Mild and selective vanadium-catalyzed oxidation of benzylic, allylic, and propargylic alcohols using air

Article abstract of DOI:10.1021/ol103107v

Transition metal-catalyzed aerobic alcohol oxidation is an attractive method for the synthesis of carbonyl compounds, but most catalytic systems feature precious metals and require pure oxygen. The vanadium complex (HQ) ₂V^V(O)(OⁱPr) (2 mol %, HQ = 8-quinolinate) and NEt₃ (10 mol %) catalyze the oxidation of benzylic, allylic, and propargylic alcoholswith air. The catalyst can be easily prepared under air using commercially available reagents and is effective for awide range of primary and secondary alcohols.

Full text of DOI:10.1021/ol103107v

ORGANIC
LETTERS
2011
Vol. 13, No. 8
1908–1911
Mild and Selective Vanadium-Catalyzed
Oxidation of Benzylic, Allylic, and
Propargylic Alcohols Using Air
Susan K. Hanson,* Ruilian Wu, and L. A. “Pete” Silks
Chemistry and Biosciences Divisions, Los Alamos National Laboratory, Los Alamos,
New Mexico 87545, United States
skhanson@lanl.gov
Received January 10, 2011
ABSTRACT
Transition metal-catalyzed aerobic alcohol oxidation is an attractive method for the synthesis of carbonyl compounds, but most catalytic systems
feature precious metals and require pure oxygen. The vanadium complex (HQ)2VV(O)(OiPr) (2 mol %, HQ = 8-quinolinate) and NEt3 (10 mol %)
catalyze the oxidation of benzylic, allylic, and propargylic alcohols with air. The catalyst can be easily prepared under air using commercially
available reagents and is effective for a wide range of primary and secondary alcohols.
The oxidation of alcohols to afford carbonyl compounds
is a key reaction in synthetic organic chemistry. Recent
years have seen major progress in the development of
catalytic aerobic alcohol oxidation, which offers economic
and environmental benefits over traditional stoichiometric
oxidants.1 Despite these advances, many reported systems
feature precious metal catalysts (Pd, Ru, Ir) and use
oxygen pressures of 1 atm or more.2-4 Due to issues of
scarcity and cost, there is considerable interest in replacing
precious metal catalysts with earth-abundant metals.5 Using
air instead of pure oxygen is also advantageous,6 reducing
the safety hazard associated with heating organic solvents
under elevated O2 pressures.
Vanadium complexes have shown potential as base-
metal catalysts for aerobic alcohol oxidation, in some cases
proving effective for substrates where palladium catalysts
display limited activity. For instance, vanadium is known
to catalyze the selective aerobic oxidation of propargylic
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r
10.1021/ol103107v
Published on Web 03/24/2011
2011 American Chemical Society

