Synlett 2013; 24(4): 437-442
DOI: 10.1055/s-0032-1318145
letter
© Georg Thieme Verlag Stuttgart · New York

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: [email protected]   Email: [email protected]
,
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: [email protected]   Email: [email protected]
,
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: [email protected]   Email: [email protected]
,
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: [email protected]   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 07 December 2012

Accepted after revision: 10 January 2013

Publication Date:
29 January 2013 (online)


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).

Supporting Information

 
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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).