Rh-Catalyzed General Method for Directed C–H Functionalization via Decarbonylation of in-Situ-Generated Acid Fluorides from Carboxylic Acids

Abstract

A Rh-catalyzed decarbonylative C–H coupling of in-situ-generated acid fluorides with amide substrates bearing ortho-Csp2–H bonds has been developed. This method enables alkyl, aryl, and alkenyl carboxylic acids to undergo decarbonylative coupling with C–H bonds of (hetero)­aromatic or alkenyl amides in generally good yields via the in situ conversion of carboxylic acids into acid fluorides and also allows for the functionalization of a series of structurally complex carboxyl-containing natural products and pharmaceuticals as well as pharmaceutical amide derivatives.

Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis

“…We hypothesized that this issue could be addressed by changing the X-type ligand on Pd II from trifluoro­acetate to a more reactive fluoride. , Previous work , has demonstrated that transition metal fluoride complexes exhibit high transmetalation activity toward various aryl boron nucleophiles. To generate a Pd II –F intermediate, we treated a THF solution of II-CHF 2 with anhydrous tetramethyl­ammonium fluoride (Me 4 NF) for 0.5 h at 25 °C (Figure ).…”

“…Moving forward, we focused on optimizing catalytic decarbonyl­ative difluoro­methyl­ation, since this was the highest yielding reaction among those in Figure . To eliminate the need for the hygro­scopic fluoride additives, we independently synthesized anhydrous DFAF as a concentrated solution in THF (see the Supporting Information for full details) and deployed it directly as the electro­phile for cross-coupling. , As shown in Table , entry 1, none of product 1 was detected at room temperature with DFAF as the electrophile, consistent with slow oxidative addition. However, upon heating this reaction to 130 °C, 1 was formed in 51% yield (Table , entry 3).…”

Recent Advances in C–F Bond Activation of Acyl Fluorides Directed toward Catalytic Transformation by Transition Metals, N-Heterocyclic Carbenes, or Phosphines

“…62 The following reaction mechanism based on experimental results can be reasonably Very recently, Su et al developed the rhodium-catalyzed ortho-C-H functionalization of (hetero)aromatics with 8quinolylamine as a bidentate directing group by in-situ preparing a series of acyl fluorides from the corresponding carboxylic acids (Scheme 33). 63 In addition, the substrate scope including a wide variety of pharmaceutical molecules was extensively explored and a possible reaction mechanism was deduced (Scheme 34). Initially, a bidentate directing group, 8-aminoquinolylamido moiety coordinates to the rhodium center, which simultaneously activates the C-F bond of the in-situ generated acyl fluoride in the process of oxidative addition to form Rh(III) complex A, from which a decarbonylation process occurs to form the Rh(III) complex C through the CO extrusion.…”

“…Very recently, Su et al developed the rhodium-catalyzed ortho-C-H functionalization of (hetero)aromatics with 8quinolylamine as a bidentate directing group that proceeded via the in situ preparation of a series of acyl fluorides from the corresponding carboxylic acids (Scheme 33). 63 In addition, the substrate scope, which included a wide variety of pharmaceutical molecules, was extensively explored and a possible reaction mechanism was deduced (Scheme 34).…”

Palladium-Catalyzed Decarbonylative Nucleophilic Halogenation of Acyl Fluorides and Chlorides: Synthesis of Aryl Halides via Reductive Elimination of the C–X (X = I, Br, and Cl) Bond and Mechanistic Implications

“…For those acyl fluorides that are not commercially available, they can be synthesized in a single step from the corresponding carboxylic acids and used directly in subsequent reactions, either by simple filtration or without further purification. Building upon the pioneering work of Schoenebeck and Keaveney in 2018, wherein Pd-catalyzed trifluoromethylation of acyl fluorides was achieved, subsequent investigations by various groups, , including our own research team, have unveiled diverse decarbonylative transformations of acyl fluoride, underscoring its distinctive reactivity. In the pursuit of methods for synthesizing organic iodides from carboxylic acid derivatives, the Pd-catalyzed decarbonylative iodination of acyl chlorides by Morandi and Arndtsen stands out, earning acclaim for their significant breakthrough in Ar–I bond formation through reductive elimination from Pd(II) species.…”