Silver Triflate/N‐Fluorobenzenesulfonimide‐Catalyzed Cycloisomerization of Tryptamine‐Ynamide to Spiro[indoline‐3,4′‐piperidine] Induced by Cation‐π‐π Interactions between Substrate and Metal Ligand

Abstract

N‐Fluorobenzenesulfonimide (NFSI), one of the most popular fluorinating agents in organic synthesis, was used as a ligand of silver triflate (AgOTf) to assist the trapping of the persistent spiroindoleninium intermediates by forming a weak noncovalent interaction between the substrate and metal ligand. The AgOTf/NFSI catalytic system was identified in the cycloisomerization of tryptamine‐ynamide to spiro[indoline‐3,4′‐piperidine] derivatives. The substrate tolerances were demonstrated by various synthetic substrates and commercially available nucleophiles. A cation‐π‐π model was proposed to elucidate the mechanism of action based on the experimental observations and density functional theory (DFT) calculations.

Diastereoselective Synthesis of N-Methylspiroindolines by Intramolecular Mizoroki–Heck Annulations

“…), 2.81 (s, 3H), 2.65 (dd, J = 14.2, 8.1 Hz, 1H), 2.07 (dd, J = 14.2, 5.6 Hz, 1H). 13 (1R,4S)-4-(2,5-Dimethyl-1H-pyrrol-1-yl)-1′-methylspiro-[cyclopentane-1,3′-indolin]-2-ene-6′-carboxylic acid (12). A reaction vial was loaded with 10 (68.3 mg, 0.166 mmol) and lithium hydroxide (20.0 mg, 0.835 mmol), and a THF:H 2 O mixture (3:1, 1 mL) was added.…”

“… To further improve the utility of these unique scaffolds as tools in biotechnology and drug development projects new synthetic methods to access spiroindolines, preferably with high stereoselectivity, are needed. Several ways of producing spiroindolines exist in the literature, such as through interrupted Fischer indolization, isomerization/spirocyclization/transfer hydrogenation, , photocatalytic [2,2]-addition, silver , and gold catalyzed cyclization, as well as palladium-catalyzed dearomative ring-closing (Supporting Information). The Mizoroki–Heck reaction is one of the prominent methods for carbon–carbon bond formation, which is well-suited for utilization in the synthesis of sterically demanding spirocyclic structures, as demonstrated in the synthesis of spirooxindoles, − spirobenzofurans, and spirolactones .…”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…After thorough experimentalo bservation and DFT calculations, the authors described ac ation-p-p model for the interaction between the substrate and ligand (Scheme 141). [162] Base-mediated, Cu-catalyzedr egioselective one-pot cyclization of aryl andh eteroaryl-tethered ynamides to differently substituted indoles and aza-indolesw as demonstrated by Frischmuth and Knochel in 2013. As depicted in Scheme 142, initial magnesiation of bromoynamide 568 followed by Cu I -catalyzed cyclization of 569 in 5-endo-dig fashion and subsequent quenching with electrophile delivers the desired poly-substituted N-heterocycles 571 in good yield.…”

“…After thorough experimental observation and DFT calculations, the authors described a cation–π–π model for the interaction between the substrate and ligand (Scheme 141). [162] …”

Computational insight into gold(i)-catalyzed intramolecular regioselectivity of tryptamine-ynamide cycloisomerizations

“…[27][28][29][30][31][32][33][34][35][36][37][38][39] These methods use noble metals and Brønsted acids. [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] Among them, gold(I)-catalyzed reactions represent one of the most efficient methods. However, depending on different substitutions of the alkynyl moiety, the intramolecular addition of functional groups in these transformations typically proceed either at the α-position or at the β-position of the ynamide moiety.…”