Aerobic oxidation of diverse primary alcohols to methyl esters with a readily accessible heterogeneous Pd/Bi/Te catalyst

Article abstract of DOI:10.1021/ol402428e

Efficient aerobic oxidative methyl esterification of primary alcohols has been achieved with a heterogeneous catalyst consisting of 1 mol % Pd/charcoal (5 wt %) in combination with bismuth(III) nitrate and tellurium metal. The Bi and Te additives significantly increase the reaction rate, selectivity, and overall product yields. This readily accessible catalyst system exhibits a broad substrate scope and is effective with both activated (benzylic) and unactivated (aliphatic) alcohols bearing diverse functional groups.

Full text of DOI:10.1021/ol402428e

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
Aerobic Oxidation of Diverse Primary
Alcohols to Methyl Esters with a
Readily Accessible Heterogeneous
Pd/Bi/Te Catalyst
000–000
Adam B. Powell and Shannon S. Stahl*
Department of Chemistry, University of Wisconsin;Madison, 1101 University Avenue,
Madison, Wisconsin 53706, United States
stahl@chem.wisc.edu
Received August 22, 2013
ABSTRACT
Efficient aerobic oxidative methyl esterification of primary alcohols has been achieved with a heterogeneous catalyst consisting of 1 mol %
Pd/charcoal (5 wt %) in combination with bismuth(III) nitrate and tellurium metal. The Bi and Te additives significantly increase the reaction rate,
selectivity, and overall product yields. This readily accessible catalyst system exhibits a broad substrate scope and is effective with both activated
(
benzylic) and unactivated (aliphatic) alcohols bearing diverse functional groups.
Heterogeneous Pd catalysts are widely used in organic
reagents, such as the Jones reagent (CrO /H SO ) or
3 2 4
4
bleach/TEMPO, tend to be more synthetically reliable.
chemistry for the reduction of organic compounds. Pro-
minent examples include simple supported catalysts such
as Pd/C and Pd/Al O , as well as more complex variants
5
6
Homogeneous and heterogeneous Pd catalysts have
been widely studied for aerobic alcohol oxidation. The
majority of this work has focused on conversion of alco-
hols to aldehydes and ketones. Methods for oxidation of
primary alcohols to carboxylic acids and esters (Scheme 1)
tend to be more limited with respect to substrate scope
2
3
such as Lindlar’s catalyst, in which Pd/CaCO is modified
3
1
by Pb(OAc) and quinoline. Similar catalysts for selective
2
oxidation of organic molecules would be appealing, but
effective examples are rare. Adam’s catalyst (PtO ) is
2
2
typically used as a hydrogenation catalyst, but it also
mediates aerobic oxidation of primary alcohols to car-
7
8,9
(e.g., benzylic alcohols) and/or catalyst accessibility.
Here, we describe a readily accessible Pd/charcoal-based
3
boxylic acids. A high catalyst loading is often required in
3
the latter application (e.g., 0.6 equiv of Pt ), and other
b
(6) (a) Zhan, B.-Z.; Thompson, A. Tetrahedron 2004, 60, 2917–2935.
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(
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(
(
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9
, 67–75. (b) Maurer, P. J.; Takahata, H.; Rapoport, H. J. Am. Chem.
Soc. 1984, 106, 1095–1098.
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Synth. 2005, 81, 195–203.
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(
(
G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774–781. (b) Stahl, S. S.
Angew. Chem., Int. Ed. 2004, 43, 3400–3420. (c) Schultz, M. J.; Sigman,
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1
0.1021/ol402428e r XXXX American Chemical Society

