Efficient and Practical Catalytic Oxidation of Alcohols Using Molecular Oxygen

Full text of DOI:10.1021/jo980770h

7576
J . Org. Chem. 1998, 63, 7576-7577
Efficien t a n d P r a ctica l Ca ta lytic Oxid a tion of
Alcoh ols Usin g Molecu la r Oxygen †
Istva´n E. Marko´,*,‡ Arnaud Gautier,‡
Isabelle Chelle´-Regnaut,‡ Paul R. Giles,‡
Masao Tsukazaki,‡ Christopher J . Urch,§ and
Stephen M. Brown
F igu r e 1.
Universite´ catholique de Louvain, De´partement de Chimie,
Laboratoire de Chimie Organique, Baˆtiment Lavoisier,
Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium,
Zeneca Agrochemicals, J ealott’s Hill Research Station,
Bracknell, Berkshire RG42 6ET, U.K., and Zeneca Process
Technology Department, Huddersfield Works, P.O. Box A38,
Leeds Road, Huddersfield HD2 1FF, U.K.
Received April 28, 1998
The oxidation of alcohols into aldehydes and ketones is a
ubiquitous functional group transformation in organic chem-
istry.1 However, despite its obvious commercial importance
and the detrimental ecological impact of the usual oxidants,
few efficient and mild catalytic oxidation procedures have
been reported that utilize dioxygen (or air) as the stoichio-
metric oxidant.2 Recently, we have disclosed two catalytic
aerobic oxidation protocols3 that allow the transformation
of alcohols 1 into carbonyl derivatives 2 in high yield and
which release water as the only byproduct (Figure 1).
Both of these systems are compatible with a variety of
sensitive functionalities and protecting groups. However,
the ruthenium-based aerobic oxidation procedure requires
5 mol % of the rather expensive tetrapropylammonium
perruthenate (TPAP) and is thus unsuitable for large-scale
operations. Moreover, the much cheaper copper chloride/
phenanthroline protocol necessitates the use of 2 equiv of
K2CO3. The stringent requirement for such a large amount
of K2CO3 was puzzling, and we initiated some studies in
order to understand the role(s) of this heterogeneous base.
In particular, we wished to find suitable reaction conditions
F igu r e 2.
in which smaller amounts of base could be employed in order
to transform our original system into a more ecologically
friendly protocol.
Therefore, a variety of other bases (Na2CO3, Li2CO3, Na2-
HPO4, NaH2PO4, Al2O3, NaOAc, KOAc, KOH, and CuCO3)
were initially tested in this aerobic oxidation system.
Surprisingly, none proved to be as efficient as K2CO3.4
Examination of the postulated mechanism of this transfor-
mation (Figure 2) suggested a number of possible roles for
K2CO3.5 First, K2CO3 should act as a base and react with
the HCl formed during the initial replacement of the chloride
ligand by the alcohol. However, if this was the sole purpose
of K2CO3, then only 5 mol % should actually be necessary
in the reaction to fulfill the requirement of catalyst forma-
tion.
Second, examination of the oxidation in toluene revealed
its heterogeneous nature. Filtration of the dark-brown
suspension gave a filtrate devoid of oxidizing activity and a
solid material that, once resuspended in toluene, smoothly
oxidized alcohols to the corresponding ketones and alde-
hydes. It thus appears that K2CO3 may also serve as a solid
support on which the copper catalyst can be anchored.
Finally, since water is released during the oxidation process,
K2CO3 might also be acting as a water scavenger.
* To whom correspondence should be addressed. Fax: 32-10-47 27 88.
E-mail: marko@chor.ucl.ac.be.
† Dedicated with deep respect to Professor S.-I. Murahashi.
‡ Universite´ catholique de Louvain.
§ Zeneca Agrochemicals.
Zeneca Process Technology Department.
(1) (a) Sheldon, R. A.; Kochi, J . K. In Metal-Catalyzed Oxidations of
Organic Compounds; Academic Press: New York, 1981. (b) Ley, S. V.;
Norman, J .; Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639. (c)
Murahashi, S.-I.; Naota, T.; Oda, Y.; Hirai, N. Synlett 1995, 733. (d) Krohn,
K.; Vinke, I.; Adam, H. J . Org. Chem. 1996, 61, 1467 and references therein.
