A Comparative Study of the Synthesis of C₂-Symmetric Chiral 2,2′-Biaziridinyls

Abstract

Two comparative synthetic routes to new enantiomeric C₂-symmetric Boc-protected biaziridinyls from tartaric ester were studied. Simplicity, high enantiomeric purity and high chemical yield of the target compound characterize the proposed methods. Also, unprotected biaziridinyl was synthesized and fully characterized.

stereoselective synthesis - azides - heterocycles - chiral auxiliaries

References

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¹H NMR (500 MHz, CDCl₃) δ 1.44 (18 H, s, t-Bu), 3.05 (2 H, m, CHO), 3.20 and 3.47 (4 H, m, CH₂NH), 5.43 (2 H,
br s, NH); ¹³C NMR (125 MHz, CDCl₃) δ 28.29 (q, J = 126.7 Hz, t-Bu), 38.24 (t, J = 126.7 Hz, CH₂NH), 55.10 (d, J = 175.0 Hz, CHO), 79.69 (s, t-Bu), 156.23 (s, CONH).CI-MS m/z (%) 303 (3) (M + H)⁺, 191 (100), 173 (39), 116 (63).

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General experimental procedure for direct ring closure: To a solution of dimesylate 6 (0.46 mmol) in anhydrous THF (5 mL) NaH (0.96 mmol, 60% dispersion in mineral oil) was added portion wise at 0 °C under Ar atmosphere. The mixture was stirred at room temperature for 5 h, quenched with water, extracted with EtOAc. The solvent was evaporated and the mixture was purified by column chromatography on silica gel affording bisaziridine 7 (0.39 mmol) in 85% yield. ¹H NMR (500 MHz, CDCl₃) δ 1.43 (18 H, s, t-Bu), 2.14 (2 H, d, J = 3.3 Hz, H-3,3′), 2.28 (2 H, d, J = 6.1 Hz, H-3,3′), 2.71 (2 H, m, H-2,2′); ¹³C NMR (125 MHz, CDCl₃) 27.82 (q, J = 127 Hz, t-Bu), 29.51 (dd, J = 176.8 Hz, 170.5 Hz, C-3.3′), 35.47 (d, J = 169 Hz, C-2,2′), 81.36 (s, t-Bu), 161.88 (s, CON). MS m/z (%) 285 (5) (M + H)⁺, 229 (18), 173 (72), 129 (18), 57 (100), 41 (76). [α]_D ²⁰ +175 (c 4.4, MeOH)

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General experimental procedure for the Staudinger reaction: To a solution of azidodiol 2 (1.1 mmol) in anhydrous acetonitrile (6 mL) PPh₃ (2.3 mmol) was added and the solution was stirred for 3 h at room temperature followed by reflux for 4 h. The mixture was cooled in the ice-bath and Et₃N (2.3 mmol) and Boc₂O (2.25 mmol) were added. The mixture was stirred overnight at room temperature, the solvent was evaporated and the residue was triturated with Et₂O. The organic layer was purified by column chromatography on silica gel affording target compound 7 in 71% yield.

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26

General experimental procedure for the Staudinger reaction using polymer-supported PPh₃: To a solution of azidodiol 2 (1.1 mmol) in anhydrous acetonitrile (12 mL) polymer-supported PPh₃ (2% DVB, 3.3 mmol) was added and the solution was stirred for 3 h at room temperature followed by reflux for 11 h. The resin was filtered, the filtrate was evaporated and the residue was purified on aluminum oxide(basic) affording target compound 10 in 25% yield. MS m/z (%); 83 (54), 68 (32), 56 (100), 42 (61); HRMS calcd for C₄H₇N₂ (M - H)⁺ 83.0609, found 83.0612.