Effects of Silver Carbonate and p-Nitrobenzoic Acid for Accelerating Palladium-Catalyzed Allylic C-H Acyloxylation

Article abstract of DOI:10.1021/acs.orglett.1c02406

An allylic C-H acyloxylation of terminal alkenes with 4-nitrobenzoic acid was assisted by a bidentate-sulfoxide-ligated palladium catalyst combined with 1,4-benzoquinone and Ag2CO3 under mild reaction conditions. The catalytic activity was remarkably enhanced by Ag2CO3 as an additive and 4-nitrobenzoic acid as a carboxylate source; both components were essential to exhibiting high catalytic activity, high branch selectivity, and a wide substrate scope with low loading of the palladium catalyst. Branch-selective allylic acyloxylation of ethyl 7-octenoate (1a) gave the product which was led to ethyl 6,8-dihydroxyoctanoate (5), a useful synthetic intermediate of (R)-α-lipoic acid.

Full text of DOI:10.1021/acs.orglett.1c02406

pubs.acs.org/OrgLett
Letter
Effects of Silver Carbonate and p‑Nitrobenzoic Acid for Accelerating
Palladium-Catalyzed Allylic C−H Acyloxylation
Aymen Skhiri, Haruki Nagae, Hayato Tsurugi,* Masahiko Seki,* and Kazushi Mashima*
Cite This: https://doi.org/10.1021/acs.orglett.1c02406
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: An allylic C−H acyloxylation of terminal alkenes with 4-
nitrobenzoic acid was assisted by a bidentate-sulfoxide-ligated palladium catalyst
combined with 1,4-benzoquinone and Ag2CO3 under mild reaction conditions.
The catalytic activity was remarkably enhanced by Ag2CO3 as an additive and 4-
nitrobenzoic acid as a carboxylate source; both components were essential to
exhibiting high catalytic activity, high branch selectivity, and a wide substrate
scope with low loading of the palladium catalyst. Branch-selective allylic
acyloxylation of ethyl 7-octenoate (1a) gave the product which was led to ethyl
6,8-dihydroxyoctanoate (5), a useful synthetic intermediate of (R)-α-lipoic acid.
xidative allylic C(sp3)−H bond functionalization of
Scheme 1. Representative Examples for Allylic C(sp3)−H
O
simple alkenes with carboxylic acids, i.e., allylic C-
Acyloxylation by Palladium Catalysts and This Work
(sp3)−H acyloxylation, is a powerful tool for preparing
synthetically useful allyl esters.1−3 Various methodologies
have been developed to date to oxidize the allylic C(sp3)−H
bond using peracids and high-valent metal complexes as
stoichiometric oxidants;4 however, owing to the high reactivity
of those oxidants, the functional group tolerance is narrow, and
stoichiometric amounts of metal wastes are produced as
byproducts. Aiming to overcome the narrow substrate scope
and environmental unfriendliness for allylic C(sp3)−H
acyloxylation, Heumann and Åkermark et al. developed
palladium-catalyzed allylic C(sp3)−H acyloxylation of cyclic
alkenes in the presence of a catalytic amount of 1,4-
benzoquinone (1,4-BQ) together with more than stoichio-
metric amounts of MnO2 or a catalytic amount of Cu(OAc)2
with O2 as the oxidants in acetic acid, giving allyl acetates in
good yield without overoxidized products (Scheme 1(a)).5,6
Uemura et al. demonstrated that a combination of tert-butyl
hydroperoxide and TeO2 was effective for acyloxylation of the
allylic C(sp3)−H bond of cyclic alkenes catalyzed by PdCl2/
AgOAc (Scheme 1(b)),7 although terminal alkenes were not
applied in this palladium-catalyzed allylic oxidation due to the
facile isomerization of the alkene moiety. Later, White et al.