Scheme 1
alcohols, a reaction using VIV(O)(acac)2 (1-5 mol %) and
molecular sieves at 80 °C.7 The combination of VIV(O)(acac)2
and DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane)
also catalyzes the oxidation of benzylic and allylic alcohols
in ionic liquid solvent at 80-100 °C.8 Vanadium catalysts
with chiral Schiff base ligands effect the oxidative kinetic
resolution of R-hydroxyesters, amides, and phosphonates.9-11
These reports are promising indications of the versatility of
vanadium catalysts, but each requires an atmosphere of
pure oxygen. Very recently, Ohde and Limberg reported a
metavanadate-cinnamic acid system that catalyzes the
oxidation of activated alcohols using mixtures of argon
and O2, but this catalyst is highly moisture sensitive.12
Here, we describe a vanadium-based system for the aero-
bic oxidation of benzylic, allylic, and propargylic alcohols.
The reactions proceed under mild conditions (air, 40-80 °C)
and in a variety of solvents. Moreover, the catalyst can be
prepared in air using commercially available reagents, mak-
ing the overall process inexpensive, simple, and accessible
without the use of a drybox or Schlenk techniques.
V
IV(O)(acac)2, VV(O)(OiPr)3, and complexes of carbox-
ylate-based ligands (dipicolinate (3) and 8-quinolinate-2-
carboxylate (4)). Complexes with more electron-donating
ligands displayed higher activity,14-16 with the highest
activity observed for the complex (HQ)2VV(O)(OiPr) (8)
(HQ = 8-quinolinate) reported by Sawyer, Floriani, and
Scheidt (Scheme 1).17-19 Complex 8 is easily prepared
in one step by the reaction of 8-hydroxyquinoline with
VIV(O)(acac)2 under air in 2-propanol.20
Table 1. Solvents Tested for the Oxidation of 4-Methoxybenzyl
Alcohola
entry
solvent
% yield (NMR)
1
2
1,2-dichloroethane
ethyl acetate
toluene
99
91 (99)
78 (96)
96 (99)
93 (98)
92b (99)b
99
3
4
THF
5
CH3CN
6
CH2Cl2
We recently studied the mechanism of alcohol oxida-
tion by dipicolinate vanadium(V) complexes and found
that a base (pyridine) promoted alcohol oxidation.13
Inspired by this finding, we tested the aerobic oxida-
tion of 4-methoxybenzyl alcohol at 60 °C under air
using several different vanadium complexes (2 mol %)
and a base promoter (10 mol % NEt3) in 1,2-dichloro-
ethane (Scheme 1). Poor yields were observed with
7
1,2-dichlorobenzene
2-methyl-THF
DMSO
8
99
9
69
10
pyridine
12
a Conditions: 2 mol % of 8, 10 mol % of NEt3, 60 °C, 24 h.
b Conditions: 5 mol % of 8, 10 mol % of NEt3, 40 °C, 24 h. Values in
parentheses indicate % yield after 48 h reaction time.
(14) Thorn, D. L.; Harlow, R. L.; Herron, N. Inorg. Chem. 1996, 35,
547–548.
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McNeill, J. H.; Rettig, S. J.; Setyawati, I. A.; Shuter, E.; Sun, Y.; Tracey,
A. S.; Yuen, V. G.; Orvig, C. J. Am. Chem. Soc. 1995, 117, 12759–12770.
(b) Sun, Y.; James, B. R.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1996, 35,
1667–1673.
(7) (a) Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.;
Kawamura, T.; Uemura, S. J. Org. Chem. 2002, 67, 6718–6724. (b)
Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.; Uemura, S.
Tetrahedron Lett. 2001, 42, 8877–8879.
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276. (b) Jiang, N.; Ragauskas, A. J. J. Org. Chem. 2007, 72, 7030–7033.
(9) Radosevich, A. T.; Musich, C.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 1090–1091.
(10) Pawar, V. D.; Bettigeri, S.; Weng, S. S.; Kao, J. Q.; Chen, C. T. J.
Am. Chem. Soc. 2006, 128, 6308–6309.
(11) Weng, S. S.; Shen, M. W.; Kao, J. Q.; Munot, Y. S.; Chen, C. T.
Proc. Nat. Acad. Sci. U.S.A. 2006, 103, 3522–3527.
(12) Ohde, C.; Limberg, C. Chem.;Eur. J. 2010, 16, 6892–6899.
(13) Hanson, S. K.; Baker, R. T.; Gordon, J. C.; Scott, B. L.; Silks,
L. A.; Thorn, D. L. J. Am. Chem. Soc. 2010, 132, 17804–17816.
(17) Scheidt, W. R. Inorg. Chem. 1973, 12, 1758–1761.
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Villa, A.; Guastini, C. Inorg. Chem. 1982, 21, 3310–3316. (b) Pasquali,
M.; Landi, A.; Floriani, C. Inorg. Chem. 1979, 18, 2397–2400.
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1875. (b) Amos, L. W.; Sawyer, D. T. Inorg. Chem. 1974, 13, 78–83.
(20) See the Supporting Information for details.
Org. Lett., Vol. 13, No. 8, 2011
1909

