Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-Catalysis Using Air as the Sole Oxidant

Article abstract of DOI:10.1021/acs.orglett.6b01130

A new metal-free catalysis protocol for the oxidative coupling of nonactivated alkenes with simple carboxylic acids has been established. This method is predicated on the cooperative interaction of a diselane and a photoredox catalyst, which allows for the use of ambient air or pure O₂ as the terminal oxidant. Under the title conditions, a range of both functionalized and nonfunctionalized alkenes can be readily converted into the corresponding allylic ester products with good yields (up to 89%) and excellent regioselectivity as well as good functional group tolerance.

Full text of DOI:10.1021/acs.orglett.6b01130

Letter
pubs.acs.org/OrgLett
Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-
Catalysis Using Air as the Sole Oxidant
Stefan Ortgies, Christian Depken, and Alexander Breder*
Institut fur Organische und Biomolekulare Chemie, Georg-August-Universitat, Tammannstrasse 2, 37077 Gottingen, Germany
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S
* Supporting Information
ABSTRACT: A new metal-free catalysis protocol for the
oxidative coupling of nonactivated alkenes with simple
carboxylic acids has been established. This method is
predicated on the cooperative interaction of a diselane and a
photoredox catalyst, which allows for the use of ambient air or
pure O2 as the terminal oxidant. Under the title conditions, a range of both functionalized and nonfunctionalized alkenes can be
readily converted into the corresponding allylic ester products with good yields (up to 89%) and excellent regioselectivity as well
as good functional group tolerance.
he oxidative derivatization of alkenes arguably constitutes
one of the most paramount categories of organic
conceptual rationale, we reasoned that simple alkenes might be
oxidatively coupled to carboxylic acids to give allylic esters8 via
light-dependent cooperative selenium catalysis (Scheme 1).
T
transformations both in industrial and scientific contexts.
Because of the economic and ecological profile of molecular
oxygen, there has been a sustained and ever-increasing interest in
the development of new reaction manifolds that capitalize on the
use of O2 as a terminal oxidant for the functionalization of
alkenes.1 Of particular interest in this context are reactions in
which O2 solely serves as an acceptor of electrons and protons
from the substrate molecules but is otherwise not involved in the
derivatization event, i.e., emulated or artificial oxidase reactions.
While there has been notable progress in the development of
transition-metal-catalyzed oxidase reactions,1 there is still only a
very limited number of reports documented in the literature that
delineate analogous and equipotent metal-free catalysis concepts
for the derivatization of simple alkenes.2,3 As a matter of fact,
selective O2-reliant allylic oxidations that are exclusively driven
by nonmetallic catalysts and in which the carbon−heteroatom
bond formation occurs via carbophilic alkene activation4 have
remained elusive thus far.2a,5
Scheme 1. Selenium-Catalyzed Oxidative Allylic Esterification
Strategies
In a series of independent investigations, both Pandey et al.
and Ragains et al. showed that organoselanes and -diselanes can
be readily oxidized under photochemical conditions using
photosensitizers such as 1,4-dicyanonaphthalene (DCN) and
Ru(bpy)3(PF6)2, respectively.6 Pandey et al. also showed that
alkenes can be converted into β-selenenylated ethers and esters
using stoichiometric quantities of (PhSe)2 in the presence of
DCN and O2 under UV irradiation.7 From these studies, we
conjectured that photosensitizers with suitable redox potentials
and photophysical properties in combination with organo-
diselanes might allow for the design of a cooperative catalysis
manifold in which simple alkenes are directly converted into
allylic oxidation products using O2 or even air as the sole oxidant.
