Polymer-Supported Bisacetoxybromate(I) Anion - An Efficient Co-Oxidant in the TEMPO-Mediated Oxidation of Primary and Secondary Alcohols

Article abstract of DOI:10.1002/adsc.200202208

A polymer-bound reagent for the efficient oxidation of primary alcohols to aldehydes and secondary alcohols to ketones in the presence of a catalytic amount of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) is described. The oxidation process is particular mild and allows one to prepare aldehydes with α-chirality without racemization. This also includes the synthesis of α-aminoaldehydes. In most cases, work-up of this heavy metal-free oxidation is achieved by simple filtration followed by removal of the solvent. Insight into the role of the bromate(I) anion in the oxidation process was gained from the TEMPO-mediated oxidation of benzaldehyde in the presence of the hypochlorite anion loaded on an anion exchange resin.

Full text of DOI:10.1002/adsc.200202208

FULL PAPERS
Polymer-Supported BisacetoxybromateꢀI) Anion --- An Efficient
Co-Oxidant in the TEMPO-Mediated Oxidation of Primary and
Secondary Alcohols
Marco Brünjes,a Georgia Sourkouni-Argirusi,b Andreas Kirschninga,*
a
Institut für Organische Chemie, Universität Hannover, Schneiderberg 1B, 30167 Hannover, Germany
Fax: ‡ 49 511 762 ± 3011, e-mail: andreas.kirschning@oci.uni-hannover.de
b
Institut für Organische Chemie, TUClausthal, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
Received: December 28, 2002; Accepted: February 8, 2003
Dedicated Prof. Dr. Peter Welzel @Leipzig) on the occasion of his 65th birthday.
Abstract: A polymer-bound reagent for the efficient achieved by simple filtration followed by removal of
oxidation of primary alcohols to aldehydes and the solvent. Insight into the role of the bromate@I)
secondary alcohols to ketones in the presence of a anion in the oxidation process was gained from the
catalytic amount of 2,2,6,6-tetramethyl-1-piperidinyl- TEMPO-mediated oxidation of benzaldehyde in the
oxyl @TEMPO) is described. The oxidation process is presence of the hypochlorite anion loaded on an
particular mild and allows one to prepare aldehydes anion exchange resin.
with a-chirality without racemization. This also
includes the synthesis of a-aminoaldehydes. In most Keywords: aldehyde; aminoaldehyde; oxidation; poly-
cases, work-up of this heavy metal-free oxidation is mer-bound reagent; radical reaction
Introduction
The use of N-oxoammonium ions like 2,2,6,6-tetra-
methylpiperidine-1-oxonium 2 and the stable free
In view of the dramatic developments in the need for nitroxyl radical precursor 1 @TEMPO) are an alternative
compound libraries in pharmaceutical and agrochem- to metal-based oxidants @Figure 1).[12] N-Oxoammoni-
ical research, polymer-supported reagents have seen um ions 2 can be applied stoichiometrically or more
renewed interest lately and have become a widely conveniently catalytically in combination with a co-
recognized synthetic technique.[1] The intrinsic advant- oxidant. The oxoammonium ion itself is transformed
age of this hybrid solid/solution phase technique lies in into the secondary hydroxylamine 3 during that process,
the simple purification and the possibility to use these but it is reoxidized by the co-oxidant in the following
reagents in excess to drive reactions in solution to steps. Numerous such co-oxidants are known. They
completion. Furthermore, they may be adapted to include halogen-based oxidants,[13] peroxide-derived
continuous flow processes and hence are useful for oxidants[14] and electrochemical methods.[15] Rychnov-
automated synthesis.[2,3]
sky and coworkers postulated that when the TEMPO-
Oxidation of alcohols is a process which has been catalyzed oxidation of alcohols is carried out in the
achieved with various polymer-bound reagents.[1] Com- presence of m-CPBA and halide ions, hypobromite was
monly, functionalized polymers were developed that are the effective oxidant which oxidizes the nitroxyl radical
functionalized with heavy metals such asÀ [C8]rO3,[4] 1 to the N-oxoammonium ion 2.[14d] In addition, it was
2± [5]
À [6]
À [6a,7]
Cr2O7À[9]
,
ClCrO3 ,
HCrO4 ,
MnO4 ,
and shown that TEMPO-catalyzed oxidations can be per-
RuO4
ions.[10] In most cases, these oxidants are formed on a large industrial scale.[16] The excellent
attached via different N-heterocycles or simple quater- activity and selectivity of N-oxoammonium ions in
nary ammonium cations to the polymeric backbone. oxidation reactions led to the development of polymer-
Recently, Kita and coworkers reported on polymer- assisted strategies. One option is the immobilization of
bound @diacetoxy)iodobenzene which, in the presence N-oxoammonium ions to a solid phase and stoichio-
of a catalytic amount of bromide, is an efficient oxidant metric employment in the presence of the alcohol or
for the transformation of secondary alcohols into catalytically and use of an stoichiometric co-oxidant in
ketones. Furthermore, it was shown that this reagent solution. Polymer-supported nitroxyl radicals have
system oxidizes primary alcohols to the corresponding widely been applied as catalysts in oxidation reac-
carboxylic acids.[11]
tions.[17,18] However, Bolm and coworkers[19] were the
first to utilize the power of these immobilized oxidants
Adv. Synth. Catal. 2003, 345, 635 ± 642
DOI: 10.1002/adsc.200202208
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Marco Brünjes et al.
FULL PAPERS
O
OH
Me
6 (3 equiv.), CH2Cl2, 40 °C, 24 h
Me
N
N
O
N
O
96%
OH
7
8
1
3
2
O
Figure 1. Species relevant in TEMPO-mediated oxidations.
6 (3 equiv.), toluene, 90 °C, 24 h
OAc
Br
7
or 8
95% from 7
88% from 8
in the oxidation of complex and delicate alcohols.[20]
They attached TEMPO to a silica support and employed
the material under Anelliꢁs and Montanariꢁs conditi-
ons.[13a, b]
9
O
6 (3 equiv.), toluene, 40 °C, 24 h
OH
In a reversed mode of application a catalytic amount
of soluble TEMPO is reoxidized by a stoichiometrically
immobilized co-oxidant. This technique has one major
advantage as it avoids minimum contamination of the
reaction mixture. Here, the stoichiometrically used
reagent is loaded onto the polymer so that no phase
separation and extraction is necessary for work-up. This
strategy is particularly appealing if the co-oxidant can
easily be regenerated. Recently, we communicated on
the use of the polymer-supported bisacetoxybromate@I)
anion 6.[21,22] Among the different modes of attachment
of active species to a polymer, ion exchange is probably
94%
11
13
10
O
6 (3 equiv.), CH2Cl2, 40 °C, 24 h
OH
78%
MeO
MeO
12
Scheme 2. TEMPO-free oxidations with bromate@I) complex
6.
best suited for regeneration. In this report, we give a when acetophenone 8 was subjected to the same
detailed account on this reagent system which includes reaction conditions thus furnishing ketone 9 with similar
its scopes and limitations.
yield. Under these uncatalyzed conditions also benzyl
alcohols 10 and 12 were converted into the correspond-
ing aldehydes 11 and 13. Apart from these selected
examples, bromate@I) complex 6 is not broadly appli-
cable for the oxidation of alcohols. Cyclohexanol was
Results and Discussions
In accordance with our related work on haloate@I) unreactive under the reaction conditions depicted in
complexes,[23] anion 6 can be prepared by oxidative Scheme 2. Indeed, earlier we showed that reagent 6 and
ligand transfer from bisacetoxyiodobenzene 5 onto its soluble analogue is well suited for 1,2-haloacetox-
anion exchange resin @IRA-900: bromide form) 4 ylation of alkenes under very mild conditions.[23a, c,24]
@Scheme 1).
However, addition of a catalytic amount of the
Electrophilic bromate@I)-complex 6 alone is not an nitroxyl radical 1 @0.5 ± 1 mol %) to the reaction mixture
efficient oxidant for most alcohols. It works solely with led to a dramatic acceleration of the oxidation process
activated alcohols such as 1-phenyl-ethanol 7 affording @Schemes 3 ± 6). For example, benzyl alcohol 10 is
high yields of acetophenone 8 at 408C @Scheme 2). The converted at room temperature into benzaldehyde 11
oxidative properties of functionalized polymer 6 are @94%) within 1 h using the reagent system TEMPO 1 and
highly dependent on the reaction conditions. Thus, when functionalized polymer 6. Similarly, primary alcohols 14,
the solvent was changed to toluene and the temperature 16 and 18 afforded aldehydes 15, 17 and 19 in excellent
was raised to 908C a-acetoxy-a-bromo ketone 9 became yields. Quantitative transformation of alcohols are
the major product. Presumably, ketone 9 was generated achieved both in dichloromethane as well as in toluene.
