Selective aerobic oxidation of allylic alcohols to carbonyl compounds using catalytic Pd(OAc)2: High intramolecular selectivity

Article abstract of DOI:10.1055/s-2007-984498

Allylic alcohols were selectively oxidized into aldehydes or ketones using a Pd(OAc)₂-Et₃N-O₂ system. Diols with one allylic function were selectively oxidized, with one of the hydroxyl groups remaining untouched. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984498

LETTER
1869
Selective Aerobic Oxidation of Allylic Alcohols to Carbonyl Compounds Using
Catalytic Pd(OAc) : High Intramolecular Selectivity
2
S
F
elective
A
ero
r
bic
O
xid
é
ation of
A
l
d
lylic Alcoho
é
ls to
C
arbo
r
nyl Com
i
pound sc Batt, Emmanuel Bourcet, Youssef Kassab, Fabienne Fache*
ICBMS, Equipe Cheops, CNRS, UMR 5246 Université Lyon 1, Bât. Raulin, 43 boulevard du 11 novembre 1918, 69622 Villeurbanne,
France
Fax +33(472)448136; E-mail: fache@univ-lyon1.fr
Received 14 February 2007
explain the poor activity of their system with linear allylic
Abstract: Allylic alcohols were selectively oxidized into aldehydes
alcohols, Sigman et al. proposed the ability of the a,b-un-
or ketones using a Pd(OAc) –Et N–O system. Diols with one
2
3
2
saturated carbonyl product to act as a ligand of Pd(0), thus
inhibiting the reaction. In our case, we think that this type
of chelation has to occur between the starting alcohol and
the catalyst to explain the allylic/nonallylic selectivity.
Nevertheless, in the case of geraniol (Table 1, entry 7) our
results (25% conversion) were quite similar to those that
Sigman reported (33% conversion) probably because the
substrate was chelated too strongly to palladium, due to its
additional double bound. For products bearing an ester
function close to the hydroxyl group (b-hydroxy ester)
(Table 1, entry 8) the same explanation could be proposed
to explain the low conversion (<10%) due to chelation by
the carbonyl group. It is nevertheless noteworthy that our
system tolerated the benzyl protecting group (Table 1, en-
try 9). Benzylic alcohols were also easily oxidized
allylic function were selectively oxidized, with one of the hydroxyl
groups remaining untouched.
Key words: palladium, oxidation, allylic alcohols, selectivity, in-
tramolecular, oxygen
The oxidation of alcohols into aldehydes or ketones is one
of the most important reactions in organic synthesis.
1
,2
Many systems, catalytic or not, have been described,
3
using metal or metal-free conditions. Several oxidants or
4
–6
co-oxidants have been used but for ecological reasons,
7
,8
oxygen was chosen more often. Among the different
9
–11
6,12
metals employed to perform the reaction,
palladium
was the most widely used. Thus, many results have been
published with the Pd/O system, and among them, we
2
(
Table 1, entries 10 and 11) and especially o-methoxy-1-
found the procedure described by Sigman and co-
1
3
phenyl ethanol, unreactive under Sigman’s conditions,
oxidized into product 11. In our case, as soon as the allylic
or benzylic substrate was added, the reaction mixture
turned black, whereas the solution remained orange with
workers of special interest: a catalytic amount of
Pd(OAc) in presence of Et N and 3 Å molecular sieves
2
3
(
MS 3A) under an atmospheric pressure of oxygen al-
lowed the oxidation of a large variety of alcohols at room
temperature. We thus examined each parameter in detail
and found that in the absence of molecular sieves and at
1
3
nonallylic alcohols. In Sigman’s case, the solution was
orange, irrespective of the alcohol. This indicates two
different mechanisms. Stahl et al.15 have studied the in-
fluence of molecular sieves in the case of quiet similar
systems: the Pd(OAc) –pyridine–O system reported by
4
5 °C both activity and selectivity of the catalytic system
were modified (Figure 1).
2
2
Uemura et al.16 and the Pd(OAc) –DMSO–O system
2
2
Pd(OAc)2 (3 mol%)
Et3N (6 mol%)
OH
O
17
reported by Larock et al. They claimed that the MS 3A
increased the catalyst stability by providing an hetero-
geneous surface that hinders the bulk aggregation of
palladium metal. We have no evidence for or against this
proposal but we assume that our catalytic system might be
different than theirs because of the absence of molecular
sieves.
R1
R2
R1
R2
45 °C, O2 (1 atm)
THF–toluene (15%)
Figure 1 Catalytic aerobic oxidation of alcohols
Thus allylic alcohols were oxidized more rapidly than
nonallylic ones (entries 3 and 4 vs. entries 1 and 2). A We thus performed competitive experiments to test the
comparison with Sigman’s results showed very signifi- level of chemoselectivity of our system.
cant differences in the case of cinnamic alcohol (entry 6).
In the presence of an allylic alcohol, 2-octanol was poorly
Even with forced conditions (5 mol% Pd instead of 3
oxidized (only 11%) whereas under the same conditions
mol% and 300 mol% Et N instead of 6 mol%) the authors
3
7
0% of 2-octanol were converted into the corresponding
could not reach more than 39% isolated yields whereas we
isolated 77% of the desired aldehyde, the only differences
being the absence of MS 3A and the heating at 45 °C. To
ketone when oxidized alone (Table 2, entry 1 compared to
Table 1, entry 2). An allylic alcohol was also more prefer-
entially oxidized than a benzylic one (Table 2, entry 2).
But the most spectacular results were obtained with diols
bearing both an allylic function and a nonallylic one. In
these substrates, we found that without molecular sieves,
the allylic alcohol was selectively oxidized whereas the
SYNLETT 2007, No. 12, pp 1869–1872
2
4
.0
7
.2
0
0
7
Advanced online publication: 25.06.2007
DOI: 10.1055/s-2007-984498; Art ID: D04207ST
©
Georg Thieme Verlag Stuttgart · New York

