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Synlett 2008(10): 1483-1486  
DOI: 10.1055/s-2008-1078419
LETTER
© Georg Thieme Verlag Stuttgart · New York

A General and Efficient Route to 3-O-Modified Carbohydrate Bis(oxazoline) Ligands

Tobias Minuth, Mike M. K. Boysen*
Institute of Organic Chemistry, Leibniz University of Hannover, Schneiderberg 1B, 30167 Hannover, Germany
Fax: +49(511)7623011; e-Mail: mike.boysen@oci.uni-hannover.de;
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Publication History

Received 20 March 2008
Publication Date:
19 May 2008 (online)

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Abstract

An efficient route to derivatives of carbohydrate-based bis(oxazoline) ligands with 3-O substituents of varying steric demand is described. The synthesis of the new ligands proceeds via a thioglucoside key intermediate, the double cyclisation reaction to the desired bis(oxazolines) is initiated with N-iodo succinimide under mild conditions. Employing this strategy, four new 3-O-modified bis(oxazoline) ligands were obtained in good yields.

Key words

carbohydrates - ligand design - oxazolines - asymmetric synthesis

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General Procedure for the Double Cyclisation of Bis(amides) with Thioglycoside Moieties A mixture of the 3-O-protected thioglycoside (280 mg, 0.38 mmol) and MS 4 Å (300 mg) in anhyd CH2Cl2 (5 mL) was stirred for 1 h under N2 atmosphere in a flame-dried flask. To this NIS (210 mg, 91 µmol) was added and the mixture was cooled to -30 °C. Then, TfOH (5 µL, 50 µmol) was added and the mixture was stirred for 1 h at -30 °C. The reaction was quenched with Et3N (0.1 mL), and the mixture was filtered through Celite, diluted with CH2Cl2, washed with sat. aq NaHCO3, aq Na2S2O3 (3 M), and dried over Na2SO4. The solvent was removed under reduced pressure, and the residue was purified by flash chromatography on SiO2 (eluants given for the respective compound) to yield the desired product.
Analytical Data for 3-O-Acetylated Compound 9 Eluant: EtOAc. 1H NMR (400 MHz, CDCl3): δ = 1.52 [6 H, s, (CH3)2C], 2.10 (6 H, s, CH3CO), 3.61 (2 H, dd ª t, J 5,6 ′ = J 6,6 ′ = 9.9 Hz, H-6′), 3.75 (2 H, ddd ª td, J 4,5 = 9.9 Hz, J 5,6 = 5.1 Hz, J 5,6 ′ = 9.9 Hz, H-5), 3.81 (2 H, dd, J 3,4 = 7.5 Hz, J 4,5 = 9.9 Hz, H-4), 4.14 (2 H, dd, J 1,2 = 7.1 Hz, J 2,3 = 2.7 Hz, H-2), 4.39 (2 H, dd, J 5,6 = 5.1 Hz, J 6,6 ′ = 10.2 Hz, H-6), 5.28 (2 H, dd, J 2,3 = 2.7 Hz, J 3,4 = 7.5 Hz, H-3), 5.51 (2 H, s, CHPh), 5.98 (2 H, d, J 1,2 = 7.1 Hz, H-1), 7.32-7.37 (6 H, m, Ph), 7.44-7.46 (4 H, m, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.1 (CH3, OAc), 23.4 [CH3, (CH3)2C], 38.9 (C, [CH3)2 C], 62.9 (CH, C-5), 67.8 (CH2, C-6), 68.2 (CH, C-2), 73.5 (CH, C-3), 78.4 (CH, C-4), 101.4 (CH, PhCH), 101.4 (CH, C-1), 126.1 (2 CH, Ph), 128.2 (2 CH, Ph), 129.0 (CH, Ph), 136.8 (C, Ph), 169.6 (C, O-C=N), 169.8 (C, C=O, Ac) ppm. ESI-HRMS (+): m/z calcd for C35H39N2O12 [M + H]+: 679.2503; found: 679.2511. [α]D 20 +106 (c 1.0, CHCl3).