developed a palladium-catalyzed linear-selective allylic C-
(sp3)−H bond acyloxylation of terminal alkenes in DMSO
aided by 1,4-BQ as the oxidant under aerobic conditions. In
addition, they successfully achieved branch-selective allylic
acyloxylation of terminal alkenes with acetic acid using a
bidentate sulfoxide-ligated palladium catalyst, i.e., the White
catalyst, in combination with 1,4-BQ (Scheme 1(c)).8,9 The
branch/linear selectivity of the allylic C(sp3)−H acyloxylation
of terminal alkenes is controlled by the supporting ligands,
monodentate (DMSO) vs a bidentate sulfoxide; the high
catalyst loading (over 5 mol %) and longer reaction time of the
Received: July 19, 2021
https://doi.org/10.1021/acs.orglett.1c02406
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
White catalyst system, however, remain serious issues. As a part
of our continuous studies on synthesizing allylic-functionalized
compounds using transition metal catalysts,10 we herein report
a significant improvement of the catalytic activity by p-
nitrobenzoic acid as a carboxylate source and Ag2CO3 as a
cocatalyst in the branch-selective allylic C(sp3)−H acylox-
ylation of terminal alkenes with unprecedentedly low loadings
of the palladium catalyst (Scheme 1(d)). Various mono- and
disubstituted terminal and internal alkenes, including cyclic
alkenes, were converted to the corresponding allyl esters in
good to excellent yields. Furthermore, we found that this
branch-selective allylic acyloxylation of terminal alkenes was
applicable to a key step in the synthesis of (R)-α-lipoic acid.
We started by searching for the best additive for allylic
acyloxylation of ethyl 7-octenoate (1a) as a model substrate
and 4-nitrobenzoic acid (2a) as a carboxylate source using
commercially available White catalyst (1 mol %) in the
presence of 2 equiv of 1,4-BQ in 1,4-dioxane (0.50 mL) under
aerobic conditions at 45 °C for 48 h, and the results are shown
in Table 1. Under the standard conditions without any
additive, the corresponding allylic carboxylate 3aa was
obtained in 23% yield (entry 1). The yield was remarkably
increased by adding Ag2CO3: treatment of the reaction mixture
with Ag2CO3 (1 mol %) afforded 3aa in 91% yield with an
exclusive branch selectivity (entry 2). We further tested the
allylic acyloxylation using several silver salts as listed in entries
3−7. Although AgNO3, Ag2O, and AgOTf exhibited better
catalytic activity compared with the standard conditions (entry
1), the yields of 3aa were much lower than the case using
Ag2CO3 (entries 3−5 vs entry 2). Silver salts such as AgOAc
and AgCl exhibited almost no additive effects (entries 6 and
7). The unprecedented high positive effects of Ag2CO3 led us
to further investigate other carbonate salts such as Cu, Mn, Ce,
and Na under the standard reaction conditions: copper and
manganese carbonate salts were previously used for allylic
acyloxylation of cyclic alkenes with Pd(OAc)2;5 however, we
observed no significant improvement of the catalytic activity
when using these carbonates (entries 8 and 9), and the use of
Ce2(CO3)3 and Na2CO3 suppressed the catalytic reaction
(entries 10 and 11), suggesting that both the silver cation and
carbonate anion were essential for efficiently improving the
catalytic performance. The specific role of additional metal
ions in Pd-catalyzed C−H bond functionalization was reported
for the formation of Pd−Ag and Pd−Na aggregates in the
reaction mixture.11 Using Ag2CO3 as the additive, we checked
the reaction conditions by shortening the reaction time to 24
h, which produced 3aa in a slightly lower yield (entry 12), and
by diluting the reaction solution concentration, 3aa was
obtained in lower yield (entry 13). By changing the amount of
1,4-BQ to 1.5 equiv and 2a to 1.0 equiv with respect to 1a, the
yield of 3aa reached 98% in 24 h with perfect branch selectivity
(entry 14). When the White catalyst was replaced with
Pd(OAc)2 under the same reaction conditions as in entry 2,
3aa was detected in only a trace amount (entry 15), indicating
