Synthesis of N-Protected Cyano Aziridines

Abstract

A concise and inexpensive route to 2-cyano aziridine-2-carboxylates and 2,2-dicyano aziridines is reported by reaction of the easily obtainable corresponding α,β-unsaturated nitriles with sulfonyloxycarbamates in the presence of calcium oxide.

aminations - Michael additions - nitriles - carbamates - ring closure

References

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Typical Experimental Procedure: All compounds were synthesized with a Carousel Reaction Station from Radleys Discovery Technologies (UK). The synthesis involved the following sequential steps. To the stirred solutions of 2.0 mmol of ethyl cyanoacetate or malononitrile in CH₂Cl₂, 2.4 mmol of aldehyde and 1.0 g of basic Al₂O₃ were added. Upon completion, reaction mixtures were filtered. To the so obtained unsaturated nitriles in CH₂Cl₂, CaO and nosyloxycarbamates were added in the amounts reported in Table [1] and Table [2] . After completion (TLC), the crude aziridines were filtered through plugs filled with silica gel using a 9:1 hexane/EtOAc mixture and obtained as pale yellow oils after solvent removal. Selected spectral data of new compounds. Compound 2a: IR (CCl₄): 2253, 1761, 1731 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.13 (t, J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.34 (t, J = 7.2 Hz, 3 H), 1.68-1.82 (m, 2 H), 3.08 (t, J = 6.6 Hz, 1 H), 4.09-4.23 (m, 2 H), 4.23-4.45 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 10.4, 14.0, 14.2, 23.3, 38.6, 51.3, 63.4, 64.1, 113.3, 157.2, 162.6. GC/MS: m/z (%) = 240 (9) [M⁺], 114 (24), 95 (46), 94 (12), 68 (100), 67 (10). HRMS (ES Q-TOF) calcd for C₁₁H₁₇N₂O₄ (M + H)⁺: 241.1188; found: 241.1200. Compound 2k: IR (CCl₄): 2253, 1756 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 1.18 (t, J = 7.3 Hz, 3 H), 1.35 (t, J = 7.3 Hz, 3 H), 1.66-1.89 (m, 2 H), 3.19 (t, J = 6.6 Hz, 1 H), 4.22-4.48 (m, 2 H). ¹³C NMR (50 MHz, CDCl₃): δ = 9.9, 14.0, 23.1, 25.0, 52.4, 64.9, 110.3, 110.8, 156.2. GC/MS: m/z (%) = 193 (3) [M⁺], 121 (21), 94 (100), 93 (53), 83 (10), 68 (15), 67 (75), 66 (38), 65 (10), 56 (23), 54 (11). HRMS (ES Q-TOF) calcd for C₉H₁₂N₃O₂ (M + H)⁺: 194.0930; found: 194.0927.

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9-Fluorenylmethyl nosyloxycarbamate (NsONHFmoc) was synthesized in 80% yield, starting from commercial 9-fluorenylmethyl N-hydroxycarbamate (HONHFmoc) and nosyl chloride following the standard procedure, see ref.¹⁰

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