For general reviews on oxidation reactions, see: (a) Larock, R. C. In
Comprehensive Organic Transformations; VCH Publishers Inc.: New York,
1989; p 604. (b) Procter, G. In Comprehensive Organic Synthesis; Ley, S.
V., Ed.; Pergamon: Oxford, 1991; Vol. 7, p 305. (c) Ley, S. V.; Madin, A. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Perga-
mon: Oxford, 1991; Vol. 7, p 251. (d) Lee, T. V. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7,
p 291.
(2) (a) Sheldon, R. A. In Dioxygen Activation and Homogeneous Catalytic
Oxidation; Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 573. (b) J ames,
B. R. In Dioxygen Activation and Homogeneous Catalytic Oxidation;
Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 195. (c) Ba¨ckvall, J .-E.;
Chowdhury, R. L.; Karlsson, U. J . Chem. Soc., Chem. Commun. 1991, 473.
(d) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron Lett.
1995, 36, 6923. (e) Mandal, A. K.; Iqbal, J . Tetrahedron 1997, 53, 7641 and
references therein.
(3) (a) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch C. J .
Science 1996, 274, 2044. (b) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle´-
Regnaut, I.; Urch C. J .; Brown, S. M. J . Am. Chem. Soc. 1997, 119, 12661.
For an independent report of the same discovery, see: Lenz, R.; Ley, S. V.
J . Chem. Soc., Perkin Trans. 1 1997, 3291. For previous work on the use of
CuCl‚Phen as a catalyst for the aerobic oxidation of alcohols, see: (a)
J allabert, C.; Riviere, H. Tetrahedron Lett. 1977, 1215. (b) J allabert, C.;
Riviere, H. Tetrahedron 1980, 36, 1191. (c) J allabert, C.; Lapinte, C.; Riviere,
H. J . Mol. Catal. 1982, 14, 75. For the use of CuCl2/TEMPO/O2 as a mild
oxidant, see: Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chon, C. S.
J . Am. Chem. Soc. 1984, 106, 3374.
The importance of the dehydrating properties of K2CO3
was clearly revealed by performing the oxidation reaction
using only 10 mol % of K2CO3 in the presence of an excess
of 4 Å MS. Although 4 Å MS proved to be less efficient than
K2CO3 in trapping the released water (larger loading and
(4) One rare exception appears to be KOBut. For example, the aerobic
oxidation of 2-undecanol (5 mol % CuCl‚Phen, 5 mol % KOBut, toluene,
80-90 °C) afforded 2-undecanone in almost quantitative yields. However,
this system appears, so far, to be limited to secondary alcohol oxidations.
(5) For a discussion of the possible mechanism of this reaction, see:
Marko´, I. E.; Tsukazaki, M.; Giles, P. R.; Brown, S. M.; Urch C. J . Angew.
Chem., Int. Ed. Engl. 1997, 36, 2208.
10.1021/jo980770h CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/06/1998

Communications
J . Org. Chem., Vol. 63, No. 22, 1998 7577
Ta ble 1. Solven t a n d Ba se Effects in th e Aer obic
Oxid a tion of 2-Un d eca n ol
Ta ble 2. Aer obic, Ca ta lytic Oxid a tion of Alcoh ols
a
The % conversion was measured by 1H NMR spectroscopy and
b
by capillary GC analysis. All yields are for pure, isolated
compounds. c The reaction was stopped after 5 h. The reaction
d
was stopped after 3 h. e The reaction was stopped after 8 h.
longer reaction time are required), the oxidation went
smoothly to completion.
