Oxoammonium Salts. 9. Oxidative Dimerization of Polyfunctional Primary Alcohols to Esters. An Interesting β Oxygen Effect†
SCHEME 1. Dimeric Oxidation of Primary Alcohols
Nabyl Merbouh, James M. Bobbitt,* and Christian Bru¨ckner Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060
[email protected] Received April 1, 2004
Abstract: The use of the oxidant 4-acetylamino-2,2,6,6tetramethylpiperidine-1-oxoammonium tetrafluoroborate in combination with pyridine for the oxidative, dimeric esterification of primary alcohols is described. The ester is the predominant product of the reaction with alcohols containing a β oxygen. In the absence of a β oxygen, the corresponding aldehyde is found in appreciable amounts, but a concentration effect can be observed. In the absence of pyridine, little ester is formed, and no appreciable reaction takes place with β-oxygenated compounds. δ Lactones have been prepared from diethylene glycol and 2,2′-thiodiethanol, without sulfur oxidation.
In an earlier publication,1 we described the facile oxidation of alcohols to aldehydes or ketones with an oxoammonium salt. One of the problems encountered in that work was that alcohols containing a β oxygen reacted so slowly that the reaction became useless. A further complication arose because the conditions were slightly acidic, and blocking groups sensitive to acid were cleaved. The earlier work was also carried out with an oxoammonium perchlorate salt, which detonated on heating.2 We have therefore shifted our attention to the oxoammonium tetrafluoroborate salt, which seems to have identical oxidizing properties. In a more recent publication, we described the first experiments with an oxoammonium tetrafluoroborate salt in the presence of pyridine, an essentially basic medium.3 In this paper, we would like to present the best conditions for the preparation of 4-acetylamino-2,2,6,6tetramethylpiperidine-1-oxoammonium tetrafluoroborate (the oxoammonium salt of choice; see Supporting Information); to describe a new (for oxoammonium salts) reaction in which highly functionalized primary alcohols containing a β oxygen are oxidatively dimerized to esters in high, clean yields; and to make some observations on the mechanisms of the various reactions. In addition, the preparation of some sulfur and oxygen containing δ lactones will be described. Oxidative Dimerizations. The oxidation of primary alcohols to aldehydes has almost always been accompanied by the formation of small amounts of a dimeric ester, but the reaction is seldom the main one. Sodium bromate and sodium bisulfite4 have been used to prepare a series of esters in good yield, but the reactions did not involve * To whom correspondence should be addressed. Tel: 860-486-6601. Fax: 860-486-2981. † For part 8 of this series, see ref 3. (1) Bobbitt, J. M. J. Org. Chem. 1998, 63, 9367-9374. (2) Bobbitt, J. M. Chem. Eng. News 1999, 77, 6. (3) Merbouh, N.; Bobbitt, J. M.; Bru¨ckner, C. Tetrahedron Lett. 2001, 42, 8793-8796.
very highly functionalized molecules. A palladium-catalyzed oxidation using an aryl halide as oxidant has been developed.5 Several other isolated cases of good yields of esters have been recorded.6-15 There are also examples of oxidative esterification being used to prepare mixed esters.11 We noted, as have others,1,16 that alcohols containing a β oxygen are oxidized very slowly by oxoammonium salts in slightly acidic media. However, we have now observed that primary alcohols with a β oxygen have a very strong tendency to form dimeric esters when the oxidations are carried out in the presence of pyridine, and