A notable implication of such a catalytic regime is the fact that
oxidants commonly employed in selenium catalysis (e.g., N-
haloimides and -amides as well as hypervalent iodine reagents),
which inevitably entail the production of significant amounts of
waste, may be replaced by O2 in certain cases. On the basis of this
Traditional methods for the synthesis of this compound class
usually rely on the use of preoxidized starting materials, such as
allylic alcohols or halides, and often require harsh reaction
conditions (e.g., strong Brønsted acids, high temperatures). The
envisioned cooperative selenocatalytic approach, on the other
hand, would provide a significantly streamlined and atom-
economic9 assembly of the allylic ester motif, since the
adjustment of the desired oxidation state within the carbon
framework and the C−O bond formation would take place in the
Received: April 19, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01130
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Organic Letters
Letter
very same event using air as the sole oxidant. As a consequence of
these considerations, we report herein the first allylic oxidation
protocol for the conversion of nonpolarized alkenes into allylic
esters via light-dependent cooperative selenium catalysis.
catalyst or light, only trace amounts of the product were detected
when air was replaced by argon. These findings indicate that the
title reaction is indeed proceeding via a cooperative mechanism.
With the optimized conditions in hand, investigations
continued with the exploration of the scope and limitations of
the title procedure. Initially, a series of different alkenes was
reacted with acetic acid (2a) (Table 2). The use of β,γ-
At the outset of our investigations, we identified 2,4,6-tris(4-
methoxyphenyl)pyrylium tetrafluoroborate (4) as the photo-
catalyst of choice since the reduction potential of its excited state
(E1/2red [4*/10] = +1.74 V vs SCE in MeCN)10 was found to be
sufficiently high to readily oxidize (PhSe)2 (E1/2red = +1.35 V vs
SCE in MeCN)11 but at the same time low enough to leave
electron-neutral, nonconjugated alkenes intact (E1/2red ≥ + 1.80
V vs SCE in MeCN).12,13 Thus, in initial experiments benzyl (E)-
pent-3-enoate (1a) was reacted with acetic acid (2a) in various
solvents (1:1; v/v) at room temperature under an atmosphere of
air and irradiation at 465 nm using 10 mol % of (PhSe)2 and 5
mol % of photocatalyst 4 (Table 1). We were pleased to find that
a
Table 2. Reaction Scope with Varying Alkenes
a
Table 1. Optimization of Reaction Conditions
entry
x (mol %)/y (mol %)
solvent
concn 1/2 (M) yield (%)
1
2
3
4
5
6
7
8
9
10
10/5
10/5
10/5
10/5
10/5
10/5
10/5
10/5
10/0
0/5
toluene
THF
0.1/8.7
0.1/8.7
0.1/8.7
0.1/8.7
0.1/8.7
0.1/8.7
0.1/7.0
0.2/7.0
0.1/7.0
0.1/7.0
0.1/7.0
0.1/7.0
27
33
DMF
29
DCE
67
acetone
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
71
83
>95
>95
0
a
0
Reactions were carried out on a 1 mmol scale (0.2 M) in acetonitrile
b
for 16−24 h under an atmosphere of ambient air or O2 (yields are
marked with an asterisk) and with irradiation at 465 nm by an LED
lamp. Yields refer to isolated compounds.
11
10/5
10/5
0
c
12
traces
a
Reactions were carried out on a 0.5 mmol scale in 5−2.5 mL of
solvent for 16 h under an atmosphere of ambient air and with
irradiation at 465 nm by an LED lamp. Yields were determined by 1H
NMR using 1,3,5-trimethoxybenzene as an internal standard.
unsaturated esters 1a and 1b, which both contained aliphatic
residues at the γ-position, resulted in very good isolated yields of
89 and 82%, respectively (entries 1 and 2). While n-hexyl ester 3c
was isolated in an acceptable yield of 69% (entry 3) the use of
alkene 1d furnished allylic ester 3d only in trace amounts under
the standard conditions. Changing from air to a neat O2
atmosphere resulted in an improved reaction outcome with an
isolated yield of 45% (entry 4). The exact reasons for the sluggish
reactivity of styrene substrate 1d under standard conditions
remain unclear at the moment; however, we speculate that the
increased steric demand of styrene derived alkenes may hamper
the attack of the selenenium electrophile (cf. compound 5,
Scheme 1).