catalyst system that promotes efficient aerobic oxidation
of primary alcohols, including benzylic and aliphatic ex-
amples, to the corresponding methyl esters. Use of Bi and
Te cocatalysts significantly improves the activity and
selectivity of the reactions and enables the broadest sub-
strate scope and functional-group compatibility reported
to date for this tranformation.
This observation prompted us to explore the synergistic
effect of Bi(NO ) in combination with Te metal and
3
3
1
with TeO (Figures 2 and S2, respectively). The two-
3
2
dimensional array in Figure 2 highlights the optimal ad-
ditivecomposition of 5 mol % Bi(NO ) and 2.5 mol % Te,
which led to a 94% yield of methyl octanoate.
3
3
Table 1. Screening of Pd Sources for the Oxidative Esterification
of 1-Octanol
Scheme 1. Pd-Catalyzed Aerobic Oxidation of 1° Alcohols to
Carboxylic Acids and Esters
a
yield (conv)
The intrinsic challenge of oxidizing aliphatic alcohols
relative to benzylic alcohols prompted us to use 1-octanol
asa substrate inour catalystdevelopmentefforts. A variety
of commercially available heterogeneous and homoge-
neous Pd sources were tested as catalysts at a 1 mol %
Pd loading for the oxidative esterification of octanol
b
entry
catalyst
no Bi(NO
3
)
3
3 3
Bi(NO )
1
2
3
4
5
6
7
8
1 wt % Pd/C
1 wt % Pd/Al
20 (22)
6 (17)
7 (40)
10 (11)
16 (20)
5 (9)
45 (54)
49 (65)
57 (58)
45 (61)
60 (60)
30 (39)
0 (0)
2
O
3
2.5 wt % Pd/C
5 wt % Pd/C
c
5 wt % Pd/Char
to methyl octanoate under 1 atm of O in methanol
2
30 wt % Pd/C
1
Table 1). Only poor conversions and yields were ob-
0
d
(
tained, with a maximum of a 20% yield using 1 wt %
PdCl2
0 (0)
d
2
Pd(OAc)
0 (0)
15 (17)
1
1
Pd/C. Main-group elements and other additives have
found widespread use as promoters in heterogeneous
catalysis with platinum group metals, and bismuth has
a
1
OH] = 1 M. H NMR
yields; int. std. = trimethoxybenzene. Bi(NO ) 5H O = Bi(NO ) unless
3 3 2 3 3
d
otherwise noted. Char = activated charcoal. 20 mg of activated carbon.
Reactions performed on 1 mmol scale; [RCH
2
b
3
c
6
b,12
been used frequently in alcohol oxidation.
1
Inclusion of
mol % Bi(NO ) in the reactions led to significantly
3
3
increased yields of methyl octanoate, and a 60% yield was
achieved with 1 mol % Pd/Char and Bi(NO ) (Table 1,
3
3
entry 5).
The beneficial effect of Bi(NO ) prompted us to exam-
3
3
ine other additives in the reaction. The majority of these
additives, such as Cu, Ag, Pb and Sb, had a negligible or
only slightly beneficial effect on the catalytic yield relative
the reaction in the absence of additives. TeO , however,
2
exhibited a beneficial effect that surpassed even Bi(NO3)3
(Figure 1). The best result was obtained with the inter-
metallic material Bi Te (87% yield of methyl octanoate).
2
3
(
9) Transfer- and acceptorless-dehydrogenation methods provide an
alternative approach to the conversion of primary alcohols to carboxylic
acids and esters: (a) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D.
J. Am. Chem. Soc. 2005, 127, 10840–10841. (b) Owston, N. A.; Nixon,
T. D.; Parker, A. J.; Whittlesey, M. K.; Williams, J. M. J. Synthesis 2009,
1578–1581. (c) Yamamoto, N.; Obora, Y.; Ishii, Y. J. Org. Chem. 2011,
76, 2937–2941. (d) Balaraman, E.; Khaskin, E.; Leitus, G.; Milstein, D.
Nat. Chem. 2013, 5, 122–125.
2
10) CAUTION: The use of pure O in combination with organic
solvents is a flammability hazard and should be limited to small scale
applications.
Figure 1. Screening of main-group additives for Pd-catalyzed
oxidative esterification of 1-octanol. Reactions carried out on
(
1
1 mmol scale. H NMR yields with trimethoxybenzene as in-
ternal standard. Loading of additive based on mol % of cation.
(
11) Similarly poor yields for aliphatic alcohol oxidation have been
noted in the literature: (a) Mallat, T.; Baiker, A. Appl. Catal. A: Gen.
991, 79, 41–58. (b) Keresszegi, C.; Mallat, T.; Grunwaldt, J.-D.; Baiker,
A. J. Catal. 2004, 138–146.
12) (a) Fiege, H.; Wedemeyer, K. Angew. Chem., Int. Ed. Engl. 1981,
0, 783–784. (b) Tsujino, T.; Ohigashi, S.; Sugiyama, S.; Kawashiro, K.;
1
The beneficial effect of the Bi(NO ) and Te is clearly
3
3
(
evident from reaction time courses with representative
benzylic and aliphatic alcohol substrates (Figure 3). In-
dependent reactions were performed in the absence and
2
Hayashi, H. J. Mol. Catal. 1992, 71, 25–35. (c) Kimura, H.; Kimura, A.;
Kokubo, I.; Wakisaka, T.; Mitsuda, Y. Appl. Catal. A: Gen. 1993, 95,
143–169. (d) Gallezot, P. Catal. Today 1997, 37, 405–418. (e) Anderson,
R.; Griffin, K.; Johnston, P.; Alsters, P. L. Adv. Synth. Catal. 2003, 345,
517–523. (f) Frassoldati, A.; Pinel, C.; Besson, M. Catal. Today 2011,
1
73, 81–88. (g) Wito nꢀ ska, I.; Frajtak, M.; Karski, S. Appl. Catal. A: Gen.
2011, 401, 73–82.
(13) For previous observations of the beneficial effect of Te promo-
ters in palladium catalyzed alcohol oxidation, see refs 12c and 12g.
B
Org. Lett., Vol. XX, No. XX, XXXX

