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243
Chromium Catalyzed Oxidation of (Homo-)Allylic and (Homo-)Propargylic Alcohols with Sodium Periodate to Ketones or Carboxylic Acids CLizette hromiumCat lyzedOxidationof(Homo-)Alylicand(Homo-)PropargylicSchmieder-van Alcohols de Vondervoort,a Sabine Bouttemy,a José M. Padrón,a Jean Le Bras,b Jacques Muzart,b a Paul L. Alsters* a
DSM Fine Chemicals-Advanced Synthesis and Catalysis, P.O. Box 18, 6160 MD Geleen, The Netherlands Fax +31(46)4767604; E-mail:
[email protected] b Unité Mixte de Recherche Réactions Sélectives et Applications, CNRS, Université de Reims Champagne-Ardenne, B.P. 1039, 51687 Reims Cedex 2, France Fax +33(3)26913166; E-mail:
[email protected] Received 14 November 2001
Abstract: Primary and secondary (homo-)allylic and (homo-)propargylic alcohols can be oxidized under slightly acidic conditions at or below room- temperature with sodium periodate in the presence of sodium dichromate as the catalyst to the corresponding carboxylic acids and ketones, respectively.
idize in high yield with other methods6 because of their tendency to undergo rearrangement to the corresponding allenic isomer (Equation) under basic7 or strongly acidic reaction conditions:8,9
Key words: alcohols, catalysis, oxidations, sodium periodate, sodium dichromate
O
O H
H
The fine chemical industry is confronted with market inquiries of increasing molecular complexity, notably in the area of advanced pharmaceutical intermediates. To respond positively to such inquiries, it needs broadly applicable synthetic methods that are effective under mild conditions and that fulfill economic and environmental constraints. With respect to alcohol oxidation, very few currently available methods meet with the above demands. Many methods have a low synthetic scope and/or require harsh conditions. Classical activated DMSO1 and chromate oxidations2 stand out for their broad applicability and effectiveness at low temperature, but they are not feasible for large scale use because of their incompatibility with economic and environmental constraints. Many TEMPO catalyzed3 and Oppenauer-type4 alcohol oxidations are of particular interest for industrial fine chemical use, provided that the requested transformation fits within their synthetic window of applicability. New alcohol oxidation methods with broad synthetic scope and large functional group tolerance are, however, still required in industrial fine chemical manufacture. We report here a simple and efficient method for the oxidation of secondary alcohols to ketones and of primary alcohols to carboxylic acids under mild reaction conditions. The method uses Na2Cr2O7/HNO3 or Na2Cr2O7/H2SO4 as the catalyst system and sodium periodate as the stoichiometric terminal oxidant,5 which can be regenerated by using in-house iodate to periodate recycling technology. The synthetic utility of this method is particularly demonstrated by the successful oxidation of some alkynols, notably homo-propargylic alcohols, which are very difficult to oxSynlett 2002, No. 2, 01 02 2002. Article Identifier: 1437-2096,E;2002,0,02,0243,0246,ftx,en;G33001ST.pdf. © Georg Thieme Verlag Stuttgart · New York ISSN 0936-5214
H
•
H
Equation
The method is also effective for the oxidation of alkenols, and homo-allylic alcohols can be oxidized without isomerization to the corresponding conjugated carbonyl compound.10 Table 1 summarizes the results for the oxidation of some selected alkenols and alkynols by this method, together with some experimental details concerning reaction conditions and work-up. The propargylic alcohol 1-octyn-3-ol, which cannot be oxidized to the ketone by activated DMSO methods11 or by pyridinium chloro-chromate,12,13 afforded a high yield of 1-octyn-3-one by oxidation with 1.1 molar equivalents NaIO4 in the presence of Na2Cr2O7.2H2O (1 mol%) and HNO3 (20 mol%) in mixed water–MeCN (1:2 v/v) medium at 0 °C and gradual warming up to 15 °C overnight (Table 1; entry 1). A good yield was also obtained with 3hexyn-2-ol, a propargylic alcohol with an internal alkyne group (entry 2). Primary homo-propargylic alcohols, either with an internal or with a terminal alkyne-group, are oxidized to the corresponding propargylic acids by 2.2 molar equivalents NaIO4. Thus, 3-butynoic acid was obtained from 3-butyn1-ol by oxidation in water at room temperature (entry 3), whereas 3-heptyn-1-ol was transformed into the acid by oxidation in aqueous MeCN at sub-ambient temperature (entry 4). 4-Heptyn-2-ol (internal alkyne group) and 5-hexyn-3-ol (terminal alkyne group) are representative examples of homo-propargylic alcohols, which fail to afford propargylic ketones by activated DMSO methods11a and afford
244 Table 1 Entry
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L. Schmieder-van de Vondervoort et al. Sodium Dichromate Catalyzed Oxidation of Alkenols and Alkynols with Sodium Periodate Alcohol
mol Alcohol equiv NaIO4 mol-% Na2Cr2O7 mol-% acid
Medium (mL)
0.05 1.1 1 20c
MeCN/H2O (100/50)
0.1 1.1 1 10c
MeCN/H2O (90/90)
H2 O (180)
3
0.1 2.2 1 5c
MeCN/H2O (70/35)
4
0.05 2.2 1 20c
MeCN/H2O (90/90)
5
0.1 1.1 1 5c
CHCl3/H2O (90/90)
6
0.1 1.1 1 5c
CHCl3/H2O (25/12)
7
0.014 1.1 1 15f
MeCN/H2O (100/50)
8
0.05 2.2 1 10f 0.001 1.1 2 20c
MeCN/H2O (2/1)
1
1 2
4
5
6
7
8
9
0–16 °C; 20 h
Yield (%)b
CH2Cl2 extr; distill
86
Et2O extr; distill
85
1’
0 °C; 20 h 2’
22 °C; 24 h
0–16 °C; 20 h
0 °C; 24 h
0 °C; 24 h
22 °C; 6.5 h
0–16 °C; 20 h
Et2O extr; precipitated by ad- 70 dition of pentane to tBuOMe solution 3’
4’
Drying and evaporation steps not indicated. Isolated yield. c HNO3 (added as 65 % solution). d Determined yield present in 85 % pure product (remainder alcohol). e 96 % pure product obtained by recrystallization at –78°C. f H2SO4 (added as 96 % solution).
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© Thieme Stuttgart · New York
82d (36)e
CH2Cl2 extr
95
CH2Cl2 extr
85
7’
8’
Et2O extr; treatment of Et2O 79 extr with aq NaOH; aq solution of Na salt acidified and product extr with Et2O Et2O extr; chromatography on silica gel (petrol ether– EtOAc, 90:10)
9’’ b
Et2O extr (recryst at –78 °C from t-BuOMe–pentane, 1:3)
6’
9’
a
Et2O extr; treatment of Et2O 72 extr with aq NaOH; aq solution of Na salt acidified and product extr with Et2O
5’
0 °C; 6 h
9
Synlett 2002, No. 2, 243–246
Work-upa
Temp; Time
2 3
Product
9’: 68 9’’: 4
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Chromium Catalyzed Oxidation of (Homo-)Allylic and (Homo-)Propargylic Alcohols
only modest yields with stoichiometric chromate methods.7a,8 Formation of the allenic isomerization product during the oxidation of 4-heptyn-2-ol could be almost completely suppressed by performing the oxidation in MeCN–water at 0 °C with only 5 mol% acid (entry 5). Conversion, however, was not complete and the product obtained after work-up consisted of a mixture of product and starting material in a ratio of ~85:15. Conversion did not increase significantly with 1.3 instead of 1.1 equiv NaIO4 or with 2 mol% instead of 1 mol% Na2Cr2O7. Ketone and alcohol could not be separated by distillation, which also led to partial isomerization of 4-heptyn-2-one to allenic products because of its thermal lability. A small amount of reasonably pure (96%) 4-heptyn-2-one could be obtained by recrystallization from t-BuOMe–pentane at –78°C and washing of the product at this low temperature with pentane. For the oxidation of 5-hexyn-3-ol to 5hexyn-3-one, which is extremely prone to isomerization,7a the use of a two-phase CHCl3–water medium instead of MeCN–water was found to prevent isomerization completely. After 24 h at 0 °C in the presence of 5 mol% acid, a near quantitative yield of pure 3-hexyn-5-one was obtained by simple evaporation of the organic solvent (entry 6).14 This example demonstrates clearly the superior results obtained with the present method for acid sensitive carbonyl products compared to the reported stoichiometric chromate oxidation, which affords only a modest yield of 80% pure product in the oxidation of 5-hexyn-3-ol.7a Simple treatment of a CDCl3 solution of 5-hexyn-3-one with dilute aqueous NaOH results in quantitative isomerization to the corresponding allene, i.e., 4,5-hexadien-3one (6’). Secondary homo-allylic 4-penten-2-ol was oxidized very cleanly to the allyl ketone in CHCl3–water without any detectable amount of the conjugated carbonyl isomer (entry 7). From primary homo-allylic trans-3-hexen-1-ol, the corresponding acid was readily obtained in MeCN–water medium (entry 8). We have recently reported that the oxidation of 1-cyclohexyl-2-buten-1-ol (9) provides information about the propensity of the active alcohol oxidizing chromium species to induce allylic rearrangement, which results in formation of product 9” besides the expected product 9' (entry 9).15 Whereas chromium catalyzed oxidation of this alcohol with tert-butyl hydroperoxide results in considerable rearrangement (9'/9” = 68:32), only very small amounts of 9” were formed during the chromium catalyzed oxidation with NaIO4 (9'/9” = 95:5). The oxidation of 4-heptyn-2-ol has been carried out with four different systems in order to gain insight about the origin of the high selectivity of the present system compared to conventional stoichiometric chromate oxidations: a) catalytic Na2Cr2O7; stoichiometric NaIO4; catalytic H2SO4 b) catalytic Na2Cr2O7; stoichiometric NaIO4; excess H2SO4
245
c) stoichiometric Na2Cr2O7; catalytic H2SO4 d) stoichiometric Na2Cr2O7; excess H2SO4 These oxidations were carried out under non-optimal conditions in MeCN–water at room temperature in order to assure appreciable isomerization of the product, thus allowing differences in selectivity between the systems to be expressed clearly. Experimental details and results concerning conversion and selectivity are collected in Table 2. Table 2 Oxidation of 4-Heptyn-2-ol at Two Acid Concentrations either by Stoichiometric Cr(VI) or by NaIO4 under Cr Catalysisa Oxidation with 1.1 equiv NaIO4 catalyzed by 1 mol% Na2Cr2O7 System
H2SO4 (mol%)
Time (h)
Conversion Selectivity (%) (%)
a
10
21
70
64
b
135
4
73
18
Oxidation with 0.8 equiv Cr(VI) in the form of Na2Cr2O7 System
H2SO4 (mol%)
Time (h)
Conversion Selectivity (%) (%)
c
10
4
0
–
d
135
4
50
48
a
A solution of 4-heptyn-2-ol (1 mmol) in CD3CN (2 mL) was added to a mixture of NaIO4 (1.1 or 0 equiv), Na2Cr2O7.2H2O (0.01 or 0.4 equiv), H2SO4 (indicated amount) and 1,2,3-trichlorobenzene (1 mmol, internal standard) in D2O (1 mL) at 20 °C. After the indicated time, the reaction mixture was separated from insoluble (per-)iodates by filtration and analyzed by 1H-NMR spectroscopy.
Remarkably, no reaction was observed for system c (oxidation by stoichiometric chromium at low acidity).16 In contrast, the highest conversion and selectivity are observed for system a, in which the same low amount of acid is used, but with a catalytic amount of chromium in the presence of NaIO4 as the oxidant. Note that the results for system a in Table 2 are inferior to the conversion and selectivity for the oxidation of 4-heptyn-2-ol in Table 1, for which the data have been obtained at 0 °C and with a lower amount of acid to increase selectivity. The lower conversion of system a, despite the fact that temperature and acidity are higher, is ascribed to the formation of a poorly soluble green Cr(III) species that cannot be reoxidized to Cr(VI) with NaIO4.17 This catalyst deactivation path is suppressed at 0 °C, where the reaction mixture retains the yellow/orange color of Cr(VI) throughout the reaction. The contrasting results between system a and c suggest that in the presence of periodate a more powerful oxidizing species is formed, which is able to oxidize alcohols even at low acidity. When a highly acidic medium is used, as for systems b and d, appreciable conversions are obtained, but with poor selectivities as a result of the sensitivity of the propargyl ketone product towards acid. Similar to system a vs. system c, also with system b higher conversions are obtained than with system d, thus demon-
Synlett 2002, No. 2, 243–246
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L. Schmieder-van de Vondervoort et al.
strating again the more powerful oxidizing nature of the active chromium species in the presence of periodate. We propose that the periodate anion reacts under the slightly acidic conditions with mono-protonated dichromate to form a neutral periodato Cr(VI) complex,18 which subsequently forms a Cr(VI) alkoxy species by reaction with the alcohol. The resulting periodato Cr(VI) alkoxy species is capable of eliminating the carbonyl product with concomitant formation of CrO3 and reduction of I(VII) to I(V) in the form of iodate, i.e., chromium retains its six valent state throughout the reaction (Scheme). O O O Cr Cr O O O O
H
O O O Cr Cr HO O O O IO4 CrO42
O O R2CHOH O O O O Cr Cr I I O O HO O O O O O H2O R R H
O
R
IO3 + H + CrO3
IO4
R
Scheme
In conclusion, the strength of the chromium catalyzed alcohol oxidation by NaIO4 is that it displays the broad scope of alcohol oxidations by Cr(VI), but without a highly acidic reaction medium (stoichiometric oxidations with chromic acid or chromium catalyzed oxidations with periodic acid) and without stoichiometric amounts of neutralizing organic nitrogen bases, as present in e.g. Collins reagent (CrO3×2C5H5N). Products are easily separated by simple extraction from the aqueous phase containing the sparingly soluble NaIO3 co-product. The method is particularly suitable for the oxidation of alcohols to carbonyl products that are sensitive to elevated temperatures and alkaline or strongly acidic conditions.
References (1) Tidwell, T. T. In Organic Reactions, Vol. 39; Wiley: New York, 1990, 297. (2) (a) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic Chemistry; Verlag: Berlin, 1984. (b) Luzzio, F. A. In Organic Reactions, Vol. 53; Wiley: New York, 1998, 1. (3) (a) Dijksman, A.; Marino-González, A.; Mairata, I.; Payeras, A.; Arends, I. W. C. E.; Sheldon, R. A. J. Am. Chem. Soc. 2001, 123, 6826; and references therein. (b) Ben-Daniel, R.; Alsters, P. L.; Neumann, R. J. Org. Chem. 2001, 66, 8650. (c) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis 1999, 1153. (d) Bobbitt, J. M.; Flores, M. C. L. Heterocycles 1988, 27, 509. (4) (a) Nait Ajjou, A. Tetrahedron Lett. 2001, 42, 13; and references therein. (b) Graauw, C. F.; Peters, J. A.; van Bekkum, H.; Huskens, J. Synthesis 1994, 1007. (5) For a review of other Cr-catalyzed oxidations of alcohols, see: Muzart, J. Chem. Rev. 1992, 92, 113. Synlett 2002, No. 2, 243–246