Next, we tested other functional groups, such as nitrile,
phosphonate, and sulfone moieties. Conversion of nitrile 1e
under aerial conditions resulted in an isolated yield of 83% (entry
5). Application of phosphonates 1f and 1g provided access to the
corresponding target allylic esters 3f and 3g in yields of 68 and
67%, respectively (entries 6 and 7). The oxidative allylic
esterification of sulfones 1h and 1i proceeded best when neat
O2 was used as the oxidant, providing allylic esters 3h and 3i in 61
and 65% (entries 8 and 9). Next, we tested alkenes in which R1
and R2 equaled hydrocarbon residues (entries 10−12).
Subjection of cyclooctene (1j) to the standard conditions
under air furnished ester 3j in 89% yield (entry 10). Both (E)-
b
c
Reaction was performed in the dark. Reaction was performed in
the absence of air. DCE = 1,2-dichloroethane.
the title procedure provided allylic ester 3a in 27% when the
reaction was conducted in toluene (entry 1). More polar
solvents, such as THF (33%, entry 2) and DMF (29%, entry 3),
resulted only in marginally improved yields. A significant increase
in the yield was observed when dichloroethane and acetone were
used as reaction media, which gave rise to target compound 3a in
67% and 71% yields, respectively (entries 4 and 5). We believe
that the difference in yield between toluene and THF on the one
hand and dichloroethane and acetone on the other is most likely
due to the insufficient solubility of photocatalyst 4 in the former
solvents. The best result (83%, entry 6) was obtained in
acetonitrile. Next, we varied the concentration of the carboxylic
acid from 100 to 5 vol %.13 These experiments revealed that 40
vol % of acetic acid gave the best yield (>95%, entry 7).
Increasing the concentration of the alkene from 0.1 to 0.2 M
(>95%, entry 8) had no negative impact on the yield.
Finally, we also conducted a series of control experiments in
which the reactions were performed in the absence of either of
the catalysts, air, and light, respectively (entries 9−12). While no
formation of allylic ester 3a was recorded in the absence of any
B
DOI: 10.1021/acs.orglett.6b01130
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Letter
and (Z)-dec-5-ene (1kE/1kZ) were converted to product 3k in
81 and 75% yield, respectively, thus indicating that the double
bond geometry does not play a significant role in these reactions
(entry 11). Eventually, we exposed monosubstituted alkene 1l to
the catalysis protocol, yielding corresponding cinnamyl acetate 3l
in 31% together with 9% of 2-acetoxy-5-(trifluoromethyl)indane
(entry 12).
Having demonstrated the feasibility, selectivity, and functional
group tolerance of the oxidative allylic esterification of acetic acid
with various alkene substrates, we then turned our attention to
the generalization of this new selenium catalysis protocol toward
other carboxylic acids. Consequently, a representative series of
different carboxylic acids with varying pKa values and steric
demands was tested next (Table 3). For this part of our
isobutyric acid (54%, entry 4), as well as cyclopropanecarboxylic
acid (57%, entry 5), led to similar yields. In contrast to the
homogeneous reaction outcomes observed within the butanoic
acid series, the set of homologous pentanoic acids displayed a
marked structural correlation between sterics and yield. While
use of isovaleric acid (entry 6) furnished ester 3r in a yield of
53%, its sterically more congested analogs pivalic and cyclo-
butanecarboxylic acid (entries 7 and 8) resulted in merely 26 and
28% isolated yield, respectively. It is noteworthy that the
conversion of the latter acid was significantly slower (96 h) than
any other acid tested.
Furthermore, we examined functionalized derivatives of acetic
acid in order to elucidate any potential correlation between their
acidity and the yield. Therefore, we independently reacted
substrate 1a with α-methoxy (entry 9; pKa = 3.53),14 α-bromo
(entry 10; pKa = 2.86),14 and trifluoroacetic acid (entry 11; pKa =
0.23)14 under the standard conditions. The respective allylic
esters 3u−w were isolated in yields ranging between 53 and 69%.