especially when carried out in concentrated solutions, Scheme 1. A number of these oxidations are shown in Table 1. In general, the yields are good, and the isolation of pure esters is trivial. Only three alcohols with a β oxygen gave poor results: glycidol (20),18 methyl 2,3-isopropylideneβ-D-ribofuranoside (30),17 and tetrahydrofurfuryl alcohol (24).17 Glycidol tends to polymerize (although its dimeric ester appears to be stable); methyl 2,3-isopropylidene-βD-ribofuranoside gives appreciable amounts of aldehyde;17 and tetrahydrofurfuryl alcohol gives low yields. It is possible that these results are caused by more highly strained situations in the hydrogen-bonded hemiacetal intermediates (like 41, in Scheme 2) due to the threeand five-membered oxygen rings involved. It is of interest that diacetone galactose gives a good yield of dimeric ester. In a previous publication, we mistakenly reported that this reaction gave different products.3 Compounds 20, 22, 24, and 26 are chiral, and the resulting dimeric esters 21,18 23,19 25,17 and 27 consist (4) Takase, K.; Masuda, H.; Kai, O.; Nishiyama, Y.; Sakagushi, S.; Ishii, Y. Chem. Lett. 1995, 871-872. (5) Tamaru, Y.; Yamada, Y.; Inoue, K.; Yamamoto, Y.; Yoshida, Z. J. Org. Chem. 1983, 48, 1286-1292. (6) Al Neirabayeh, M.; Pujol, M. D. Tetrahedron Lett. 1990, 31, 2273-2276. (7) Gopinath, R.; Patel, B. K. Org. Lett. 2000, 2, 577-579. (8) Liu, H.-J.; Chan, W. H.; Lee, S. P. Tetrahedron Lett. 1978, 46, 4461-4464. (9) Ogawa, T.; Matsui, M. J. Am. Chem. Soc. 1976, 98, 1629-1630. (10) Sakuragi, H.; Tokumaru, K. Chem. Lett. 1974, 475-476. (11) Tohma, H.; Maegawa, T.; Kita, Y. Synlett 2003, 5, 723-725. (12) Wang, L.; Eguchi, K.; Arai, H.; Seiyama, T. Chem. Lett. 1986, 1173-1176. (13) Wang, L.; Eguchi, K.; Arai, H.; Seiyama, T. Appl. Catal. 1987, 33, 107-117. (14) Wang, L.; Tsuda, M.; Eguchi, K.; Arai, H.; Seiyama, T. Chem. Lett. 1987, 1889-1892. (15) Robertson, G. R. Organic Syntheses; Wiley: New York, 1941; Collect. Vol. I, pp 138-140. (16) Miyazawa, T.; Endo, T. J. Org. Chem. 1985, 50, 3930-3931. (17) Papaioannou, D.; Francis, G. W.; Aksnes, D. W.; Brekke, T.; Maartmann-Moe, K. Acta Chem. Scand. 1990, 44, 90-95. (18) Razuvaev, G. A.; E Ä tlis, V. S.; Beshenova, E. P. J. Org. Chem. USSR (Engl. Transl.) 1966, 2, 2003-2006. 10.1021/jo049461j CCC: $27.50 © 2004 American Chemical Society
5116
J. Org. Chem. 2004, 69, 5116-5119
Published on Web 06/26/2004
TABLE 1. Synthesis of Dimeric Esters
c
a References refer to previous preparations of these esters. b Spectral data for these compounds are given in the Supporting Information. The reaction was performed on 60% pure commercial acetoxyethanol; analysis was by GC.
J. Org. Chem, Vol. 69, No. 15, 2004 5117
SCHEME 2.
Stepwise Reaction Sequence
of mixtures of two (racemic) diastereomers. Double lines show up in some of the 13C NMR spectra shown in the Supporting Information. No attempt was made to separate the mixtures. The two sugar derivatives, 28 and 30 are, of course, optically pure, as are their dimers 299 and 31.17 Esters 17 and 27 have been prepared for the first time. The other esters have been described, and references are given in Table 1. In cases where complete spectral data are not known and for previously unknown compounds such as 9,20 15,21 17, 21,18 27, and 29,9 the spectra are given in the Supporting Information. The stoichiometry of the oxidative dimerization is summarized in eq 5 in Scheme 2. The reaction requires 4 (19) Ermolenko, L.; Sasaki, N. A.; Potier, P. Synlett 2001, 10, 15651566. (20) U. S. Patent 1,479,345, 1938. (21) U. S. Patent 2,444,924, 1945.
