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(Rhodium: "(pseudo)Ephedrine to Meth w/ Raney-Nickel", Stimulants)Deiodination of Iodolactones by Transfer Hydrogenolysis Using Raney Nickel and 2-PropanolRobert C. Mebane, Kimberly D. Grimes, Summer R. Jenkins, Jonathan D. Deardorff, and Benjamin H. GrossSynthetic Communications, 32(13), 2049–2054 (2002)AbstractRaney nickel in refluxing 2-propanol is an effective catalytic system for reducing iodolactones into their corresponding lactones.Iodolactonization of suitable unsaturated carboxylic acids followed by reductive deiodination constitutes an important synthesis of lactones.[1] This synthetic methodology has been widely utilized in natural product synthesis[2] and in the synthesis of complex organic molecules.[3] A number of different reagents have been used in iodolactonizations and have been thoroughly summarized by Simonot and Rousseau.[4] Two of the more common methods[5] for deiodination are metal catalyzed hydrogenolysis with
molecular hydrogen[6] and radical cleavage with tri-n-butyl tin hydride.[7] Although tri-n-butyl tin hydride is an effective reducing agent, there are toxicological and ecological concerns regarding its use as clearly described by Chatgilialoglu.[8] In addition, products are often contaminated with trace organotin compounds which are difficult to remove.[9] A disadvantage to the metal catalyzed hydrogenolysis procedure is the special handling precautions which must be exercised when using molecular hydrogen. In this report we describe an attractive alternative to deiodination of iodolactones which is based on catalytic transfer hydrogenolysis using Raney nickel and 2-propanol as the hydrogen donor. Raney nickel is widely recognized as a versatile catalyst for e.ecting reductive transformations of organic compounds.[10] Less well known and utilized is Raney nickel’s ability to catalyze reductions using hydrogen donors, such as 2-propanol, instead of molecular hydrogen.[11] Although the literature is somewhat sparse, Raney nickel catalyzed transfer hydrogenations utilizing 2-propanol have been reported for the reduction of ole.ns,[12] ketones,[12–14] phenols,[12] aromatic nitro compounds,[15,16] and certain aromatic hydrocarbons.[12,17] The experimental procedure for the catalytic transfer hydrogenolysis of iodolactones is simple and straightforward and a.ords lactones in good yields. The overall reaction is described in Figure 1 and a summary of our results is presented in Table 1. Iodolactones previously described in the literature were used in this study.[18] The yields reported in Table 1 are isolated yields and represent the average of at least two reactions. Yields as determined by glc were essentially quantitative. The low isolated yield observed for lactone 10 may result from our inability to remove the lactone from the catalyst surface due to a strong adsorptive interaction between the phenyl group in 10 and the nickel surface.[19] Isolation of lactone 7 was hindered by its volatility.
The optimal substrate to catalyst ratio found for the hydrogenolysis of iodolactones was 1:10 by weight. This high catalyst loading is necessary because of the poisoning effect of the HI that is generated in the reaction. The need for higher catalyst ratios when cleaving C–X bonds with Raney nickel and molecular hydrogen is well documented.[20,21] The catalyst load could be reduced with the addition of at least one equivalent of base such as KOH, NaHCO3, Et3N, or pyridine or with the use of ammonium formate[22] as the hydrogen donor. Good yields of lactones were obtained with the inclusion of base; however, in all cases minor amounts (5–20%) of ring-opening products were also obtained. Although a high catalyst load was necessary in our deiodination reactions, we did find that the Raney nickel catalyst could be reused repeatedly (at least 6x) after a simple regeneration step consisting of re.uxing the catalyst in 2-propanol containing KOH (0.12 g/1 g catalyst used) for 15 min followed by rinsing the catalyst with cold 2-propanol (3x). In conclusion, catalytic transfer hydrogenolysis with Raney nickel and 2-propanol is an effective method for the conversion of iodolactones into lactones. Furthermore, this environmentally-friendly and inexpensive method is an attractive alternative to catalytic hydrogenolysis with molecular hydrogen and the widely used procedure which employs tri-n-butyl tin hydride.
ExperimentalRaney 2800 nickel was obtained from W.R. Grace Company, Chattanooga Davison. The catalyst was washed prior to use with distilled water (6) and 2-propanol (3) and stored in 2-propanol. 1H NMR spectra were recorded on a Varian Gemini 300 using tetramethylsilane as internal reference. IR spectra were recorded on a Nicolet Impact 410 spectrometer. The IR and NMR spectra of the lactones prepared in this work were identical to the spectra described in the literature.[23–27]
As an illustrative example of the hydrogenolysis procedure, iodolactone 3 (0.50 g, 2.1 mmol) was re.uxed in a magnetically stirred suspension of Raney nickel (5 g) in 2-propanol (30 mL) for 15 min with the condenser open to the atmosphere. After cooling to room temperature the organic layer was decanted from the Raney nickel[28] and the catalyst was washed with 2-propanol (3x10mL). The combined organic layers were .ltered through Celite and the solvent was removed by rotary evaporation and high vacuum to give dihydro-5-ethyl-2(3H)-furanone (9) as an oil in 90% yield.
