English

• 1.   Introduction

  Amino alcohols are very important motifs frequently found in many natural products^[1-6] and synthetic pharmacologically active molecules.^[7-10] They are also widely used for the design of chiral ligands and auxiliaries for asymmetric synthesis (Figure 1).^[11-12] Given their prominent roles within organic and medicinal chemistry, a wide variety of synthetic routes to these scaffolds have been developed.^[13-17] Among them, hydroxyamination of alkenes is efficient and attractive because the starting materials are inexpensive and readily available. Pioneered by Sharpless and co-workers, ^[18-26] aminohydroxylation of alkenes has been recognized as a facile access to amino alcohols by using catalysts such as osmium, palladium, copper, iron, platinum and so on.

  图 1

  

  Figure 1.  Selected examples bearing amino alcohol scaffold

  下载: 全尺寸图片 幻灯片

  Recently, our group focused on 1, 3-dibromo-5, 5-dime- thyl hydantoin (DBH) mediated one-pot metal-free transformation of olefins, including the preparations of α-bromo/ amino ketones, ^[27] α, α-dibromoacetophenones, ^[28] amides, ^[29] and 2-aminothiazoles.^[30] Based on these works, we envisaged that the utility of DBH, a readily available eco-friendly reagent, might be expanded to metal-free synthesis of amino alcohols. Herein, we would like to report a practical one-pot synthesis of amino alcohols from styrenes via treatment with DBH, followed by amination in aqueous medium.

  2.   Results and discussion

  As shown in Table 1, our exploration was carried out by using styrene and 4-methylpiperidine as model substrates in different solvents (Entries 1~5). The best result was obtained by using acetone in water (Entry 3), while other solvents such as acetonitrile, dioxane, tetrahydrofuran (THF) and N, N-dimethylformamide (DMF), gave inferior results. The yields reduced slightly when increasing or decreasing the amount of diethylene glycol (DBH) (Entries 6 and 7). While using more DBH (Entry 8 vs 3), the yield decreased dramatically due to the over-oxidation of styrene. Much more α-bromoketone was detected under this condition, which was produced by excessive DBH. More amines helped to improve the yield, but not significantly (Entry 10 vs 3). On the other hand, 2.0 equiv. of 4-methylpiperidine was insufficient because it could not consume the newly formed bromohydrin intermediates thoroughly (Entry 9). Next, we adjusted the ratio of organic solvent (Entries 11~13) and found that this two-step one-pot transformation worked well in mixture of acetone and water with volume ratio of 2:1 (Entry 12).

  表 1

  

  Table 1.  Optimization of the reaction conditions^a

  下载: 导出CSV

  Entry	DBH/equiv.	4-Methylpiperidine/equiv.	Solvent (V:V)	Isolated yield/%
  1	0.55	3.0	Acetonitrile/H2O(5:1)	75
  2	0.55	3.0	Dioxane/H2O (5:1)	71
  3	0.55	3.0	Acetone/H2O (5:1)	81
  4	0.55	3.0	THF/H2O (5:1)	43
  5	0.55	3.0	DMF/H2O (5:1)	38
  6	0.50	3.0	Acetone/H2O (5:1)	77
  7	0.60	3.0	Acetone/H2O (5:1)	76
  8	0.70	3.0	Acetone/H2O (5:1)	64
  9	0.55	2.0	Acetone/H2O (5:1)	66
  10	0.55	4.0	Acetone/H2O (5:1)	83
  11	0.55	3.0	Acetone/H2O (1:1)	68
  12	0.55	3.0	Acetone/H2O (2:1)	84
  13	0.55	3.0	Acetone/H2O (10:1)	75
  a Olefin (5.0 mmol), DBH (2.75 mmol), water (10 mL) and acetone (20 mL).

