TEMPO, 2,2,6,6-Tetramethylpiperidinyloxy
2,2,6,6-Tetramethylpiperidinyloxy is a stable nitroxyl radical, which serves in oxidations as catalyst. By substitution in position 4 (4-hydroxy-TEMPO, 4-acetamido-TEMPO) its reactivity can be steered.
For example, processes with oxygen and 5 mol-% TEMPO permit environmentally benign reactions as alternatives to some oxidations, where so far e.g. chrome reagents were used.
Proposed mechanism for the oxidation of primary alcohols under basic
conditions
M. Angelin, M. Hermansson, H. Dong, O. Ramström, Eur. J. Org. Chem., 2006,
4323-4326.
2-azaadamantane N-Oxyl (AZADO), 9-Azabicyclo[3.3.1]nonane N-Oxyl (ABNO), 9-Azanoradamantane N-oxyl (Nor-AZADO) form a less hindered class of nitroxyl radicals and exhibit an enhanced reactivity compared with TEMPO.
Recent Literature
A convenient method enables the preparation of a silica gel supported
TEMPO catalyst. The catalyst prepared from [4-hydroxy-TEMPO + NaCl]/SiO2
was used for an aerobic oxidation of alcohols to carbonyls under mild reaction
conditions in the presence of Fe(NO3)3 • 9 H2O.
Alcohols were converted to the corresponding carbonyls in good to excellent
yields. After a simple filtration, the catalyst can be reused at least six times.
N. Tamura, T. Aoyama, T. Takido, M. Kodomari, Synlett, 2012,
1397-1407.
A rapid oxidation of primary and secondary alcohols using catalytic amounts of
TEMPO and Yb(OTf)3 in combination with a stoichiometric amount of
iodosylbenzene afforded carbonyl compounds in excellent yields without
over-oxidation. Oxidation of primary alcohols in the presence of secondary
alcohols proceeded with good selectivity.
J.-M. Vatèle, Synlett, 2006,
2055-2058.
An aerobic oxidation of primary and secondary alcohols to aldehydes and
ketones using TEMPO-CuCl as catalyst in the ionic liquid [bmin][PF6]
has been developed. The system needs no bubbling of O2 due to
its good solubility in the ionic liquid. The resulting aldehydes (with
no traces of carboxylic acids) and ketones can be extracted with organic
solvents. The ionic liquid can be reused after washing with water and
drying under high vacuum (8 runs for the oxidation of benzyl alcohol:
yields of 72%, 70, 68, 70, 65, 64, 62, and 60).
I. A. Ansari, R. Gree, Org. Lett., 2001, 1507-1509.
A highly efficient 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) catalyzed
reaction using recyclable 1-chloro-1,2-benziodoxol-3(1H)-one as the
terminal oxidant allows the conversion of various alcohols to their
corresponding carbonyl compounds in high to excellent yields at room temperature
in ethyl acetate, which is an environmentally friendly organic solvent.
X.-Q. Li, C. Zhang, Synthesis, 2009,
1163-1169.
The combination of TEMPO and CAN can be used for the aerobic oxidation
of benzylic and allylic alcohols into their corresponding carbonyl
compounds. However, steric hindrance has been observed to impede the
reaction with some substituted allylic systems. The present method is
superior to others currently available due to its relatively short
reaction times and excellent yields.
S. S. Kim, H. C. Jung, Synthesis,
2003, 2135-2137.
The reaction of KBrO3 and NH2OH • HCl in situ generates NOx
and Br anion, which allows in the presence of 2,2,6,6-tetramethylpiperidine-N-oxide
(TEMPO) an activation of dioxygen to oxidize various benzylic alcohols
quantitatively to their corresponding carbonyl compounds under mild conditions.
G. Yang, W. Wang, W. Zhu, C. An, X. Gao, M. Song, Synlett, 2010,
437-440.