5118 J. Org. Chem., Vol. 69, No. 15, 2004
equiv of oxidant 1 and 4 equiv of pyridine (3) to 2 equiv of alcohol 2, leading to 1 equiv of dimeric ester 4, 4 equiv of a nitroxide 6, and 4 equiv of pyridinium tetrafluoroborate (5). The reaction conditions are crucial for good yields of pure products. First, it is necessary to use about 25% excess of the oxidant, that is, 2.5 equiv for 1 equiv of substrate. Second, if water is present, one obtains small amounts of the acid derived by further oxidation of the aldehyde. To avoid this, we used activated molecular sieve17 in the reaction mixtures. When we used an excess of pyridine, it showed up in the products. We found that if we used only 2.3 equiv of pyridine, and at the end of the reaction, some methanol to use up any excess oxidant, we could convert essentially all of the pyridine to its tetrafluoroborate salt and remove it by filtration. The oxidations are carried out in high concentrations (about 1 M) in CH2Cl2. The oxidant, the substrate, and the molecular sieves were stirred together for 30 min, and the pyridine, dissolved is the same amount of CH2Cl2, was added slowly over about 5 min. After 3 h, a small amount of methanol was added. After a further 30 min, the reaction mixture was treated as described below. The reaction products are pyridinium tetrafluoroborate, nitroxide, and the desired ester, along with traces of methanol, formaldehyde, and oxidant. The pyridinium tetrafluoroborate, excess oxidant, and molecular sieves are removed by filtration. The nitroxide 6, fortuitously, is only slightly soluble in diethyl ether. Thus, if the filtered reaction mixture is evaporated to dryness and the semisolid mass is thoroughly extracted with ether, most of the nitroxide is left behind and can be recycled. The ether filtrate contains a small amount of the orange nitroxide which can be removed by passing it through a short silica gel column. The product is obtained in pure form by evaporation of the column eluate. In all of the examples except the ribose derivative, no starting alcohol, aldehyde, or acid was observed (GC) in the products, and no further purification was required. Only with methyl 2,3-isopropylidene-β-D-ribofuranoside, 30, was any appreciable amount of aldehyde formed, although aldehyde may have been formed in some of the other cases and lost during the isolation procedures. The ester 30 was isolated by chromatography in 25% yield, although by GC it appeared to be present in about 50% yield. As stated above, oxidations without pyridine are carried out in a slightly acidic medium. This caused problems with blocking groups such as acetals and silyl ethers.1 Furthermore, benzyl groups are slowly cleaved by oxoammonium salts.36 In the pyridine reactions cataloged in Table 1, it is clear that acetal groups, benzyloxy groups, ester groups, epoxides, and double bonds are stable. This may be because of the base present or it may be due to the fast reactions in the pyridine series. In our initial paper3 on pyridine reactions, we have shown similar effects. The interrelations between the various reaction conditions are summarized in Figure 1. In the absence of pyridine, compounds having a β oxygen (such as 8) are not easily oxidized at all,1 but these data are not plotted in the figure. In the absence of pyridine, compounds having no β oxygen (such as 7) give aldehyde and very little ester
FIGURE 1. GC-determined product distribution in the oxidations of butoxyethanol (8) and 1-octanol (7): (O) 7 with no pyridine; (4) 7 with pyridine; (0) 8 with pyridine.
(O in Figure 1).1 In the presence of pyridine and no β oxygen, 7 gives amounts of ester depending on concentration (4 in Figure 1). In the presence of pyridine, compounds having a β oxygen (such as 8) give almost entirely ester, with no effect of concentration (0 in Figure 1). Overall, pyridine seems to favor ester formation, but does so much more strongly in high concentrations or in the presence of a β oxygen. Lactone Formation. Lactone formation has been observed previously from oxoammonium salt oxidations of appropriate diols.16 Furthermore, γ and δ lactones were formed from appropriate diols and nitroxide-catalyzed hypochlorite reactions.22 Tetraethylene glycol was converted to a 12-membered lactone ring with oxoammonium salts supported on a polymer surface.23 Under conditions described above, but using 4.4 equiv of oxidant, diethylene glycol (32) and 2,2′-thiodiethanol (34) were converted to their lactones, 33 and 35, in 94% yield. It is of note that the sulfur derivative was not oxidized at the sulfur atom.24 Mechanistic Considerations. Although the overall conversion of oxidant to nitroxide is a one-electron reaction (1 to 6), there is no evidence of a radical mechanism. Thus, the reaction is visualized in Scheme 2 as a series of known two-electron reactions, with eq 5 as the net reaction. (22) Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. J. Org. Chem. 1989, 54, 2970-2972. (23) Weik, S.; Nicholson, G.; Jung, G.; Rademann, J. Angew. Chem. Int. Ed. 2001, 40, 1436-1439. (24) Fetizon, M.; Golfier, M.; Louis, J.-M. Tetrahedron 1975, 31, 171-176. (25) Golubev, V. A.; Rozantsev, E Ä . G.; Neiman, M. B. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1965, 1898 (Engl. Transl.). (26) Bobbitt, J. M.; Flores, M. C. L. Heterocycles 1988, 27, 509533. (27) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis 1996, 1153-1175. (28) Merbouh, N.; Bobbitt, J. M.; Bru¨ckner, C. Org. Prep. Proced. Int. 2004, 36, 1-31. (29) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 6750-6755. (30) Koskimies, J. K. Acta Chem. Scand. 1984, B 38, 101-108. (31) Koskimies, J. K. J. Chem. Soc., Perkin Trans. 2 1985, 14491455. (32) Koskimies, J. K. Magn. Reson. Chem. 1986, 24, 131-135. (33) Hashimoto, K.; Sumitomo, H.; Kitao, O. J. Polym. Sci., Polym. Chem. Ed. 1975, 13, 1257-1263. (34) Shimizu, K.; Imamura, J. Bull. Chem. Soc. Jpn. 1981, 54, 3200-3204. (35) Shuikin, A. N.; Kliger, G. A.; Glebov, L. S.; Marchevskaya, E. V.; Zaikin, V. G. Petroleum Chem. 1996, 36, 440-444. (36) Miyazawa, T.; Endo, T. Tetrahedron Lett. 1986, 37, 3395-3398.