  Having established the optimal reaction conditions, the generality of this protocol with a wide range of styrenes was then explored (Table 2). Both substituted styrenes bearing electron-donating (2b~2d) and electron-withdrawing (2e~2j) groups worked well with satisfactory yields (64%~88%). Ortho-, meta-, and para-chlorostyrene gave similar results (2f~2h). Other amine such as diethyl amine also worked well with this protocol (2k~2n). Tulobuterol, a β2-adrenergic agonist widely used in the treatment of bronchial asthma and chronic obstructive pulmonary disease, was prepared by using this method in gram scale in good yield (2o).

  表 2

  

  Table 2.  Transformation of terminal alkenes to amino alcohols^a

  下载: 导出CSV

  a Olefin (5.0 mmol), DBH (2.75 mmol), amine (15 mmol), water (10 mL) and acetone (20 mL).

  As discussed previously, ^{[27, 29, 31]} a possible mechanism of this two-step one-pot reaction is shown in Scheme 1. The role of water was essential, which was used as reaction media and reactant.^[32] Briefly, bromohydrin (3) was generated from styrene with DBH in water, which underwent nucleophilic attack by amine in situ affording desired amino alcohol (2a). Less DBH was inefficient to produce enough bromohydrin intermediate, while excessive DBH oxidized the bromohydrin to undesired α-bromo ketone (4), decreasing the total yield of amino alcohol.

  图式 1

  

  Scheme 1.  Possible mechanism

  下载: 全尺寸图片 幻灯片

  3.   Conclusions

  In conclusion, a convenient procedure for the synthesis of amino alcohols from styrenes mediated by DBH in aqueous medium has been developed. This metal-free one-potprotocol is easy to handle, and facile accessible to various amino alcohols. Bioactivity studies of these newly prepared compounds are currently ongoing in our laboratory and will be reported in due course.

  4.   Experimental section

  4.1   General information

  Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker 500 MHz spectrometer as indicated in the data list. ¹H NMR spectra were reported relative to the signal residual (CDCl₃ at δ 7.26) or TMS. ¹³C NMR spectra were reported relative to the center line of the CDCl₃ triplet at δ 77.16. The MS data were obtained with a Finnigan Mat TSQ-7000 mass spectrometer (ESI-HRMS). Reactions were magnetically stirred and monitored by thin layer chromatography (TLC) with silica gel plates (60F-254) using UV light. Yields refer to pure compounds.

  4.2   General procedure for the synthesis of amino alcohols 2a~2o

  To a mixture of olefin (5.0 mmol) in water (10 mL) and acetone (20 mL), DBH (2.75 mmol) was added. The resultant mixture was stirred at room temperature. After the olefin was consumed completely, amine (15 mmol) was added. After being stirred for another 4 h at room temperature, the reaction mixture was extracted with ethyl acetate (20 mL×3), washed with brine, and dried over Na₂SO₄ subsequently. After being concentrated in vacuo, the crude product was purified by silica column chromatography using CH₂Cl₂/MeOH (V:V＝15:1) as eluant to give the pure product. For compound 2o, the experiment was carried out on 20 mmol scale (2.78 g of 1-chloro-2-vinylbenzene was used).

  2-(4-Methylpiperidin-1-yl)-1-phenylethan-1-ol (2a): White solid, yield 84%. m.p. 83~84 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.35 (dt, J＝15.0, 7.5 Hz, 4H), 7.26 (t, J＝7.1 Hz, 1H), 4.71 (dd, J＝10.5, 3.6 Hz, 1H), 4.21 (s, 1H), 3.12 (d, J＝11.4 Hz, 1H), 2.76 (d, J＝11.6 Hz, 1H), 2.54~2.37 (m, 2H), 2.29 (td, J＝11.5, 2.3 Hz, 1H), 2.00 (td, J＝11.6, 2.3 Hz, 1H), 1.71~1.56 (m, 2H), 1.44~1.17 (m, 3H), 0.94 (d, J＝6.4 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 142.50, 128.29, 127.36, 125.85, 68.77, 66.56, 55.59, 52.14, 34.68, 34.31, 30.73, 21.89; IR (KBr) ν: 3114, 2924, 2853, 2812, 1451, 1073, 911 cm^－1; ESI-HRMS calcd for C₁₄H₂₂- ON [M+H]⁺ 220.16959, found 220.16972.