A major breakthrough was accomplished during the study
of the influence of the solvent on the amount of K2CO3
required for the aerobic oxidation of 2-undecanol into 2-un-
decanone (Table 1).6
a
All yields are for pure, isolated compounds. Complete conver-
b
sions were achieved unless specified. In this case, the reaction
was stopped after 70% conversion. The recovered alcohol amounted
to ∼30%. c No racemization was observed in this oxidation reac-
tion. The aldehyde was reduced to the alcohol (LiAlH4 in THF),
and the ee of the resulting amino alcohol was measured by HPLC
Whereas in toluene 2 equiv of K2CO3 is necessary to
achieve complete conversion of alcohol 12 into ketone 13
(Table 1, entries 1-3), we were quite surprised to find that
only a mediocre yield of the desired ketone was obtained in
fluorobenzene (Table 1, entry 4) under comparable condi-
tions.7 Unexpectedly, low er in g th e a m ou n t of K2CO3
d r a m a tica lly in cr ea sed th e con ver sion of 12 in to 13,
r ea ch in g a 100% con ver sion even w h en on ly 25 m ol %
of th e ba se w a s em p loyed (Table 1, entry 7). Under these
conditions, 2-undecanone 13 could be isolated in up to 99%
yield. These optimized conditions were then applied to the
aerobic oxidation of a variety of structurally representative
alcohols. The results are summarized in Table 2.
It is quite remarkable that essentially every type of alcohol
is smoothly oxidized into the corresponding carbonyl deriva-
tive in high yield and with good to complete conversion.
Under these conditions, primary aliphatic, allylic, and
benzylic alcohols afford the expected aldehydes and second-
ary alcohols are smoothly transformed into ketones. Ge-
raniol affords geranial and nerol gives neral with no
detectable loss of the geometric integrity of the C-C double
bond (Table 2, entries 5 and 6). The catalyst tolerates both
sulfur and nitrogen substituents (Table 2, entries 2, 4, and
8). Protected â-amino alcohols are smoothly converted into
the corresponding aldehydes without detectable racemiza-
tion (Table 2, entries 4 and 8). It is also noteworthy that
the reaction conditions are sufficiently mild as to be compat-
ible with the Boc protecting group (Table 2, entry 8).
Remarkably, steric hindrance does not seem to play a
major role in determining the outcome of this oxidation.
i
analysis: Daicel chiralpak column; 2% PrOH in hexane; 1 mL/
min; T ) 20 °C; λ ) 254 nm; (R)-Bn2valinol, 11.16 min; (S)-
d
Bn2valinol, 12.70 min; ee > 99%. No double-bond isomerization
took place under these conditions. e No racemization was observed
in this oxidation reaction. The ee was measured by chiral GC (CP-
Chiral-Dex CB, 25 m; L ) 0.25 mm, DF ) 0.25 µm, 130 °C for 12
min then 1 °C per min) of the derived bis-Boc-prolinol obtained
by LiAlH4 reduction of Boc-prolinal followed by derivatization with
Boc2O (tR (R)-enantiomer, 43.1 min; tR (S)-enantiomer, 43.6 min).
Indeed, both endo- and exo-borneol are oxidized to camphor
at the same rate, despite the tremendous difference in the
steric environment of these two alcohols (Table 2, entries 9
and 10).
In summary, we have discovered an efficient, aerobic,
catalytic oxidation procedure that allows the transformation
of alcohols into aldehydes and ketones in high yield and
under mild conditions. The property of fluorobenzene that
is responsible for its unequaled behavior is not known at
present. The new conditions described in this paper repre-
sent a significant step toward a highly efficient and truly
ecologically friendly oxidation protocol for alcohols.
Ack n ow led gm en t. Financial support of this work was
provided by Zeneca Ltd., through the Zeneca Strategic
Research Fund. I.E.M. is grateful to Zeneca for receiving
the Zeneca Fellowship (1994-1997). Fluorobenzene is a
commercial product manufactured by Zeneca Ltd. We are
grateful to Zeneca for suppling us with this remarkable
solvent.
(6) It is interesting to note that other solvents gave repeatedly poorer
conversions (benzene, xylenes) or destroyed the catalyst activity (CH2Cl2,
CHCl3, ClCH2CH2Cl, DMF, and MeCN).
(7) It is interesting to note that fluorobenzene was also used successfully
by Mukaiyama and co-workers as a solvent in their Mn(salen)-catalyzed
epoxidation of alkenes using the O2/aldehyde protocol: Yamada, T.; Ima-
gawa, K.; Nagata, T.; Mukaiyama, T. Chem. Lett. 1992, 11, 2231.
Su p p or tin g In for m a tion Ava ila ble: Fluorbenzene data
and a typical experimental procedure (1 page).
J O980770H