from alcohol 7 by double electrophilic bromination Considering that a polymer-bound reagent is employed,
followed by nucleophilic displacement of one bromine the reactions proceed rather rapidly. Importantly, over-
atom by the acetate ion. This hypothesis was proven oxidation is not observed. The reaction is terminated by
filtration and removal of the solvent. In solution acetic
acid may be present as a by-product which either can be
scavenged by addition of the weakly basic resin Am-
berlite A-21 or by removal of the solvent in high
vacuum.[25]
In an attempt to prepare @À)-cystothiazol E,[26] it
became necessary to synthesize 2-isopropylthiazole-4-
carbaldehyde 21 by oxidation of the corresponding
alcohol 20. Under the usual reaction conditions we did
Scheme 1. Preparation of polymer-bound bromate@I) com-
plex 6.
636
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Polymer-Supported Bisacetoxybromate@I) Anion
FULL PAPERS
6 (3 equiv.), CH2Cl2, rt, 3.5 h, TEMPO (cat.)
mon protecting groups for alcohols such as acetals,
benzyl and silyl ethers are stable under the conditions
employed. The compatibility with other functional
groups is also demonstrated in the oxidative trans-
formation of alcohol 34 which contains a thioether
substituent of the tetrazole heterocycle. This moiety is a
O
CH3(CH2)10CH2OH
CH3(CH2)10C
H
93%
15
14
Me
CHO
Me
6 (3 equiv.), CH2Cl2, rt, 3.5 h, TEMPO (cat.)
OH
Me
Me
Me
95%
Me
17
16
Â
suitable precursor of the Kocienski variant of the Julia
6 (3 equiv.), CH2Cl2, rt, 1.5 h, TEMPO (cat.)
olefination.[28] After Wittig homologation of the crude
aldehyde alkene 35 was obtained in good yield.[29]
Protected aminoaldehydes are particularly versatile
for preparing b-amino acids and alkaloids. For their
preparation solid phase assisted oxidation of the corre-
sponding aminoalcohol is particularly helpful, as work-
up of these labile aldehydes which are prone to
racemization can be carried out very rapidly. In our
case, Boc- and Z-protected aminoalcohols 36, 38 and 40
were consumed within two hours to yield the a-amino-
BMPO
CHO
BMPO
OH
95%
18
19
6 (3 equiv.), CH2Cl2, rt, 2 h, TEMPO (cat.)
OH
O
H
S
S
Me
Me
N
56%
N
Me
Me
20
21
Scheme 3. TEMPO-mediated oxidations of primary alcohols.
not observe any oxidation of the sulfur atom. In direct aldehydes 37, 39 and 41. For most of these transforma-
comparison with existing methods[27] the isolated yield tions there is no need for a final purification due to the
of aldehyde 21 was satisfying after chromatographic negligible contamination with TEMPO. Further chro-
purification.
matographic purification @Scheme 5, reduced yields in
Aldehydes with a stereogenic center in the a-position parenthesis after chromatographic isolation due to
are also smoothly generated without racemization of the lability of aldehyde) inevitably lead to a dramatically
chiral center @Scheme 4). In contrast to this observation, reduced yield. Unfortunately N,N-dialkylated amino-
we found that silyl-protected aldehyde 25 undergoes alcohols seem to be inapplicable for this method due to
partial racemization when prepared from alcohol 24 by complete decomposition of the starting material within
the Swern oxidation. In addition, the examples depicted 15 minutes.[30]
in Scheme 4 demonstrate that this oxidation method is
Finally, this reagent system allows one to oxidize
compatible with diverse other functional groups. Com- secondary aryl-substituted as well as aliphatic alcohols
6 (3 equiv.), CH2Cl2, rt, 1.5 h, TEMPO (cat.)
OR
OR
CHO
OH
Me
Me
22 R = TBS
24 R = TBPS
26 R = OPMB
23 90%
25 99%
27 88%
OMOM
Me
6 (3 equiv.), CH2Cl2, rt, 2 h, TEMPO (cat.)
OMOM
Me
OHC
99%
OH
OSiPh2tBu
OSiPh2tBu
28
29
OMOM
Me
6 (3 equiv.), CH2Cl2, 40 °C, 0.5 h, TEMPO (cat.)
OMOM
Me
Me
HO
Me
96%
OBn
CHO OBn
OSiPh2tBu
OSiPh2tBu
30
31
6 (3 equiv.), CH2Cl2, 40 °C, 24 h, TEMPO (cat.)