1
870
F. Batt et al.
LETTER
1
4
Table 1 Different Alcohols Oxidized by the Pd(OAc) –Et N–O System
2
3
2
a
b
Entry
1
Substrate
1-octanol
Product
Conversion (%)
1
-octanal
56
1
2
2
-octanone
-octen-3-one
-octen-1-al
2
3
4
2-octanol
70
1
3
1-octen-3-ol
2-octen-1-ol
100 (95)
80
2
4
5
6
100 (85)
86 (77)
O
OH
5
6
O
OH
7
8
9
25
O
OH
E/Z = 89:11
7
O
O
O
<10
O
O
OH
8
BnO
100 (95)c
BnO
O
OH
9
1
1
O
O
OH
1
0
100 (95)
68 (45)
0
1
OMe
OMe OH
11
a
1
Estimated by H NMR after 20 h of reaction. It is noteworthy that when the conversion was not complete after 20 h, Pd black precipitated and
there was no more evolution of the reaction.
b
Isolated yield.
c
Pd(OAc) (2 × 3 mol%) and Et N (2 × 6 mol%) were used.
2
3
nonallylic function remained untouched (Table 2, entries described18 for the same purpose. In both cases, a large
–6). No trace of dicarbonyl compounds was detected. excess of reagents was necessary (10 equiv or more). We
This high level of chemoselectivity (allylic alcohol vs. thus propose here a very selective method for allylic
3
19
nonallylic one) is noticeable as it avoids the use of protect- alcohols, even in the presence of other alcohols, which
ing groups.
is catalytic, generates water as the only by-product and is
very easy to handle. Investigations into the reasons for the
observed selectivity are in progress in our laboratory, as
aerobic oxidation chemistry remains a subject of critical
importance in the course of studies on green methods for
organic transformations.
Among the published methods, only very few allowed the
selective oxidation of allylic alcohols in the presence of
nonallylic alcohols. The most known procedure very com-
monly proposed in organic synthesis uses MnO . Chromi-
um(VI) reagents associated with amine ligands were also
2
Synlett 2007, No. 12, 1869–1872 © Thieme Stuttgart · New York

