A very mild and chemoselective oxidation of alcohols to carbonyl compounds

Article abstract of DOI:10.1021/ol016501m

matrixpresented Efficient oxidation of primary alcohols and β-amino alcohols to the corresponding aldehydes and α-amino aldehydes can be carried out at room temperature and in methylene chloride, using trichloroisocyanuric acid in the presence of catalytic TEMPO: aliphatic, benzylic, and allylic alcohols, and β-amino alcohols are rapidly oxidized without no overoxidation to carboxylic acids. Secondary carbinols are slowly oxidized so that the reaction is highly chemoselective.

Full text of DOI:10.1021/ol016501m

ORGANIC
LETTERS
2
001
Vol. 3, No. 19
041-3043
A Very Mild and Chemoselective
Oxidation of Alcohols to Carbonyl
Compounds
3
Lidia De Luca, Giampaolo Giacomelli,* and Andrea Porcheddu
Dipartimento di Chimica, UniVersit a` degli Studi di Sassari, Via Vienna 2,
I-07100 Sassari, Italy
ggp@ssmain. uniss.it
Received July 26, 2001
ABSTRACT
Efficient oxidation of primary alcohols and â-amino alcohols to the corresponding aldehydes and r-amino aldehydes can be carried out at
room temperature and in methylene chloride, using trichloroisocyanuric acid in the presence of catalytic TEMPO: aliphatic, benzylic, and
allylic alcohols, and â-amino alcohols are rapidly oxidized without no overoxidation to carboxylic acids. Secondary carbinols are slowly
oxidized so that the reaction is highly chemoselective.
In view of their importance as intermediates in organic
synthesis, many methods for oxidation of primary alcohols
to aldehydes have been documented in the literature. In
sulfoxide as a reagent and very low temperatures and, mainly,
from the presence of dimethyl sulfide as a byproduct.
Moreover, the oxidation is not chemoselective.
1
particular, oxidation of â-amino alcohols to the corresponding
R-amino aldehydes is synthetically useful as the carbonyl
group present in the amino carbonyl compounds readily
On this basis and following our interest in the use of [1,3,5]
triazine derivatives in organic synthesis, herein we report a
very mild, efficient procedure for the general oxidation of
carbinols into the corresponding carbonyl compounds that
is easy to use and chemoselective for the quantitative
conversion of primary alcohols into aldehydes (Scheme 1).
5
2
undergoes successive transformations. Moreover, there is a
continuous demand to develop synthetic methods for dis-
criminating efficiently various functional groups. In this
context, chemoselective methods allowing for oxidation of
primary alcohols without competition of secondary alcohols
remain challenging. Relatively few methods allow this type
Scheme 1
3
of selectivity, and often the restrictions that accompany some
of them make new, mild, and selective procedures highly
desirable.
Until now, Swern oxidation has been shown to be a
4
favorable method for the oxidation of alcohols: however,
this procedure suffers from the use of activated dimethyl
(
1) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry:
The procedure is based on the addition of 1 molar equiv
of 1,3,5-trichloro-2,4,6-triazinetrione (trichloroisocyanuric
acid), a very cheap reagent, to a CH Cl solution of the
2 2
Reactions, Mechanisms, and Structure, 5th ed.; Wiley-Interscience: New
York, 2001; pp 1514-1517.
(
2) Jurczak, J.; Golebiowski, A, Chem. ReV. 1989, 89, 149.
(3) Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J. L. J. Org. Chem.
alcohol followed by catalytic amounts of 2,2,6,6-tetramethyl-
1
996, 61, 7452 and references therein.
4) Mancuso, A. J.; Swern, D. Synthesis 1981, 165.
6
(
1-piperidinyloxy (TEMPO). This system operates rapidly,
1
0.1021/ol016501m CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/30/2001

at room temperature, without addition of water or base, with
the oxidation of the primary alcoholic group being practically
quantitative within 20 min (Table 1). No noticeable over-
rapid (5 min) and furnishes a high yield of the cinnamalde-
hyde along with the corresponding chloride (<10%). In this
case, a reverse addition procedure has to be followed: the
2 2
trichloroisocyanuric acid is added portionwise to a CH Cl
solution of the alcohol containing TEMPO (0.01 molar
equiv). Indeed, employing the normal procedure causes an
exothermic reaction with prevalent formation of (3-chloro-
propenyl)benzene.
Table 1. Conversion of Alcohols into the Corresponding
Carbonyl Compounds
Under the usual conditions, even N-protected â-amino
alcohols are oxidized to N-protected R-amino aldehydes, with
slightly reduced rates: however, the oxidation is complete
within 20 min. Moreover, the method is compatible with the
common N-protecting groups and no deprotection was noted.
Upon comparison to previously studied reactions of this
7
type, the data collected show that significant racemization
of the chiral center on the R-carbon atom does not occur. In
2
5
fact, a sample of (S)-2,3,3-trimethyl-1-butanol, [R]
D
+39.1
+79.4
25
(
(
c 2, EtOH), gave (S)-2,3,3-trimethylbutanal, [R]
D
8
,9
c 4, heptane). Analogously, (S)-N-benzyloxycarbonyl-2-
2
0
amino-3-phenylpropan-1-ol, [R]
D
-40.2 (c 0.5, MeOH),
gave (S)-N-benzyloxycarbonyl-2-amino-3-phenylpropion-
2
0
10
aldehyde, with [R]
D
-51.3 (c 1, MeOH).
The system we report on allows oxidation of secondary
carbinols too, under the same reaction conditions (Table 2).
Table 2. Conversion of Secondary Alcohols into Ketones
a
After 6 h.
a
After 15 min. b (3-Chloropropenyl)benzene (7%) was recovered too.
The reaction gives quantitatively the corresponding ketones,
but the rate is very low and the process requires more than
1
1
oxidation to carboxylic acids was detected even using a
6 h for completion. The reaction rate seems to be
particularly reduced with sterically constrained alcohols.
This observation suggested a possible use of this reaction
as a chemoselective method for oxidizing primary alcohols
2-fold excess of trichloroisocyanuric acid.
Aliphatic, benzylic, and allylic alcohols are oxidized at
the same rate. With cinnamyl alcohol, the reaction is very
3042
Org. Lett., Vol. 3, No. 19, 2001

