Tempo-catalyzed oxidations of alcohols using m-CPBA: The role of halide ions

Full text of DOI:10.1021/jo9819032

310
J . Org. Chem. 1999, 64, 310-312
Ta ble 1. Effect of a d d itives on m -CP BA/TEMP O
Oxid a tion s of 2-octa n ola
TEMP O-Ca ta lyzed Oxid a tion s of Alcoh ols
Usin g m -CP BA: Th e Role of Ha lid e Ion s
Scott D. Rychnovsky* and Rajappa Vaidyanathan
Department of Chemistry, University of California,
Irvine, California 92697-2025
entry
catalyst
additive
None
None
None
conversion (%)
1b
2
TEMPO
TMP
54
66
100
6
70
73
5
6
92
8
Received September 18, 1998
3
TMP‚HBr
TEMPO
TEMPO
TEMPO
TEMPO
None
TEMPO
None
None
4b
5b
6b
7b
8
CSA
Nitroxyl radical catalyzed oxidations of alcohols play
an increasingly important role in organic synthesis.1
Desirable characteristics of these oxidations include the
use of 1 mol % or less of the catalyst and only 1 equiv of
the bulk oxidant and good selectivity for primary alcohols.
Many different bulk oxidants have been used in this
reaction including m-CPBA,2,3 sodium hypochlorite,4 N-
chlorosuccinimide,5 sodium bromite,6 [bis(acetoxy)iodo]-
benzene,7 high-valent metal salts,8 and electrooxida-
tion.1,9 The TEMPO-bleach oxidation developed by Anelli
is the most useful for large-scale oxidations,4 although
it does not work well with unsaturated alcohols. Our
interest was drawn to the TEMPO-catalyzed m-CPBA
oxidations2,3 when we observed an unprecedented race-
mization of a chiral nitroxyl radical under similar condi-
tions.10 The results of our investigation are reported
below.
The development of nitroxyl radical catalyzed peracid
oxidations arose from Cella’s report of an unexpected
alcohol oxidation.2c Cella found that the reaction was
catalyzed by HCl and developed a convenient oxidation
procedure using m-CPBA and 2,2,6,6-tetramethylpiperi-
dinium hydrochloride (TMP‚HCl) as the catalyst pre-
cursor.2a The HCl was reported to act as a general acid
catalyst to facilitate the oxidation of the nitroxyl radical
to an N-oxo ammonium salt, the ultimate oxidant in the
catalytic cycle.1 Although the reaction was reported to
be catalyzed by mineral acids, HCl was the only acid
investigated.
Bu4NPF6
Bu4NOTf
Bu4NOTf, CSA
Bu4NCl
Bu4NCl
Bu4NBr
Bu4NBr, CSA
Bu4NBr
Bu4NBr, CSA
9
10
11
12
13
5
100
100
TEMPO
TEMPO
a
b
See the Experimental section for reaction conditions. The
control reaction without TEMPO led to <1% conversion.
catalyst and additive shown for 2 h at 23 °C, and the
conversion to 2-octanone was determined by GC analysis.
TEMPO and m-CPBA together led to 54% conversion
under these conditions (Table 1, entry 1). Tetrameth-
ylpiperidine (TMP), a catalyst precursor, gave a 66%
conversion with m-CPBA (Table 1, entry 2). Surprisingly,
the addition of camphorsulfonic acid (CSA) as an additive
reduced the conversion to only 6% (Table 1, entry 4).11
Addition of 5 mol % trifluoroacetic acid also inhibited the
reaction. The TMP‚HBr salt, on the other hand, led to
100% conversion without any additives (Table 1, entry
3). Clearly the reaction is not catalyzed by acid, but the
counterion is implicated.
The effect of redox-inert counterions is outlined in
entries 5-7 of Table 1. Without TEMPO, none of the
reactions show any significant conversion. TEMPO-
catalyzed oxidation in the presence of PF6- or OTf- leads
to a slightly higher conversion than in the presence of
TEMPO alone (Table 1, entries 5 and 6 vs entry 1). Once
again, added CSA strongly inhibits the oxidation, reduc-
ing the conversion from 73% to only 5% (Table 1, entry
6 vs 7). Inert counterions have little effect on the
oxidation.
Table 1 outlines our initial investigation of the oxida-
tion reaction. A solution of m-CPBA (1.2 equiv) and
2-octanol was allowed to react with 1 mol % of the
(1) (a) de Nooy, A. E. J .; Besemer, A. C.; Bekkum, H. v. Synthesis
1996, 1153-74. (b) Bobbitt, J . M.; Flores, M. C. L. Heterocycles 1988,
27, 509-33.
(2) (a) Cella, J . A.; Kelley, J . A.; Kenehan, E. F. J . Org. Chem. 1975,
40, 1860-2. (b) Cella, J . A.; McGrath, J . P.; Kelley, J . A.; El Soukkary,
O.; Hilpert, L. J . Org. Chem. 1977, 42, 2077-80. (c) Cella, J . A.; Kelley,
J . A.; Kenehan, E. F. J . Chem. Soc., Chem. Commun. 1974, 943.
(3) Ganem, B. J . Org. Chem. 1975, 40, 1998-2000.
(4) (a) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J . Org. Chem.
1987, 52, 2559-62. (b) Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S.
J . Org. Chem. 1989, 54, 2970-2. (c) Anelli, P. L.; Montanari, F.; Quici,
S. Org. React. 1990, 69, 212-9.
Redox-active counterions have a profound effect on the
oxidation reaction. Addition of 1 mol % Bu4NCl increased
the conversion from 54% to 92% (Table 1, entry 9).
Addition of 1 mol % Bu4NBr increased the conversion to
100% (Table 1, entry 12). In this case, addition of CSA
had no effect (Table 1, entry 13). Both Bu4NCl and Bu4-
NBr gave a small amount of oxidation even without the
TEMPO catalyst (Table 1, entries 8 and 10). These slow
background oxidations are akin to the phase-transfer
oxidations of alcohols using hypochlorite solutions.12 Both
bromide and chloride catalyze the TEMPO-mediated
oxidation of alcohols with m-CPBA.
(5) Einhorn, J .; Einhorn, C.; Ratajczak, F.; Pierre, J .-L. J . Org.
Chem. 1996, 61, 7452-4.
(6) Inokuchi, T.; Matsumoto, S.; Nishiyama, T.; Torii, S. J . Org.
Chem. 1990, 55, 462-6.
(7) Mico, A. D.; Margarita, R.; Parlanti, L.; Vescovi, A.; Piancatelli,
G. J . Org. Chem. 1997, 62, 6974-7.
(8) (a) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chou, C. S.
J . Am. Chem. Soc. 1984, 106, 3374-6. (b) Miyazawa, T.; Endo, T. J .
Mol. Catal. 1985, 32, 357-60.
(9) (a) Semmelhack, M. F.; Chou, C. S.; Cortes, D. A.; J . Am. Chem.
Soc. 1983, 105, 4492-4. (b) Inokuchi, T.; Matsumoto, S.; Torii, S. J .
Org. Chem. 1991, 56, 2416-21. (c) Kashiwagi, Y.; Yanagisawa, Y.;
Kurashima, F.; Anzai, J .; Osa, T.; Bobbitt, J . M. Chem. Commun. 1996,
2745-6.
(10) Rychnovsky, S. D.; Beauchamp, T.; Vaidyanathan, R.; Kwan,
T. J . Org. Chem. 1998, 63, 6363-74.
(11) Use of 5 mol % trifluoroacetic acid with m-CPBA and TEMPO
did not lead to oxidation. However, TFA with m-CPBA, TEMPO and
Bu4NBr led to complete oxidation.
(12) Lee, G. A.; Freedman, H. H. Tetrahedron Lett. 1976, 20, 1641-
4.
10.1021/jo9819032 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/17/1998

Notes
J . Org. Chem., Vol. 64, No. 1, 1999 311
Ta ble 2. Oxid a tion of Alcoh ols w ith m -CP BA Ca ta lyzed
efficient counterion than Cella’s TMP‚HCl, and unlike
the hydrochloride, TMP‚HBr is nonhygroscopic.14 Table
2, entry 6, shows that TMP‚HBr and m-CPBA together
constitute an effective oxidant system for the conversion
of alcohols into ketones.
by TEMP O a n d Bu 4NBr a
Con clu sion s
Nitroxyl radicals catalyze peracid oxidations of alco-
hols. Bromide and chloride ions are effective as cocata-
lysts, whereas general acids inhibit the oxidation. Inert
counterions have almost no effect on the oxidation. Two
new catalysts were found to be effective in this transfor-
mation: TEMPO with Bu4NBr or TMP‚HBr. Both of
these catalysts lead to rapid and efficient oxidations of
secondary alcohols to ketones.
Exp er im en ta l Section
Gen er a l Exp er im en ta l. All reagents were purchased from
Aldrich Chemical Co. or Acros and were used as received, unless
otherwise stated. TMP‚HBr was prepared as described by
Collum.14
Oxid a tion of 2-Octa n ol u n d er Va r iou s Con d ition s. A 20-
mL vial was charged with 1.5 mL of a CH2Cl2 solution containing
0.5 mmol of 2-octanol, 0.005 mmol of the appropriate catalyst,
and 0.005 mmol of the appropriate additive. A solution of 0.6
mmol of m-CPBA in 1.0 mL of CH2Cl2 was added dropwise, and
the mixture was stirred at room temperature for 1.5 h. The
reaction was quenched by the addition of 1 N NaOH. The layers
were separated, and the aqueous phase was extracted with CH2-
Cl2. The combined organic layers were washed with brine, dried
over Na2SO4, concentrated, passed through a plug of SiO2, and
analyzed by GC.
a
Consult the Experimental Section for reaction conditions.
Unless otherwise noted, all reactions were performed on a 10-mmol
b
scale with 1 mol % TEMPO and 1 mol % Bu4NBr. Yields are
based on the weight of pure product. c The yield was adjusted to
d
reflect 94% GC purity of the product. Reaction was carried out
on a 5-mmol scale; 2.4-mol equiv of m-CPBA was used. e TMP‚HBr
(1 mol %) was used instead of TEMPO and Bu4NBr.
Gen er a l P r oced u r e for th e Oxid a tion of Secon d a r y
Alcoh ols Usin g TEMP O a n d Bu 4NBr . A 100-mL flask was
charged with a solution of 10 mmol of the alcohol, 0.1 mmol of
TEMPO, and 0.2 mmol of Bu4NBr in 25 mL of CH2Cl2 and cooled
to 0 °C. A solution of m-CPBA (12 mmol) in 20 mL of CH2Cl2
was added dropwise over a period of 15 min. The reaction
mixture turned bright orange upon addition of m-CPBA. The
reaction was stirred at 0 °C for 10 min and at 23 °C for 30 min,
by which time the orange color had faded away. The reaction
was quenched by the addition of 1 N NaOH (20 mL), and the
layers were separated. The aqueous layer was extracted with
CH2Cl2 (3 × 20 mL). The combined organic layers were washed
with brine (2 × 20 mL), dried (Na2SO4), filtered, and concen-
trated, and the residue was chromatographed.
Oxid a tion of cis-Cycloh exa n e-1,2-d im eth a n ol. A 100-mL
flask was charged with a solution of 5 mmol of the diol, 0.1 mmol
of TEMPO, and 0.2 mmol of Bu4NBr in 25 mL of CH2Cl2 and
cooled to 0 °C. A solution of m-CPBA (12 mmol) in 20 mL of
CH2Cl2 was added dropwise over a period of 15 min. The reaction
mixture turned bright orange upon addition of m-CPBA. The
reaction was stirred at 0 °C for 10 min and at 23 °C for 30 min,
by which time the orange color had faded away. The reaction
was quenched by the addition of 0.25 M Na2SO3 (10 mL) and
saturated NaHCO3 (10 mL), and the layers were separated. The
aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were washed with saturated NaHCO3
(2 × 20 mL), brine (2 × 20 mL), dried (Na2SO4), filtered, and
concentrated, and the residue was chromatographed.
Oxid a tion of Secon d a r y Alcoh ols Usin g TMP ‚HBr . A
100-mL flask was charged with a solution of 10 mmol of the
alcohol and 0.1 mmol of TMP‚HBr in 25 mL of CH2Cl2 and cooled
to 0 °C. A solution of m-CPBA (12 mmol) in 20 mL of CH2Cl2
was added dropwise over a period of 15 min. The reaction
mixture turned bright orange upon addition of m-CPBA. The
reaction was stirred at 0 °C for 10 min and at 23 °C for 30 min,
by which time the orange color had faded away. The reaction
was quenched by the addition of 0.25 M Na2SO3 (10 mL) and
saturated NaHCO3 (10 mL), and the layers were separated. The
aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The
Discu ssion
General acids inhibit rather than catalyze the oxida-
tion of secondary alcohols with m-CPBA and TEMPO.11
Both bromide and chloride anions catalyze the oxidation,
and bromide is more effective than chloride. These
conclusions are related to Anelli’s observation that the
TEMPO-bleach oxidations are catalyzed by bromide ion.
Anelli explained that the bromide is oxidized to hypo-
bromous acid by the hypochlorite solution and that the
hypobromous acid rapidly oxidizes the nitroxyl radical
to the ultimate oxidant, an N-oxo ammonium ion. Pre-
sumably the Bu4NBr or TMP‚HBr in the present reac-
tions leads to the formation of hypobromous acid, which
oxidizes the nitroxyl radical to N-oxo ammonium ion. In
Cella’s catalyst system, TMP‚HCl is the source of both
TEMPO and the HCl cocatalyst. The role of the HCl is
not as an acid catalyst, but rather it is a source of
hypochlorous acid, which oxidizes TEMPO to the N-oxo
ammonium ion. For efficient oxidations, both a nitroxyl
radical and a halide ion should be present.
Two new procedures for the oxidation of alcohols to
ketones have been developed. Both are modifications of
Cella’s procedure. A catalyst composed of 1 mol %
TEMPO and 1 mol % Bu4NBr led to rapid oxidation of
alcohols to ketones. Table 2, entries 1-5, show that this
catalyst system gave a nearly quantitative yield in the
oxidation reaction.13 An alternative is to use 1 mol % of
TMP‚HBr as a catalyst. The bromide ion is a more
(13) The oxidation was not effective with unsaturated alcohols.
(14) Hall, P. L.; Gilchrist, J . H.; Collum, D. B. J . Am. Chem. Soc.
1991, 113, 9571-4.

312 J . Org. Chem., Vol. 64, No. 1, 1999
Notes
combined organic layers were washed with saturated NaHCO3
(2 × 20 mL), brine (2 × 20 mL), dried (Na2SO4), filtered, and
concentrated, and the residue was chromatographed.
Ack n ow led gm en t. Support has been provided by
the University of California, Irvine. S.D.R. acknowl-
edges Pfizer and Zeneca for support of his research
program.
Oxid a tion P r od u cts. Simple ketones and lactones obtained
by oxidation were characterized by the usual techniques (1H
NMR, 13C NMR, GC) and compared with literature data.
J O9819032