Chiral NHC/Cu(I)-Catalyzed Asymmetric Hydroboration of Aldimines: Enantioselective Synthesis of α-Amido Boronic Esters

Shu-Sheng Zhang; Yi-Shuang Zhao; Ping Tian; Guo-Qiang Lin

doi:10.1055/s-0032-1318145

Synlett, Table of Contents

Synlett 2013; 24(4): 437-442
DOI: 10.1055/s-0032-1318145

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Chiral NHC/Cu(I)-Catalyzed Asymmetric Hydroboration of Aldimines: Enantioselective Synthesis of α-Amido Boronic Esters

Shu-Sheng Zhang

Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Fax: +86(21)64166263 Email: tianping@sioc.ac.cn Email: lingq@sioc.ac.cn

,

Yi-Shuang Zhao

Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Fax: +86(21)64166263 Email: tianping@sioc.ac.cn Email: lingq@sioc.ac.cn

,

Ping Tian*

Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Fax: +86(21)64166263 Email: tianping@sioc.ac.cn Email: lingq@sioc.ac.cn

,

Guo-Qiang Lin*

Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Fax: +86(21)64166263 Email: tianping@sioc.ac.cn Email: lingq@sioc.ac.cn

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Abstract

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Abstract

Non-C ₂-symmetric (N-alkyl, N-aryl)-hybrid chiral NHC/Cu(I) complex catalyzed asymmetric hydroboration of N-benzoyl aldimines has been developed. The reaction proceeded smoothly at room temperature, giving α-amido boronic esters in excellent yields (up to 94%) and good enantioselectivities (up to 86% ee).

Key words

chiral NHCs - copper - asymmetric hydroboration - aldimines - α-amido boronic esters

