Triphenylphosphine-Catalyzed [3+2] Cycloaddition of Allenoate and Active Olefins: Syntheses of Spirooxindole Derivatives

Abstract

A series of spiro compounds was achieved by triphenylphosphine-catalyzed [3+2] cycloaddition between active methylenemalononitrile and ethyl 2,3-butadienoate. Careful investigation showed that the present method had high regioselectivity. The products have a spirooxindole skeleton, which is a motif common in many natural products and pharmaceutically active compounds.

Key words

oxindoles - spirocycle - cycloaddition - allenoate - active olefins

References and Notes

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CCDC 763015 for compound 3b contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystal-lographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.

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Typical Experimental Procedure
Ph₃P (10%) was added to a solution of alkene 1 (0.5 mmol) and allenoate 2 (0.6 mmol) in 5 mL toluene at r.t. in the air. The stirred mixture was allowed to react for given the time in Table  [²] , and the process was monitored using TLC detection. After completion of present reaction, the reaction mixture was concentrated under vacuum. The residue was purified by column chromatography on silica gel [silica: 200-300 mesh; eluant: PE-EtOAc] to afford the desired product 3.
Selected Spectroscopic Data of Product 3
Compound 3a: White solid, mp 140.3-142.1 ˚C (uncorrected). ^¹H NMR (500 MHz, CDCl₃): δ = 7.48-7.44 (m, 2 H), 7.16 (t, J = 7.5 Hz, 2 H), 6.97 (d, J = 8.0 Hz, 1 H), 4.02-3.91 (m, 2 H), 3.80 (dd, J ₁ = 17.5 Hz, J ₂ = 2.0 Hz, 1 H), 3.48 (dd, J ₁ = 17.5 Hz, J ₂ = 3.0 Hz, 1 H), 3.30 (s, 3 H), 0.99 (t, J = 7.0 Hz, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 171.7, 161.1, 144.6, 142.7, 136.5, 131.4, 125.5, 123.8, 123.5, 114.3, 112.9, 109.3, 64.8, 61.4, 43.5, 45.1, 27.1, 13.8. IR (KBr): ν = 3066, 2940, 2255, 1712, 1613, 1475. MS (ESI): m/z = 322 [M + H⁺], 344 [M + Na⁺], 360 [M + K⁺]. HRMS (MALDI): m/z calcd for C₁₈H₁₆N₃O₃ ⁺ [M + H]⁺: 322.1193; found: 322.1186.