Synlett, Table of Contents Synlett 2014; 25(12): 1764-1768DOI: 10.1055/s-0033-1340195 letter © Georg Thieme Verlag Stuttgart · New York One-Pot Sequential 1,4- and 1,2-Reductions of α,β-Unsaturated δ-Lactones to the Corresponding δ-Lactols with CuCl and NaBH4 in Methanol Yasunobu Matsumoto* a Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan b Discovery Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan Fax: +81(0)298472037 Email: y7-matsumoto@hhc.eisai.co.jp , Masahiro Yonaga a Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan b Discovery Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan Fax: +81(0)298472037 Email: y7-matsumoto@hhc.eisai.co.jp › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract An efficient, one-pot method for the highly chemoselective synthesis of δ-lactols from α,β-unsaturated δ-lactones using CuCl and NaBH4 in methanol was developed. Key words Key wordscopper - hydrides - lactones - lactols - reduction Full Text References References and Notes For example, see: 1a Bhattacharjee A, Soltani O, De Brabander JK. Org. Lett. 2002; 4: 481 1b Statsuk AV, Liu D, Kozmin SK. J. Am. Chem. Soc. 2004; 126: 9546 1c Taillier C, Gille B, Bellosta V, Cossy J. J. Org. Chem. 2005; 70: 2097 1d Su Q, Dakin LA, Panek JS. J. Org. Chem. 2005; 72: 2 1e Ferrié L, Reymond S, Capdevielle P, Cossy J. Org. Lett. 2007; 9: 2461 1f Harutyuntan S, Zhao Z, den Hartog T, Bouwmeester K, Minnaard AJ, Feringa BL, Govers F. Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 8507 1g Ilardi EA, Isaacman MJ, Qin Y, Shelly SA, Zakarian A. Tetrahedron 2009; 65: 3261 1h Trost BM, Amanos D, Seganish WM, Chung CK. J. Am. Chem. Soc. 2009; 131: 17087 1i Hendrix AJ. M, Jennings MP. Tetrahedron Lett. 2010; 51: 4260 1j Liu G, Romo D. Angew. Chem. Int. Ed. 2011; 50: 7537 1k Sabitha G, Reddy SS. S, Raju A, Yadav JS. 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Soc. 1999; 121: 9473 6b Hughes G, Kimura M, Buchwald ST. J. Am. Chem. Soc. 2003; 125: 11253 6c Lipshutz BH, Servesko JM, Taft BR. J. Am. Chem. Soc. 2004; 126: 8352 6d Deutsch C, Krause N, Lipshutz BH. Chem. Rev. 2008; 108: 2916 7 It is noteworthy to mention that the reduction of an saturated lactone to a lactol with CuCl and NaBH4 in MeOH has not been reported previously. 8 Wiberg KB, Waldron RF. J. Am. Chem. Soc. 1991; 113: 7705 9 General Procedure NaBH4 (10 mmol, 10 equiv) was added in three roughly equal portions to a stirred solution of an α,β-unsaturated δ-lactone (1.0 mmol) in MeOH (10 mL; lactone concentration, 0.1 M) at –50 °C in a reaction flask connected to a drying tube containing CaCO3. After the solution was stirred for 15 min at –50 °C, the drying tube was removed, and CuCl (0.5 mmol, 0.5 equiv) was added to the reaction mixture, which immediately turned into a black suspension and evolved H2 gas (the flask was kept open to let out the gas). The reaction temperature was warmed to –20 °C over the course of 1 h, and the reaction was quenched at that temperature with sat. aq NH4Cl. Then EtOAc and H2O were added to the mixture, which was vigorously stirred for 30 min at r.t. The resulting clear solution was extracted with EtOAc, and the combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude mixture of products was purified by silica gel flash column chromatography with gradient of EtOAc and n-heptane as eluents to afford the desired δ-lactol. 6-Benzyltetrahydro-2H-pyran-2-ol (5b) White solid (90%, cis/trans = 1.4:1). 1H NMR (600 MHz, CDCl3): δ = 7.30–7.27 (m, 4 H, cis trans), 7.22–7.20 (m, 6 H, cis trans), 5.28 (br s, 1 H, trans), 4.66 (m, 1 H, cis), 4.19 (m, 1 H, trans), 3.64 (m, 1 H, cis), 3.06 (d, J = 4.0 Hz, 1 H, cis-OH), 2.95 (dd, J = 14.0, 7.0 Hz, 1 H, cis), 2.81 (dd, J = 14.0, 7.0 Hz, 1 H, trans), 2.73 (dd, J = 14.0, 7.0 Hz, 1 H, cis), 2.67 (dd, J = 14.0, 7.0 Hz, 1 H, trans), 2.55 (br s, 1 H, trans-OH), 1.87–1.80 (m, 3 H, cis trans), 1.71–1.42 (m, 6 H, cis trans), 1.35–1.28 (m, 2 H, cis trans), 1.25–1.18 (m, 1 H, cis). 13C NMR (150 MHz, CDCl3): δ = 138.7 (trans), 138.5 (cis), 129.4 (cis), 129.4 (trans), 128.2 (cis), 128.2 (trans), 126.2 (cis), 126.1 (trans), 96.5 (cis), 92.0 (trans), 77.3 (cis), 69.7 (trans), 42.8 (trans), 42.6 (cis), 32.5 (cis), 30.9 (trans), 30.0 (cis), 29.6 (trans), 21.9 (cis), 17.3 (trans). IR (ATR): ν = 3318, 2942, 2861, 1353, 1142, 1047, 1010, 903, 746, 700 cm–1. HRMS (ESI+): m/z calcd for: C12H20NO2 [M + NH4]+: 210.1489; found: 210.148. Supplementary Material Supplementary Material Supporting Information
