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Synlett 2013; 24(4): 437-442
DOI: 10.1055/s-0032-1318145
DOI: 10.1055/s-0032-1318145
letter
Chiral NHC/Cu(I)-Catalyzed Asymmetric Hydroboration of Aldimines: Enantioselective Synthesis of α-Amido Boronic Esters
Further Information
Publication History
Received: 07 December 2012
Accepted after revision: 10 January 2013
Publication Date:
29 January 2013 (online)
![](https://www.thieme-connect.de/media/synlett/201304/lookinside/thumbnails/10.1055-s-0032-1318145-1.jpg)
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
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References
- 1a Huber EM, Groll M. Angew. Chem. Int. Ed. 2012; 51: 8708
- 1b Smoum R, Rubinstein A, Dembitsky VM, Srebnik M. Chem. Rev. 2012; 112: 4156
- 1c Moreau P, Richardson PG, Cavo M, Orlowski RZ, San Miguel JF, Palumbo A, Harousseau J.-L. Blood 2012; 120: 947
- 1d Baker SJ, Ding CZ, Akama T, Zhang Y.-K, Hernandez V, Xia Y. Future Med. Chem. 2009; 1: 1275
- 1e Yang W.-Q, Gao X.-M, Wang B.-H. Biological and Medicinal Applications of Boronic Acids. In Boronic Acids . Hall DG. Wiley-VCH; Weinheim, Germany: 2005. Chap. 13 48
- 2 See: http://www.velcade.com.
- 3 Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J. Cancer Res. 2010; 70: 1970
- 4 Monami M, Lamanna C, Desideri CM, Mannucci E. Adv. Ther. 2012; 29: 14
- 5 Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G. Blood 2008; 111: 2765
- 6a Matteson DS, Sadhu KM. J. Am. Chem. Soc. 1981; 103: 5241
- 6b Matteson DS. (α-Haloalkyl)boronic Esters in Asymmetric Synthesis. In Boronic Acids . Hall DG. Wiley-VCH; Weinheim, Germany: 2005. Chap. 8 305
- 6c Matteson DS, Beedle EC. Tetrahedron Lett. 1987; 28: 4499
- 6d Jadhav PK, Man H. J. Org. Chem. 1996; 61: 7951
- 7 Gazić SmilovićI, Casas-Arcé E, Roseblade SJ, Nettekoven U, Zanotti-Gerosa A, Kovačevič M, Časar Z. Angew. Chem. Int. Ed. 2012; 51: 1014
-
8 Beenen MA, An C.-H, Ellman JA. J. Am. Chem. Soc. 2008; 130: 6910
- 9 Ellman JA, Owens TD, Tang TP. Acc. Chem. Res. 2002; 35: 984
- 10 Solé C, Gulyás H, Fernández E. Chem. Commun. 2012; 48: 3769
- 11a Ohmura T, Awano T, Suginome M. J. Am. Chem. Soc. 2010; 132: 13191
- 11b Awano T, Ohmura T, Suginome M. J. Am. Chem. Soc. 2011; 133: 20738
- 12 O’Brien JM, Lee K.-S, Hoveyda AH. J. Am. Chem. Soc. 2010; 132: 10630
-
13a Lee Y, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 3160
- 13b Corberán R, Mszar NW, Hoveyda AH. Angew. Chem. Int. Ed. 2011; 50: 7079
-
14 Lee Y, Jang H, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 18234
-
15 For a recent review about synthetic routes to N-heterocyclic carbene precursors, see: Benhamou L, Chardon E, Lavigne G, Bellemin-Laponnaz S, César V. Chem. Rev. 2011; 111: 2705
- 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.
-
17 Park JK, Lackey HH, Rexford MD, Kovnir K, Shatruk M, McQuade DT. Org. Lett. 2010; 12: 5008
- 18a Contreras-Martel C, Amoroso A, Woon EC. Y, Zervosen A, Inglis S, Martins A, Verlaine O, Rydzik AM, Job V, Luxen A, Joris B, Schofield CJ, Dessen A. ACS Chem. Biol. 2011; 6: 943
- 18b Woon EC. Y, Zervosen A, Sauvage E, Simmons KJ, Zivec M, Inglis SR, Fishwick CW. G, Gobec S, Charlier P, Luxen A, Schofield CJ. ACS Med. Chem. Lett. 2011; 2: 219
- 18c Morandi F, Caselli E, Morandi S, Focia PJ, Blazquez J, Shoichet BK, Prati F. J. Am. Chem. Soc. 2003; 125: 685
- 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).
For recent reviews on peptide α-amino boronic acids as protease inhibitors, see:
For an important synthetic use of enantioenriched α-(acylamino)benzylboronic esters in Suzuki–Miyaura coupling, see:
For pharmaceutically interesting α-amido boronic acids, see: