Rational development of regioselective difunctionalizations of arenes using carboxylates as deciduous directing groups

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Within a novel conceptual framework based on the use of carboxylates as deciduous directing groups, we intend to develop new methods for the regioselective synthesis of disubstituted arenes starting from benzoic acids. According to this concept, the carboxylate initially acts as a directing group by guiding a first substituent into its ortho position, leading to a regioselective C-H functionalization. This triggers a decarboxylation step in which the deciduous COOH group is discarded. The resulting organometallic intermediate is trapped by an electrophile, leading to the regioselective formation of a second C-C or C-heteroatom bond. The carboxylate thus stays in place as long as it is needed to control the regioselectivity of the C-H functionalization, but is shed tracelessly within the catalytic cycle, precluding any unwanted ortho,ortho-difunctionalization. The validity of this unprecedented reaction mode has been demonstrated in preliminary work. The key targets of the proposed research are to clarify the nature of the aryl-metal intermediate and to steer the reaction towards a second arene functionalization rather than protonolysis in order to maximize the diversity of obtainable products.