OHC
O
O
O
O
O
HO
99%
O
O
O
O
N
O
33
32
N
1. 6 (3 equiv.), CH2Cl2, rt, 3.5 h,
TEMPO (cat.)
N
N
N
N
HO
S
N
S
N
2. Ph3P=CH2, (2 equiv.),
THF, 0 °C, 0.5 h
Ph
Ph
34
57% (2 steps)
35
Scheme 4. TEMPO-mediated oxidation of primary alcohols with a stereogenic center in the a-position.
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Marco Brünjes et al.
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O
OAc
Br
6 (3 equiv.), CH2Cl2, rt, 2 h, TEMPO (cat.)
NMe3 Br
+ OAc
NMe3
NMe3 OAc
Ph
H
Ph
OH
NHBoc
OAc
NHBoc
99% (50%)
4
6
36
37
2x
O
H
+
Br
R1
+
OAc
N
O
6 (3 equiv.), CH2Cl2, rt, 2 h, TEMPO (cat.)
AcO Br
via
Ph
Ph
OH
NHZ
52
2
NHZ
OH
99% (50%)
H
R2
R1
R2
39
38
2x
O
+ OAc
N
O
6 (3 equiv.), CH2Cl2, rt, 2 h, TEMPO (cat.)
Me
O
Me
OH
H
1
NHBoc
NHBoc
95%
40
41
N
O
HOAc
+ HOAc
Scheme 5. TEMPO-mediated oxidation of a-aminoalcohols.
N
2
OH
OAc
3
OH
Me
O
6 (3 equiv.), CH2Cl2, rt, 24 h, TEMPO (cat.)
Scheme 7. Proposed mechanism of TEMPO-mediated oxida-
tion of alcohols using polymer-bound bromate@I) complex 6
as co-oxidant.
Me
96%
7
8
O
OH
6 (3 equiv.), CH2Cl2, 40 °C, 24 h, TEMPO (cat.)
oxidants for secondary alcohols which are attached to a
solid phase have been reported. For example, we found
that although chromium@VI)-based polymer-bound-
reagents[6a,7,21] are strong oxidants with comparable
reactivity to our reagent system, the polystyrene-based
versions tend to decompose which results in substantial
contamination of the solution and difficulties during the
filtration. On the other hand, immobilization of the
permanganate@VII) anion to exchange resins[8,21] leads
to an oxidant which allows one to transform allylic and
benzylic alcohols to the corresponding aldehydes but
fails to effectively oxidize secondary alcohols.
81%
43
42
44
OH
6 (3 equiv.), toluene, rt, 24 h, TEMPO (cat.)
O
96%
45
O
OH
6 (3 equiv.), CH2Cl2, rt, 24 h, TEMPO (cat.)
80%
47
A possible mechanism of this process is depicted in
Scheme 7. The bisacetoxybromate@I) anion 6 or hypo-
bromite 52 which may be formed upon fragmentation of
6 initiates the process by oxidation of two equivalents of
TEMPO 1 to the active catalyst the N-oxoammonium
ion 2.[31] One equivalent of the latter species is respon-
sible for the oxidation of the hydroxy group. Thereby,
hydroxylamine 3 is formed as by-product. Finally, rapid
syn proportionation between the oxoammonium salt 2
and hydroxylamine 3 occurs to give two nitroxyl radicals
1.
46
OH
O
6 (3 equiv.), toluene, rt, 24 h, TEMPO (cat.)
94%
48
49
6 (3 equiv.), CH2Cl2, rt, 24 h, TEMPO (cat.)
Me
Me
96%
OMe OH
OMe O
50
51
At this point we searched for primary evidence that
the polymer-bound bromate anion 6 is not the active co-
oxidant for TEMPO but rather the acylated hypobro-
mite 52. We reckoned that it is slowly released from the
ion exchange resin into solution prior to oxidation of
Scheme 6. TEMPO-mediated oxidation of secondary alco-
hols.