  2-(4-Methylpiperidin-1-yl)-1-(p-tolyl)ethan-1-ol (2b): White solid, yield 75%. m.p. 86~88 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.25 (d, J＝4.1 Hz, 2H), 7.15 (d, J＝7.9 Hz, 2H), 4.68 (dd, J＝10.3, 3.8 Hz, 1H), 4.18 (s, 1H), 3.11 (d, J＝11.8 Hz, 1H), 2.76 (d, J＝11.8 Hz, 1H), 2.47~2.38 (m, 2H), 2.33 (s, 3H), 2.28 (td, J＝11.5, 2.5 Hz, 1H), 1.99 (td, J＝11.6, 2.5 Hz, 1H), 1.70~1.58 (m, 2H), 1.45~1.35 (m, 1H), 1.33~1.19 (m, 2H), 0.94 (d, J＝6.4 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 139.48, 136.99, 129.01, 125.84, 68.65, 66.63, 55.63, 52.14, 34.72, 34.35, 30.77, 21.91, 21.15; IR (KBr) ν: 3121, 2924, 2808, 1511, 1448, 1097 cm^－1; ESI-HRMS calcd for C₁₅H₂₄ON [M+H]⁺ 234.18524, found 234.18533.

  2-(4-Methylpiperidin-1-yl)-1-(m-tolyl)ethan-1-ol (2c): White solid, yield 64%. m.p. 66~68 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.29~7.12 (m, 4H), 4.74 (dd, J＝8.9, 4.6 Hz, 1H), 3.87 (s, 1H), 3.17 (d, J＝11.5 Hz, 1H), 2.85 (d, J＝11.8 Hz, 1H), 2.54~2.43 (m, 2H), 2.35~2.31 (t, J＝10.4 Hz, 4H), 2.12~2.01 (m, 1H), 1.66 (t, J＝13.2 Hz, 2H), 1.42~1.24 (m, 3H), 0.95 (d, J＝6.2 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 139.24, 137.11, 129.05, 128.23, 126.52, 125.84, 122.98, 68.66 (d, J＝17.8 Hz), 66.44, 55.56, 52.27, 34.36, 34.03, 30.61, 21.81, 21.14; IR (KBr) ν: 3137, 2952, 2924, 2808, 1716, 1448, 825 cm^－1; ESI-HRMS calcd for C₁₅H₂₄ON [M+H]⁺ 234.18524, found 234.18542.

  1-(4-(tert-Butyl)phenyl)-2-(4-methylpiperidin-1-yl)-ethan-1-ol (2d): White solid, yield 82%. m.p. 102~103 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.36 (d, J＝8.3 Hz, 2H), 7.30 (d, J＝8.3 Hz, 2H), 4.69 (dd, J＝9.8, 4.4 Hz, 1H), 4.17 (s, 1H), 3.13 (d, J＝11.5 Hz, 1H), 2.77 (d, J＝11.6 Hz, 1H), 2.51~2.38 (m, 2H), 2.29 (td, J＝11.5, 2.4 Hz, 1H), 1.99 (td, J＝11.6, 2.4 Hz, 1H), 1.74~1.59 (m, 2H), 1.49~1.16 (m, 3H), 1.31 (s, 9H), 0.94 (d, J＝6.4 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 150.34, 139.39, 125.67, 125.26, 68.61, 66.50, 55.66, 52.14, 34.75, 34.54, 34.37, 31.42, 30.80, 21.94; IR (KBr) ν: 3155, 2929, 2953, 2804, 1444, 1097, 829 cm^－1; ESI-HRMS calcd for C₁₈H₃₀ON [M+H]⁺ 276.23219, found 276.23260.

