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

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.

Key words

diastereoselective reduction - chiral acetal - 1,3-dioxane - 1,3-polyol - polyketide

• References and Notes


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• 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: R_f = 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.