A palladium-catalyzed regioselective hydroesterification of alkenylphenols to lactones with phenyl formate as CO source

Article abstract of DOI:10.1021/ol403171p

An effective Pd(OAc)₂-PPh₃ catalyzed hydroesterification of alkenylphenols with phenyl formate as CO surrogate is described. A variety of lactones are obtained in generally high yields with high regioselectivities. In one case, 76% ee is obtained with a chiral ligand.

Full text of DOI:10.1021/ol403171p

Letter
pubs.acs.org/OrgLett
A Palladium-Catalyzed Regioselective Hydroesterification of
Alkenylphenols to Lactones with Phenyl Formate as CO Source
Haining Wang,† Ben Dong,† Yang Wang,† Jingfu Li,† and Yian Shi*,†,‡,§
†State Key Laboratory of Coordination Chemistry, Center for Multimolecular Organic Chemistry, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093, China
‡Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China
§Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States
S
* Supporting Information
ABSTRACT: An effective Pd(OAc)2-PPh3 catalyzed hydro-
esterification of alkenylphenols with phenyl formate as CO
surrogate is described. A variety of lactones are obtained in
generally high yields with high regioselectivities. In one case,
76% ee is obtained with a chiral ligand.
actones such as benzofuran-2(3H)-ones (2) and 3,4-
dihydrocoumarins (3) are important functional moieties
Scheme 2
L
present in a wide variety of biologically significant compounds1
and materials.2 Among various methods toward this class of
molecules,3 the Reppe-type cyclocarbonylation process presents
an attractive approach (Scheme 1).3a,b,4−10 However, these
Scheme 1
(Z)-2-(Pent-1-enyl)phenol (1a) was used as the test
substrate. Formic acid and its derivatives were initially
examined for the reaction with Pd(OAc)2-PPh3 catalyst in
mesitylene at 90 °C (Table 1, entries 1−5). While few lactones
were obtained with HCO2H, HCO2Et, and HCO2Bn (Table 1,
entries 1−3), the desired benzofuran-2(3H)-one (2a) was
obtained as essentially one regioisomer in 86% yield in the
presence of HCO2Ph (Table 1, entry 4). The reaction also
proceeded well with N-formylbenzotriazole (4e), giving lactone
2a in 79% yield (Table 1, entry 5). Studies showed that
Pd(OAc)2 was a more effective catalyst than other palladium
species, such as Pd(dba)2, PdCl2, and PdCl2(CH3CN)2 (Table
1, entries 6−8). Comparable results were obtained with
bidentate phosphines such as dppp, dppb, and dppf (Table 1,
entries 10−12). No product was obtained without ligand added
(Table 1, entry 13). The reaction was further improved by
adding formic acid, giving lactone 2a in essentially quantitative
yield (Table 1, entry 14).16 Acetic acid was also found to be
beneficial to the reaction (Table 1, entry 15). However, TsOH
and Et3N were found to be detrimental to the reaction (Table
1, entries 16 and 17).
types of processes have been typically carried out under high
pressure of toxic CO at high temperature, which sometimes
makes them inconvenient to be used and explored in
laboratories. In recent years, there has been a growing trend
in using various CO surrogates in carbonylation processes to
circumvent the use of external CO.11 A number of metal-
catalyzed hydroesterification methods with formates and related
compounds have been reported, mostly with Ru3(CO)12 as
catalyst.12,13 However, the palladium-catalyzed process is less
well explored with only limited olefin examples being
reported.13m Furthermore, little has been reported for metal-
catalyzed asymmetric hydroesterification without the use of
external CO gas. In general, lactones 2 and 3 can be formed via
an intramolecular hydroesterification of formate 53g or an
intermolecular hydroesterification and subsequent lactoniza-
tion14 (Scheme 2). As part of our general interest in olefin
functionalization,15 we have investigated palladium-catalyzed
hydroesterification of alkenylphenols to lactones using phenyl
formate as CO source and have found that the reaction can
proceed efficiently and regioselectively. Moreover, the
enantioselective process is shown to be feasible. Herein, we
wish to report our preliminary results on this subject.
Received: November 3, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol403171p | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Screening of Reaction Conditions
Table 2. Hydroesterification of Alkenylphenols
yield
c
b
entry
4
Pd
ligand
additive
2a:3a
(%)
1
4a
4b
4c
4d
4e
4d
4d
4d
4d
4d
4d
4d
4d
4d
4d
4d
4d
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(dba)2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
dppe
dppp
dppb
dppf
0
0
2
3
0
4
>99:1
>99:1
>99:1
86
79
12
0
5
6
7
PdCl2
8
PdCl2(CH3CN)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
0
9
89:11
94:6
38
77
85
80
0
10
11
12
13
14
15
16
17
98:2
>99:1
PPh3
PPh3
PPh3
PPh3
HCO2H
AcOH
TsOH
Et3N
>99:1
>99:1
99
93
0
0
a
The reactions were carried out with 1a (0.50 mmol), 4 (0.60 mmol),
[Pd] (0.025 mmol), and ligand (0.05 or 0.10 mmol, P/Pd = 4/1) in
mesitylene (0.5 mL) at 90 °C for 16 h unless otherwise stated. For
b
entries 14−17, additive (1 equiv) was used. The ratio was determined
c
1
by H NMR analysis of the crude reaction mixture. Isolated yield.
The hydroesterification can be extended to a wide variety of
alkenylphenols to give the corresponding lactones in 47−99%
yields (Table 2). Both cis and trans disubstituted alkenylphenols
were effective substrates, giving five-membered lactones as
major products (Table 2, entries 1−6) (the X-ray structure of
2d is shown in Figure 1). The regioselectivity was generally
Figure 1. X-ray structure of compound 2d.
high except for phenyl-substituted olefin 1f (Table 2, entry 6).
Trisubstituted and monosubstituted terminal olefins also gave
five-membered lactones as essentially single regioisomers in
high yields (Table 2, entries 7−9). The regioselectivity was
reversed for 1,1-disubstituted olefins, predominantly giving six-
membered lactones in high yields (Table 2, entries 10−13) (the
X-ray structure of 3j is shown in Figure 2). In the case of 2-
allylphenol (1n), the five-membered lactone was obtained in
99% yield (Table 2, entry 14). It is likely that the double bond
underwent isomerization under the reaction conditions. For
substrate 1o in which the double bond isomerization was
blocked by the two methyl groups, seven-membered lactone 3o
was obtained as major regioisomer in 47% yield (Table 2, entry
15). 2-Vinylbenzyl alcohol (1p) was also an effective substrate,
a
The reactions were carried out with 1 (0.50 mmol), 4d (0.60 mmol),
Pd(OAc)2 (0.025 mmol), PPh3 (0.10 mmol), and HCO2H (0.50
mmol) in mesitylene (0.5 mL) at 90 °C for 16 h unless otherwise
b
c
stated. For 24 h. Isolated yield for the major product. For entries 2,
4, 6, 12, and 15, the ratio of two regioisomers was determined by H
NMR analysis of the crude reaction mixture. In other cases, the other
regioisomer was barely detectable if there was any. Combined yield of
1
d
2f and 3f.
giving 6-exo product 2p as essentially one regioisomer in 73%
yield (Table 2, entry 16).
1
No significant amounts of formate 5a were detected by H
NMR spectroscopic analysis of the crude reaction mixture with
B
dx.doi.org/10.1021/ol403171p | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, characterization data, X-ray struc-
tures, data for the determination of enantiomeric excess, and
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
Figure 2. X-ray structure of compound 3j.
*E-mail: yian@lamar.colostate.edu.
Notes
(Z)-2-(pent-1-enyl)phenol (1a) as substrate. When preformed
formate 5a was subjected to the reaction conditions without
phenyl formate, lactone 2a was obtained in 93% yield (Scheme
3). At this moment, it is not clear if formate 5a is a possible
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Natural Science
Foundation of China (21202082) and Nanjing University for
the financial support. We also thank Mr. Xiaodong Qiu, Mr.
Zhangxi Gu, and Mr. Ning Jin at Nanjing University for some
experimental contributions.
Scheme 3
REFERENCES
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Scheme 4
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In summary, we have developed an efficient Pd(OAc)2-PPh3
catalyzed hydroesterification of alkenylphenol using phenyl
formate as CO source. A wide variety of lactones have been
obtained in generally high yields (up to 99%) with high
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C
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