7, 42, 44, 46, 48 and 50 with similar efficiency compared reagent 1. For obtaining indirect evidence, we immobi-
to primary alcohols. Due to the reduced activity, lized hypochlorite anion by ion exchange to yield
oxidation of secondary alcohols took longer compared functionalized resin 53.[32] Hypochlorite is a well estab-
to primary alcohols. At this point it is not clear why the lished co-oxidant for the catalytic use of TEMPO in
conditions for oxidizing acetophenone 7 in the absence alcohol oxidations.[12] However, in this context function-
@refer to Scheme 2) or in the presence of TEMPO alized resin 53 was inactive. Likewise, the corresponding
@Scheme 6) are comparable. However, these transfor- ion exchange resin which was loaded with the hypobro-
mations are noteworthy because not many versatile mite anion did not induce TEMPO-catalyzed oxidation
638
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Polymer-Supported Bisacetoxybromate@I) Anion
FULL PAPERS
60P254 and detected either by UV-absorption or by staining with
H2SO4/4-methoxybenzaldehyde in ethanol. Where necessary,
flash column chromatography was performed on silica gel 60
@230 ± 400 mesh). Except for alcohols 18, 20, 22, 24, 26, 28, 30,
34, 36, and 38 all starting compounds are commercially
available. Alcohols 22, 24, and 26 were prepared from
commercial @2R)-3-hydroxy-2-methylpropionic methyl ester
by standard protection of the alcohol group and dibal-
promoted reduction of the ester functionality under standard
conditions. In a similar manner, aminoalcohols 36, 38 and 40
were prepared from the corresponding amino acid esters.
Alternatively, alcohols 36 @Acros) and 38 @Fluka) are com-
mercially available. Polymer-bound bromide 4 was purchased
from Fluka @3.5 mmol/g bromide). Recycling of used polymer
was achieved by treatment with aqueous HBr for 1 h at room
temperature. Aldehydes and ketones 8, 11, 13, 15, 17, 43, 45, 47,
49 and 51 are known and are commercially available. The
spectroscopic and physical data of aldehydes and ketones 19,[33]
21,[36] 23,[34] 37,[37] 39[38] and 41[39] are listed in the literature.
NMe3
OCl
O
53
+ aq. HCl (1 equiv.)
OH
H
cat.
97% 11
10
N
O
1
Scheme 8. TEMPO-mediated oxidation of alcohols using
polymer-bound hypochlorite 53 as co-oxidant in the presence
of a proton source.
either. Only when one equivalent of acid @6 M aqueous
HCl or 60 mM HCl in wet CH2Cl2) was added did we
observe rapid oxidation of benzyl alcohol 10 to benzal-
dehyde 11 in the presence of TEMPO. Addition of a
proton source results in release of hypochloric acid into
solution where it initiates oxidation of TEMPO to the
oxonium ion 2. Similar to the TEMPO-catalyzed
oxidation of alcohols mediated by hypochlorite as co-
oxidant it was necessary to add a minimum amount of
water @wet CH2Cl2) to the reaction medium when
employing polymer-attached hypochlorite. Based on
these observations, it is reasonable to assume that these
immobilized anions are not able to oxidize TEMPO 1.
Instead, neutral co-oxidants in solution are required to
initiate the catalytic cycle.
Preparation of BisacetoxybromateꢀI) Resin 6
A suspension of polymer-bound halide 4 @available from
Fluka; 3.5 g/mmol bromide) and PhI@OAc)2 5 @1.8 equivs.) in
dry CH2Cl2 @2.5 mL/mmol halide anion) under nitrogen was
shaken at 300 rpm for 12 h at room temperature. The yellowish
suspension was protected from light. Filtration and washing of
the resin with CH2Cl2 @3 Â ) and drying under vacuum afforded
the light yellow reagent. The functionalized resin can be stored
under nitrogen at À 208C for 6 months without loss of activity.
General Procedure for the Oxidation of Alcohols
Conclusion
A mixture of the alcohol @1 equiv.) resin 6 @typically 3
theoretical equivalents based on the loading given by the
In summary, we have developed a new polymer-bound
non-heavy metal-based oxidant. In the presence of a commercial provider) in dry CH2Cl2 @2.5 mL/mmol bromide)
with optional @refer to Schemes) 2,2,6,6-tetramethyl-1-piper-
idinyloxyl @TEMPO) under nitrogen was shaken at 300 rpm.
The reaction temperature @room temperature, 408C or 908C)
varied according to the choice of alcohol. Completion of the
reaction was monitored by TLC. Filtration terminated the
reaction. The resin was washed with CH2Cl2 @3 Â ) and the
combined organic washings and filtrate were concentrated
under reduced pressure. Typically, further purification steps
were unnecessary @ > 95% purity) and the carbonyl com-
pounds could directly be employed for the next step. Still, for
generating analytically pure samples and in order to remove
oligomeric impurities from the resin purification by flash
column chromatography was carried out in some cases. We
found that these oligomeric impurities commonly arose when
charges of the commercial resins were employed for the first
time. After regeneration and reuse we typically did not note
this phenomenon.
catalytic amount of TEMPO it is a powerful reagent for
the oxidation of primary and secondary alcohols. In view
of the easy recycability of the co-oxidant and the purity
of the products this procedure may find application in
large-scale processes of industrial relevance. In this
context however, more atom-efficient and cheaper co-
oxidants such as resin 53 need to be investigated in
greater detail.
