N the case of methyl benzoate, methyl methacrylate unexpectedly resulted in

N the case of methyl benzoate, methyl methacrylate unexpectedly resulted in the formation of two stable products in 10 yields. Once the structures of these products were established, it became evident that no C-O insertion had taken place in the starting ester 55. Instead, because of the favorable configuration of the methacrylate unit, a set of two ene-reactions apparently occurs to produce the two ester products 56 and 57 (Scheme 8). After optimization studies, it was found that running the methyl methacrylate reaction in acetonitrile at room temperature in the presence of an excess of the benzyne (3 equiv), the diarylated product 57 can be isolated in an 80 yield. Other methods leading to stereodefined trisubstituted alkenes usually utilize multiple synthetic steps and require the use of expensive rhodium catalysts.43 We therefore examined the scope of our aryne ene reaction. Unfortunately, allylic systems similar to methyl methacrylate, such as methacrylonitrile, methyl trans-2-butenoate, 3-methyl-2cyclohexenone, allyl and benzyl cyanides, resulted in only a very low conversion of the starting material or in the formation of mixtures of unidentified products. While a few ene reactions with a benzyne intermediate have been observed before,43 our reaction of methyl methacrylate proceeds under very mild conditions (MeCN, room temperature) and allows one to obtain the diarylated product 57 in a high yield.3. ConclusionsIn conclusion, we have developed an efficient and simple route to o-hydroxyaryl ketones, xanthones, 4-chromanones, flavones and their analogues by aryne incorporation into the CO bond of easily accessible carboxylic acids and subsequent reactions. Various functionalTetrahedron.Etesevimab Author manuscript; available in PMC 2014 April 01.Tezepelumab Dubrovskiy and LarockPagegroups have proven to be compatible with the reaction conditions. The method should prove useful and reliable for accessing these biologically and pharmaceutically important heterocyclic structures.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript4. Experimental section4.1. General The 1H NMR spectra were recorded at 300, 400, and 600 MHz as specified for particular compounds. The 13C NMR spectra were recorded at 75, 100, and 150 MHz. Chemical shifts are reported in units (ppm) by assigning the TMS resonance in the 1H NMR spectrum as 0.00 ppm and the CDCl3 resonance in the 13C NMR spectrum as 77.23 ppm. All coupling constants (J) are reported in Hertz (Hz). Thin layer chromatography was performed using 60 mesh silica gel plates, and visualization was effected by short wavelength UV light (254 nm). All melting points are uncorrected. High resolution mass spectra (HRMS) were recorded using EI at 70 eV or using a QTOF mass spectrometer (APCI at a voltage of 70 eV).PMID:23865629 All reagents were used directly as obtained commercially, unless otherwise noted. The characterization of compounds 3, 6, 12-15, 18, 21, 23, 29, 30, 32, 34, 36-40, 42, 48, and 49 can be found in our earlier report.9 4.2. General procedure for the reaction of carboxylic acids with arynes The aryne precursor (1.5 equiv) was added to a mixture of the carboxylic acid (0.25 mmol) and CsF (4.0 equiv) in 15 mL of freshly distilled THF, and the reaction mixture was then stirred in a closed vial at 125 for 18 h. After the reaction mixture was allowed to cool to room temperature, it was eluted through a plug of silica gel with ethyl acetate and the solvent was removed under reduced pressure. The.