Efficient Synthesis of Benzothiophenes by an Unusual Palladium‐Catalyzed Vinylic CS Coupling

Abstract

The simultaneous construction of a CS and a CC bond under catalytic conditions forms the basis of an efficient route to diversely functionalized benzothiophenes from gem‐dihalovinyl thiophenols. The CC bond can be formed in this tandem catalytic process with an organoboron reagent as shown in the scheme (R1=H, Me, F, Cl, Br, OCH2O; R2=H, Me; R3=aryl, heteroaryl, alkenyl, alkyl), or by Heck or Sonogashira coupling with an alkene or alkyne.

Synthesis of Functionalized Benzo[b]thiophenes by the Intramolecular Copper‐Catalyzed Carbomagnesiation of Alkynyl(aryl)thioethers

“…[12] Also, a novel tandem reaction consisting of an intramolecular S-vinylation and a subsequent intermolecular CÀC bond formation has been reported by Lautens and co-workers. [13] Since ortho-alkynyl benzenethiols are not accessible by Sonogashira coupling, [14] we envisioned a metalative cyclization involving alkynyl(aryl)thioethers, which are readily available in three straightforward steps starting from the corresponding 1,2-bromoiodoarenes (Scheme 1). [15] Herein, we report a mild and general method for the preparation of functionalized benzo [b]thiophenes and benzo [b]thieno[2, 3-d]thiophenes by means of an intramolecular catalytic carbocupration [16,17] reaction starting from alkynyl(aryl)thioethers.…”

Extremely Efficient Cross‐Coupling of Benzylic Halides with Aryltitanium Tris(isopropoxide) Catalyzed by Low Loadings of a Simple Palladium(II) Acetate/Tris(p‐tolyl)phosphine System

“…Solvents were dried by refluxing for at least 24 h over P 2 O 5 (dichloromethane) or sodium/benzophenone (THF, n-hexane or toluene) and were freshly distilled prior to use. 1 H NMR spectra were obtained with a Varian Mercury-400 (400 MHz) spectrometer, and 13 C NMR spectra were recorded with the Varian Mercury-400 (100.70 MHz) spectrometer. 3 reagents were prepared according to literature procedures.…”

“…[1][2][3][4][5][6] Recent studies have focused on the development of catalytic systems for coupling reactions of inert substrates, [7][8][9][10] formation of the C À N, [11] C À O, [12] or C À S [13] bond, and catalytic systems with metal Cu, [14] Ni, [15] or Fe [16] centers. In addition, ArTi(OR) 3 compounds have been recently found to be excellent aryl sources.…”

Sequentially Palladium-Catalyzed Processes in One-Pot Syntheses of Heterocycles

“…If the gem-dihalovinyl group was placed ortho to the amino group in amino-pyridines or anilines, the catalytic system performed a Buchwald-Hartwig amination followed by subsequent Suzuki- [104,105] or Heck-coupling [106], respectively. In a related fashion, the Lautens group could employ the same concept for a thioanellation furnishing 2-substituted benzothiophenes by sequentially Pd-catalyzed CS-and CC-bond formation [107]. Furthermore, the developed Pd-catalyzed Buchwald-Hartwig amination Suzuki-coupling methodology has been applied to the synthesis of kinase insert domain-containing receptor (KDR) kinase inhibitors, which pose as promising compounds in anti-tumor therapy [105].…”