These findings clearly showcase that the title procedure remains
effective within at least 4 orders of magnitude of pKa values, thus
underscoring the overall utility of the cooperative selenium
catalysis concept. Another noteworthy feature of this method is
the fact that even amino acids can be used as reactants.
Conversion of phthaloyl-protected leucine with alkene 1c under
an O2 atmosphere resulted in an isolated yield of 68% as a 1:1
mixture of diastereomers (entry 12).
a
Table 3. Reaction Scope with Varying Carboxylic Acids
From a series of control experiments (see the Supporting
Information), we learned that the reaction proceeds through
acyloxy selenation intermediate 7 (Nu = acyloxy, Scheme 2).
Furthermore, we found that selenide 7 can be readily converted
into ester 3 in the presence of photocatalyst 4 but without
Scheme 2. Mechanistic Hypothesis for the Cooperative
Selenium-Catalyzed Oxidative Esterification of Alkenes
a
Reactions were carried out on a 1 mmol scale (0.2 M) in acetonitrile
for 16−24 h under an atmosphere of ambient air and with irradiation
b
at 465 nm by an LED lamp. Yields refer to isolated compounds. The
c
d
reaction time was 72 h. The reaction time was 96 h. 5 equiv of N-
phthaloylleucine were reacted with 1c under an O2 atmosphere.
investigation, benzyl hex-3-enoate (1a) was chosen as the model
substrate. The conversion of 1a with formic acid under an
atmosphere of air led to allylic ester 3m in an isolated yield of
81% (entry 1). In order to determine whether there is any
correlation between the yield of the ester products and the steric
demand of the acid, we tested propionic acid as well as several
isomeric forms of butanoic and pentanoic acid. Starting with
propionic acid, the corresponding allylic ester derivative 3n was
obtained in 63% yield (entry 2). Within the series of butanoic
acids, all isomeric forms, i.e., butyric acid (55%, entry 3),
C
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Organic Letters
Letter
K.; Warratz, S.; Kornhaaß, C.; Ackermann, L. Angew. Chem., Int. Ed.
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may initially activate (PhSe)2 via single-electron transfer (SET)
followed by fragmentation of the resulting radical cation to give
ArSe+ species 5.7,15 The reduced sensitizer 9, in turn, may
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efficient selenium-catalyzed oxidase protocol exemplified in the
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b01130.
Experimental procedures and compound characterization
data (PDF)
(13) For details on the full optimization study, see the Supporting
Information.
AUTHOR INFORMATION
Corresponding Author
■
(14) Dippy, J. F. J.; Hughes, S. R. C.; Rozanski, A. J. Chem. Soc. 1959,
2492.
(15) The verisimilitude of this hypothesis is supported by fluorescence
quenching experiments (cf. Supporting Information) in which the
fluorescence intensity of pyrylium salt 4 was plotted against varying
concentrations of both (PhSe)2 and alkene 1d.
*E-mail: abreder@gwdg.de.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This work was financially supported by the Deutsche
Forschungsgemeinschaft (DFG, Emmy Noether Fellowship to
A.B.) and the Fonds der Chemischen Industrie (FCI,
Chemiefonds Fellowship to S.O. and Ph.D. Fellowship to
C.D.). We thank Prof. Dr. Lutz Ackermann (University of
Gottingen, Germany) for the generous donation of solvents and
technical equipment. We are grateful to F. Kramm (University of
(17) In this context, we speculate that the conversion of intermediate 7
into radical cation 8 may be inhibited by (PhSe)2 at sufficiently high
concentrations of the latter in comparison to the concentration of
intermediate 7. This assumption is supported by the observation that
compound 7a (Nu = AcO, R1 = Et, R2 = CO2Bn) furnishes product 3a
only in low quantities when additional (PhSe)2 is present. We also
hypothesize that intermediate 7 represents the resting state of the
catalytic cycle.
̈
Gottingen, Germany) for providing four of the alkene precursors.
̈
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DOI: 10.1021/acs.orglett.6b01130
Org. Lett. XXXX, XXX, XXX−XXX