Halide-mediated Selective Cyclization Of O-alkynylbenzyl Alcohol (formic Acid)

The carbon-carbon triple bond is among the most important functional groups in organic chemistry and has been widely utilized in organic synthesis.The intramolecular cyclization of alkynes is an effective method for constructing various heterocyclic compounds.Over the past years,the intramolecular regioselective cyclization of aromatic acetylenes through neighboring group-participation is occupied an important position in organic synthesis.In this work,We have successfully developed a novel method for neighbouring amide（carboxy）groups-participated and intramolecular regioselective cyclization of aromatic acetylene to synthesize a potentially biologically active heterocyclic skeleton under mild conditions.1.TBAI-promoted 5-exo-dig cyclization of 2-alkynylbenzamidesWe have developed a regioselective amide-participating 5-exo-dig oxo-cyclization of aryl acetylene.The use of TBAI in combination with oxone,equivalent TBAI-mediated oxidative5-exo-dig iodo-oxycyclization of 2-alkynylbenzamide is used for the synthesis of various isobenzofuran derivatives.We have found that the use of water in a mixed solvent could change the reaction pathway and realize a high reaction regioselectivity.The optimum conditions:TBAI（2.0 equiv）,K₂CO₃（3.0 equiv）,oxone（2.0 equiv）in THF:H₂O（v/v,1:1）and 10%of aqueous HCl（0.5 mL）at room temperature.Many substituents tolerate the reaction conditions and produce carbonyl compounds in moderate to good yields.Furthermore,the application of the developed procedure was demonstrated by the synthesis of phthalazin-1（2H）-one and aryl-substituted isobenzofurans.2.TBAB-catalyzed cyclization of 2-alkynylbenzamidesWe have developed a catalytic TBAB-mediated oxidative 6-endo-dig oxy-cyclization of2-alkynylbenzamide is described herein for the synthesis of isocoumarin-1-imines.The optimum conditions:TBAB（0.1 equiv）,oxone（2.0 equiv）,K₂CO₃（3.0 equiv）,THF:H₂O（v/v=1:1）and 80°C.when N-phenyl 2-trimethylsilylethynylbenzamides are used as substrates an array of isobenzofuran-1-imines is also achieved under standard conditions.The reaction was environmentally benign and metal-free.3.TBAB-controlled cyclization of 2-Alkynylbenzoic AcidWe have developed a TBAB-controlled switchable synthesis of isocoumarin and isobenzofuran from the cyclization of 2-alkynylbenzoic acid.When the optimum conditions are TBAB（0.1 equiv）,oxone（2.0 equiv）,H₂O（2.0 mL）and 80°C,occuring regioselective6-endo-dig cyclization to synthesize various isocoumarins.When the optimum conditions are TBAB（2.0 equiv）,oxone（2.0 equiv）,H₂O（2.0 mL）and 80°C,occuring regioselective5-exo-dig cyclization to synthesize various isobenzofurans.the procedure reported herein represents a cleaner route towards isocoumarin and isobenzofuran with a higher reaction atom economy.