  1-(4-Fluorophenyl)-2-(4-methylpiperidin-1-yl)ethan-1-ol(2e): White solid, yield 88%. m.p. 97~99 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.33 (dd, J＝8.5, 5.5 Hz, 2H), 7.02 (t, J＝8.7 Hz, 2H), 4.68 (dd, J＝10.6, 3.5 Hz, 1H), 4.24 (s, 1H), 3.10 (d, J＝11.6 Hz, 1H), 2.75 (d, J＝11.7 Hz, 1H), 2.45 (dd, J＝12.5, 3.6 Hz, 1H), 2.41~2.33 (m, 1H), 2.29 (td, J＝11.5, 2.4 Hz, 1H), 2.00 (td, J＝11.6, 2.4 Hz, 1H), 1.69~1.60 (m, 2H), 1.47~1.36 (m, 1H), 1.33~1.19 (m, 2H), 0.94 (d, J＝6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 163.13, 161.19, 138.20 (d, J＝3.0 Hz), 127.47 (d, J＝8.0 Hz), 115.20, 115.03, 68.22, 66.57, 55.61, 52.14, 34.68, 34.31, 30.72, 21.88; IR (KBr) ν: 3103, 2927, 2816, 1601, 1506, 1218, 1105, 1083, 835 cm^－1; ESI-HRMS calcd for C₁₄H₂₁ONF [M+H]⁺ 238.16017, found 238.16034.

  1-(2-Chlorophenyl)-2-(4-methylpiperidin-1-yl)ethan-1-ol (2f): White solid, yield 84%. m.p. 111~113 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.66 (d, J＝7.5 Hz, 1H), 7.30~7.25 (m, 2H), 7.24~7.11 (m, 1H), 5.13 (dd, J＝10.3, 3.0 Hz, 1H), 4.27 (s, 1H), 3.16 (d, J＝11.1 Hz, 1H), 2.79~2.64 (m, 2H), 2.31~2.22 (m, 2H), 2.05 (td, J＝11.7, 2.3 Hz, 1H), 1.71~1.55 (m, 2H), 1.43~1.36 (m, 1H), 1.33~1.19 (m, 2H), 0.94 (d, J＝6.4 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 139.99, 131.71, 129.17, 128.27, 127.27, 127.11, 65.94, 64.27, 55.62, 52.15, 34.72, 34.33, 30.75, 21.92; IR (KBr) ν: 3073, 2952, 2972, 2808, 1464, 1435, 1090, 1031, 760 cm^－1; ESI-HRMS calcd for C₁₄H₂₁ONCl [M+H]⁺ 254.13062, found 254.13124.

  1-(3-Chlorophenyl)-2-(4-methylpiperidin-1-yl)ethan-1-ol (2g): White solid, yield 78%. m.p. 70~71 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.39 (s, 1H), 7.28~7.20 (m, 3H), 4.67 (dd, J＝10.7, 3.5 Hz, 1H), 4.26 (s, 1H), 3.12~3.04 (m, 1H), 2.81~2.69 (m, 1H), 2.48 (dd, J＝12.4, 3.6 Hz, 1H), 2.40~2.25 (m, 2H), 2.01 (td, J＝11.6, 2.5 Hz, 1H), 1.73~1.57 (m, 2H), 1.44~1.35 (m, 1H), 1.33~1.19 (m, 2H), 0.94 (d, J＝6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 144.77, 134.25, 129.55, 127.44, 125.99, 123.96, 68.20, 66.30, 55.55, 52.11, 34.64, 34.27, 30.68, 21.86; IR (KBr) ν: 3108, 2928, 2864, 2808, 1574, 1433, 1131, 1112, 972 cm^－1; ESI-HRMS calcd for C₁₄H₂₁ONCl [M+H]⁺ 254.13062, found 254.13113.

