Pd(0)-catalyzed intramolecular Heck reaction: A general route for fused oxepine derivatives

Abstract

General Remarks1 Characterization data for compounds 3a-3k and 4a-4k 2-8 Characterization data for compounds 5b-5k and 7b-7k 8-14 Copy of 1 H NMR and 13 C 15-26 General Remarks:1 H NMR (200 MHz), 1 H NMR (400 MHz) spectra were recorded on a BRUKER-AC 200MHz.and 400MHz spectrometer. Chemical shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (deuterochloroform: 7.26 ppm). Data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, dd = double doublet), coupling constant (Hz). 13 C NMR (50 MHz), 13 C NMR (100MHz) spectra were recorded on a BRUKER-AC 200 MHz and 400MHz Spectrometer with complete proton decoupling. Chemical shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (deuterochloroform: 77.0 ppm). EIMS (70 ev) spectra were taken using a VG Autospec mass spectrometer. Chromatographic purification was done with either 60-120 or 100-200 mesh silica gel (SRL). For reaction monitoring, precoated silica gel 60 F254 TLC sheets (Merck) were used. Petroleum ether refers to the fraction boiling in the range 60-80 ºC. DMF was dried, distilled and stored over molecular sieves (4 Å). Experimental detailsGeneral procedure for the synthesis of bromoaldehydes (1): 1 A mechanically stirred solution of dimethylformamide(3 mmol) in anhydrous chloroform was cooled in ice bath while phosphorous tribromide (2.7 mmol) was added drop-wise over a period of 15 min. The resulting white suspension was warmed to rt and stirred for additional 20 min. A solution of starting ketomethylene compound (1 mmol) in chloroform was added drop-wise over 10 min. Stirring was continued for 8 h at rt. The reaction mixture was then poured in ice water. Solid sodium bicarbonate was carefully added to neutralize the acids and the mixture was extracted several times with dichloromethane. The organic part was then washed with cold water thoroughly, dried with sodium sulphate and evaporated. Purification of the residue was done by silica gel (60-120 mesh) column chromatography.General procedure for the synthesis ofAromaticbromoaldehydes (2): 2 β-Bromovinyl aldehyde (1 mmol) and DDQ (dichlorodicyano benzoquinone) (6 mmol) were kept in round bottom flask. Then dry benzene (6 mL) was added to the reaction vessel. After that, the total reaction mixture was heated for 16 h then the crude reaction mixture was filtered by dichloromethane (20 mL). The filtrate was dried and the crude product was purified by column chromatography. General procedure for the synthesis of bromoalcohols (3) 1,2Bromoaldehydes1(1 mmol) or aromaticbromoaldehydes2 (1 mmol) and sodiumborohydride (2 equiv.) were kept in two naked flask. Then acetonitrile solvent (5-6 mL) was added and stirred at room temperature for 2-3 h. After completetion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate (20 mL × 3) and dried over anhydrous Na 2 SO 4 . The solvent was evaporated and the crude product was puri...

Synthesis of Seven Membered Oxacycles: Recent Developments and New Approaches

“…The last entry in this section was published by Adak and coworkers, where the cyclization method is based on an intramolecular Heck reaction, following other similar approaches mentioned in the present text (Scheme 16). [37] Scheme 15. AuCl3-catalyzed cyclization of ortho-O-propagyl-1-one substituted arylaldehydes 59.…”

“…Adapted from ref. [37] The full mechanism for this transformation has been previously well documented, [38] so only a simplified version is presented here. The cyclization begins with the oxidative addition of Pd(OAc) 2 to the C-Br bond, to generate the intermediate 67.…”