Figure 2. Effect of 1-octanol oxidative esterification with
Bi(NO ) and Te metal. Reactions carried out on 1 mmol scale.
H NMR yields with trimethoxybenzene as internal standard.
3
3
1
presence of the Bi/Te additives. In the oxidation of
-methoxybenzyl alcohol without additives (Figure 3a),
4
all of the substrate was consumed within 1 h, and a
significant quantity of aldehyde (32%) intermediate was
detected. The aldehyde gradually disappeared and was
completely consumed within 4 h. The yield of methyl ester
maximized at 63%. A significant quantity of anisole
Figure 3. Time courses of Pd/Char-catalyzed oxidative esterifi-
cation of (a) 4-methoxybenzyl alcohol without additives; (b)
(
g15% yield) was detected in the final reaction mixture,
suggesting that decarbonylation of the aldehyde is a
4
additives; and (d) 1-octanol with additives. H NMR yields with
-methoxybenzyl alcohol with additives; (c) 1-octanol without
1
1
4
trimethoxybenzene as internal standard (std. dev. ( 3%).
significant side reaction (Figure S3). When the reaction
was carried out in the presence of Bi(NO ) and Te, full
3
3
conversionofthe substrate occurredwithin1h (Figure3b).
In this case, no aldehyde intermediate was observed and
the reaction exhibited excellent mass balance. The ester
product was formed in near-quantitative yield (>98%)
after 2 h and remained stable under the reaction con-
ditions.
The time courses in Figure 3 highlight the intrinsically
slower rates and more challenging reactivity of aliphatic
alcohols relative to benzylic alcohols. They further reveal
that inclusion of Bi(NO ) and Te enhances both reaction
selectivity and catalyst activity, enabling high yields to be
obtained with both classes of substrates.
3
3
Consistent with the catalyst-development data pre-
sented above, oxidative esterification of 1-octanol showed
poor conversion and yield in the absence of the Bi/Te
additives (Figure 3c). Only a 20% yield of the ester was
observedafter 2 h and slowly increased to∼40% after 12 h.
In contrast to the reaction of the benzylic alcohol, no
aldehyde intermediate was observed during the reaction.
In the presence of the Bi/Te additives, faster rates were
observed together with higher conversion and yield
This Pd/Bi/Te catalyst system exhibits the broadest
substrate scope reported to date for the oxidative ester-
ification of alcohols (Scheme 2). Diverse benzylic alco-
hol substrates (1aÀ1n), including heterocyclic examples
(
1oÀ1q), were subjected to the optimized catalyst condi-
tions. High yields of methyl esters were obtained for the
majority of examples, including products bearing ether (2c,
2d, 2l), tertiary amine (2e), and thioether (2m, 2p) func-
tional groups. Electron-deficient benzylic alcohols (1gÀ1i)
react more slowly and undergo side reactions, but good-
to-excellent yields (61À100%) could still be obtained.
Halogenated benzyl alcohols (1jÀ1k) are susceptible to
(
Figure3d). A 90% yield of methyloctanoatewas obtained
after 12 h with excellent mass balance, and again, no
aldehyde intermediate was detected.
(
15) For additional examples of allylic alcohol oxidation by hetero-
(
14) For similar observations with related catalysts and mechanistic
geneous Pd catalysts, see: (a) Enache, D. I.; Edwards, J. K.; Landon, P.;
Solsona-Espriu, B.; Carley, A. F.; Herzing, A. A.; Watanabe, M.; Kiely,
C. J.; Knight, D. W.; Hutchings, G. J. Science 2006, 311, 362–365. (b)
Parlett, C. M. A.; Bruce, D. W.; Hondow, N. S.; Newton, M. A.; Lee,
A. F.; Wilson, K. ChemCatChem 2013, 5, 939–950.
insights into the promotion effect of Bi on Pd-catalyzed alcohol oxida-
tion, see: (a) Ferri, D.; Mondelli, C.; Krumeich, F.; Baiker, A. J. Phys.
Chem. B 2006, 110, 22982–22986. (b) Burgener, M.; Wirz, R.; Mallat, T.;
Baiker, A. J. Catal. 2004, 152–161.
Org. Lett., Vol. XX, No. XX, XXXX
C

reaction temperature to 25 °C. Esterification of allylic
alcohol derivatives 1r and 1s proceed with high conver-
sions, but the yields are reduced owing to the alkene
hydrogenation side product. Again, the best yields were
Scheme 2. Scope of Aerobic Alcohol Esterification with
Pd/Char, Bi(NO ) , Te Catalyst System
3 3
a
1
5
obtained by running the reaction at 25 °C. This catalyst
system is not well suited for recycling. For example, the
yield of 2d dropped from 98% to 85% (NMR yield) after
filtering theused catalystand reusing itinasecondreaction
of 1d in methanol with 1 equiv of KOMe. Ongoing studies
are focused on developing a more robust catalyst formula-
tion better suited for reuse and large-scale applications.
The significant scope enhancement enabled by the Bi/Te
cocatalysts is evident in reactions of aliphatic alcohols
(
1tÀ1af). Excellent yields were obtained with diverse sub-
strates bearing simple hydrocarbon side chains (1tÀ1z),
including thosewithconsiderablesterichindranceadjacent
to the alcohol (1vÀ1x). Pyridine substituents often poison
homogeneous Pd oxidation catalysts, but substrate 1aa,
with a remote pyridyl group, afforded the methyl ester in
good yield. A primary alkyl chloride 2ab was well tolerated
in the reaction. Good mass balance was observed (77%
yield; 82% conversion); unlike the reaction of the aryl
chloride substrate 1j, dehydrohalogenation did not occur.
Ether-containing substrates were effective, including the
benzylether substrate 1ac, which could be susceptible to
cleavage of the benzylic CÀO bond in the presence of
heterogeneous Pd catalysts. Finally, the Boc-protected
secondary and primary amine-containing substrates 1ae
and 1af reacted successfully, affording the corresponding
methyl esters in good yields.
In summary, 1 mol % Pd/charcoal, together with Bi-
NO ) and Te, represents a highly effective catalyst system
(
3 3
for aerobic oxidation of primary alcohols to methyl esters.
Successful substrates include aliphatic examples and those
bearing diverse functional groups. Each of the components
of this catalyst system is shelf-stable, commercially avail-
able, and inexpensive, offering advantages over homoge-
neous catalysts, which typically require a higher catalyst
loading and/or expensive ligands.
Acknowledgment. We are grateful to Maaz Ahmed for
assistance for verification of the yields in Scheme 2 as
well as Drs. Anna Davis and William J. Kruper (Dow
Chemical) for useful discussions and to Dow Chemical for
financial support. Instrumentation was partially funded by
the NSF (CHE-1048642 - NMR spectrometers and CHE-
9304546 - mass spectrometers).
Supporting Information Available. Experimental pro-
cedures, catalyst screening and reaction optimization
data, full characterization for all new compounds,
and NMR spectra for all reported products. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
a
2
Reactions carried out on 1 mmol scale; [RCH OH] = 1 M; isolated
d
b
c
yields. Aldehyde starting material. 25 °C. Isolated with methyl
e
f
benzoate. 1,4-Bis(hydroxymethyl)benzene starting material. 60 °C for
g
h
1
5 h. 70 °C. 50 °C for 12 h.
The authors declare the following competing financial interest(s):
This work is currently being considered by our tech transfer office for a
possible patent application.
dehydrohalogenation, although a good yield of the chlori-
nated substrate 1j could be obtained by lowering the
D
Org. Lett., Vol. XX, No. XX, XXXX