the importance of the bidentate sulfoxide ligand for the
reaction. No product was obtained without the palladium
catalyst (entry 16), and to double the amount of AgOTf (2
mol %) was not effective for the acyloxylation (entry 17). The
importance of the para-nitro substituent was significant: other
electron-withdrawing and -donating substituents on the
benzoic acid derivatives resulted in much lower yields for the
acyloxylation (below 40%).12 In addition, typical carboxylic
acids for the acyloxylation such as acetic acid and pivalic acid
were ineffective under the optimized reaction conditions.12
We next evaluated the substrate scope of mono- and
disubstituted terminal alkenes (Table 2). Allylic acyloxylation
with simple terminal alkenes such as 1-hexene (1b), 1-octene
(1c), and 1-decene (1d) gave the branch-selective allylic
acyloxylation products in excellent yields. The size of the alkyl
group adjacent to the allylic position affected the reactivity: the
yield gradually decreased with increasing bulkiness of the
Table 1. Screening of Additives and Optimization for Allylic
a
Acyloxylation of 1a with 2a
time
(h)
conv. of 1a
yield of 3aa
entry
additive
(%)
(%)
L/B ratio
1
2
3
4
5
6
7
8
-
48
48
48
48
48
48
48
48
48
48
48
24
48
24
48
48
48
26
93
42
34
46
23
21
24
42
<5
10
76
30
>99
<5
<1
39
23
91
38
32
45
18
16
22
1/99
1/99
1/99
3/97
<1/>99
1/99
2/98
<1/>99
<1/>99
-
Ag2CO3
AgNO3
Ag2O
AgOTf
AgOAc
AgCl
CuCO3
MnCO3
Ce2(CO3)3
Na2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgOTf
9
41
10
11
12
13
14
15
16
17
trace
trace
74
-
t
3/97
1/99
<1/>99
-
secondary (1e, Cy) to a tertiary counterpart (1f, Bu), though
b
29
the branch-selective products were obtained exclusively. When
allylbenzene (1g) was used as the substrate, the branch
product 3ga was obtained with the corresponding linear one in
1.0:1.2 ratio in a moderate yield with the catalyst loading of 2
mol %. Interestingly, allyl ester 1h was applicable under the
reaction conditions without its degradation to afford 3ha in a
moderate yield. Alkyl bromide 1i was tolerant under the
reaction conditions to form 3ia without dehalogenation.
Similar to the model substrate 1a, allylic acyloxylation of the
related carboxylic acid derivatives, methyl ester (1j) and
tertiary amide (1k), afforded 3ja and 3ka, respectively in good
yields. In addition, the ketal moiety in 1l remained intact
during the catalytic reaction to form 3la in a good yield,
cde
,
,
98 (89)
trace
n.d.
37
f
g
-
h
<1/>99
a
Conditions: 1a (0.30 mmol), 2a (0.60 mmol, 2.0 equiv), Pd cat. (1
mol %), additive (1 mol %), 1,4-BQ (2.0 equiv) in 1,4-dioxane (0.50
b
c
mL) at 45 °C for 48 h. 1,4-Dioxane (2.0 mL). 1,4-BQ (1.5 equiv).
d
e
Yield in parentheses is isolated yield. 2a (0.30 mmol, 1.0 equiv). 1
mmol scale reaction gave 3aa in 84% isolated yield. Details were
shown in the Supporting Information. Pd(OAc)2 instead of White
catalyst. Without Pd cat. n.d. = not detected. AgOTf (2 mol %) was
used as the additive.
f
g
h
B
https://doi.org/10.1021/acs.orglett.1c02406
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 2. Substrate Scope for Terminal Alkenes
The compound 3aa′ obtained by allylic acyloxylation of
ethyl 7-octenoate (1a) is a useful starting material for
synthesizing ethyl 6,8-dihydroxyoctanoate 5, a key synthetic
intermediate for a biologically active α-lipoic acid.13,14 Under
hydroboration−oxidation conditions employing 9-BBN and
H2O2, hydroxylated compound 4 was obtained in 45% yield
without decomposition of the ester functionality. Subsequent
hydrolysis in the presence of sodium ethoxide afforded ethyl
6,8-dihydroxyoctanoate 5 in 78% yield (Scheme 2). The allylic
carboxylate 3aa thus-obtained was further transformed to
chiral allyl acetate (S)-3aa′ by kinetic resolution (Scheme 3).
a
Conditions: 1 (0.30 mmol), 2a (0.30 mmol, 1.0 equiv), Pd cat. (1
mol %), Ag2CO3 (1 mol %), 1,4-BQ (1.5 equiv) in 1,4-dioxane (0.50
mL) at 45 °C for 24 h. Pd cat. (2 mol %) and Ag2CO3 (2 mol %)
were used for 24 h. Branch and linear ratio, 1.0:1.2. Pd cat. (2 mol
%) and Ag2CO3 (2 mol %) were used for 48 h.