Experimental Section
General Remarks and Starting Materials
1H and 13C NMR spectra were measured on DPX 200 @Bruker)
with 200 MHz @50 MHz) and AM-400, ARX 400 @Bruker)
400 MHz @100 MHz), respectively, using tetramethylsilane as
the internal standard. CDCl3 is the solvent for all NMR
experiments. Mass spectra were recorded on a type LCT-
spectrometer @Micromass). Optical rotations [a] were collect-
ed on a Polarimeter 341 @Perkin Elmer) at a wavelength of
589 nm. All solvents used were of reagent grade and were
further dried. Reactions were monitored by TLC on silica gel
Acetic Acid 1-Bromo-2-oxo-2-phenylethyl Ester ꢀ9)
By treatment of 1-phenylethanol 7 @61.1 mg, 0.5 mmol) with
reagent 6 in toluene at 908C for 24 h the title compound 9
@123 mg, 0.48 mmol, 95%) was prepared. Under these con-
ditions, conversion of 7 was quantitative. Final purification was
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Marco Brünjes et al.
FULL PAPERS
achieved by flash column chromatography @petroleum ether/
ethyl acetate 7:1). Colorless crystals; mp 508C; IR @KBr): n ˆ
694, 773, 899, 957, 1017, 1053, 1103, 1201, 1229, 1381, 1452,
1597, 1710, 1748, 1765, 2953 cmÀ1; 1H NMR @CDCl3): d ˆ
8.25 ± 7.25 @m, 5H), 7.6 @s, 1H), 2.18 @s, 3H); 13C NMR
@CDCl3): d ˆ 188.7 @s), 168.6 @s), 134.2 @d), 133.1 @s), 128.8
@d), 128.7 @d), 86.2 @d), 20.6 @q); anal. calcd. for C10H9BrO3: C
46.72, H 3.53, Br 31.08; found: C 46.55, H 3.57, Br 30.78.
Likewise, acetophenone 8 @60 mg, 0.5 mmol) was used to
prepare the title compound 9 @114 mg, 0.44 mmol, 88%)
according the procedure described above.
135.5 @d), 133.3 @s), 129.7 @d), 127.6 @d), 97.1 @t), 82.6 @d), 64.4
@t), 55.9 @q), 37.9 @d), 26.7 @q), 19.1 @s), 10.9 @q); anal. calcd. for
C23H32O4Si: C 68.96, H 8.05; found: C 68.77, H 8.11.
ꢀ2R,3S,4S,6S)-4-Benzyloxy-7-ꢀtert-
butyldiphenylsiloxy)-2,6-dimethyl-5-
methoxymethoxyheptanal ꢀ31)
By treatment of heptanol 30 @0.56 g, 1.0 mmol) with reagent 6
and TEMPO in CH2Cl2 at 408C for 0.5 h the title compound 31
1
was prepared; yield: 0.540 g @0.96 mmol, 96%); oil; H NMR
ˆ
@CDCl3): d ˆ 9.5 @d, 1H, J 2.2 Hz), 7.69 ± 7.61 @m, 4H), 7.45 ±
ˆ
7.23 @m, 11H), 4.71 and 4.66 @2d, 2H, J 6.6 Hz), 4.68 and 4.42
ꢀ2R)-3-ꢀtert-Butyldiphenylsiloxy)-2-methyl-1-propanal
ꢀ25)
ˆ
ˆ
@2d, 2H, J 11.7 Hz), 3.85 @dd, 1H, J 3.2 Hz, 6.5 Hz), 3.67 @dd,
ˆ
ˆ
1H, J 7.5 Hz, 10.0 Hz), 3.56 @ddd, 1H, J 2.7 Hz, 6.5 Hz,
ˆ
By treatment of @2S)-3-@tert-butyldiphenylsiloxy)-2-methyl-1-
propanol 24 @65.6 mg, 0.2 mmol) with reagent 6 and TEMPO in
CH2Cl2 at room temperature for 1.5 h the title compound 25
was prepared; yield: 65 mg @0.2 mmol, 99%); oil; [a]2D3: À 248
@CHCl3, c 1); IR @film): n ˆ 428, 613, 702, 740, 823, 937, 1035,
10.1 Hz), 3.48 @dd, 1H, J 6.5 Hz, 10.0 Hz), 2.43 @dddq, 1H,
ˆ
ˆ
J 2.2 Hz, 6.4 Hz, 7.0 Hz, 7.4 Hz), 1.94 @dddq, 1H, J 3.2 Hz,
ˆ
6.5 Hz, 6.7 Hz, 7.5 Hz), 1.87 @ddd, 1H, J 6.4 Hz, 10.1 Hz,
ˆ
14.8 Hz), 1.47 @ddd, 1H, J 2.7 Hz, 7.4 Hz, 14.2 Hz), 1.05 @s,
9H), 0.99 @d, 3H, J 0.7 Hz), 0.92 @d, 3H, J 6.7 Hz); 13C NMR
@CDCl3): d ˆ 204.6 @d), 138.0 @s), 2Â129.6 @d), 128.3, 2Â128.1,
5Â127.6 @d), 98.2 @t), 78.8, 78.3 @d), 72.7 @t), 66.4 @t), 55.9 @d),
44.0 @d), 36.7 @d), 32.7 @d), 26.9 @d), 19.2 @s), 13.6 @d), 11.6@d);
anal. calcd. for C34H46O5Si: C 72.56, H 8.24; found: C 72.45, H
8.31.
