Synthesis of isoquinolone via rhodium(III)-catalyzed C-H activation with 1,4,2-dioxazol-5-ones as oxidizing directing group

Isoquinolone Syntheses by Annulation Protocols

“…The experimental and theoretical studies indicate that the reaction to the inverse annulation follows the Ru(II)-Ru(IV)-Ru(II) pathway involving N-O bond cleavage prior to alkyne insertion. [46], with N-iminopyridinium ylides (Scheme (c)) [47]. However, with the use of AgNTf 2 as co-catalyst, the reactions of 2-aryloxazolines with alkynes afford N-substituted isoquinolones (Scheme 10 (d)) [48].…”

“…bonds. As shown in Scheme 10, with the use of [Cp*RhCl 2 ] 2 as catalyst, the annulations of alkynes with benzoyl hydrazines (Scheme 10 (a)) [45], with 1,4,2-dioxazol-5-ones occur at room temperature (Scheme 10 (b))[46], with N-iminopyridinium ylides (Scheme (c))[47]. However, with the use of AgNTf 2 as co-catalyst, the reactions of 2-aryloxazolines with alkynes afford N-substituted isoquinolones (Scheme 10 (d))[48].…”

Synthesis of Isoquinolones by Sequential Suzuki Coupling of 2-Halobenzonitriles with Vinyl Boronate Followed by Cyclization

“…Preparative and analytical thin-layer chromatography (PTLC and TLC) was carried out on Merck silica gel plates with a QF-254 indicator and visualized by UV or KMnO 4 . 1 H and 13 C NMR spectra were recorded on an Agilent DD 2 500 (500 MHz 1 H; 125 MHz 13 C), Agilent DD 2 600 (600 MHz 1 H; 150 MHz 13 C), or Agilent DD 2 400 (400 MHz 1 H; 100 MHz 13 C) spectrometer at room temperature. Chemical shifts were reported in ppm relative to the residual CDCl 3 (δ 7.26 ppm 1 H; δ 77.0 ppm 13 C), CD 3 OD (δ 3.31 ppm 1 H; δ 49.0 ppm 13 C), or DMSO-d 6 (δ 2.50 ppm 1 H; δ 39.5 ppm 13 C).…”

“…1 H NMR (500 MHz, DMSO-d 6 ) δ 7.42 (d, J = 12.7 Hz, 1H), 7.39 (d, J = 8.7 Hz, 1H), 6.60 (d, J = 2.2 Hz, 1H), 6.39 (dd, J = 8.8, 2.6 Hz, 1H), 5.89 (d, J = 12.7 Hz, 1H), 3.94 (q, J = 7.0 Hz, 2H), 3.42−3.00 (m, 4H), 2.08−1.66 (m, 4H), 1.27 (t, J = 7.0 Hz, 3H). 13 4-(Dimethylamino)-2-[(E)-2-ethoxyvinyl]benzonitrile (2e). This compound was prepared following the procedure described above to give 250 mg (87% yield) of pure product as a yellow oil.…”

“…1 H NMR (400 MHz, DMSO-d 6 ) δ 7.68−7.44 (m, 2H), 7.17 (d, J = 2.5 Hz, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 5.90 (d, J = 12.7 Hz, 1H), 3.94 (q, J = 7.0 Hz, 2H), 3.80 (s, 3H), 1.25 (t, J = 7.0 Hz, 4H). 13 2-[(E)-2-Ethoxyvinyl]-4-formylbenzonitrile (2g). This compound was prepared following the procedure described above to give 304 mg (66% yield) as a white amorphous solid and was characterized as a mixture of isomers (E:Z ratio ≈ 3:1).…”