An Efficient Route to Access Spirooxindole–Pyrazolone-Fused Cyclopentenes by a Diastereoselective [3+2] Annulation

Abstract

A DMAP-catalyzed, highly diastereoselective, [3+2] cycloaddition of pyrazolone-derived Morita–Baylis–Hillman carbonates to 3-methyleneoxindoles has been developed. A variety of structurally diverse and complex spiropyrazolone-fused oxindoles bearing three contiguous chiral centers have been synthesized in high yields (up to 98%) and with excellent diastereoselectivities (up to 99:1). Moreover, the synthetic potential of this protocol has been demonstrated by performing a Suzuki coupling reaction.

Key words

annulation - spiropyrazolones - diastereoselectivity - Morita–Baylis–Hillman carbonates - spirooxindoles

Publication History

Received: 05 November 2022

Accepted after revision: 16 January 2023

Accepted Manuscript online:
16 January 2023

Article published online:
11 May 2023

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• 26 Product 3a; Typical Procedure An oven-dried round-bottomed flask was charged with the MBH carbonate 1a (35 mg, 0.094 mmol), the indolinone 2a (24 mg, 0.112 mmol), DMAP (2.28 mg, 0.019 mmol), and CHCl₃ (2 mL), and the mixture was stirred at rt for 12 h. When the reaction was complete (TLC), the solvent was evaporated under reduced pressure and the crude product was directly purified by column chromatography [silica gel (100–200 mesh), PE–EtOAc (70:30)] to give a brown solid; yield: 45 mg (92%, 99:1 dr); mp 78–80 °C. R_f = 0.3 (PE–EtOAc, 70:30). ¹H NMR (400 MHz, CDCl₃): δ = 8.0 (d, J = 7.0 Hz, 2 H), 7.6 (m, 3 H), 7.5–7.4 (m, 2 H), 7.4–7.3 (m, 3 H), 7.2–7.1 (m, 2 H), 7.1 (d, J = 2.2 Hz, 1 H), 6.8 (d, J = 25.2 Hz, 2 H), 4.9 (d, J = 2.3 Hz, 1 H), 3.7 (s, 3 H), 3.3 (s, 3 H), 2.2 (s, 3 H). ¹³C {¹H} NMR (100 MHz, CDCl₃): δ = 190.9, 174.1, 172.5, 169.1, 156.5, 144.7, 143.3, 142.8, 137.3, 136.8, 133.6, 130.1, 129.9, 128.9, 128.8, 125.9, 125.0, 124.0, 123.4, 119.7, 108.6, 67.2, 65.0, 53.8, 53.0, 26.9, 15.9. HRMS (ESI TOF): m/z [M + H]⁺ calcd for C₃₁H₂₆N₃O₅: 520.1872; found: 520.1876.