b
c
d
Scheme 2. Synthesis of Ethyl 6,8-Dihydroxyoctanoate 5
from 3aa′
whereas 5-hexene-2-one, the ketone variant of 1l, was not
applicable in this reaction. 3-Methyl-1-hexene (1m) was less
reactive under these catalytic conditions due to the steric
congestion by methyl and n-propyl groups at the allylic
position. The reactivity of 1,1-disubstituted alkenes 1n,o was
next evaluated under the reaction conditions. When 2-methyl-
1-hexene (1n) was used, C−H acyloxylation occurred
preferentially at the n-butyl chain over the methyl group to
produce a mixture of 3na and 3na′ with 5:1 ratio in a moderate
yield, in which the n-alkyl chain was preferentially function-
alized over the methyl group. Methylenecyclohexane (1o) was
oxidized at the α-position of the cyclohexane ring to give
acyloxylation product 3oa without isomerization of the CC
moiety into the six-membered ring.
Scheme 3. Kinetic Resolution for Synthesizing (S)-Acetoxy
Compound (S)-3aa′
We further evaluated the reactivity of this C(sp3)−H
acyloxylation for internal alkenes, as depicted in eqs 1 and 2.
Allylic acyloxylation of cyclic alkenes 1p−1r afforded the
corresponding products in excellent yields without contami-
nation by doubly C−H acyloxylation products. When using 1-
methyl-1-cyclohexene (1s) as the substrate, C(sp3)−H
acyloxylation occurred at the less sterically congested
methylene position, giving 3sa in a moderate yield without
isomerization of the CC moiety as well as no formation of
the linear acyloxylation product at the methyl group (eq 1). In
contrast, (1R)-(+)-α-pinene (1t), a naturally occurring 1-
methyl-1-cyclohexene motif, was converted to the correspond-
ing acyloxylation product 3ta in a moderate yield. It was
noteworthy that 1t was initially isomerized to methylenecy-
clohexane, and the methylene position adjacent to the CC
moiety was acyloxylated, which was different from the reaction
with 1s, probably due to the steric hindrance at the allylic
position of the cyclohexene ring of 1t.
After hydrolysis of 3aa by following a similar procedure from
4 to 5, racemic allylic alcohol 6 was obtained. Subsequent
enzymatic kinetic resolution15 using Novozyme435 in vinyl
acetate gave the (S)-acetoxylated compound (S)-3aa′ in 19%
isolated yield with 98% ee along with recovering 39% of (R)-6
(88% ee). Combined with the diol synthesis shown in Scheme
3, this palladium-catalyzed allylic oxidation became an effective
synthetic pathway to obtain chiral (R)-α-lipoic acid.
In summary, we achieved a remarkable reaction rate and
yield acceleration for branch-selective allylic acyloxylation of
alkenes catalyzed by a disulfoxide-ligated palladium catalyst
C
https://doi.org/10.1021/acs.orglett.1c02406
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press:
Oxford, 1991; Vol. 4, Chapter 3.3, p 596. (b) Trost, B. M.; Crawley,
M. L. Asymmetric Transition-Metal-Catalyzed Allylic Alkylations:
Applications in Total Synthesis. Chem. Rev. 2003, 103, 2921−2944.
(c) Pan, D.; Jiao, N. Palladium-Catalyzed Heck-Type Coupling of
Allyl Esters: β-Hydride versus β-Acetoxy Elimination. Synlett 2010,
2010, 1577−1588.
(White catalyst) using 4-nitrobenzoic acid as the carboxylate
source and Ag2CO3 as the additive. This reaction system was
widely applicable to various terminal mono- and disubstituted
alkenes and internal alkenes while maintaining high branch
selectivity. One of the allylic acyloxylation products, 3aa, was a
good source for the synthesis of ethyl 6,8-dihydroxyoctanoate
5, a synthetic key intermediate for (R)-α-lipoic acid. Further
elaboration to clarify the effect of Ag2CO3 is ongoing in our
laboratory.
(3) Examples for the synthetic utility of allyl esters: (a) Trost, B. M.;
Verhoeven, T. R. Allylic alkylation. Palladium-catalyzed substitutions
of allylic carboxylates. Stereo- and regiochemistry. J. Am. Chem. Soc.
1980, 102, 4730−4743. (b) Hayashi, T.; Kanehira, K.; Hagihara, T.;
Kumada, M. Asymmetric synthesis catalyzed by chiral ferrocenyl-
phosphine-transition metal complexes. 5. Palladium-catalyzed asym-
metric allylation of active methine compounds. J. Org. Chem. 1988,
53, 113−120. (c) Sawamura, M.; Nagata, H.; Sakamoto, H.; Ito, Y.
