Stereoselective Synthesis of Polyfunctionalized Nitrones through Conjugate Addition of α-Halo Hydrazones to Nitroso Compounds

Abstract

In the presence of Na₂CO₃, conjugate addition of α-halo hydrazones to nitroso compounds proceeded readily to give polyfunctionalized nitrones in reasonable chemical yields and excellent stereoselectivities. The chemical structure and the stereochemical configuration of the products were unambiguously identified by an X-ray single-crystal structural analysis.

Key words

conjugate addition - halo hydrazones - nitroso compounds - nitrones - stereoselectivity

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• 10 N-(1Z,2Z)-2-[Oxido(phenyl)imino]-1-phenylethylidene}acetohydrazide (3aa); Typical ProcedureNa₂CO₃ (2.0 equiv, 0.40 mmol) was added to a solution of α-bromo hydrazone 1a (1.0 equiv, 0.20 mmol) and nitroso compound 2a (1.2 equiv, 0.24 mmol) in dry CH₂Cl₂ (1.0 mL) under air at rt, and the mixture was stirred for 20 h. When the reaction was complete (TLC), the mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography [silica gel, PE–EtOAc (3:1)] to give a yellow solid; yield: 51.7 mg (92%); mp 133.3–133.8 °C. ¹H NMR (400 MHz, CDCl₃): δ = 11.05–10.42 (m, 1 H), 8.10 (s, 1 H), 7.83 (s, 2 H), 7.68 (s, 2 H), 7.54 (s, 3 H), 7.41 (s, 3 H), 2.41–2.10 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 174.5, 146.8, 138.0, 135.8, 131.5, 131.0, 129.7, 129.5, 128.7, 127.2, 121.9, 20.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₆N₃O₂: 282.12370; found: 282.12405.
• 11 CCDC 2075055 contains the supplementary crystallographic data for compound 3aa. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.