ˆ
ˆ
1112, 1391, 1427, 1472, 1736, 2858, 2932, 3071, 3384 cmÀ1;
1
ˆ
H NMR @CDCl3): d ˆ 9.76 @d, 1H, J 1.6 Hz), 7.7 ± 7.35 @m,
ˆ
ˆ
10H), 3.90 @dd, 2H, J 5.2 Hz, 10.4 Hz), 3.85 @dd, 1H, J
6.2 Hz, 10.4 Hz), 2.57 @dddq, 1H, J 1.6 Hz, 5.2 Hz, 6.2 Hz,
7.0 Hz), 1.10 @d, 3H, J
@CDCl3): d ˆ 204.5 @d), 135.5 @d), 133.1 @s), 129.7 @d), 127.7 @d)
64.0 @t), 48.7 @d), 26.7 @q), 19.1 @s), 10.2 @q); anal. calcd. for
C20H26O2Si: C 73.57, H 8.03; found: C 73.76, H 8.07.
ˆ
7.0 Hz), 1.04 @s, 9H); 13C NMR
ˆ
1,2:3,4-Di-O-isopropylidene-6-oxo-a-d-
galactopyranose ꢀ33)
By treatment of 1,2:3,4-di-O-isopropylidene-a-d-galactopyr-
anose 32 @130 mg, 0.5 mmol) with reagent 6 and TEMPO in
CH2Cl2 at 408C for 24 h the title compound 33 was prepared;
yield: 129 mg @0.49 mmol, 99%); 1H NMR @CDCl3): d ˆ 9.63 @s,
ꢀ2R)-3-ꢀ4-Methoxybenzyloxy)-2-methyl-1-propanal
ꢀ27)
By treatment of @2S)-3-@4-methoxybenzyloxy)-2-methyl-1-
propanol 26 @39 mg, 0.185 mmol) with reagent 6 and TEMPO
in CH2Cl2 for 1.5 h the title compound 27 was prepared; yield:
34 mg @0.163 mmol, 88%); oil; [a]2D0: À 338 @CHCl3, c 1);
1H NMR @CDCl3): d ˆ 9.64 @d, 1H, J ˆ 1.5 Hz, 1-H), 7.16,
6.80 @2Âm, 2Â2H, H-aromat.), 4.38 @s, 2H, CH2PhOMe), 3.73
@s, 3H, OMe), 3.58 @dd, 1H, J ˆ 9.3, 6.7 Hz, 3-H), 3.53 @dd, 1H,
J ˆ 9.3, 5.3 Hz, 3-Hꢁ), 2.58 @m, 1H, 2-H), 1.05 @d, 3H, J ˆ 7.2 Hz,
2-Me); 13C NMR @CDCl3): d ˆ 203.9 @d), 159.2 @s), 129.9 @s),
2Â129.2 and 2Â113.8 @4Âd), 72.9 @t), 69.8 @t), 55.2 @q), 46.7 @d),
10.7 @q). For additional spectroscopic and physical data refer to
ref.[35]
ˆ
ˆ
1H) 5.67 @d, 1H, J 5.0 Hz), 4.65 @2dd, 2H, J 2.2 Hz, 8.0 Hz),
ˆ
ˆ
4.39 @dd, 1H J 2.2 Hz, 4.8 Hz), 4.2 @d, 1H, J 2.2 Hz), 1.52,
1.44, 1.36, 1.32 @3 s, 12H); 13C NMR @CDCl3): d ˆ 200.3 @d),
110.0 @s), 109,0 @s) 96.2 @d), 73.2 @d), 71.7 @d), 70.4 @d), 70.3 @d),
25.9 @q), 25.8 @q), 24.8 @q), 24.2 @q). For additional spectroscopic
and physical data refer to ref.[40]
ꢀ2S)-5-ꢀ2-Methyl-3-butenylsulfanyl)-1-phenyl-1H-
tetrazole ꢀ35)
By treatment of alcohol 34 @134 mg, 0.535 mmol) with reagent
6 @6 equivs.) and a catalytic amount of TEMPO in CH2Cl2 at
room temperature for 3.5 h the corresponding aldehyde was
prepared; yield: 130 mg @0.524 mmol, 98%).
