Short Communication Samarium (II) Iodide Mediated Synthesis of 3,5-dimethyl-hexahydrocyclopenta[b]furnan-2-one Makama B.Y. Dept. of Chemistry, Faculty of Science and Science Education, Kano University of Science and Technology, Wudil, Kano, NIGERIA Available online at: www.isca.in Received 30th May 2012, revised 31st May 2012, accepted 13th June 2012 Abstract Selective reduction of the aldehyde of (157) with sodium borohydride gave the alcohol (243) with an excellent yield of 80%. The alcohol was then converted to alkyl Iodide which was readily reduced with SmI2 in NiI2 to give carbocyclic compound (220) with overall yield of 74%. The structures of these products were determined using 1H NMR, 13C NMR, Mass spect. and IR analysis Key Words: Selective reduction, aldehyde, SmI2, NiI2, carbocyclic. Introduction In our previous report1, we showed an efficient regioselective synthesis of ?-butenoildes mediated by silvertrifluroacetate with ß-halo acetals. Herein it is our desire to demonstrate the versatility of samarium diiodide (SmI2) medited cyclization of ?-butenoildes. Samarium diiodide (SmI2) is a strong single electron transfer reagent for promoting reduction and has been used in many important synthetic reactions reported successful reduction of organic halides by SmI2 in THF2. Later it was shown that these reactions are faster when hexamethylphosphoramide is incorporated to the reaction mixture3. Over the years there was increasing efforts directed at finding other promoters of SmI2 reduction. Some of the alternatives includes N,N-dimethylpropyleneurea, transition metal salts such as NiI2. In our attempt to synthesize 3,5-dimethyl-hexahydrocyclopenta[b]furnan-2-one. It was decided to consider the chemistry reported by Molander in which alkyl halides act as a precursor in an intramolecular conjugate addition to a,ß-unsaturated lactones4. Material and Methods Commercial reagents were obtained from Aldrich and Lancaster chemical suppliers and were used directly as supplied or purified prior to use. Dichloromethane was refluxed over and distilled from CaH2 prior to use. Diethyl ether and ethanol were obtained dry from Aldrich. THF was dried by distillation from the sodium benzophenone ketyl radical under nitrogen. Light petroleum is the fraction of petroleum ether boiling in the range 30-40 oC, and it was fractionally distilled through a 36 cm Vigreux column before use. Non-aqueous reagents were transferred under argon via syringe. Organic solutions were concentrated under reduced pressure on a Büchi rotary evaporator using a water bath. Thin-layer chromatography (TLC) was performed on Merck aluminium-backed plates coated with 0.2 mm silica gel 60-F plates. Visualization of the developed chromatogram was performed by UV fluorescence quenching at 254nm, or by staining with a KMnO4 solution. 1H and 13C NMR spectra were recorded on a Bruker DPX250 (250 MHz for protons) and a Brüker AMX400 (400 MHz for protons). Data for 1H NMR are reported as follows: chemical shift (d-ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), integration, coupling constant in (Hz). Data for 13C NMR spectra are reported in terms of chemical shift (ppm) down field from TMS. IR spectra were recorded on a Perkin Elmer Paragon 1000 or a Perkin Elmer 881 spectrometer as a thin film between sodium chloride plates or as a KBr disk. All absorptions are reported in terms of frequency of absorption (cm-1). Mass spectrometric data were recorded on VG Autospec, under conditions of chemical ionisation (C.I) using ammonia as the ionising source. Peaks are quoted in the form (m/z) (relative intensity). Results and Discussion Initially, selective reduction of the aldehyde of (157) with sodium borohydride furnished the alcohol (243)5. sodium borohydride was added to a solution of aldehyde (157) in ethanol at room temperature and the reaction mixture was stirred for further 30 minutes. Colourless oil was obtained after column chromatography and this was shown to be the desired alcohol, isolated in 80% yield. The 1H NMR showed the disappearance of the aldehyde peak and the presence of a multiplet at d 3.59-3.41 ppm indicated a methylene group adjacent to