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References

References

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16 See Supporting Information for the detailed procedure of the preparation of chiral imidazolinium salts NHC₂ –NHC₇ . Analytical data of some typical imidazolinium salts: NHC₅ : [α]_D ²³ +318.7 (c = 1.37, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 9.86 (s, 1 H), 8.17 (d, J = 7.6 Hz, 1 H), 7.17–7.56 (m, 16 H), 6.97 (d, J = 7.6 Hz, 2 H), 4.99 (d, J = 10.0 Hz, 1 H), 4.39 (d, J = 10.0 Hz, 1 H), 3.88 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.04, 137.94, 137.77, 134.10, 133.95, 132.02, 130.82, 129.83, 129.64, 129.51, 129.42, 129.16, 129.10, 129.04, 128.58, 128.28, 127.48, 75.83, 74.60, 35.20. MS (ESI): m/z = 389.2 [C₂₈H₂₅IN₂ – I]⁺. HRMS: m/z [M]⁺ calcd for C₂₈H₂₅N₂: 389.20177; found: 389.20140. NHC₆ : [α]_D ²³ +454.0 (c = 0.845, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 8.67 (s, 1 H), 7.54 (m, 3 H), 7.32–7.42 (m, 10 H), 7.12–7.17 (m, 3 H), 6.81 (d, J = 7.6 Hz, 2 H), 5.14 (d, J = 8.8 Hz, 1 H), 3.88 (m, 1 H), 1.69–1.94 (m, 6 H), 1.54 (m, 1 H), 1.32–1.42 (m, 1 H), 1.09–1.27 (m, 3 H), 1.19 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 155.83, 152.92, 138.12, 135.44, 135.39, 134.82, 131.53, 130.44, 129.94, 129.58, 129.44, 129.22, 129.18, 128.21, 127.92, 127.23, 126.46, 75.96, 72.09, 57.94, 34.65, 31.44, 30.75, 25.08, 24.90, 24.44. MS (ESI): m/z = 513.3 [M – BF₄]⁺. HRMS: m/z [M – BF₄]⁺ calcd for C₃₇H₄₁N₂ ⁺: 513.32697; found: 513.32435.
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19 General Procedure for NHC₆/CuCl-Catalyzed Asymmetric Hydroboration of Aldimines: In the glovebox, an oven-dried Schlenk tube equipped with a stir bar, imidazolinium tetrafluoroborate salt NHC₆ (36 mg, 0.06 mmol), t-BuONa (12 mg, 0.12 mmol), and CuCl (5 mg, 0.05 mmol) were placed and anhyd toluene (2.0 mL) was added. After the solution was allowed to stir for 2 h at 25 °C under an anhyd N₂ atmosphere, it was filtered through a syringe filter (rinsed with 1.0 mL of toluene) and placed in a separate oven-dried Schlenk tube. The resulting solution was charged with B₂(Pin)₂ (2, 152 mg, 0.6 mmol) and N-benzoyl aldimine (0.5 mmol). The Schlenk tube was removed from the glovebox and the mixture was allowed to stir for 12 h at r.t. After the reaction completed, the mixture was filtered through a short plug of Celite and rinsed with EtOAc, and the solution was concentrated under reduced pressure. The products²⁰ were isolated by rapid silica gel chromatography on deactivated silica gel (containing 35% H₂O) using PE–EtOAc (2:1) mixtures and were visualized with CAM (Ceric Ammonium Molybdate) stain.
20 Analytical data of some typical compounds: 3a: [α]_D ²⁸ –22.1 (c = 0.95, CHCl₃) for 63% ee. ¹H NMR (400 MHz, CDCl₃): δ = 3.67 (s, 3 H), 3.99 (s, 3 H), 4.58 (q, J = 10.4 Hz, 2 H), 6.54 (s, 4 H), 7.13 (d, J = 8.8 Hz, 1 H), 7.32–7.52 (m, 5 H), 7.89–7.94 (m, 3 H), 9.36 (s, 1 H). HPLC: Chiralcel AS-H Column (250 mm); detected at λ = 220 nm; n-hexane–i-propanol = 95:5; flow = 0.6 mL/min; t _R = 8.6 min (minor), t _R = 11.5 min (major). 3b: [α]_D ²⁸ –1.24 (c = 0.56, DMSO) for 74% ee; mp 142–144 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.89 (s, 1 H), 8.07 (d, J = 7.6 Hz, 2 H), 7.73(t, J = 7.4 Hz, 1 H), 7.62 (t, J = 7.6 Hz, 2 H), 7.03–7.13(m, 4 H), 3.77 (s, 1 H), 1.03 (s, 6 H), 0.93 (s, 6 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 171.53, 160.78 (d, J = 954.0 Hz), 138.81 (d, J = 12.0 Hz), 134.51, 129.59, 128.86, 128.57 (d, J = 32.4 Hz), 126.69, 114.72 (d, J = 84.8 Hz), 79.80, 25.65, 25.39. MS (ESI): m/z = 378.2 [M + H]⁺. HRMS: m/z [M + Na]⁺ calcd for C₂₀H₂₃BFNO₃: 377.16835; found: 377.16957. HPLC: Chiralcel AS-H Column (250 mm); detected at λ = 220 nm; n-hexane–i-propanol = 95:5; flow = 0.6 mL/min; t _R = 9.1 min (minor), t _R = 11.2 min (major). 3h: [α]_D ²³ –29.7 (c = 0.21, DMSO) for 80% ee; mp 156–157 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 9.84 (s, 1 H), 7.99 (d, J = 7.6 Hz, 2 H), 7.68 (t, J = 7.4 Hz, 1 H), 7.58 (t, J = 7.8 Hz, 2 H), 2.38 (m, 4 H), 1.50–1.83 (m, 7 H), 0.99–1.32 (m, 4 H), 0.913 (s, 12 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 170.39, 133.66, 129.27, 128.60, 79.88, 39.69, 31.21, 29.49, 26.73, 26.68, 26.66, 26.02, 25.83. MS (ESI): m/z = 366.3 [M + H]⁺. HRMS: m/z [M + Na]⁺ calcd for C₂₀H₃₀BNO₃: 365.22528; found: 365.22450. HPLC: Chiralpak AD-H Column (250 mm); detected at λ = 220 nm; n-hexane–i-propanol = 95:5; flow = 0.6 mL/min; t _R = 5.4 min (minor), t _R = 6.9 min (major). 3i: [α]²³ _D –48.66 (c = 0.385, DMSO) for 84% ee; mp 144–146 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.00 (s, 1 H), 7.97 (d, J = 7.2 Hz, 2 H), 7.67 (t, J = 7.2 Hz, 1 H), 7.56 (t, J = 7.6 Hz, 2 H), 2.57 (m, 1 H), 1.83 (m, 1 H), 1.31 (m, 2 H), 1.11 (s, 12 H), 0.90 (d, J = 6.4 Hz, 6 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 170.19, 133.76, 129.28, 128.61, 127.89, 79.89, 44.36, 25.86, 25.73, 25.49, 23.91, 22.57. MS (ESI): m/z = 340.2 [M + Na]⁺. HRMS: m/z [M + Na]⁺ calcd for C₁₈H₂₈BNO₃: 339.20963; found: 339.20870. HPLC: Chiralpak AD-H Column (250 mm); detected at λ = 220 nm; n-hexane–i-propanol = 95:5; flow = 0.6 mL/min; t _R = 7.8 min (minor), t _R = 8.9 min (major).

Supplementary Material

Supporting Information