Lewis acid-catalyzed [3 + 2] annulations of oxindole based spirocyclic donor–acceptor cyclopropanes with ynamides

Abstract

[3 + 2] annulations of spirocyclopropyl oxindoles with ynamides to offer biologically important spirocyclopenteneoxindoles in high yields with good diastereoselectivities were developed.

Asymmetric Synthesis of Spiro-3,3′-cyclopropyl Oxindoles via Vinylogous Michael Initiated Ring Closure Reaction

“…1 H NMR (500 MHz, CDCl 3 ): δ 7.29−7.18 (m, 5H), 7.14 (td, J = 7.8, 1.1 Hz, 1H), 7.03−6.99 (m, 1H), 6.88−6.83 (m, 1H), 6.73 (d, J = 7.8 Hz, 1H), 5.08 (d, J = 15.9 Hz, 1H), 4.79 (d, J = 15.8 Hz, 1H), 4.33−4.08 (m, 4H), 4.06 (s, 1H), 2.52 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.17 (d, J = 7.3 Hz, 3H); 13 C{1H} NMR (125 MHz, CDCl 3 ): δ 171. (6). Light yellowish oil, trace conversion.…”

“…Diethyl-(1S,3R)-1′-acetyl-3-(3-methyl-4-nitroisoxazol-5-yl)-2′oxospiro[cyclopropane-1,3′-indoline]-2,2-dicarboxylate (6). Light yellowish oil, trace conversion.…”

“…13 C{ 1 H} NMR (125 MHz, CDCl 3 ): δ 169.0, 166. 6,163.2,157.1,148.3,142.3,133.1 (d,J = 32.8 Hz),131.8,130.1,128.9,127.3,126.7,125.6 (d,J = 3.1 Hz),124.0,118.8,118.3,85.8,63.6,63.0,49.2,42.1,31.80, 28.1, 14.0, 13.9. 19 2,.…”

“…The enantiomeric ratio was determined by HPLC analysis using a Daicel Chiralpak IC3 column (hexane/2propanol = 85:15, flow rate 0.5 mL/min, λ = 254 nm), t R = 47.5 min (major), t R = 110.8 min (minor). 1 H NMR (500 MHz, CDCl 3 ): δ 7.86 (d, J = 9.0 Hz, 1H), 6.88 (dd, J = 9.0, 2.7 Hz, 1H), 6…”

“…1,2 In particular, a spiro-3,3′-cyclopropyl oxindole core can be found as a privileged structural motif in various bioactive natural products and pharmaceuticals including anti-HIV drugs (I and II), obesity inhibitors (III), adrenaline agonists (IV), and anti-RSV medicines (V) (Figure 1). 3 Owing to the inherent strain, spiro-cyclopropyl oxindoles are labile intermediates, which participate in interesting transformation to spiro[pyrrolidin-3,3-oxindole], 4,5 biologically important spirocyclopenteneox-indoles, 6 and oxindole-based spirocyclic tetrahydro-1,2-oxazines. 7,8 The structural complexity of spiro-cyclopropyl oxindoles and the pharmaceutical and synthetic importance of these frameworks have continuously attracted the synthetic chemists over the last decade.…”