a hydroxyl. A broad absorption in the IR centred at 3648 cm-1 also indicated the presence of the alcohol. Mass spectrometric analysis confirmed the mass ion to be m/z 170 scheme 1.10. (a) NaBH4, ethanol, 80% Scheme 1.10 The conversion of the alcohol to alkyl halides has also been reported using hydrogen chloride in toluene6 and phosphorus trichloride or phosphorus pentachloride in petroleum ether. These methods give mixtures of alkyl halides, which became difficult to separate; tedious fractionation was required to isolate the alky halides7. It was envisaged that this procedure could mediate the conversion of the alcohol (243) to the corresponding alkyl iodide (218) in moderate yield without any problem. Initially 5-(3-hydroxy-2-methyl-2-methylpropyl)-3-methylfuran-2(5H)-one (243) was added to a stirred solution of triphenylphosphine, iodine and imidazole in anhydrous DCM. Once the reaction was complete the mixture was concentrated in vacuo and was rapidly purified by flash column chromatography on silica gel to afford (218) in 42% yield. 1H NMR analysis indicated the material to be the desired iodide with the position of the methylene adjacent to the alcohol moving from d 3.59-3.41 ppm to d 3.28-3.15 ppm confirming a methylene adjacent to iodine scheme 2.10. (a) imidazole, PPh3, I2, DCM, 25oC, 42% Scheme 2.10 Following the radical cyclization procedure reported by Molander et al8 , NiI2 was added to a solution of SmI2 in THF and the mixture was cooled to -78 oC. After addition of (218) (0.08 mmol) in THF the resulting mixture was stirred for 1 hour, when TLC analysis indicated two spots with one corresponding to the staring material. However, after work up the 1H NMR spectrum showed the starting material had been recovered. At this point this radical approach was abandoned, the reason being that the final reaction would lead to a product that could not be readily functionalized further scheme 3.10. (a) NiI2, SmI2, THF Scheme 3.10 Experimental Procedures: 5-(3-hydroxy-2-methylpropyl)-3-methylfuran-2(5H)one (243): To a stirred solution of 2-methyl-3-(4-methyl-5-oxo-2, 5-dihydrofuran-2-yl) propanal (157) (50.0 mg, 0.30 mmol 1.00 equiv) in ethanol (4 mL) in an Erlenmeyer flask was added NaBH4 at room temperature (14.5 mg, 0.38 mmol, 1.30 equiv) in small portions over 15 minutes. The reaction mixture was stirred for further 30 minutes and then poured into ice water (3 mL). Six drops of dilute hydrochloric acid (5%) were added; the organic layer was extracted with ether (2 x 6 mL), dried over MgSO4 and concentrated in vacuo. Column chromatography on silica eluting with ether : hexane (5:1) afforded the desired compound as a colourless oil (41 mg, 80%); ?max (thin film/cm-1), 3750, 3649, 3566, 2985, 1734, 1653; dH (250 MHz, CDCl3) 6.98 (1H, bd, J 1.6 Hz, CH=C), (1H, bd, J 1.6 Hz, CH=C), 5.00-4.91 (1H, m, CHO), 5.00-4.91 (1H, m, CHO), 3.59-3.41 (2H, m CH2OH), (2H, m CH2OH), 1.88-1.85 (2H, m, CHCH3), 1.88-1.85 (2H, m, CHCH3), 1.86 (3H, bs, CH3C=), 1.86 (3H, bs, CH3C=C), 1.59-1.49 (2H, m, CH2), 1.59-1.49 (2H, m, CH2), 0.95 (3H dd, J 2.0 CH3CH), 0.95 (3H dd, J 2.0 Hz, CH3CH); dC (62.5 MHz, CDCl3) 176.3, 149.7, 149.5, 130.2, 129.5, 80.2, 79.9, 68.3, 67.7, 38.0, 37.7, 33.5, 33.3, 17.6, 16.9; m/z (C.I) 171 (MH+, 63%), 153 (100%), 97 (79%), C9H 15O3, requires 171.1022, found ,171.1021 5-(3-iodo-2-methylpropyl)-3-methylfuran-2(5H)one (218): To a stirred solution of triphenylphosphine (61.0 mg, 0.23, mmol, 1.30 equiv) in anhydrous DCM (2 mL) under argon was added imidazole (12.3 mg, 0.18 mmol, 1.00 equiv). Once the imidazole had dissolved, iodine (45.6 mg, 0.18 mmol, 1.00 equiv) was added and a white suspension formed. A solution of 5-(3-hydroxy-2-methylpropyl)-3-methylfuran-2(5H) one (243) (30.0 mg, 0.18 mmol, 1.00 equiv) in anhydrous DCM was added via syringe and stirring was continued for 45 minutes at room temperature. The reaction mixture was concentrated in vacuo and the crude product was rapidly purified by flash column chromatography on silica eluting with hexane : ethyl acetate (2:1) to afford the title compound as a colourless oil (21 mg, 42%); ?max (thin film/cm-1), 3448, 2978, 2929, 2874, 1750; dH (250 MHz, CDCl3) 6.97 (2H, bd, J 1.5 Hz, CH=C), (1H, bd, J 1.5 Hz, CH=C), 4.85-4.84 (1H, m, CHO), 3.28-3.15 4.85-4.84 (1H, m, CHO), 3.28-3.15 (1H, m CH2I), 1.86-1.85 (1H, m, CHCH3), 1.86-1.85 (1H, m, CHCH3) 1.85 (3H, bs, CH3C=), 1.85 (3H, bs, CH3C=C), 1.03 (2H, d, J 6.4 CH2), 1.01 (2H, d, J 4.4 CH2), 0.78 (3H dd, J 2.0, CH3CH), 0.78 (3H dd, J 2.0, CH3CH); m/z (C.I) 281 (MH+, 100%), 153 (63%), 130 (29%), C9H 14IO2, requires 281.1003, found , 281.0029 5-methyl-3-methylene-hexahydropenta[b]furan-2-one (220) To a stirred solution of SmI2 (147 mg, 0.36, mmol, 1.30 equiv) in anhydrous THF (5 mL) under argon was added NiI2 (43.82 mg, 0.14 mmol, 0.50 equiv), the mixture was cooled to -78 oC and 5-(3-iodo-2-methylpropyl)-3-methylfuran-2(5H)one (218) (80.0 mg, 0.28 mmol, 1.00 equiv) was added. The reaction was allowed to stir overnight and was concentrated in vacuo. (5 mL) of water was added and the organic layer was extracted with ether (2x 7 mL), dried over MagSO4 and concentrated in vacuo and the crude product was rapidly purified by flash column chromatography on silica eluting with petroleum ether : ethyl acetate (2:1) to afford the title compound as a colourless oil (32 mg, 74%); ?max (thin film/cm-1), 2922, 2919, 1728, dH (250 MHz, CDCl3) 4.41-4.39 (1H, m, CHO), 2.41 (1H, m, CHCHO), 1.29 (3H, d, J 3.4 CH3CO), 1.09 (3H, d, J 3.4 CH3CH); dC (62.5 MHz, CDCl3) 171.2, 84.3, 46.7, 44.9, 41.3, 41.1, 31.1, 20.4, 13.9; m/z (C.I) 281 (MH+, 100%), 139 (29%), 124 (41%), C9H 14O2, requires 154.0994, found , 152.0993 Conclusion The result demonstrated the versatility of Samarium (II) Iodide as a potential promoter in the synthesis of bicyclic lactones in which alkyl halides act as a precursor in an intramolecular conjugate addition to a,ß-unsaturated lactones. These lactones are recurrent features of many biologically active natural products Acknowledgements I would like to express my most profound gratitude to Professor Laurence of the University of the Reading, United Kingdom. Thanks a lot Boss for everything. Dr Frank Lewis I will never forget with you and I thank you so much for the Irish Hospitality in Reading. References 1. Makama B.Y., Regioselective Synthesis of ?-Butenoildes Mediated by Silvertrifluroacetate with ß-Halo Acetals, Research Journal of Recent Sciences, 1(1), 85-88 (2012) 2. Kagan H.B. and Divalent J., Lanthanide derivatives in organic synthesis. 1. Mild preparation of samarium iodide and ytterbium iodide and their use as reducing or coupling agents, J. Am. Chem. Soc., 102 (8), 2693-2698 (1980) 3. Inanaga J., Ishikawa M. and Yamaguchi M.A., Mild and Convenient Method for the Reduction of Organic Halides by Using a SmI2-THF Solution in the Presence of Hexamethylphosphoric Triamide (HMPA), Chem. Lett., 16(7) 1485-1486 (1987) 4. Molander G.A. and Harris C.R.J., Conjugate Addition Reactions Mediated by Samarium(II) Iodide, J. Org. Chem., 62(21), 7418-7429 (1997) 5. Harwood L.M., Moody C.J. and Percy J.M., In Experimental Organic Chemistry, Blackwell Scientific, Oxford, 2nd edition (1999) 6. Simonsen J.L. and Owen L.N., In The Terpenes, Cambridge University Press, 63, 50 (1953) 7. Barnard D. and Bateman L., Experiments relating to the synthesis of homogeranic acid, J. Chem. Soc. 926- 932 (1950) 8. Molander G.A. and David J., Samarium (II) Iodide-Mediated Intramolecular Conjugate Additions of a, ß-Unsaturated Lactones, J. Org. Chem., 67(11), 3861-3865 (2002) Research Journal of Chemical Sciences _______________________________________________________ ISSN 2231-606X Vol. 1(5), 1-7, Aug. (2011) Res.J.Chem.Sci. International Science Congress Association 8 Research Journal of Recent Sciences _________________________________________________ ISSN 2277-2502 Vol. 1(7), 87-89, July (2012) Res.J.Recent Sci. International Science Congress Association 87 Research Journal of Recent Sciences ______________________________________________________________ ISSN 2277-2502 Vol. 1(7), 87-89, July (2012) Res. J. Recent Sci. International Science Congress Association 88 Research Journal of Chemical Sciences________________________________________________ ISSN 2231-606X Vol. 1(5), 1-7, Aug. (2011) Res.J.Chem.Sci International Science Congress Association 5