Analytical Data for 3-O-Methylated Compound 11a Eluant: PE-EtOAc (1:2). 1H NMR (400 MHz, CDCl3): δ = 1.53 [6 H, s, (CH 3)2C], 3.54 (6 H, s, OCH3), 3.60-3.71 (8 H, m, H-3, H-4, H-5, H-6′), 4.11 (2 H, dd, J 1,2 = 7.5 Hz, J 2,3 = 2.4 Hz, H-2), 4.33-4.41 (2 H, m, H-6), 5.56 (2 H, s, CHPh), 5.97 (2 H, d, J 1,2 = 7.5 Hz, H-1), 7.32-7.37 (6 H, m, Ph), 7.44-7.47 (4 H, m, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.4 [CH3, (CH3)2C], 39.0 [C, (CH3)2 C], 58.5 (CH3, OCH3), 62.6 (CH, C-5), 67.8 (CH, C-2), 68.2 (CH2, C-6), 80.1 (CH, C-3), 81.7 (CH, C-4), 101.3 (CH, PhCH), 102.2 (CH, C-1), 126.1 (2 CH, Ph), 128.2 (2 CH, Ph), 129.0 (CH, Ph), 137.1 (C, Ph), 168.8 (C, O-C=N) ppm. ESI-HRMS (+): m/z calcd for C33H38N2O10 [M + H]+: 662.2526; found: 662.2534. [α]D 20 +124 (c 1.0, CHCl3).
Analytical Data for 3-O-Benzylated Compound 11b
Eluant: PE-EtOAc (1:1). 1H NMR (400 MHz, CDCl3): δ = 1.51 [6 H, s, (CH3)2C], 3.63 (2 H, dd ª t, J 5,6 ′ = J 6,6 ′ = 9.6 Hz, H-6′), 3.68 (2 H, ddd ª td, J 4,5 = J 5,6 ′ = 9.6 Hz, J 5,6 = 4.1 Hz, H-5), 3.78 (2 H, dd, J 3,4 = 7.5 Hz, J 4,5 = 9.6 Hz, H-4), 3.93 (2 H, dd, J 2,3 = 3.0 Hz, J 3,4 = 7.5 Hz, H-3), 4.23 (2 H, dd, J 1,2 = 7.5 Hz, J 2,3 = 3.0 Hz, H-2), 4.38 (2 H, dd, J 5,6 = 4.1 Hz, J 6,6 ′ = 9.6 Hz, H-6), 4.77 (2 H, d, J = 12.0 Hz, CH 2Ph), 4.82 (2 H, d, J = 12.0 Hz, CH2Ph), 5.57 (2 H, s, CHPh), 5.98 (2 H, d, J 1,2 = 7.5 Hz, H-1), 7.25-7.46 (20 H, m, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.4 [CH3, (CH3)2C], 38.9 [C, (CH3)2 C], 62.8 (CH, C-5), 68.4 (CH, C-2), 68.6 (CH2, C-6), 72.4 (CH2, PhCH2) 79.7 (CH, C-3), 80.1 (CH, C-4), 101.1 (CH, PhCH), 102.2 (CH, C-1), 126.0 (2 CH, Ph), 127.6 (CH, Ph), 127.8 (2 CH, Ph), 128.1 (2 CH, Ph), 128.2 (2 CH, Ph), 128.9 (CH, Ph), 137.1 (C, Ph), 137.9 (C, Ph), 168.8 (C, O-C=N) ppm. ESI-HRMS (+): m/z calcd for C45H47N2O10 [M + H]+: 775.3231; found: 775.3234. [α]D 20 +82 (c 1.0, CHCl3).
Analytical Data for 3-O-Silylated Compound 11c Eluant: PE-EtOAc (1:1). 1H NMR (400 MHz, CDCl3): δ = 0.65 (12 H, t, J = 7.8 Hz, SiCH 2CH3), 0.93 (18 H, t, J = 7.8 Hz, SiCH2CH 3), 1.50 [6 H, s, (CH 3)2C], 3.55-3.66 (6 H, m, H-4, H-5, H-6′), 3.93 (2 H, dd, J 2,3 = 3.8 Hz, J 3,4 = 7.2 Hz, H-3), 3.98 (2 H, dd, J 1,2 = 7.2 hz, J 2,3 = 3.8 Hz, H-2), 4.36 (2 H, dd, J 5,6 = 3.1 Hz, J 6,6 ′ = 8.9 Hz, H-6), 5.53 (2 H, s, CHPh), 5.95 (2 H, d, J 1,2 = 7.2 Hz, H-1), 7.32-7.37 (6 H, m, Ph), 7.45-7.49 (4 H, m, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 4.73 [CH3, (CH3CH2)3Si], 6.71 [CH2, (CH3 CH2)3Si], 23.4 [CH3, (CH3)2C], 39.0 [C, (CH3)2 C], 63.2 (CH, C-5), 68.6 (CH2, C-6), 70.8 (CH, C-2), 74.4 (CH, C-3), 81.1 (CH, C-4), 101.4 (CH, PhCH), 102.7 (CH, C-1), 126.0 (2 CH, Ph), 128.0 (2 CH, Ph), 128.8 (CH, Ph), 137.3 (C, Ph), 168.5 (C, O-C=N) ppm. ESI-HRMS (+): m/z calcd for C43H63N2O10Si2 [M + H]+: 823.4021; found: 823.4003. [α]D 20 +106 (c 0.9, CHCl3).