Equations 1 and 3 are the usual oxidation reactions1 (although pyridine is present). The equilibrium in eq 2 is crucial. If it is shifted toward the hydrogen-bonded hemiacetal intermediate 41, the product will be ester. If not, the product will be the simple aldehyde. Equation 4 is the base-promoted reverse of the acid-catalyzed disproportionation of nitroxides, as originally carried out by Golubev25 and summarized by many others.26-28 There are three mechanistic points to consider: why a β oxygen slows oxidation in the slightly acidic conditions;1 why pyridine allows such an oxidation to take place; and why a β oxygen seems to promote dimeric esterification. We think that the hydrogen-bonded structure (2, as redrawn in Scheme 2) may prevent oxidation in the mildly acidic conditions in CH2Cl2. The pyridine could disrupt the hydrogen-bonded ring and also provide a stronger external base for proton removal. It is much harder to explain why the β oxygen promotes dimeric esterification. We have some preliminary results showing that various pyridine derivatives change the results appreciably. These reactions are under further study. Experimental Section General Oxidative Esterification Procedure. To the alcohol (5 mmol, 1 equiv) in CH2Cl2 (5 mL) were added 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (2.5 equiv) and powdered, activated (red heat under vacuum) molecular sieves (4 Å, 0.1 g/mL of solvent), and the solution was stirred at rt. After 30 min, pyridine (2.3 equiv) in CH2Cl2 (5 mL) was added dropwise over a period of 5 min. The solution was stirred at rt for an additional 3 h. The color of the reaction mixture turned in course of the reaction from bright yellow to orange. After 3 h, 5 drops of MeOH were added, and the mixture was stirred a further 30 min. The precipitated, colorless pyridinium tetrafloroborate salt was removed by filtration and washed with CH2Cl2. The filtrate was reduced to dryness in vacuo, the residue was triturated with dry Et2O (25 mL), and the resulting suspension was filtered. The filtered solid was further triturated with four 10-mL portions of Et2O. The resulting ethereal solution was concentrated in vacuo to approximately 5 mL and was chromatographed over silica gel (5 × 1 cm) using Et2O as an eluent. The elution was stopped when the red coloration reached the bottom of the silica plug. The solvent was removed in vacuo to afford the ester in good yield. Oxidation of Methyl 2,3-O-Isopropylidene-β-D-ribofuranoside (30). The oxidation was carried out as described above. However, since the final product contained appreciable amounts of aldehyde, the ester was purified by chromatography on silica gel using Et2O/hexane (1:1) as eluent. The ester was isolated in 25% yield as a colorless oil, having the same analytical and spectral properties as described by Papaioannou et al.17 Oxidation of Diethylene Glycol (32) and 2,2′-Thiodiethanol (34). The oxidations were carried out as described above using 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (4.4 equiv) and pyridine (4.4 equiv). The resulting lactones29-32 were isolated according to the general oxidation method described above.
Acknowledgment. We acknowledge financial support (for J.M.B.) from Grant No. CJS-0335345 from the National Science Foundation. Supporting Information Available: Experimental methods, the preparation of 1, and the 1H and 13C NMR spectra of compounds 9, 13, 15, 17, 21, 27, and 29. This material is available free of charge via the Internet at http://pubs.acs.org. JO049461J
J. Org. Chem, Vol. 69, No. 15, 2004 5119