Chiral phosphine ligands modified by crown ethers: an application to
palladium-catalyzed asymmetric allylation of.beta.-diketones. J. Am.
Chem. Soc. 1992, 114, 2586−2592. (d) Trost, B. M.; Organ, M. G.
Deracemization of Cyclic Allyl Esters. J. Am. Chem. Soc. 1994, 116,
10320−10321. (e) Trost, B. M.; Radinov, R.; Grenzer, E. M.
Asymmetric Alkylation of β-Ketoesters. J. Am. Chem. Soc. 1997, 119,
7879−7880. (f) Trost, B. M.; Ariza, X. Catalytic Asymmetric
Alkylation of Nucleophiles: Asymmetric Synthesis of α-Alkylated
Amino Acids. Angew. Chem., Int. Ed. Engl. 1997, 36, 2635−2637.
(g) Trost, B. M. Asymmetric Allylic Alkylation, an Enabling
Methodology. J. Org. Chem. 2004, 69, 5813−5837.
(4) Examples for allylic C−H acyloxylation with a stoichiometric
amount of oxidants: (a) Kharasch, M.; Fono, A. A New Method of
Introducing Peroxy Groups into Organic Molecules. J. Org. Chem.
1958, 23, 324−325. (b) Kharasch, M.; Sosnovsky, G. The Reaction of
t-Butyl Perbenzoate and OlefinsA Stereospecific Reaction. J. Am.
Chem. Soc. 1958, 80, 756. (c) Umbreit, M. A.; Sharpless, K. B. Allylic
oxidation of olefins by catalytic and stoichiometric selenium dioxide
with tert-butyl hydroperoxide. J. Am. Chem. Soc. 1977, 99, 5526.
(d) Morimoto, T.; Machida, T.; Hirano, M.; Zhung, X. Allylic
oxidation of olefins by cobalt (III), manganese(III), and cerium (IV)
acetates in acetic acid in the presence of sodium bromide. J. Chem.
Soc., Perkin Trans. 2 1988, 909−913. (e) Kaur, R.; Singh, H. B.; Patel,
R. P. Synthesis, characterisation and reactions of bis[2-(dimethyla-
minomethyl)-phenyl] diselenide: its structure and that of [2-
(dimethylaminomethyl)phenyl]-selenium bromide. J. Chem. Soc.,
Dalton Trans. 1996, 2719. (f) Ren, T. L.; Xu, B. H.; Mahmood, S.;
Sun, M. X.; Zhang, S. J. Cobalt-catalyzed oxidative esterification of
allylic/benzylic C(sp3)−H bonds. Tetrahedron 2017, 73, 2943.
Related review: (g) Bayeh, L.; Tambar, U. K. Catalytic Asymmetric
Intermolecular Allylic Functionalization of Unactivated Internal
Alkenes. ACS Catal. 2017, 7, 8533−8543.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c02406.
Detailed experimental procedures for Pd-catalyzed C−H
acyloxylation, characterization data for the acyloxylation
products, and copies of 1H and 13C NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Kazushi Mashima − Department of Chemistry, Graduate
School of Engineering Science, Osaka University, Toyonaka,
Osaka, Japan; orcid.org/0000-0002-1316-2995;
Email: mashima@chem.es.osaka-u.ac.jp
Hayato Tsurugi − Department of Chemistry, Graduate School
of Engineering Science, Osaka University, Toyonaka, Osaka,
Japan; orcid.org/0000-0003-2942-7705;
Email: tsurugi@chem.es.osaka-u.ac.jp
Masahiko Seki − Tokuyama Corporation, Tsukuba, Ibaraki,
Japan; orcid.org/0000-0002-9942-377X; Email: ma-
seki@tokuyama.co.jp
Authors
Aymen Skhiri − Department of Chemistry, Graduate School of
Engineering Science, Osaka University, Toyonaka, Osaka,
Japan
Haruki Nagae − Department of Chemistry, Graduate School of
Engineering Science, Osaka University, Toyonaka, Osaka,
Japan; orcid.org/0000-0002-5589-7375
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c02406
(5) (a) Heumann, A.; Åkermark, B. Oxidation with Palladium Salts:
Catalytic Preparation of Allyl Acetates from Monoolefins Using a
Three-Component Oxidation System. Angew. Chem., Int. Ed. Engl.