Encouraged by these results, we screened several differ-
ent solvents for the oxidation of 4-methoxybenzyl alcohol
using 8 (2 mol %) and NEt3 (10 mol %). High yields of the
aldehyde were observed after 24 h at 60 °C in THF, ethyl
acetate, and acetonitrile, with >99% NMR yield observed
in 1,2-dichloroethane, 1,2-dichlorobenzene, and 2-methyl-
tetrahydrofuran (Table 1, entries 1-8).
Table 3. Substrate Scope of the Catalytic Oxidationa
The effect of the additive was then examined for the
oxidation of 4-methoxybenzyl alcohol using 8 (2 mol %) in
1,2-dichloroethane (Table 2). Triethylamine, diisopropy-
lethylamine, and TEMPO were all effective promoters of
the vanadium complex, affording high yields of 4-methoxy-
benzaldehyde after 24 h at 60 °C (entries 2-5). In contrast,
less than 5% yield was observed with the vanadium
complex alone (no additive, entry 1), suggesting a key role
for the nitrogen base.
Table 2. Additives Tested for the Oxidation of 4-Methoxybenzyl
Alcohola
entry
additive (10 mol %)
none
% yield (NMR)
1
2
4
triethylamine
triethylamine (5 mol %)
diisopropylethylamine
TEMPO
99 (49)
99 (42)
99 (31)
99 (8)
83
3
4
5
6
DABCO
7
DMAP
NaOtBu
28
8
19
9
Na2CO3
16
10
11
12
DBU
5
proton sponge
NaOAc
6
1
a Conditions: 2 mol % of 8, 10 mol % of additive, 1,2-dichloroethane
solvent, 60 °C, 24 h. Values in parentheses indicate % yield after 4 h
reaction time.
The substrate scope of the alcohol oxidation was inves-
tigated using 8 (2 mol %) and NEt3 (10 mol %) in 1,2-
dichloroethane (Table 3). A range of benzylic alcohols
were oxidized and the aldehydes or ketones isolated in high
yields (entries 1-8). Steric bulk around the alcohol slowed
the reaction, with the more hindered R-isopropyl- and
R-tert-butyl benzyl alcohols showing only 20 and 0%yield,
respectively (entries 7 and 8). Cinnamyl alcohol, 3-methyl-
2-cyclohexen-1-ol, 5-hydroxymethylfurfural (HMF), and
2-hydroxymethylpyridine were oxidized to the correspond-
ing aldehyde or ketone in high yields (entries 9-12).
2-Allyloxybenzylalcohol has been used by Galli and co-
workers as a substrate probe in catalytic oxidations to
detect the intermediate formation of a carbon-based radi-
cal, which has been reported to undergo an intramolecular
ring closure as shown in Scheme 2.21,22 This substrate was
a Conditions: 2 mol % of 8, 10 mol % of NEt3, 1,2-dichloroethane
solvent, 60 °C, 24 h. b 80 °C. c 100 °C, dichlorobenzene solvent. d 48 h.
e 72 h. f = 1 equivalent NEt3. Values in parentheses indicate NMR yield.
oxidized to the corresponding aldehyde in 95% isolated
yield (entry 13); none of ring-closed product A was de-
tected by 1H NMR.21,23
(21) (a) Astolfi, P.; Brandi, P.; Galli, C.; Gentili, P.; Gerini, M. F.;
Greci, L.; Lanzalunga, O. New J. Chem. 2005, 29, 1308–1317. (b)
Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.;
Faletti, R.; Paganelli, R.; Pedulli, G. F. Eur. J. Org. Chem. 2004, 109–
119.
(22) Bentley, J.; Nilsson, P. A.; Parsons, A. F. J. Chem. Soc., Perkin
Trans. 1 2002, 1461–1469.
(23) The oxidation of 2-allyloxybenzyl alcohol was also performed
on a 10 mmol scale, affording 2-allyloxybenzaldehyde in 94% isolated
yield. A minor product identified as 2-allyloxycinnamyl aldehyde was
also detected in ca. 2-4% yield; the origin of this product is still under
investigation. See the Supporting Information for details.
1910
Org. Lett., Vol. 13, No. 8, 2011

