Palladium‐Catalyzed Regioselective C‐2 Arylation of Benzofurans with N′‐Acyl Arylhydrazines

Abstract

A novel ligand‐free palladium‐catalyzed C‐2 arylation of benzofurans has been developed using N′‐acyl arylhydrazines as the coupling partners and TEMPO as an oxidant. This protocol features a wide functional‐group tolerance and highly regioselective products with good to excellent yields.

Palladium-Catalyzed C–H Arylation of Benzofurans with Triarylantimony Difluorides for the Synthesis of 2-Arylbenzofurans

“…Aryl donors such as previously known aryl halides, [ 15 , 16 , 17 , 18 , 19 , 20 ] arylboron reagents, [ 21 , 22 ] and aryl sulfonyl chlorides [ 24 , 25 ] often require bases, ligands for Pd catalyst, oxidants, high temperature, inert atomosphere, and/or acidic conditions. In contrast, Ph 3 SbF 2 is similar to arylhydrazines [ 29 ] and much more stable than the aryldiazonium salt [ 23 ], and the reaction proceeds smoothly only by adding an oxidant under mild conditions. However, Ph 3 SbF 2 has a low atom economy similar to the hypervalent iodine reagents, [ 26 , 27 , 28 ] and only one of the three aryls can be used in the reaction.…”

“…In addition, sterically hindered ortho-substituted Ar 3 SbF 2 2i gave coupling product 13i without difficulty. There are few reports of the Pd-catalyzed C–H arylation of benzofuran bearing an electron-donating or electron-withdrawing substituent at the 5-position [ 19 , 20 , 29 ]. The reactions of various benzofurans 1 with Ph 3 SbF 2 2a afforded the corresponding 2-phenylbenzofurans 13j – n in moderate-to-excellent yields.…”

“…The Celite plug was flushed with CH 2 Cl 2 , and the filtrate was evaporated to dryness under reduced pressure. The crude product was purified on a silica gel column chromatography to give the desired product 13a – n ( 13a – c , i , k : [ 19 ], 13d , g , j : [ 20 ], 13e , l : [ 29 ], 13f : [ 42 ], 13m : [ 22 ] 13n : [ 43 ]). See Supplementary Materials for copies of NMR spectra.…”

“…In addition, McGlacken and Wan independently reported the use of PdO-Fe 3 O 4 and a solid-based Pd catalyst for the reaction of benzofuran and diaryliodonium salts [ 27 , 28 ]. Tang et al demonstrated the C–2 arylation of benzofurans using N’ -acyl arylhydrazines in the presence of a PdCl 2 (MeCN) 2 catalyst and the 2,2,6,6-tetramethylpiperidine 1-oxyl radical (TEMPO) [ 29 ]. These procedures could be used complementarily; however, each reaction has several drawbacks in substrate scope and efficiency.…”

Recent Developments in C−H Functionalisation of Benzofurans and Benzothiophenes

“…In 2018, Tang and co‐workers reported the regioselective palladium‐catalysed C2‐arylation of benzofurans 17 using N ′‐acyl arylhydrazines 97 as a coupling partner (Scheme 19). [26] The reaction proceeded using a PdCl 2 (MeCN) 2 catalyst in the absence of a ligand with TEMPO as an oxidant in dioxane heated at 100 °C for 24 h. This resulted in the arylated products 98 in good yields between 57–93 %.…”