1984, 23, 453−454. (b) Hansson, S.; Heumann, A.; Rein, T.;
Aakermark, B. Preparation of allylic acetates from simple alkenes by
palladium(II)-catalyzed acetoxylation. J. Org. Chem. 1990, 55, 975−
984. (c) Bystroem, S.; Larsson, E. M.; Aakermark, B. Palladium-
catalyzed allylic oxidation of cyclohexenes using molecular oxygen as
oxidant. J. Org. Chem. 1990, 55, 5674−5675. (d) Aakermark, B.;
Larsson, E. M.; Oslob, J. D. Allylic Carboxylations and Lactonization
Using Benzoquinone and Hydrogen Peroxide or tert-Butyl Hydro-
peroxide as Oxidants. J. Org. Chem. 1994, 59, 5729−5733.
(6) (a) McMurry, J. E.; Kocotovsky, P. A method for the palladium-
catalyzed allylic oxidation of olefins. Tetrahedron Lett. 1984, 25,
4187−4190. A seminal work for Pd-catalyzed oxidative acyloxylation
of dienes: (b) Bäckvall, J. E.; Awasthi, A. K.; Renko, Z. D. Biomimetic
Aerobic 1,4-Oxidation of 1,3-Dienes Catalyzed by Cobalt Tetraphe-
nylporphyrine-Hydroquinone-Palladium(II). An Example of Triple
Catalysis. J. Am. Chem. Soc. 1987, 109, 4750−4752.
(7) Uemura, S.; Fukuzawa, S.; Toshimitsu, A.; Okano, M. Palladium-
catalyzed allylic oxidation of olefins by t-butyl hydroperoxide and
tellurium(IV) oxide. Tetrahedron Lett. 1982, 23, 87−90.
Notes
The authors declare no competing financial interest.
REFERENCES
■
(1) Reviews for C−H bond acyloxylation at the allylic position:
(a) Wu, Y.; Liu, G. Palladium-catalyzed allylic C-H bond
functionalization of olefins. Top. Curr. Chem. 2009, 292, 195−209.
(b) Li, H.; Li, B.-J.; Shi, Z.-J. Challenge and progress: palladium-
catalyzed sp3 C−H activation. Catal. Sci. Technol. 2011, 1, 191−206.
(c) Liron, F.; Oble, J.; Lorion, M. M.; Poli, G. Direct Allylic
Functionalization Through Pd-Catalyzed C−H Activation. Eur. J. Org.
Chem. 2014, 2014, 5863−5883. (d) Fernandes, R. A.; Nallasivam, J. L.
Catalytic allylic functionalization via π-allyl palladium chemistry. Org.
̀
Biomol. Chem. 2019, 17, 8647−8672. (e) Pamies, O.; Margalef, J.;
Canellas, S.; James, J.; Judge, E.; Guiry, P. J.; Moberg, C.; Bäckvall, J.-
̃
̀
E.; Pfaltz, A.; Pericas, M. A.; Diéguez, M. Recent Advances in
Enantioselective Pd-Catalyzed Allylic Substitution: From Design to
Applications. Chem. Rev. 2021, 121, 4373−4505.
(2) Book and reviews for utilization of allyl esters with transition
metal catalysts: (a) Godleski, S. A. In Comprehensive Organic Synthesis;
D
https://doi.org/10.1021/acs.orglett.1c02406
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(8) Pd-catalyzed oxidative acyloxylation of an allylic C−H bond by
White’s group: (a) Chen, M. S.; White, M. C. A Sulfoxide-Promoted,
Catalytic Method for the Regioselective Synthesis of Allylic Acetates
from Monosubstituted Olefins via C−H Oxidation. J. Am. Chem. Soc.
2004, 126, 1346−1347. (b) Chen, M. S.; Prabagaran, N.; Labenz, N.
A.; White, M. C. Serial Ligand Catalysis: A Highly Selective Allylic
C−H Oxidation. J. Am. Chem. Soc. 2005, 127, 6970−6971.