  1-(4-Chlorophenyl)-2-(4-methylpiperidin-1-yl)ethan-1-ol (2h): White solid, yield 83%. m.p. 90~91 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.30 (s, 4H), 4.67 (dd, J＝10.7, 3.5 Hz, 1H), 4.25 (s, 1H), 3.09 (d, J＝11.9 Hz, 1H), 2.78~2.69 (m, 1H), 2.46 (dd, J＝12.4, 3.5 Hz, 1H), 2.39~2.24 (m, 2H), 2.00 (td, J＝11.6, 2.5 Hz, 1H), 1.70~1.58 (m, 2H), 1.50~1.35 (m, 1H), 1.43~1.19 (m, 2H), 0.94 (d, J＝6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 141.09, 132.94, 128.44, 127.21, 68.17, 66.40, 55.58, 52.13, 34.66, 34.29, 30.69, 21.87; IR (KBr) ν: 3116, 2924, 2808, 1489, 1135, 1108, 829 cm^－1; ESI-HRMS calcd for C₁₄H₂₁ONCl [M+H]⁺ 254.13062, found 254.13132.

  1-(3-Bromophenyl)-2-(4-methylpiperidin-1-yl)ethan-1-ol (2i): White solid, yield 85%. m.p. 84~85 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.54 (s, 1H), 7.38 (d, J＝7.9 Hz, 1H), 7.28 (d, J＝7.7 Hz, 1H), 7.20 (t, J＝7.8 Hz, 1H), 4.66 (dd, J＝10.7, 3.5 Hz, 1H), 4.26 (s, 1H), 3.09 (d, J＝11.8 Hz, 1H), 2.74 (d, J＝11.7 Hz, 1H), 2.48 (dd, J＝12.4, 3.6 Hz, 1H), 2.39~2.26 (m, 2H), 2.01 (td, J＝11.6, 2.4 Hz, 1H), 1.71~1.60 (m, 2H), 1.43~1.37 (m, 1H), 1.33~1.19 (m, 2H), 0.94 (d, J＝6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 145.03, 130.38, 129.87, 128.90, 124.44, 122.50, 68.14, 66.31, 55.55, 52.10, 34.64, 34.27, 30.68, 21.87; IR (KBr) ν: 3108, 2926, 2866, 2808, 1569, 1429, 1131, 1112, 695 cm^－1; ESI-HRMS calcd for C₁₄H₂₁ONBr [M+H]⁺ 298.08010, found 298.08154.

  2-(4-Methylpiperidin-1-yl)-1-(4-nitrophenyl)ethan-1-ol (2j): White solid, yield 88%. m.p. 99~101 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 8.19 (d, J＝8.7 Hz, 2H), 7.55 (d, J＝8.7 Hz, 2H), 4.80 (dd, J＝10.6, 3.6 Hz, 1H), 4.42 (s, 1H), 3.10 (d, J＝11.2 Hz, 1H), 2.74 (d, J＝11.2 Hz, 1H), 2.55 (dd, J＝12.4, 3.7 Hz, 1H), 2.37~2.29 (m, 2H), 2.05 (td, J＝11.6, 2.5 Hz, 1H), 1.70~1.63 (m, 2H), 1.44~1.37 (m, 1H), 1.34~1.18 (m, 2H), 0.95 (d, J＝6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 150.34, 147.23, 126.44, 123.55, 68.07, 65.93, 55.50, 52.11, 34.59, 34.23, 30.61, 21.81; IR (KBr) ν: 3078, 2946, 2933, 1378, 1340, 1075, 702 cm^－1; ESI-HRMS calcd for C₁₄H₂₁O₃N₂ [M+H]⁺ 265.15467, found 265.15491.

