Silver-Catalyzed Enantioselective Propargylic C–H Bond Amination through Rational Ligand Design

Abstract

reaction mixture was diluted with E2O and washed with H2O. The aqueous layer was extracted with E2O three times. The combined organic layer was washed with H2O (three times) and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (0→70% EtOAc/hexanes) to afford the desired trifluoromethylated alkyne S5 as a white solid (0.26 g, 44% yield); 1 H NMR (500 MHz, CDCl3) δ

Biocatalytic, Intermolecular C−H Bond Functionalization for the Synthesis of Enantioenriched Amides

“…Methyl substitution at para-, ortho-, and meta-position (7-9) was tolerated. Naphthyl derivative (10), five-and six-membered rings (11,21), and propylbenzenes were competent substrates (12,13). Halogenated substrates (14-17) gave moderate to low TTNs (215-1000), consistent with the trend of electron-rich substrates performing better than electron-poor ones.…”

“…[6][7][8] In the presence of an appropriate organometallic catalyst (typically Rh, Ru, Ir, or Co), the resulting acyl(metal)nitrenoid species can undergo enantioselective CÀH insertion reactions to form amides. [9] This strategy has largely been confined to intramolecular lactam formation [10][11][12][13][14][15][16] and some cases of C(sp 2 )-H functionalization. [17,18] Only three enantioselective, intermolecular versions have been reported for C(sp 3 )-H amidation.…”

Taming Nitrene Reactivity with Silver Catalysts

“…Inspired by the success of bis(oxazoline) ligands in achieving regioselective intramolecular C-H insertion and asymmetric aziridination reactions, efforts towards designing a BOX catalyst for intramolecular asymmetric propargylic C-H insertion were undertaken. 39 A brief survey of ligands revealed that aryl-box ligands gave moderate ee for propargylic C-H bond amidation. Electronic modifications to these scaffolds and attempts to utilize NCIs to improve ee Scheme 12 Late-stage functionalization utilizing Ag-catalyzed NT.…”

Stereoretentive and regioselective selenium-catalyzed intermolecular propargylic C–H amination of alkynes

“…However, propargylic C-H amination has received relatively little attention (Scheme 1). Though several examples of intramolecular C-H amination of alkynes using metal nitrenoids have been reported, [24][25][26][27][28][29][30][31] the need for an appropriately tethered nucleophile fundamentally limits their substrate scope and generality. In contrast, intermolecular propargylic C-H aminations are surprisingly rare.…”