TEMPO-derived reagents tagged with multiple perfluoroalkyl chains and
triazole moieties promote the oxidation of alcohols to aldehydes in organic
solvent/water mixtures with reaction rates comparable to homogeneous TEMPO
reagents, but can be easily recovered by liquid/emulsion filtration.
A. Gheorghe, T. Chinnusamy, E. Cuevas-Yañez, P. Hilgers, O. Reiser, Org. Lett.,
2008,
10, 4171-4174.
A. Gheorghe, T. Chinnusamy, E. Cuevas-Yañez, P. Hilgers, O. Reiser, Org. Lett.,
2008,
10, 4171-4174.
A four-component system consisting of acetamido-TEMPO/Cu(ClO4)2/TMDP/DABCO
in DMSO allows an efficient room-temperature aerobic alcohol oxidation
of various alcohols into their corresponding aldehydes or ketones in
good to excellent yields. The catalytic system can be recycled.
N. Jiang, A. J. Ragauskas, J. Org. Chem., 2006,
71, 7087-7090.
The system Cu(ClO4)2/acetamido-TEMPO/DMAP catalyses
the room-temperature aerobic oxidation of primary alcohols to aldehydes in
the ionic liquid [bmpy]PF6. The catalysts can be recycled and
reused.
N. Jiang, A. J. Ragauskas, Org. Lett., 2005,
7, 3689-3692.
A highly efficient and mild procedure for the oxidation of different types of
alcohols uses TEMPO as catalyst, iodobenzene dichloride as stoichiometric
oxidant, and pyridine as base. Oxidation of 1,2-diols gives α-hydroxy ketones or
α-diketones depending on the amount of oxidant used. High yielding procedures
for the preparation of iodoarene dichlorides have been developed.
X.-F. Zhao, C. Zhang, Synthesis, 2007, 551-557.
X.-F. Zhao, C. Zhang, Synthesis, 2007,
551-557.
The use of NaClO/TEMPO/Co(OAc)2 enabled a benzylic oxidation of alkyl
arenes to yield various aromatic aldehydes and ketones in very good yields. The
reaction reactivity, selectivity, and scope of the reaction were investigated.
C. Jin, L. Zhang, W. Su, Synlett, 2011,
1435-1438.
A one-pot two-step sequence involving an oxidation/imine-iminium formation/reduction
allowed the N-alkylation of amines by alcohols. Optically active alcohols
and amines can be converted without any epimerization.
C. Guérin, V. Bellosta, G. Guillamot, J. Cossy, Org. Lett., 2011,
13, 3478-3481.
A sequential one-pot synthesis for the oxidation of primary and secondary
tert-butyldimethylsilyl (TBDMS) ethers, using the presence of PhIO or
PhI(OAc)2 and catalytic amounts of metal triflates and TEMPO in THF
or acetonitrile tolerates acid-sensitive protecting groups and leaves tert-butyldiphenylsilyl
ethers and phenolic TBDMS groups untouched.
B. Barnych, J.-M. Vatèle, Synlett, 2011,
2048-2052.
A Cu-catalyzed oxidative amidation-diketonization reaction of terminal alkynes
leads to α-ketoamides. In this copper-catalyzed radical process, O2
not only participates as the ideal oxidant but also undergoes dioxygen
activation under ambient conditions.
C. Zhang, N. Jiao, J. Am. Chem. Soc., 2010,
132, 28-29.
Passerini three-component reaction under catalytic aerobic conditions allows the
conversion of alcohols instead of aldehydes. The reaction of alcohols,
isocyanides, and carboxylic acids in toluene in the presence of a catalytic
amount of cupric chloride, NaNO2, and TEMPO afforded, under an oxygen
atmosphere, the P-3CR adducts in good yields.
J. Brioche, G. Masson, J. Zhu, Org. Lett., 2010,
12, 1432-1435.
A highly convenient organocatalytic method for the mono-oxidation of
unprotected glycosides relies on the chemoselective properties of TEMPO
in combination with trichloroisocyanuric acid under very mild, basic
conditions. The resulting dialdo-glycosides are efficiently purified
with the use of solid-phase imine capture.