  2-(Diethylamino)-1-phenylethan-1-ol (2k): Colorless viscous liquid, yield 78%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.46~7.23 (m, 5H), 4.64 (dd, J＝10.6, 3.5 Hz, 1H), 3.74 (s, 1H), 2.74 (dq, J＝14.5, 7.3 Hz, 2H), 2.66~2.52 (m, 3H), 2.45 (dd, J＝12.7, 10.7 Hz, 1H), 1.07 (t, J＝7.1 Hz, 6H); ¹³C NMR (CDCl₃, 150 MHz) δ: 142.67, 128.31, 127.36, 125.84, 69.23, 61.84, 46.90, 11.99; IR (KBr) ν: 3105, 2928, 2808, 1504, 1408, 1097 cm^－1; ESI-HRMS calcd for C₁₂H₂₀ON [M+H]⁺ 194.15394, found 194.15408.

  1-(4-Chlorophenyl)-2-(diethylamino)ethan-1-ol (2l): Colorless viscous liquid, yield 75%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.33 (dd, J＝8.5, 5.5 Hz, 2H), 7.01 (t, J＝8.7 Hz, 2H), 4.60 (dd, J＝10.6, 3.4 Hz, 1H), 4.01 (s, 1H), 2.70 (dt, J＝14.4, 7.2 Hz, 2H), 2.62~2.45 (m, 3H), 2.38 (dd, J＝12.8, 10.6 Hz, 1H), 1.06 (td, J＝7.2, 2.6 Hz, 6H); ¹³C NMR (CDCl₃, 150 MHz) δ: 141.26, 132.91, 128.43, 127.18, 68.62, 61.69, 46.89, 11.97; IR (KBr) ν: 3128, 2904, 2808, 1507, 1428, 1087 cm^－1; ESI-HRMS calcd for C₁₂H₁₉ONCl [M+H]⁺ 228.11497, found 228.11511.

  1-(3-Bromophenyl)-2-(diethylamino)ethan-1-ol (2m): Colorless viscous liquid, yield 68%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.53 (s, 1H), 7.38~7.34 (m, 1H), 7.26 (d, J＝7.7 Hz, 1H), 7.17 (t, J＝7.8 Hz, 1H), 4.57 (dd, J＝10.5, 3.6 Hz, 1H), 4.19 (s, 1H), 2.75~2.47 (m, 5H), 2.36 (dd, J＝12.8, 10.5 Hz, 1H), 1.03 (t, J＝7.1 Hz, 6H); ¹³C NMR (CDCl₃, 150 MHz) δ: 145.17, 130.22, 129.76, 128.75, 124.33, 122.39, 68.54, 61.54, 46.79, 11.89; IR (KBr) ν: 3111, 2914, 2805, 1507, 1438, 1092 cm^－1; ESI-HRMS calcd for C₁₂H₁₉ONBr [M+H]⁺ 272.06445, found 272.06450.

  2-(Diethylamino)-1-(3-nitrophenyl)ethan-1-ol (2n): Co- lorless viscous liquid, yield 66%. ¹H NMR (CDCl₃, 400 MHz) δ: 8.26 (s, 1H), 8.15~8.06 (m, 1H), 7.73 (d, J＝7.7 Hz, 1H), 7.52 (dd, J＝10.5, 5.3 Hz, 1H), 4.74 (dd, J＝10.4, 3.7 Hz, 1H), 4.43 (s, 1H), 2.88~2.67 (m, 3H), 2.60 (dq, J＝13.9, 7.0 Hz, 2H), 2.40 (dd, J＝12.8, 10.5 Hz, 1H), 1.07 (t, J＝7.1 Hz, 6H); ¹³C NMR (CDCl₃, 150 MHz) δ: 148.15, 145.07, 131.82, 129.07, 122.07, 120.61, 68.31, 61.28, 46.73, 11.76; IR (KBr) ν: 3101, 2929, 2812, 1499, 1438, 1085 cm^－1; ESI-HRMS calcd for C₁₂H₁₉O₃N₂ [M+H]⁺ 239.13902, found 239.13911.

