Sequential Carboxylation/Intramolecular Cyclization Reaction Of O-Alkynyl Ketones Using CO₂

Catalytic transformations of carbon dioxide (CO2) into fine chemicals have attracted considerable attentions, since CO2is an attractive, abundant and inexpensive Cl source. During the past decades, various new reactions of CO2incorporation have been successfully developed using CO2as a carboxylative reagent. In the presence of transition-metal catalyst, less reactive carbon nucleophiles can be smoothly carboxylated with CO2, which represent more attractive methods to access carboxylic acids bearing various functional groups. Also, hydro-, sila-or bora-carboxylation reaction of unsaturated compounds represents another attractive protocol to synthesize functionalized carboxylic acid and derivatives that are previously inaccessible by reaction of unsaturated compounds and CO2. Recently, direct carboxylation of terminal alkynes, direct carboxylation of C-H bond and direct carboxylation of electrophiles with CO2were successfully developed, which represented more economical methods to synthesize carboxylic acid and derivatives, avoiding tedious and costly preactivation steps.It is well-known that the a C-H bond in some ketones can undergo carboxylation reaction with CO2in the presence of suitable organic or inorganic bases. However, the products β-ketocarboxylic acids are inherently unstable due to rapid decarboxylation and difficult to be isolated. Therefore, further conversion of in situ formed β-ketocarboxylic acids into corresponding esters or β-hydroxycarboxylic acids were required after the carboxylation reaction. Base on this insight, we envisioned that introduce of another function group in the ketone to react with in situ formed enol would provide an opportunity to access the more stable carboxylated products under milder reaction conditions, more importantly, to gain some more useful intermediates for the preparation of biologically active compounds and other fine chemicals, which are inaccessible by other traditional methods.This thesis built up a new sequential carboxylation/intramolecular cyclization reaction of o-alkynyl ketone using CO2. The optimize the reaction conditions was established by a model reaction using2-(phenylethynyl)phenylethanone as substrate:CO2(balloon), AgBF4(2mol%), MTBD (2equiv), DMF,25℃,12h (for alkyl-substituted substrates:CO2(2MPa), AgOTf (10mol%), DBU (2equiv), DMF,50℃12h). Synthetically important1(3H)-isobenzofuranylidene acetic acids and corresponding esters were obtained in good yield and excellent selectivity under very mild reaction conditions (room temperature, CO2balloon).