A multipolymer system for organocatalytic alcohol oxidation

Article abstract of DOI:10.1039/b500965k

A system involving two polymer-supported reagents for the selective and organocatalytic oxidation of alcohols to aldehydes or ketones has been developed in which both polymeric reagents can be recovered and reused. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b500965k

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C O M M U N I C A T I O N
A multipolymer system for organocatalytic alcohol oxidation
a
b
b
a
Tracy Yuen Sze But, Yousuke Tashino, Hideo Togo and Patrick H. Toy*
a
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong,
People’s Republic of China. E-mail: phtoy@hku.hk; Fax: 852 2857 1586; Tel: 852 2859 2167
Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho 1-33, Inage-ku,
Chiba, 263-8522, Japan
b
Received 20th January 2005, Accepted 1st February 2005
First published as an Advance Article on the web 14th February 2005
A system involving two polymer-supported reagents for
the selective and organocatalytic oxidation of alcohols to
aldehydes or ketones has been developed in which both
polymeric reagents can be recovered and reused.
1
2
Polymer-supported reagents, including organic catalysts, have
become widely used in organic synthesis and a great variety
of these materials have been reported. Most of the supports
used to immobilize reagents are insoluble, and as such, the
attached functional groups react heterogeneously. Thus one
of the major limitations in using such supported reagents is
that they generally cannot be used together in reactions that
require the interaction of two or more reagents with one another
prior to reaction with the substrate, such as would be the case
in Mitsunobu reactions. They can only be used together in
reactions that involve the sequential reaction of the supported
reagents with the substrate, and a handful of such applications
Scheme 1 Simultaneous use of PSDIB (1) and JJ-TEMPO (2) for
alcohol oxidation.
H
2
O (40 : 1) at rt for 24 h. The polymer was filtered, washed
sequentially with additional CH Cl , Et O and hexanes, and
2
2
2
dried to afford 2 in 84% yield. The nitrogen content of 2 was
3,4
have been reported.
Only when a soluble carrier is used for immobilization can
a polymer-supported reagent or substrate be used to react
with another polymer-supported substrate or reagent. To our
knowledge, there are only two published exceptions to this:
measured by elemental analysis to be 2.88%, which corresponds
5
−1
to a nitroxyl loading level of 2.0 mmol TEMPO g .
Gratifyingly, initial attempts to use 1 and 2 simultaneously for
the selective oxidation of 2-phenylethanol to the corresponding
aldehyde were successful and the optimal reaction conditions
were found to be 2.0 eq. of 1 in conjunction with 0.01 eq. of 2 in
6,7
(
1) the report by Murphy et al., in which an insoluble anion
◦
exchange resin was used to cleave tertiary amines from REM
1,2-dichloroethane at 70 C. Having established the feasibility
8
resin, and (2) the report by Yasuda and Ley in which supported
of our strategy, we studied the oxidation of a wide range of
primary and secondary aliphatic, allylic and benzylic alcohols
(Table 1). Yields of all aldehyde and ketone products were high,
with the activated benzylic alcohols being formed more rapidly.
Even sterically hindered secondary alcohols could be oxidized
using our multipolymer system in good to excellent yield after
extended reaction times (Table 1, entries 4 and 5). Furthermore,
no evidence of acid formation was observed with any of the
primary alcohols used. Notably, the products could be isolated
efficiently after several filtration and concentration operations
(see Experimental section).
We next examined if it was possible to reuse the mixture of
the excess, unreacted 1 together with 2 recovered at the end of
each oxidation reaction. Thus, the oxidation of 2-phenylethanol
was performed 3 successive times using the recovered polymer
mixture supplemented by additional 1 (so that 2 eq. of the
oxidant were used in each reaction). Even after the second
recycling (third oxidation reaction), the product was formed
in nearly quantitative (98%) yield (Table 1, entry 1).
In conclusion, we have developed a multipolymer system
for the selective, and organocatalytic oxidation of alcohols to
aldehydes or ketones in which the polymeric reagents can be
recovered and reused. This process is noteworthy because the
polymeric reagents react with one another (1 oxidizes 2) prior to
reaction with the substrate. Furthermore, it is environmentally
friendly since the polymers can be recycled and it should
be amenable to use in medicinal chemistry parallel synthesis
procedures where small quantities of highly pure products are
desired with minimal purification necessary. Ongoing studies
include further examining the scope of this reaction system, its
scale-up and the recyclability of spent 1.
perchlorate and nitroxyl reagents oxidized alcohols to carboxylic
9
acids. Along these lines, we have recently described the first
example where two soluble polymer-supported reagents react
with one another prior to reacting with the substrate in the
context of organic synthesis. The report describes Mitsunobu
reactions that involve polymer-supported phosphine and azodi-
10
carboxylate reagents. Herein, we present an extension of this
concept to the development of a multipolymer system for the
selective and organocatalytic oxidation of alcohols to aldehydes
or ketones, in which one polymeric reagent is non-cross-linked
and becomes soluble as the reaction progresses and the other is
cross-linked and remains insoluble throughout the process.
We have previously described polymer-supported reagents
for use in various oxidation reactions, including a fluorinated
11
ketone for use in dioxirane mediated reactions, sulfoxides for
12
use in Swern oxidation reactions, and recyclable polystyrene-
1
3,14
supported diacetoxyiodosobenzene (1, PSDIB)
for use in a
15,16
variety of rearrangement reactions.
that 1, in conjunction with a nitroxyl radical catalyst, can
We subsequently found
17
1
8
oxidize alcohols to either aldehydes or ketones, or carboxylic
19
acids. Thus we were eager to see if 1 could be used together with
a polymer-supported nitroxyl reagent, as shown in Scheme 1.
A variety of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
regents have been recently reported that use both insoluble and
soluble polymer supports in oxidation reactions. However, due
20
21
to the increased swelling of the JandaJel (JJ) resins in organic
22
solvents, and their overall ease of use, we decided to use this
polymer platform as our support for TEMPO. Thus, 4-hydroxy-
TEMPO (1.2 eq.) was attached to JJ-CH
2
Cl (ca. 2.0 mmol
−
1
Cl g ) using NaOH (3 eq.) and Bu
4
NI (0.1 eq.) in CH Cl –
2
2
9
7 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 9 7 0 – 9 7 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5

