Synlett 2015; 26(13): 1872-1874
DOI: 10.1055/s-0034-1378725
letter
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Reduction of β-(1,3-Dioxan-4-yl)ketones

Akira Matsumoto
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan   Email: asano.keisuke.5w@kyoto-u.ac.jp   Email: matsubara.seijiro.2e@kyoto-u.ac.jp
,
Keisuke Asano*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan   Email: asano.keisuke.5w@kyoto-u.ac.jp   Email: matsubara.seijiro.2e@kyoto-u.ac.jp
,
Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan   Email: asano.keisuke.5w@kyoto-u.ac.jp   Email: matsubara.seijiro.2e@kyoto-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 04 March 2015

Accepted after revision: 07 May 2015

Publication Date:
07 July 2015 (online)


Abstract

Stereoselective reduction of β-(1,3-dioxan-4-yl)ketones is an important step in the efficient synthesis of chiral 1,3-polyols, a typical structure of polyketides. In this study, we carried out investigations to optimize the conditions for diastereoselective reduction.

Supporting Information

 
  • References and Notes


    • For reviews on the utility of chiral acetals in asymmetric synthesis, see:
    • 1a Alexakis A, Mangeney P. Tetrahedron: Asymmetry 1990; 1: 477
    • 1b Carreira EM, Kvaerno L In Classics in Stereoselective Synthesis . Wiley-VCH; Weinheim: 2009. Chap. 6
    • 2a Asano K, Matsubara S. Org. Lett. 2012; 14: 1620
    • 2b Fukata Y, Miyaji R, Okamura T, Asano K, Matsubara S. Synthesis 2013; 45: 1627
  • 3 Mori Y, Kuhara M, Takeuchi A, Suzuki M. Tetrahedron Lett. 1988; 29: 5419
  • 4 Rohr J. Angew. Chem. Int. Ed. 2000; 39: 2847

    • For selected examples, see:
    • 5a Hunter TJ, O’Doherty GA. Org. Lett. 2001; 3: 2777
    • 5b Smith CM, O’Doherty GA. Org. Lett. 2003; 5: 1959
    • 5c Li M, O’Doherty GA. Org. Lett. 2006; 8: 6087
    • 5d Guo H, Mortensen MS, O’Doherty GA. Org. Lett. 2008; 10: 3149
    • 5e Wang Y, Xing Y, Zhang Q, O’Doherty GA. Chem. Commun. 2011; 47: 8493
    • 5f Wang Y, O’Doherty GA. J. Am. Chem. Soc. 2013; 135: 9334
    • 5g Evans PA, Grisin A, Lawler MJ. J. Am. Chem. Soc. 2012; 134: 2856
  • 6 Procedure for the Reduction of 2-[(2R*,4R*)-2-Pentyl-1,3-dioxan-4-yl]-1-phenylethanone (6a) To a 20 mL flask were added sequentially 2-[(2R*,4R*)-2-pentyl-1,3-dioxan-4-yl]-1-phenylethanone (6a, 0.10 mmol), Et2O (1.8 mL), and EuCl3 (0.30 mmol). After the mixture was stirred under Ar atmosphere at –78 °C for 0.5 h, a solution of LiBH4 in Et2O (0.2 mmol, 1.0 M, 0.2 mL) was added. The resulting mixture was additionally stirred at –78 °C for 1 h. The reaction was quenched by 1 M aq NaOH, and the mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification by flash column chromatography [silica gel, hexane–EtOAc (v/v = 5:1)] gave (R*)-2-[(2R*,4R*)-2-pentyl-1,3-dioxan-4-yl]-1-phenylethanol (5a). Analytical Data for (R*)-2-[(2R*,4R*)-2-Pentyl-1,3-dioxan-4-yl]-1-phenylethanol (5a) Colorless oil; yield 99%, dr = 13:1; TLC: Rf = 0.37 (hexane–EtOAc, 3:1). IR (neat): 3462, 2953, 2925, 2858, 1465, 1378, 1364, 1139, 1087, 1028, 760, 700, 665 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.47–7.33 (m, 4 H), 7.27 (m, 1 H), 4.97 (dd, J = 9.5, 3.5 Hz, 1 H), 4.58 (t, J = 5.5 Hz, 1 H), 4.09 (ddd, J = 11.5, 5.0, 1.0 Hz, 1 H), 3.92 (tt, J = 11.0, 2.5 Hz, 1 H), 3.75 (ddt, J = 12.0, 2.5, 1.0 Hz, 1 H), 2.04 (m, 1 H), 1.80–1.72 (m, 2 H), 1.67–1.62 (m, 2 H), 1.44–1.38 (m, 3 H), 1.35–1.27 (m, 4 H), 0.89 (t, J = 7.0 Hz, 3 H). 13C NMR (125.7 MHz, CDCl3): δ = 144.4, 128.6, 127.7, 126.0, 102.3, 74.1, 66.7, 45.4, 35.2, 31.9, 31.7, 24.0, 22.8, 14.3. HRMS: m/z [M + H]+ calcd for C17H27O3: 279.1955; found: 279.1945.