RESUMEN
The Pd(0)-mediated umpolung reaction of an alkyne to achieve trans-difunctionalization is a potential synthetic methodology, but its insightful activation mechanism of Pd(0)-alkyne interaction has yet to be established. Here, a Pd(0)-π-Lewis base activation mode is proposed and investigated by combining theoretical and experimental studies. In this activation mode, the Pd(0) coordinates to the alkyne group and enhances its nucleophilicity through π-back-donation, facilitating the nucleophilic attack on the aldehyde to generate a trans-Pd(ii)-vinyl complex. Ligand-effect studies reveal that the more electron-donating one would accelerate the reaction, and the cyclization of the challenging flexible C- or O-tethered substrates has been realized. The origin of regioselectivities is also explicated by the newly proposed metal π-Lewis base activation mode.
RESUMEN
The transition metal-catalyzed asymmetric hydro-functionalization of 1,3-dienes has been well explored, but most reactions focus on electron-neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4-dienyl hydrazones and oximes can be efficiently utilized in the hydro-cyclization reaction under co-catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron-deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α-regioselective protonation of dienyl substrates by acid and concurrent π-Lewis base activation of Pd0 complex is energetically favoured in the formation of active π-allylpalladium intermediates, and an outer-sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.
RESUMEN
The alkyne group can undergo facile transformations under palladium catalysis, such as hydropalladation, Wacker reaction, etc. Here we demonstrate that a chiral Pd0 complex can chemoselectively dihapto-coordinate to the alkyne moiety of 2-indolyl propiolates, and raise the Highest Occupied Molecular Orbital (HOMO)-energy ofthe deactivated heteroarenes via π-Lewis base catalysis. As a result, asymmetric C3-selective Friedel-Crafts addition to activated alkenes occurs, finally affording [3 + 2] or [3 + 4] annulation products with high enantioselectivity and exclusive E-selectivity. Moreover, this π-Lewis base vinylogous HOMO-activation strategy can be extended to remote Friedel-Crafts reaction of diverse five-membered heteroarenes tethered to a 2-enone or 2-acrylate motif with imines or 1-azadienes, and excellent enantiocontrol is generally achieved for the multifunctional adducts, which can be effectively converted to diverse frameworks with higher molecular complexity. In addition, NMR and density functional theory calculation studies are conducted to elucidate the catalytic mechanism.
RESUMEN
A relay catalytic protocol using pyrrolidine and palladium catalysis has been developed for asymmetric synthesis of 1,3-diamine derivatives from 3-substituted 1,3-dienes, sulfuric diamide, and aldehydes. This one-pot, three-component reaction features the advantages of a high atom step economy and operational simplicity, providing an efficient and straightforward access to valuable 1,3-diamines incorporating quaternary and tertiary stereogenic centers with moderate to good enantioselectivity.
RESUMEN
The first catalytic asymmetric alkenylation of isatin imines is described. The reaction, which is promoted by a chiral bis(oxazoline)-copper complex, gives structurally diverse 3-alkenyl-3-aminooxindole derivatives in excellent yields, and with excellent diastereoselectivities and high-to-excellent enantioselectivities. The products can be readily converted to polycyclic indole derivatives without loss of enantioselectivity. A plausible chirality-induced mechanism is proposed to explain the observed stereoselective control.