LETTER
Selective Aerobic Oxidation of Allylic Alcohols to Carbonyl Compounds
1871
Table 2 Chemoselective Oxidation of Allylic Alcohols
a
b
Entry
1
Substrate
-octanol
Product
Conversion (%)
2
2-octanone 2
+
2 (11%)
+
+
1
-octen-3-ol
1-octen-3-one 3
3 (100%)
1
-octen-3-ol
1-octen-3-one 3
+
+
OH
O
3 (100%)
2
+
1
0 (55%)
1
0
3
4
O
O
100 (80)c
100 (95)d
OH
OH
HO
HO
HO
1
2
HO
1
3
HO
5
HO
100 (94)
80 (77)e
O
OH
1
4
OH
OH
5
6
5
O
OH
1
5
a
1
Estimated by H NMR after 20 h of reaction. It noteworthy that when the conversion was not complete after 20 h, Pd black precipitated and
there was no more evolution of the reaction.
b
Isolated yield.
Conditions: r.t., 8 h.
c
d
Pd(OAc) (2 × 3 mol%) and Et N (2 × 6 mol%) were used.
2
3
e
Conditions: r.t., 40 h.
Acknowledgment
(12) Stahl, S. S. Science 2005, 309, 1824.
(
13) Schultz, M. J.; Hamilton, S. S.; Jensen, D. R.; Sigman, M. S.
The authors thank Professor O. Piva for scientific support. F. Batt
and E. Bourcet thank the ‘Ministère Français de l’Education Su-
périeure et de la Recherche’ for financial support.
J. Org. Chem. 2005, 70, 3343.
(
14) Typical Procedure: Pd(OAc) (0.015 mmol, 3 mol%) and
2
Et N (0.03 mmol, 6 mol%) were dissolved in THF–toluene
3
(15%; 1.7 mL). Then the substrate (0.5 mmol) was added
and the reaction mixture was heated to 45 °C under 1 atm of
References and Notes
O (balloon) for 20 h. The reaction was monitored by TLC.
2
In the case of total conversion, the product was obtained in
its pure form after evaporation of the solvents, precipitation
(
(
(
(
1) Schultz, M. J.; Sigman, M. S. Tetrahedron 2006, 62, 8227.
2) Lenoir, D. Angew. Chem. Int. Ed. 2006, 45, 3206.
3) Sharma, V. B.; Jain, S. L.; Sain, B. Synlett 2005, 173.
4) Guram, A. S.; Bei, X.; Turner, H. W. Org. Lett. 2003, 5,
of Pd in Et O and filtration on celite. In other cases, it was
2
purified by chromatography on silica.
(
(
15) Steinhoff, B. A.; King, A. E.; Stahl, S. S. J. Org. Chem.
2485.
2006, 71, 1861.
(
(
5) Hunsen, M. Tetrahedron Lett. 2005, 46, 1651.
6) (a) Muzart, J. Tetrahedron 2003, 59, 5789. (b) Muldoon, J.;
Brown, S. N. Org. Lett. 2002, 4, 1043.
16) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. J. Org.
Chem. 1999, 64, 6750.
(
(
(
17) Peterson, K. P.; Larock, R. C. J. Org. Chem. 1998, 63, 3185.
18) Guziec, F. S. Jr.; Luzzio, F. A. J. Org. Chem. 1982, 47, 1787.
(7) Zhan, B.-Z.; Thompson, A. Tetrahedron 2004, 60, 2917.
(8) Mallat, T.; Baiker, A. Chem. Rev. 2004, 104, 3037.
(9) Ji, H.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Tetrahedron
Lett. 2002, 43, 7179.
1
19) All the products have been fully characterized by H NMR
1
3
(
300 MHz) and C NMR (75 MHz) and the analyses are in
agreement with published data. Data that were not found in
(
(
10) Velusamy, S.; Srinivasan, A.; Punniyamurthy, T.
Tetrahedron Lett. 2006, 47, 923.
11) Guan, B.; Xing, D.; Cai, G.; Wan, X.; Yu, N.; Fang, Z.;
Yang, L.; Shi, Z. J. Am. Chem. Soc. 2005, 127, 18004.
1
the literature are as follows: Product 5: H NMR (300 MHz,
CDCl ): d = 0.83 (s, 9 H), 0.87 (d, J = 6.6 Hz, 3 H), 1.10 (dd,
3
J = 6.4, 14.0 Hz, 1 H), 1.17 (dd, J = 4.0, 14.0 Hz, 1 H), 2.06
Synlett 2007, No. 12, 1869–1872 © Thieme Stuttgart · New York

1
872
F. Batt et al.
LETTER
(
1
m, 1 H), 2.35 (dd, J = 7.9, 15.5 Hz, 1 H), 2.47 (dd, J = 5.8,
146.4, 200.9 (C ). IR (neat): 3399, 2932, 1675, 1627, 1369,
1184, 1128, 1050, 948, 735 cm . Product 14: H NMR (300
q
–
1
1
5.5 Hz, 1 H), 5.73 (d, J = 10.3 Hz, 1 H), 6.12 (d, J = 17.5
1
3
Hz, 1 H), 6.28 (dd, J = 10.3, 17.5 Hz, 1 H). C NMR (75
MHz, CDCl ): d = 23.1, 26.4, 30.3, 31.4 (C ), 49.6, 51.2,
1
CDCl ): d = 1.13 (d, J = 7.0 Hz, 3 H), 3.19 (m, 1 H), 3.48 (m,
1
1
MHz, CDCl ): d = 1.08 (d, J = 7.2 Hz, 3 H), 3.01 (m, 2 H),
3
3.62 (dd, J = 4.5, 11.1 Hz, 1 H), 3.72 (dd, J = 7.2, 11.1 Hz, 1
H), 5.78 (dd, J = 1.3, 10.1 Hz, 1 H), 6.24 (dd, J = 1.3, 17.5
3
q
1
28.1, 137.3, 201.0 (C ). Product 9: H NMR (300 MHz,
q
1
3
Hz, 1 H), 6.39 (dd, J = 10.1, 17.5 Hz, 1 H). C NMR (75
MHz, CDCl ): d = 13.8, 45.6, 64.4, 129.3, 135.4, 204.3 (C ).
3
H), 3.70 (m, 1 H), 4.49 (d, J = 3.2 Hz, 2 H), 5.80 (dd, J =
3
q
.1, 10.3 Hz, 1 H), 6.28 (dd, J = 1.1, 17.5 Hz, 1 H), 6.46 (dd,
IR (neat): 3402, 2973, 2880, 1677, 1611, 1458, 1405, 1238,
1
–1
1
J = 10.6, 17.5 Hz, 1 H), 7.31 (m, 5 H). Product 12: H NMR
1193, 1025, 977, 735 cm . Product 15: H NMR (300 MHz,
(
300 MHz, CDCl ): d = 2.50 (td, J = 1.0, 5.3 Hz, 2 H), 3.18
CDCl ): d = 1.31 (m, 6 H), 1.57 (m, 4 H), 1.80 (m, 1 H), 2.55
3
3
(m, 1 H, OH), 3.69 (td, J = 1.0, 5.3 Hz, 1 H), 6.09 (s, 1 H),
(t, J = 7.3 Hz, 2 H), 3.60 (t, J = 6.6 Hz, 2 H), 5.79 (dd, J =
1.3, 10.3 Hz, 1 H), 6.18 (dd, J = 1.3, 17.5 Hz, 1 H), 6.35 (dd,
1
3
6
3
2
.38 (s, 1 H), 9.53 (s, 1 H). C NMR (75 MHz, CDCl ): d =
3
1
3
1.8, 60.9, 136.6, 147.1 (C ), 195.3 (C ). IR (neat): 3394,
J = 10.3, 17.5 Hz, 1 H). C NMR (75 MHz, CDCl ): d =
q
q
3
–
1
1
932, 1686, 1437, 1267, 1043, 950, 736 cm . Product 13: H
24.2, 25.8, 29.5, 33.0, 39.9, 63.2, 128.3, 136.9, 201.5 (Cq).
IR (neat): 3391, 2930, 2857, 1681, 1615, 1463, 1403, 1268,
NMR (300 MHz, CDCl ): d = 2.33 (s, 3 H), 2.49 (t, J = 6.1
3
–
1
Hz, 2 H), 3.65 (t, J = 6.1 Hz, 2 H), 5.89 (s, 1 H), 6.08 (s, 1
1075, 736 cm .
H). 13C NMR (75 MHz, CDCl ): d = 26.0, 34.7, 62.0, 128.0,
3
Synlett 2007, No. 12, 1869–1872 © Thieme Stuttgart · New York

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