ꢀ2S,3R)-4-ꢀtert-Butyldiphenylsiloxy)-2-
ꢀmethoxymethoxyl)-3-methyl-1-butanal ꢀ29)
The crude product was dissolved in dry THF @20 mL),
cooled to 08C and added to a solution of Ph3PCH3Br @2 equiv.)
and LDA @2 equiv.; 2 M in THF/n-heptane) in dry THF
@100 mL). After work up with aqueous NH4Cl and extraction
of the aqueous phase, the crude product was purified by
column chromatography @silica gel; petroleum ether/ethyl
acetate, 10:1) to afford the title product 35; yield: 74 mg
@0.3 mmol; 57% after two steps); oil; [a]2D0: À 15.98 @CHCl3, c 1);
1H NMR @CDCl3): d ˆ 7.49 ± 7.63 @m, 5H), 5.75 @ddd, 1H, J ˆ
17.3 Hz, 10.2 Hz, 2 Hz), 5.02 ± 5.12 @m, 2H), 3.42 @d, 1H, J ˆ
2.5 Hz), 3.41 @d, 1H, J ˆ 3.1 Hz), 2.68 @pseudo-sept, 1H, J ˆ
7.0 Hz), 1.17 @d, 3H, J ˆ 6.8 Hz); 13C NMR @CDCl3): d ˆ 154.5
By treatment of @2S,3R)-4-@tert-butyldiphenylsiloxy)-2-@me-
thoxymethoxyl)-3-methyl-1-butanol 28 @40.2 mg, 0.1 mmol)
with reagent 6 and TEMPO in CH2Cl2 at room temperature for
2 h the title compound 29 was prepared; yield: 40 mg
@0.1 mmol, 99%); oil; [a]2D3: À 68 @CHCl3, c 1); IR @film): n ˆ
449, 613, 703, 741, 823, 919, 1036, 1111, 1154, 1215, 1390, 1428,
À1
1
ˆ
1472, 1732, 2932 cm ; H NMR @CDCl3): d ˆ 9.74 @d, 1H, J
1.6 Hz), 7.70 ± 7.33 @m, 10H), 4.72 and 4.70 @2d, 2H), 4.22 @dd,
ˆ
ˆ
1H, J 1.2 Hz, 3.8 Hz), 3.64 @ddd, 1H, J 5.6 Hz, 10.0 Hz), 3.60
ˆ
@dd, 1H, J 7.8 Hz, 10.0 Hz), 3.40 @s, 3H), 2.22 @m, 1H), 1.05 @s,
9H), 0.86 @d, 1H, J 7.0 Hz); 13C NMR @CDCl3): d ˆ 203.7 @d),
ˆ
640
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Polymer-Supported Bisacetoxybromate@I) Anion
FULL PAPERS
@s), 140.8 @d), 133.7 @s), 130.0 @d), 129.7 @d), 123.8 @d), 115.3 @t),
39.5 @t), 37.3 @d), 19.3 @q); HRMS @EI): calcd. for C12H14N4S:
246.0939; found: 246.0934.
[12] Review on TEMPO: A. E. J. de Nooy, A. C. Besemer, H.
van Bekkum, Synthesis 1996, 1153 ± 1175.
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Acknowledgements
This work was supported by the Fonds der Chemischen
Industrie. We thank Solvay Pharmaceuticals 'Hannover) for
the donation of chemicals. We are grateful to Dr. H. Monen-
schein and C. Jasper for expert preparative assistance. Finally,
we thank Prof. Dr. M. Kalesse 'FU Berlin) for providing us with
selected alcohols.
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642
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asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 635 ± 642