(c) Fraunhoffer, K. J.; Bachovchin, D. A.; White, M. C. Hydrocarbon
Oxidation vs C−C Bond-Forming Approaches for Efficient Syntheses
of Oxygenated Molecules. Org. Lett. 2005, 7, 223−226. (d) Fraun-
hoffer, K. J.; Prabagaran, N.; Sirois, L. E.; White, M. C. Macro-
lactonization via Hydrocarbon Oxidation. J. Am. Chem. Soc. 2006,
128, 9032−9033. (e) Delcamp, J. H.; White, M. C. Sequential
Hydrocarbon Functionalization: Allylic C−H Oxidation/Vinylic C−
H Arylation. J. Am. Chem. Soc. 2006, 128, 15076−15077. (f) Covell,
D. J.; White, M. C. A Chiral Lewis Acid Strategy for Enantioselective
Allylic C-H Oxidation. Angew. Chem., Int. Ed. 2008, 47, 6448−6451.
(g) Vermeulen, N. A.; Delcamp, J. H.; White, M. C. Synthesis of
Complex Allylic Esters via C−H Oxidation vs C−C Bond Formation.
J. Am. Chem. Soc. 2010, 132, 11323−11328.
(9) Selected examples for Pd-catalyzed allylic C−H bond
acyloxylation: (a) Campbell, A. N.; White, P. B.; Guzei, I. A.; Stahl,
S. S. Allylic C−H Acetoxylation with a 4,5-Diazafluorenone-Ligated
Palladium Catalyst: A Ligand-Based Strategy To Achieve Aerobic
Catalytic Turnover. J. Am. Chem. Soc. 2010, 132, 15116−15119.
(b) Kondo, H.; Yu, F.; Yamaguchi, J.; Liu, G.; Itami, K. Branch-
Selective Allylic C−H Carboxylation of Terminal Alkenes by Pd/sox
Catalyst. Org. Lett. 2014, 16, 4212−4215. (c) Louafi, F.; Lorion, M.
M.; Oble, J.; Poli, G. Dichotomous Reaction Pathways for the
Oxidative Palladium(II)-Catalyzed Intramolecular Acyloxylation of
Alkenes. Synlett 2015, 26, 2237−2242. (d) Li, Y. G.; Li, L.; Yang, M.
Y.; He, G.; Kantchev, E. A. B. A Bulky Disulfoxide Ligand for Pd-
Catalyzed Oxidative Allylic C−H Amination with 2,2,2-Trichloroethyl
Tosyl Carbamate. J. Org. Chem. 2017, 82, 4907−4917. (e) Jaworski, J.
N.; McCann, S. D.; Guzei, I. A.; Stahl, S. S. Detection of Palladium(I)
in Aerobic Oxidation Catalysis. Angew. Chem., Int. Ed. 2017, 56,
3605−3610. (f) Jaworski, J. N.; Kozack, C. V.; Tereniak, S. J.; Knapp,
S. M. M.; Landis, C. R.; Miller, J. T.; Stahl, S. S. Operando
Spectroscopic and Kinetic Characterization of Aerobic Allylic C−H
Acetoxylation Catalyzed by Pd(OAc)2/4,5-Diazafluoren-9-one. J. Am.
Chem. Soc. 2019, 141, 10462−10474. (g) Kozack, C. V.; Tereniak, S.
J.; Jaworski, J. N.; Li, B.; Bruns, D. L.; Knapp, S. M. M.; Landis, C. R.;
Stahl, S. S. Benzoquinone Cocatalyst Contributions to DAF/
Pd(OAc)2-Catalyzed Aerobic Allylic Acetoxylation in the Absence
and Presence of a Co(salophen) Cocatalyst. ACS Catal. 2021, 11,
6363−6370.
T.; Dutta, S.; Maiti, D. Deciphering the Role of Silver in Palladium-
Catalyzed C-H Functionalizations. ACS Catal. 2021, 11, 9702−9714.
(12) See Supporting Information for the screening of carboxylic
acids.
(13) Neufeld, K.; Henssen, B.; Pietruszka, J. Enantioselective Allylic
Hydroxylation of ω-Alkenoic Acids and Esters by P450 BM3Mo-
nooxygenase. Angew. Chem., Int. Ed. 2014, 53, 13253−13257.
