Achard, M.;
Bruneau, C. Chem. Soc. Rev. 2012, 41, 4467−4483. (b) Lumbroso, A.;
Cooke, M. L.; Breit, B. Angew. Chem., Int. Ed. 2013, 52, 1890−1932.
(c) Butt, N. A.; Zhang, W. Chem. Soc. Rev. 2015, 44, 7929−7967.
(3) (a) Houk, K. N. Chem. Rev. 1976, 76, 1−74. (b) Liu, J.; Liu, Q.;
Franke, R.; Jackstell, R.; Beller, M. J. Am. Chem. Soc. 2015, 137, 8556−
8563. (c) Michigami, K.; Mita, T.; Sato, Y. J. Am. Chem. Soc. 2017, 139,
6094−6097. (d) van Gemmeren, M.; Borjesson, M.; Tortajada, A.;
̈
Sun, S.-Z.; Okura, K.; Martin, R. Angew. Chem., Int. Ed. 2017, 56,
6558−6562.
D
DOI: 10.1021/acs.orglett.7b02801
Org. Lett. XXXX, XXX, XXX−XXX