M. Angelin, M. Hermansson, H. Dong, O. Ramström, Eur. J. Org. Chem., 2006,
4323-4326.
An efficient and highly selective method for the oxidative conversion of
primary amines to the corresponding nitriles using trichloroisocyanuric
acid in the presence of catalytic TEMPO provides a new entry to the
synthesis of various aliphatic, aromatic and heterocyclic nitriles in
excellent yield.
F.-E. Chen, Y.-Y. Kuang, H.-F. Dai, L. Lu, M. Huo, Synthesis,
2003, 2629-2631.
Iodine was compared to other positive halogens as terminal oxidant in
chemoselective oxidations of alcohols using catalytic TEMPO and was shown to be
superior in cases of electron-rich and heteroaromatic benzylic alcohols.
R. A. Miller, R. S. Hoerrner, Org. Lett.,
2003, 5, 285-287.
A novel, metal-free oxidation system for the catalytic synthesis of aldehydes
and ketones using TEMPO and a quarternary ammonium salt as catalysts and Oxone
as oxidant proved especially successful for the synthesis of ketones. The mild
conditions tolerate even sensitive silyl protective groups which can otherwise
be cleaved in the presence of Oxone.
C. Bolm, A. S. Magnus, J. P. Hildebrand, Org. Lett., 2000,
2, 1173-1175.
C. Bolm, A. S. Magnus, J. P. Hildebrand, Org. Lett., 2000,
2, 1173-1175.
1 mol-% TEMPO and a catalytic amount of
1,3-dibromo-5,5-dimethylhydantoin and NaNO2 is a highly
efficient catalytic system for the aerobic oxidations of benzylic
alcohols in water.
R. Liu, C. Dong, X. Liang, X. Wang, X. Hu, J. Org. Chem., 2005,
70, 239-244.
Benzylic ethers are oxidatively cleaved by
4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate in wet
MeCN at room temperature to give the corresponding aromatic aldehydes and
alcohols in high yield. Primary and secondary alkyl alcohols are further
oxidized to give carboxylic acids and ketones, respectively.
P. P. Pradhan, J. M. Bobbitt, W. F. Bailey, J. Org. Chem., 2009,
74, 9501-9504.
Oxoammonium salts enable a practical and highly efficient oxidative
rearrangement of tertiary allylic alcohols to β-substituted α,β-unsaturated
carbonyl compounds. Acyclic substrates as well as medium membered ring
substrates and macrocyclic substrates can be oxidized.
M. Shibuya, M. Tomizawa, Y. Iwabuchi, J. Org. Chem., 2008,
73, 4750-4752.
CuCl/DABCO/4-HO-TEMPO as the catalysts and oxygen as the terminal oxidant
enabled an efficient aerobic oxidative synthesis of 2-substituted quinazolines
and 4H-3,1-benzoxazines from the one-pot reaction of aldehydes with
2-aminobenzylamines and 2-aminobenzyl alcohols, respectively.
B. Han, X.-L. Yang, C. Wang, Y.-W. Bai, T.-C. Pan, X. Chen, W. Yu, J. Org. Chem., 2012,
77, 1136-1142.
A one-pot dehydrogenative Povarov/oxidation tandem reaction of N-alkyl anilines
with mono- and 1,2-disubstituted aryl and alkyl olefins enables the synthesis of
a various substituted quinolines. The simple protocol uses cheap and benign
iron(III)chloride as the Lewis acid catalyst and a TEMPO oxoammonium salt as a
nontoxic, mild, efficient oxidant.
H. Richter, O. G. Mancheño, Org. Lett., 2011,
13, 6066-6069.
Cross coupling of ortho-substituted aryl Grignard reagents with
alkynyl Grignard reagents can be performed without adding any transition metal
in the presence of 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO)
as an environmentally benign organic oxidant. Importantly, functional groups
such as esters, amides, and cyanides are tolerated.
M. S. Maji, S. Murarka, A. Studer, Org. Lett., 2010,
12, 3878-3881.