Scheme 2
Scheme 3
The secondary propargylic alcohol 4-phenyl-3-butyn-2-ol
was also oxidized in high yield (96%, entry 14). Primary
propargylic alcohols 3-phenyl-2-propyn-1-ol and 2-decyn-1-
ol were oxidized to the corresponding aldehydes in good
1
yields (80% and 60% H NMR yields, entries 15 and 16,
respectively). Oxidation of the terminal alkyne 1-phenyl-2-
propyn-1-ol was less selective, affording the ketone product in
only 38% yield (1H NMR, entry 17) at complete conversion.
Simple aliphatic alcohols such as 1-butanol and 2-buta-
nol underwent little or no oxidation, even when heated at
100 °C (entries 18 and 19). This observed selectivity for
activated alcohols was confirmed by oxidation of a mix-
ture of 4-methoxybenzyl alcohol (5 mmol) and 1-octanol
(5 mmol), which resulted in complete oxidation of the
benzylic alcohol with no formation of 1-octanal.20
For several of the benzylic alcohols, the oxidation pro-
ceeded selectively with no solvent (neat) using 8 (2 mol %)
and NEt3 (10 mol %) for 24 h at 100 °C.20 However, lower
selectivities were observed for the oxidations of cinnamyl
alcohol, 5-hydroxymethylfurfural, and 4-phenyl-3-butyn-
2-ol when no solvent was used.20
To gain insight into the role of the base additive, (HQ)2
VV(O)(OC6H4OCH3) (9) was prepared from the reaction
of 8 with 4-methoxybenzyl alcohol in acetonitrile. In the
absence of base, complex 9 was relatively stable in CD2Cl2
solution, with less than 5% reacting after 16 h at room
temperature. However, a rapid reaction occurred when a
CD2Cl2 solutionof9 was treated withNEt3 (2 equiv) under
argon, affording the vanadium(IV) complex (HQ)2VIV(O)
(10), 4-methoxybenzaldehyde (0.5 equiv, 100% yield), and
4-methoxybenzyl alcohol (0.5 equiv, 100% yield) within 2
h atroomtemperature (Scheme3). Theincreased reactivity
observed in the presence of NEt3 suggests a key role for the
base additive in promoting the alcohol oxidation step.
When the reaction of 9 with NEt3 was carried out under
air in CD2Cl2, quantitative conversion to the cis-dioxo
vanadium(V) complex (HQ)2VV(O)2HNEt3 (11) and4-meth-
oxybenzaldehyde was observed after 22 h at room tempera-
ture. Complex 11 was independently prepared by the
reaction of the μ-oxo complex [(HQ)2VV(O)]2μ-O (12)18a
with H2O and NEt3 in CH2Cl2. When tested for the
oxidationof 4-methoxybenzyl alcohol incombination with
10 mol % of NEt3, both complexes 10 and 11 were effective
catalysts, affording complete conversion in 24 h at 60 °C.
Initial experiments suggest that mass transport of oxy-
gen may be a rate-limiting factor in the oxidation of
4-methoxybenzyl alcohol.24 When the oxidation was car-
ried out in two different reaction vessels under otherwise
identical conditions and stopped at an intermediate reac-
tion time (4 h),25 the shape of the reaction vessel affected
the extent of conversion. In a wide 100 mL round-bottom
flask, 55% conversion was observed after 4 h, while in a
narrow 10 mL reaction tube, only 31% conversion oc-
curred. The stir rate also affected the extent of conversion
in two identical reactions conducted in 25 mL round-
bottom flasks.20
In 1,2-dichloroethane, the catalytic oxidation of 4-meth-
oxybenzyl alcohol was not found to be significantly affected
by added water. When excess water (5 equiv, 5 mmol) was
added to the oxidation of 4-methoxybenzyl alcohol (1
mmol), >98% conversion to the aldehyde was observed
after 24 h at 60 °C. This tolerance of water allows the
catalytic reaction to be carried out in the absence of drying
agent, in contrast to several other reported vanadium
catalysts which require the addition of molecular sieves.7,12
In conclusion, the 8-quinolinate vanadium complex 8
catalyzes the oxidation of benzylic, allylic, and propargylic
alcohols using air. A base promoter is required for the
catalytic oxidation, with very low yield observed in the
absence of any basic additives. The catalyst can be pre-
pared in one step under air using commercially available
reagents, making the overall process easy, versatile, and
mild. Mechanistic studies of the catalytic reaction and
efforts to develop more effective catalysts for aliphatic
alcohols are currently underway.
Acknowledgment. This work was supported by Los
Alamos National Laboratory LDRD (ER 20100160 and
Director’s PD Fellowship to S.K.H.).
Supporting Information Available. Experimental pro-
cedures, synthesis and characterization of vanadium
complexes, and NMR spectra of reaction products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(24) Steinhoff, B. A.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348–
4355.
(25) Conditions: 2 mol % of 8, 10 mol % of NEt3, 1,2-dichloroethane
solvent, 60 °C.
Org. Lett., Vol. 13, No. 8, 2011
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