  2-(tert-Butylamino)-1-(2-chlorophenyl)ethan-1-ol (tulo- buterol, 2o): White solid, yield 77%. m.p. 90~93 ℃ (lit.^[33] 91~93 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.63 (dd, J＝7.7, 1.3 Hz, 1H), 7.34~7.25 (m, 2H), 7.19 (td, J＝7.7, 1.6 Hz, 1H), 4.99 (dd, J＝8.6, 3.5 Hz, 1H), 3.02 (dd, J＝12.1, 3.5 Hz, 1H), 2.47 (dd, J＝12.0, 8.6 Hz, 1H), 1.09 (s, 9H); ¹³C NMR (125 MHz, CDCl₃) δ: 140.91, 131.63, 129.12, 128.18, 127.46, 126.91, 68.78, 50.42, 48.12, 29.00; IR (KBr) ν: 3125, 2928, 2806, 1507, 1458, 1096 cm^－1; ESI-HRMS calcd for C₁₂H₁₉ONCl [M+H]⁺ 228.11497, found 228.11557. The data is agreement with literature reported.^[33]

  Supporting Information ¹H NMR and ¹³C NMR spectra of targets compounds 2a~2o. The Supporting Information is available free of charge via the Internet at http://sioc- journal.cn.

  
  
• 1. [1]

     Umezawa, H.; Aoyagi, T.; Morishima, H.; Matauzaki, H.; Hamada, M.; Takeuchi, T. J. Antibiot. 1970, 23, 259.

  2. [2]

     Rinehart, K. L.; Gloer, J. B.; Cook, J. C.; Mizsak, S. A.; Scahill, T. A. J. Am. Chem. Soc. 1981, 103, 1857.

  3. [3]

     Shimojima, Y.; Shirai, T.; Baba, T.; Hayashi, H.J. Med. Chem. 1985, 28, 3.

  4. [4]

     Shimojima, Y.; Hayashi, H. J. Med.Chem. 1983, 26, 1370.

  5. [5]

     He, A.-W. R.; Cory, J. G. Anticancer Res.1999, 19, 421.

  6. [6]

     Bergmeier, S. C. Tetrahedron 2000, 56, 2561.

  7. [7]

     Efange, S. M. N.; Kamath, A. P.; Khare, A. B.; Kung, M.-P.; Mach, R. H.; Parsons, S. M. J. Med. Chem. 1997, 40, 3905.

  8. [8]

     Ohta, Y.; Shinkai, I. Bioorg. Med.Chem. 1997, 5, 465.

  9. [9]

     Tok, J. B.-H.; Rando, R. R. J. Am.Chem. Soc. 1998, 120, 8279.

  10. [10]

      Hallinan, E. A.; Tsymbalov, S.; Finnegan, P. M.; Moore, W. M.; Jerome, G. M.; Currie, M. G.; Pitzele, B. S. J. Med. Chem. 1998, 41, 775.

  11. [11]

      Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835.

  12. [12]

      Studer, A. Synthesis 1996, 793.

  13. [13]

      Reetz, M. T. Chem. Rev. 1999, 99, 1121.

  14. [14]

      Scriven, E.; Turnbull, K. Chem. Rev. 1988, 88, 297.

  15. [15]

      Knapp, S. Chem. Soc. Rev. 1999, 28, 6.

  16. [16]

      Donohoe, T. J.; Callens, C. K. A.; Flores, A.; Lacy, A. R.; Rathi, A. H. Chem.-Eur. J. 2011, 17, 58.

  17. [17]

      Reiser, O.; Nilov, D. Adv. Synth. Catal. 2002, 344, 1169.

  18. [18]

      Yin, G.; Mu, X.; Liu, G. Acc. Chem. Res. 2016, 49, 2413.