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(6) (a) Soler, M. A.; Martín, V. S. Tetrahedron Lett. 1999, 40, 2815. (b) Li, L. T.; Ma, S. M. Youji Huaxue 2000, 20, 850; Chem. Abstr. 2001, 134, 192946. (7) (a) Brandsma, L.; Verkruijsse, H. D. Studies in Organic Chemistry 8, Synthesis of Acetylenes, Allenes and Cumulenes; Elsevier: Amsterdam, 1981, 236. (b) Huché, M. Tetrahedron 1980, 36, 331. (c) Crombie, L.; Jacklin, A. G. J. Chem. Soc. 1955, 1740. (8) Preparation of allenic carbonyl compounds by oxidation of homo-propargylic alcohols with chromic acid: (a) Le Gras, J. C. R. Acad. Sc. Paris (C) 1966, 263, 1460. (b) Bertrand, M. C. R. Acad. Sc. Paris (C) 1957, 244, 1790. (c) Jones, E. R. H.; Mansfield, G. H.; Whiting, M. C. J. Chem. Soc. 1954, 3208. (9) A related Cr catalyzed method based on periodic acid has recently been reported: Zhao, M.; Li, J.; Song, Z.; Desmond, R.; Tschaen, D. M.; Grabowski, E. J. J.; Reider, P. J. Tetrahedron Lett. 1998, 39, 5323; this method obviously works under much more acidic conditions than the present sodium periodate method, which uses a catalytic amount of acid. (10) An overview of homo-allylic alcohols that have been successfully oxidized without isomerization by stoichiometric Cr(VI) reagents containing organic nitrogen bases can be found in ref.2b (11) (a) Ref.1, p 315, 349. (b) Mancuso, A. J.; Swern, D. Synthesis 1981, 165. (12) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978, 43, 2480. (13) The CrO3 complex with 3,5-dimethylpyrazole is capable of oxidizing 1-octyn-3-ol: Corey, E. J.; Fleet, G. W. J. Tetrahedron Lett. 1973, 14, 4499. (14) Typical Procedure; preparation of 5-hexyn-3-one: A 250 mL jacketed reactor, equipped with a mechanical stirrer, was charged with water (90 mL), 65% aq HNO3 (0.49 g; 5 mmol HNO3), and Na2Cr2O7.2H2O (0.300 g; 1 mmol). The solution was cooled to 0 °C, and NaIO4 (23.53 g; 110 mmol) was added at maximum speed of mechanical stirring. Subsequently, a cooled solution (0 °C) of 5-hexyn-3-ol (9.86 g; 100 mmol) in CHCl3 (90 mL) was added in one portion. The mixture was vigorously stirred for 24 h at 0 °C. The organic phase was separated from the aqueous slurry, which was subsequently extracted with CH2Cl2 (2 ´ 100 mL). After drying (Na2SO4) of the combined organic phases and evaporation of the solvents at 20 °C/150 mbar, a yellow oil was obtained, which according to NMR consisted of pure 5hexyn-3-one (9.1 g; 95% yield). The product is unstable and should be stored in the freezer. 1H NMR (CDCl3): 3.15 (d), 2.51 (q), 2.15 (t), 0.93 (t). 13C NMR (CDCl3): 204.7, 77.0, 73.1, 34.9, 33.6, 7.8. Other reactions were carried out similarly; see Table 1 for experimental details. (15) Riahi, A.; Hénin, F.; Muzart, J. Tetrahedron Lett. 1999, 40, 2303. (16) The kinetics for the oxidation of alcohols with chromic acid follows a rate law that depends on the concentration of the acid chromate ion HCrO4– rather than on total Cr(VI). At low acidity, alcohol oxidation by chromic acid proceeds very slowly because the concentration of HCrO4– is negligible: Wiberg, K. B. In Oxidation in Organic Chemistry Part A; Academic Press: New York, 1965, 161. (17) During Cr(VI) catalyzed alcohol oxidation with periodic acid, a similar formation of a green Cr(III) species was observed, see ref. 9 (18) For evidence of complexation of periodate to chromate, see: Okumura, A.; Kitani, M.; Murata, M. Bull. Chem. Soc. Jpn. 1994, 67, 1522.
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