in the presence of secondary ones. Indeed, the present system
is highly chemoselective. The reaction of a 1:1 mixture of a
primary alcohol with a secondary one occurs after 15 min
in a quantitative conversion of the primary alcohol into an
aldehyde, with the reduction in the amount of ketone formed
of 1-(4-hydroxymethylphenyl)ethanol gives similar results,
with 4-(1-hydroxyethyl)benzaldehyde being the only product
recovered.
The procedure for the oxidation of 3-(N-benzyloxycar-
bonyl)aminopropane-1,2-diol is representative for all cases.
Trichloroisocyanuric acid (2.32 g, 10.0 mmol) was added
(Table 3). Even better results are obtained when primary and
to a solution of the alcohol (2.14 g, 9.5 mmol) in CH
2
Cl
2
(20 mL), and the solution was stirred and maintained at 0
°
C, followed by addition of TEMPO (0.015 g, 0.1 mmol).
Table 3. Selective Oxidations of Diols
After the addition, the mixture was warmed to room
temperature and stirred for 15 min and then filtered on Celite,
and the organic phase was washed with 15 mL of a saturated
solution of Na
organic layer was dried (Na
2
CO
3
, followed by 1 N HCl and brine. The
SO ), and the solvent was
2
4
evaporated to yield 3-(N-benzyloxycarbonyl)amino-2-hy-
droxypropionaldehyde that was isolated without further
1
purification (95%): H NMR δ 10.1 (s, 1H), 7.99 (s, 1H),
7
2
1
.44-7.38 (m, 5H), 5.22 (m, 1H), 5.17 (bs, 2H), 3.67 (m,
1
3
H), 3.40 (bs, 1H); C NMR δ 192.4, 157.4, 134.4, 129.7,
28.0, 66.9, 58.8, 29.7. Anal. Calcd for C11
H
13NO
4
(223.08): C, 59.19; H, 5.87; N, 6.27. Found C, 59.19, H,
5
.89, N, 6.24.
In conclusion, the procedure reported here is simple and
allows for rapid oxidation of primary alcohols to aldehydes
under very mild conditions with a high degree of chemo-
selectivity. The method seems to be as convenient for
oxidizing both primary and secondary carbinols as other
methods reported in the literature and can be used as a valid
alternative to the classical Swern oxidation, therefore avoid-
ing very low temperature and the use of toxic reagents.
a
After 15 min.
secondary carbinol groups are in competition on the same
skeleton. In the reaction carried out with 3-(N-benzyloxy-
carbonyl)aminopropane-1,2-diol, the only product recovered
after 15 min is 3-(N-benzyloxycarbonyl)amino-2-hydroxy-
propionaldehyde, without contamination of either the dicar-
bonyl compound or the isomeric keto alcohol. The oxidation
12
Acknowledgment. The work was financially supported
by the University of Sassari (Fondi ex-60%).
OL016501M
(8) Marcacci, F.; Giacomelli, G.; Menicagli, R. Gazz. Chim. Ital. 1980,
1
10, 195.
(
5) (a) Falorni, M.; Porcheddu, A.; Taddei, M. Tetrahedron Lett. 1999,
(9) On the basis of this datum, it is possible to conclude that this oxidation
6
4
0, 4395. (b) Falorni, M.; Giacomelli, G.; Porcheddu, A.; Taddei, M. J.
method proceeds with better stereochemistry than the DCC-DMSO system.
(10) (a) Sharma, R. P.; Gore, M. G.; Akhtar, M. J. Chem. Soc., Chem.
Commun. 1979, 875. (b) Soucek, M.; Urban, J Collect. Czech. Chem.
Commun. 1995, 60, 693.
(11) Hiegel and Nalbandy (Hiegel, G. A.; Nalbandy, M. Synth. Commun.
1992, 22, 1595) reported that in combination with pyridine secondary
alcohols are rapidly oxidized to ketones by trichloroisocyanuric acid.
(12) Finn, P. J.; Gibson, N. J.; Fallon, R.; Hamilton, A.; Brown, T.
Nucleic Acids Res. 1996, 24, 3357.
Org. Chem. 1999, 64, 8962. (c) Falchi, A.; Giacomelli, G.; Porcheddu, A.;
Taddei, M. Synlett 2000, 275. (d) De Luca, L.; Giacomelli, G.; Taddei, M.
J. Org. Chem. 2001, 66, 2534. (e) De Luca, L.; Giacomelli, G.; Porcheddu,
A. Org. Lett. 2001, 3, 1519.
(6) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987,
5
3
2, 2559.
(7) Leanna, M. R.; Sowin, T. J.; Morton, H. E. Tetrahedron Lett. 1992,
3, 5029.
Org. Lett., Vol. 3, No. 19, 2001
3043