References[1] (a) Dowle,M.D.; Davies, D.I. Chem. Soc. Rev. 1979, 8, 171;
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(b) Larock, R.C. Comprehensive Organic Transformations: A Guide to Functional Group Preparations; Wiley-VCH: New York, 1999, Chapter 8 and references therein;
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(c) Harding, K.E.; Tiner, T.H. In Comprehensive Organic Synthesis; Trost, B.M., Ed.; Pergamon Press: New York, 1991; Vol. 4, p. 363.
[2] For examples:
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(a) MacMillan, J.; Taylor, D.A. J. Chem. Soc., Perkin Trans. 1 1985, 837;
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(b) Zanoni, G.; Vidari, G. J. Org. Chem. 1995, 60, 5319;
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(c) Yamada, S.; Nakayama, K.; Takayama, H. J. Org. Chem. 1982, 47, 4770.
[3] For examples:
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(a) Paquette, L.A.; Wyvratt, M.J.; Schallner, O.; Schneider, D.F.; Begley, W.J.; Blankenship, R.M. J. Am. Chem. Soc. 1976, 98, 6744–6745;
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(b) Chuang, C.-P.; Hart, D.J. J. Org. Chem. 1983, 48, 1782;
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(c) Whitlock, H.W. J. Am. Chem. Soc. 1962, 84, 3412–3413.
[4] (a) Simonot, B.; Rousseau, G. J. Org. Chem. 1993, 58, 4; See also:
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(b) Royer, A.C.; Mebane, R.C.; Swa.ord, A.M. Synlett 1993, 899.
[5] Zinc–Copper couple and ammonium chloride in methanol solution has been used to reduce an iodolactone, see ref. 3(a).
[6] (a) Klein, J. J. Am. Chem. Soc. 1959, 81, 3611;
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(b) House, H.O.; Carlson, R.G.; Babad, H. J. Org. Chem. 1963, 28, 3359.
[7] (a) House, H.O.; Boots, S.G.; Jones, V.K. J. Org. Chem. 1965, 30, 2519;
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(b) Kuivila, H.G. Acc. Chem. Res. 1968, 1, 299.
[8] Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188.
[9] Curran, D.P.; Chang, C.-T. J. Org. Chem. 1989, 54, 3140.
[10] Augustine, R.L. Heterogeneous Catalysis for the Synthetic Chemist; Marcel Dekker: New York, 1996.
[11] (a) Brieger, G.; Nestrick, T. J. Chem. Rev. 1974, 74, 567;
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(b) Johnstone, R.A.W.; Wilby, A.H.; Entwistle, I.D. Chem. Rev. 1985, 85, 129.
[12] Andrews, M.J.; Pillai, C.N. Indian J. Chem. 1978, 16B, 465.
[13] Stevovic, L.S.; Soskic, V.; Juranic, I.O. J. Serb. Chem. Soc. 1995, 60, 1071.
[14] Gonikberg, E.M.; le Noble, W.J. J. Org. Chem. 1995, 60, 7751.
[15] Banerjee, A.A.; Mukesh, D. J. Chem. Soc., Chem. Commun. 1988, 1275.
[16] Kuo, E.; Srivastava, S.; Cheung, C.K.; le Noble, W.J. Synth. Commun. 1985, 15, 599.
[17] Srivastava, S.; Minore, J.; Cheung, C.K.; le Noble, W.J. J. Org. Chem. 1985, 50, 394.
[18] Iodolactones were prepared by the method described in ref. 4b.
[19] Reference 10, page 11.
[20] Pattison, J.N.; Degering, E.F. J. Am. Chem. Soc. 1951, 73, 611.
[21] Denton, D.A.;McQuillin, F.J.; Simpson, P.L. J. Chem. Soc. 1964, 5535.
[22] Banik, B.K.; Barakat, K.J.; Wagle, D.R.; Manhas, M.S.; Bose, A.K. J. Org. Chem. 1999, 64, 5740.
[23] The lactones prepared in this work were found to be >95% pure by
1H- and
13C-NMR. No over-reduction products were detected.
[24] Hullot, P.; Cuvigny, T.; Larcheveque, M.; Normant, H. Can. J. Chem. 1977, 55, 266.
[25] Hanazawa, T.; Okamoto, S.; Sato, F. Org. Lett. 2000, 2, 2369.
[26] Burnell, D.J.; Wu, Y.-J. Can. J. Chem. 1990, 68, 804.
[27] Nicolaou, K.C.; Seitz, S.P.; Sipio, W.J.; Blount, J.F. J. Am. Chem. Soc. 1979, 101, 3884.
[28] Raney nickel is paramagnetic and sticks to the magnetic stir bar which facilitates decantation.