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Abstract A stepwise copper‐catalyzed boracarboxylation then palladium‐catalyzed Suzuki‐Miyaura cross‐coupling methodology was developed to access 2,3‐diarylpropionic acid derivatives regioselectively by pre‐setting the position of the carboxylic acid in the boracarboxylation reaction. This method provides access to a wide range of aryl and heteroaryl products in up to 80% isolated yield. Pharmaceutical potential was demonstrated by synthesizing a glucagon receptor antagonist drug in three steps (31% overall yield) from commercially available 4‐tert‐butylstyrene. 

A unique class of β-boron-functionalized non-steroidal anti-inflammatory compound (pinB-NSAID) was previously synthesized via copper-catalyzed 1,2-difunctionalization of the respective vinyl arene with CO2 and B2pin2 reagents. Here, pinacolylboron-functionalized ibuprofen (pinB-ibuprofen) was used as a model substrate to develop the conditions for pinacol deprotection and subsequent boron functionalization. Initial pinacol-boronic ester deprotection was achieved by transesterification with diethanolamine (DEA) from the boralactonate organic salt. The resulting DEA boronate adopts a spirocyclic boralactonate structure rather than a diazaborocane–DABO boronate structure. The subsequent acid-mediated hydrolysis of DEA and transesterification/transamination provided a diverse scope of new boron-containing ibuprofen derivatives. 

In this comment, insights gained from density functional the- ory into the mechanism by which the Cu(I)-catalyzed boracar- boxylation of vinyl arenes occurs with specific focus on the CO2 insertion step are presented. Preliminary calculations indicated a potential non-covalent interaction between boron and CO2 in the carboxylation transition state, implicating cooperative CO2 activation. A study of boron Lewis acidity was conducted through substitution of sp2 mono-boron substituents. An inverse correlation between boron valence deficiency (BVD) and the enthalpic barrier of CO2 insertion into the β- borylbenzyl-Cu(I) bond was revealed, supporting Lewis acid/ base cooperativity between boron and the proximal oxygen of CO2 at the carboxylation insertion transition state. These find- ings suggest that future methodology development should consider strategic incorporation of similar Lewis acidic func- tionality to facilitate carboxylation of challenging substrates.