  19. [19]

      Li, G.; Chang, H.-T.; Sharpless, K. B. Angew. Chem., Int.Ed. Engl. 1996, 35, 451.

  20. [20]

      Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem.Soc. 2005, 127, 7690.

  21. [21]

      Li, J.; Grubbs, R. H.; Stoltz, B. M. Org. Lett. 2016, 18, 5449.

  22. [22]

      Desai, L. V.; Sanford, M. S. Angew. Chem., Int.Ed. 2007, 46, 5737.

  23. [23]

      Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179.

  24. [24]

      Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. J. Am. Chem.Soc. 2008, 130, 6610.

  25. [25]

      Legnani, L.; Morandi, B. Angew. Chem., Int. Ed.2016, 55, 2248.

  26. [26]

      Zeng, T.; Liu, Z.; Schmidt, M. A.; Eastgate, M. D.; Engle, K. M. Org.Lett. 2018, 20, 3853.

  27. [27]

      Xu, S.; Wu, P.; Zhang, W. Org. Biomol. Chem. 2016, 14, 11389.

  28. [28]

      Wu, P.; Xu, S.; Xu, H.; Hu, H.; Zhang, W. Tetrahedron Lett. 2017, 58, 618.

  29. [29]

      Ma, C.; Fan, G.; Wu, P.; Li, Z.; Zhou, Y.; Ding, Q.; Zhang, W. Org.Biomol. Chem. 2017, 15, 9889.

  30. [30]

      Ma, C.; Miao, Y.; Zhao, M.; Wu, P.; Zhou, J.; Li, Z.; Xie, X.; Zhang, W. Tetrahedron 2018, 74, 3602.

  31. [31]

      Wu, C.; Xin, X.; Fu, Z.-M.; Xie, L.-Y.; Liu, K.-J.; Wang, Z.; Li, W.; Yuan, Z.-H.; He, W.-M. Green Chem. 2017, 19, 1983.

  32. [32]

      Cao, Z.; Zhu, Q.; Lin, Y.-W.; He, W.-M. Chin. Chem. Lett.2019, 30, 2132.

  33. [33]

      Nobuta, T.; Xiao, G.; Ghislieri, D.; Gilmore, K.; Seeberger, P. H. Chem. Commun. 2015, 51, 15133.

• 

  Figure 1  Selected examples bearing amino alcohol scaffold

  下载: 全尺寸图片 幻灯片
  

  Scheme 1  Possible mechanism

  下载: 全尺寸图片 幻灯片

  Table 1.  Optimization of the reaction conditions^a

  Entry	DBH/equiv.	4-Methylpiperidine/equiv.	Solvent (V:V)	Isolated yield/%
  1	0.55	3.0	Acetonitrile/H2O(5:1)	75
  2	0.55	3.0	Dioxane/H2O (5:1)	71
  3	0.55	3.0	Acetone/H2O (5:1)	81
  4	0.55	3.0	THF/H2O (5:1)	43
  5	0.55	3.0	DMF/H2O (5:1)	38
  6	0.50	3.0	Acetone/H2O (5:1)	77
  7	0.60	3.0	Acetone/H2O (5:1)	76
  8	0.70	3.0	Acetone/H2O (5:1)	64
  9	0.55	2.0	Acetone/H2O (5:1)	66
  10	0.55	4.0	Acetone/H2O (5:1)	83
  11	0.55	3.0	Acetone/H2O (1:1)	68
  12	0.55	3.0	Acetone/H2O (2:1)	84
  13	0.55	3.0	Acetone/H2O (10:1)	75
  a Olefin (5.0 mmol), DBH (2.75 mmol), water (10 mL) and acetone (20 mL).

  下载: 导出CSV

  Table 2.  Transformation of terminal alkenes to amino alcohols^a

  a Olefin (5.0 mmol), DBH (2.75 mmol), amine (15 mmol), water (10 mL) and acetone (20 mL).

  下载: 导出CSV
•