Zinc Chloride Mediated Synthesis of 1,4‐Oxazepines from N‐Propargylic β‐Enaminones

Abstract

An efficient and general method for the synthesis of 1,4‐oxazepines is described. When reacted with ZnCl2 in DCM at 40 °C or CHCl3 at 61 °C, N‐propargylic β‐enaminones undergo 7‐exo‐dig cyclization to afford 2‐methylene‐2,3‐dihydro‐1,4‐oxazepines in good to high yields. This cyclization has been found to be general for a diverse range of N‐propargylic β‐enaminones, and proceeds with high efficiency and with broad functional group tolerance. The reactions in refluxing CHCl3 produced 1,4‐oxazepines in comparatively short reaction times and with better yields that those obtained in refluxing DCM. This operationally easy method may provide rapid access to a library of functionalized 1,4‐oxazepine derivatives of pharmacological interest.

Zinc Chloride Mediated Synthesis of 3H‐Oxazol‐2‐one and Pyrrolo‐oxazin‐1‐one from Ynamide

“…The infrared spectra of compounds were recorded on a Thermo Scientific Nicolet iS10. 1 H, 13 C and 19 F NMR spectra were recorded on a spectrometer at 250 MHz ( 13 C, 62.9 MHz) or 400 MHz ( 13 C,100 MHz;19 F: 376 MHz CPD). Chemical shifts are given in parts per million from tetramethylsilane (TMS) as internal standard.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ 3H),2H),7.30 (dd,J = 3.7,1.7 Hz,1H),7.15 (dd,J = 2.8,1.5 Hz, 1H), 6.48 (dd, J = 3.9, 2.8 Hz, 1H), 6.02 (d,J = 54.8 Hz,1H), 3.25 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): 13 C NMR (100 MHz, CDCl 3 ): δ = 155. 8, 133.0, 130.0, 128.9, 127.0, 126.0, 119.8, 117.8, 112.7, 103.8, 90.2 (J = 210 Hz), 51.2.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ = 7.69-7.66 (m, 2H), 7.56-7.54 (m, 2H), 7.50 (s, 1H), 7.32-7.30 (m, 1H), 7.21-7.19 (m, 1H), 6.63-6.62 (m, 1H), 0.29 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): δ = 154. 5, 141.5, 132.4, 130.3, 125.8, 123.9, 121.5, 116.8, 116.0, 113.8, 104.9, 104.3, 96.4, -0.10 3-(4-{2-[4-(Trifluoromethyl)phenyl]ethynyl}phenyl)pyrrolo-[2,1-c][1,4]oxazin-1-one (7b): Flash-column chromatography on silica gel with petroleum ether/ethyl acetate (90:10) as eluent gave 7b as a colorless oil (67 mg, 68 %) according to GP4.…”

“…The remaining free‐alpha‐position to the nitrogen atom may afford the possibility of performing further functionalization on this site. It is noteworthy that the formation of ring systems using zinc halides is scarce; only one example of zinc chloride‐catalyzed cycloisomerization of alkynes has been reported in the literature to date …”

“…that the formation of ring systems using zinc halides is scarce; only one example of zinc chloride-catalyzed cycloisomerization of alkynes has been reported in the literature to date. [13]…”