Palladium‐Catalyzed Decarbonylative Borylation of Carboxylic Acids: Tuning Reaction Selectivity by Computation

Abstract

Decarbonylative borylation of carboxylic acids is reported. Carbon electrophiles are generated directly after reagent‐enabled decarbonylation of the in situ accessible sterically‐hindered acyl derivative of a carboxylic acid under catalyst controlled conditions. The scope and the potential impact of this method are demonstrated in the selective borylation of a variety of aromatics (>50 examples). This strategy was used in the late‐stage derivatization of pharmaceuticals and natural products. Computations reveal the mechanistic details of the unprecedented C−O bond activation of carboxylic acids. By circumventing the challenging decarboxylation, this strategy provides a general synthetic platform to access arylpalladium species for a wide array of bond formations from abundant carboxylic acids. The study shows a powerful combination of experiment and computation to predict decarbonylation selectivity.

Synthesis of Biaryls via Decarbonylative Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Carboxylic Acids

“…To this end, metal-catalyzed C–H functionalizations directed by a carboxylic acid ( 3ae ) as well as metal-free electrophilic halogenation ( 3af ) significantly expand the pool of carboxylic acid precursors available for cross-coupling (Twilton et al., 2017, Knappke and Jacobi von Wangelin, 2010). The combination with decarbonylative borylation (Liu et al., 2018) to furnish organoboranes directly from carboxylic acids ( 3ag ) and valorization of toluenes ( 3ah ) (Figure 3C) offers a new opportunity for adopting in synthetic processes.…”

Metal‐Free Decarboxylation of α,β‐Unsaturated Carboxylic Acids for Carbon–Carbon and Carbon–Heteroatom Coupling Reactions

“…Among them, the construction of C-B bond has attracted more and more attention. Although some advances have been achieved in metal-catalyzed decarboxylative reactions for the formation of C-B bond, [77] alternative metal-free versions have not yet been developed.…”

Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C–H Borylation and Suzuki Coupling

“…With the advent of transition metal-catalyzed reactions [ 40 , 41 , 42 , 43 , 44 ], derivatization of preformed pyrrole ring has grown as an alternate strategy for the synthesis of arylated pyrroles. However, preparation of pyrrole-based organometallic reagents employing halogen-metal exchange requires Boc-protection of the acidic N-H proton ( Figure 2 ) [ 45 ].…”