(14) (a) Rama Rao, A.V.; Gurjar, M. K.; Garyali, K.;
Ravindranathan, T. Enantiospecific synthesis of (R-(+)-α-lipoic acid
from d-glucose. Carbohydr. Res. 1986, 148, 51−55. (b) Rao, A. V. R.;
Mysorekar, S. V.; Gurjar, M. K.; Yadav, J. S. Synthesis of (3R,4R)-1,5-
hexadien-3,4-diol and its unsymmetricalderivatives: Application to
(R)-(+)-lipoic acid. Tetrahedron Lett. 1987, 28, 2183−2186.
(c) Gopalan, A. S.; Jacobs, H. K. Stereochemical control of yeast
reductions: Synthesis of R-(+)-α-lipoic acid. Tetrahedron Lett. 1989,
30, 5705−5708. (d) Gopalan, A. S.; Jacobs, H. K. Bakers’ yeast
reduction of alkyl 6-chloro-3-oxohexanoates: synthesis of (R)-(+)-α-
lipoic acid. J. Chem. Soc., Perkin Trans. 1 1990, 1897−1900.
(e) Chavan, S. P.; Praveen, C.; Ramakrishna, G.; Kalkote, U. R.
Enantioselective synthesis of R-(+)-α and S-(−)-α-lipoic acid.
Tetrahedron Lett. 2004, 45, 6027−6028. (f) Chavan, S. P.; Pawar,
K. P.; Praveen, C.; Patil, N. B. Chirality induction and chiron
approaches to enantioselective total synthesis of α-lipoic acid.
Tetrahedron 2015, 71, 4213−4218.
(15) Reviews for kinetic resolution: (a) Mohr, J. T.; Ebner, D. C.;
Stoltz, B. M. Catalytic enantioselective stereoablative reactions: an
unexploited approach to enantioselective catalysis. Org. Biomol. Chem.
2007, 5, 3571−3576. (b) Harwood, L. A.; Wong, L. L.; Robertson, J.
Enzymatic Kinetic Resolution by Addition of Oxygen. Angew. Chem.,
Int. Ed. 2021, 60, 4434−4447.
(10) (a) Nagae, H.; Xia, J.; Kirillov, E.; Higashida, K.; Shoji, K.;
Boiteau, V.; Zhang, W.; Carpentier, J.-F.; Mashima, K. Asymmetric
Allylic Alkylation of β-Ketoesters via C−N Bond Cleavage of N-Allyl-
N-methylaniline Derivatives Catalyzed by a Nickel−Diphosphine
System. ACS Catal. 2020, 10, 5828−5839. (b) Kita, Y.; Kavthe, R. D.;
Oda, H.; Mashima, K. Asymmetric Allylic Alkylation of β-Ketoesters
with Allylic Alcohols by a Nickel/Diphosphine Catalyst. Angew.
Chem., Int. Ed. 2016, 55, 1098−1101. (c) Kita, Y.; Sakaguchi, H.;
Hoshimoto, Y.; Nakauchi, D.; Nakahara, Y.; Carpentier, J.-F.; Ogoshi,
S.; Mashima, K. Pentacoordinated Carboxylate π-Allyl Nickel
Complexes as Key Intermediates for the Ni-Catalyzed Direct
Amination of Allylic Alcohols. Chem. - Eur. J. 2015, 21, 14571−14578.
(11) (a) Fang, L.; Saint-Denis, T. G.; Taylor, B. L. H.; Ahlquist, S.;
Hong, K.; Liu, S.; Han, L.; Houk, K. N.; Yu, J.-Q. Experimental and
Computational Development of a Conformationally Flexible
Template for the meta-C−H Functionalization of Benzoic Acids. J.
Am. Chem. Soc. 2017, 139, 10702−10714. (b) Zhuang, Z.; Yu, C.-B.;
Chen, G.; Wu, Q.-F.; Hsiao, Y.; Joe, C. L.; Qiao, J. X.; Poss, M. A.; Yu,
J.-Q. Ligand-Enabled β-C(sp3)−H Olefination of Free Carboxylic
Acids. J. Am. Chem. Soc. 2018, 140, 10363−10367. (c) Zhuang, Z.;
Herron, A. N.; Fan, Z.; Yu, J.-Q. Ligand-Enabled Monoselective β-
C(sp3)−H Acyloxylation of Free Carboxylic Acids Using a Practical
Oxidant. J. Am. Chem. Soc. 2020, 142, 6769−6776. (d) Bhattacharya,
E
https://doi.org/10.1021/acs.orglett.1c02406
Org. Lett. XXXX, XXX, XXX−XXX