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Synlett 2005(14): 2187-2190  
DOI: 10.1055/s-2005-871974
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Functionalized Bicyclic Triazoles from Chiral Aziridines

Min Sung Kima, Hyo Jae Yoona, Baeck Kyong Leea, Ji Hyun Kwona, Won Koo Lee*a, Yongeun Kimb, Hyun-Joon Ha*b
a Department of Chemistry and Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul 121-742, Korea
Fax: +82(2)7010967; e-Mail: wonkoo@sogang.ac.kr;
b Department of Chemistry, Hankuk University of Foreign Studies, Yongin, Kyunggi-Do 449-719, Korea
Fax: +82(31)3304566; e-Mail: hjha@hufs.ac.kr;
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Publication History

Received 9 June 2005
Publication Date:
20 July 2005 (online)

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Abstract

Enantiomerically pure 3-substituted-5-amino-4-hydroxy-5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazoles were synthesized efficiently from the sequential reactions including a regioselective ring-opening of 1-aziridine-2-yl-propargylic alcohols by azidotrimethylsilane and the subsequent intramolecular 1,3-dipolar cycloaddition between alkyne and azide.

Key words

aziridine - triazole - cycloaddition - alkyne - azide

15

Preparation of (4 S ,5 S )-4-Hydroxy-3-phenyl-5-{(1 R )-1-phenylethylamino)-5,6-dihydro-4 H -pyrrolo[1,2- c ][1,2,3]triazole(5a).
To a solution of aziridine-(2S)-propargyl alcohol (3a, 110 mg, 0.40 mmol) in 2.00 mL of CH2Cl2 under nitrogen atmosphere was added TMSN3 at r.t. The mixture was stirred for 3 h at r.t. then quenched with 6 N HCl. The aqueous layer was extracted with CH2Cl2. The combined extracts were dried over MgSO4, and the solvent was evaporated to give product as yellow oil. The crude reaction product was dissolved in 2.10 mL of DMF at r.t. The mixture was stirred under a nitrogen atmosphere for 16 h at 130 °C. The solvent was evaporated to give the crude product as a yellow oil which was purified by silica gel flash chromatography with 50% EtOAc-hexane to give 106 mg of 5a as a white solid in 83% yield; mp 128-129 °C; [α]D 24 = +38.2 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.82 (d, J = 7.4 Hz, 2 H), 7.37-7.25 (m, 8 H), 4.78 (d, J = 5.6 Hz, 1 H), 4.51 (dd, J = 11.6, 6.9 Hz, 1 H), 4.10 (dd, J = 11.5, 6.8 Hz, 1 H), 4.01 (q, J = 6.4 Hz, 1 H), 3.92 (td, J = 6.9, 5.6 Hz, 1 H), 1.46 (d, J = 6.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 144.0, 142.3, 138.1, 130.4, 129.1, 128.9, 128.2, 128.0, 126.9, 126.2, 64.5, 62.9, 57.2, 51.1, 24.3. Anal. Calcd for C19H20N4O: C, 71.2; H, 6.29; N, 17.5. Found: C, 71.3; H, 6.30; N, 17.2.

18

Removal of α-Methylbenzyl Nitrogen Protecting Group from 5a.
To a solution of phenylethylamino bicyclic triazole (5a, 110 mg, 0.34 mmol) in 1.90 mL of MeOH was added Pd(OH)2 at r.t. The mixture was stirred for 30 h under 120 psi of H2 (g)at r.t. then the catalyst was filtered and washed with MeOH. The solvent was evaporated to give product as yellow oil which was purified by recrystallization from CH2Cl2 to give 61 mg (84%) of 3-phenyl-5-amino-4-hydroxy-5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazole(9a) as a white solid; mp 197-198 °C; [α]D 24 = +106.5 (c 0.7, CH3OH). 1H NMR (500 MHz, CDCl3): δ = 7.82 (d, J = 8.0 Hz, 2 H), 7.38 (t, J = 7.3 Hz, 2 H), 7.28 (t, J = 7.5 Hz, 1 H), 5.03 (d, J = 5.5 Hz, 1 H), 4.55 (dd, J = 11.1, 7.4 Hz, 1 H), 4.14 (td, J = 7.4, 5.6 Hz, 1 H), 3.96 (dd, J = 11.1, 7.3 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 141.6, 139.3, 130.6, 128.8, 128.2, 125.9, 65.4, 58.6, 51.7. Anal. Calcd for C11H12N4O: C, 61.1; H, 5.59; N, 25.9. Found: C, 61.2; H, 5.53; N, 26.0.