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a
Table 1 Results of alcohol oxidation using 1 (2 eq.) and 2 (0.01 eq.)
b
Entry
1
Starting material
2-phenylethanol
Time (h)
Yield (%)
c
c
c
5
cycle 1: 96
cycle 2: 95
cycle 3: 98
d
2
3
4
5
6
7
8
9
cyclohexylmethanol
cyclohexanol
24
7
77
71
90
67
c
d
(−)-menthol
48
60
e
d
1,2:4,5-di-O-cyclohexylidene-b-D-fructopyranose
2-cyclohexen-1-ol
c
5
6
5
100
d
cinnamyl alcohol
benzyl alcohol
benzyhydrol
benzoin
1-(4-bromophenhyl)ethanol
1,2,3,4-tetrahydro-1-naphthol
71
80
100
100
d
e
d
7
d
1
1
1
0
1
2
12
12
7
d
100
d
91
a
b
All aldehyde and ketone products are known in the literature or commercially available. Time required for complete consumption of starting
c
d
e
alcohol. GC yield. Isolated yield. 0.05 eq. 2 was used.
Experimental
5 (a) P. H. Toy and K. D. Janda, Acc. Chem. Res., 2000, 33, 546; (b) T. J.
Dickerson, N. N. Reed and K. D. Janda, Chem. Rev., 2002, 102, 3325;
(c) D. E. Bergbreiter, Chem. Rev., 2002, 102, 3345.
General procedure for alcohol oxidation
6
(a) For examples of soluble polymer-supported reagents or substrates
reacting with insoluble polymer-supported reagents or substrates,
see: H. Frank and H. Hagenmaier, Experientia, 1975, 31, 131; (b) G.
Heusel, G. Bovermann, W. G o¨ hring and G. Kung, Angew. Chem.,
Int. Ed. Engl., 1977, 16, 642; (c) D. E. Bergbreiter and R. Chandran,
J. Am. Chem. Soc., 1987, 109, 174; (d) H. Han and K. D. Janda,
Angew. Chem. Int. Ed. Engl., 1997, 36, 1731; (e) P. H. Toy, T. S. Reger
and K. D. Janda, Org. Lett., 2000, 2, 2205.
For a report of two different soluble-polymer bound substrates
reacting with one another in a convergent and combinatorial manner,
see: J.-M. Ahn, P. Wentworth, Jr. and K. D. Janda, Chem. Commun.,
2003, 480.
JJ-TEMPO (2, 0.001 mmol) and PSDIB (1, 0.2 mmol) were
added to a solution of alcohol (0.1 mmol) in ClCH
2
CH Cl
2
◦
(
2 mL). The mixture was shaken at 70 C until the alcohol
was no longer detectable by TLC analysis. At this time the
reaction was filtered to remove a mixture of excess 1 and
catalyst 2, and concentrated in vacuo. The resulting residue
was then filtered through a plug of silica gel (20% EtOAc in
hexanes) to remove reacted 1. Removal of the solvent afforded
the desired product that was essentially pure as determined
7
1
13
by H and C NMR analysis. Additionally, LRMS analysis
indicated the correct molecular mass of all products, which were
found to be spectroscopically identical to authentic samples of
them.
8
9
X. H. Ouyang, R. W. Armstrong and M. M. Murphy, J. Org. Chem.,
1
998, 63, 1027.
K. Yasuda and S. V. Ley, J. Chem. Soc., Perkin Trans. 1, 2002, 1024.
1
0 A. M. Harned, H. S. He, P. H. Toy, D. L. Flynn and P. R. Hanson,
J. Am. Chem. Soc., 2005, 127, 52.
1
1
1 J. T. W. Kan and P. H. Toy, Tetrahedron Lett., 2004, 45, 6357.
2 (a) M. K. W. Choi and P. H. Toy, Tetrahedron, 2003, 59, 7171;
Acknowledgements
(
b) M. K. W. Choi and P. H. Toy, Tetrahedron, 2004, 60, 2875.
Financial support was provided by the Research Grants Council
of the Hong Kong Special Administrative Region, P. R. of China
1
3 For a review of polymer-supported hypervalent iodine reagents, see:
H. Togo and K. Sakuratani, Synlett, 2002, 1966. For a review of
hypervalent iodine reagents in oxidation reactions, see:; H. Tohma
and Y. Kita, Adv. Synth. Catal., 2004, 346, 111.
4 (a) S. V. Ley, A. W. Thomas and H. Finch, J. Chem. Soc., Perkin
Trans. 1, 1999, 669; (b) H. Tohma, S. Takizawa, T. Maegawa and
Y. K i t a , Angew. Chem., Int. Ed., 2000, 39, 1306; (c) S. Ficht, M.
M u¨ lbaier and A. Giannis, Tetrahedron, 2001, 57, 4863.
(
Project No. HKU 7112/02P).
1
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