RESUMEN
Enantioenriched complex fused-tricyclic azepanes or bridged-polycyclic azocanes were constructed via a two-step sequence involving an enantioselective organocascade followed by superacid activation of the domino adduct. The activated oxa-bridged azepane acts as a key hidden heptacyclic chiral N-acyl iminium ion triggering a chemo- and diastereoselective intramolecular mono- or di-arylation.
Asunto(s)
Estereoisomerismo , IonesRESUMEN
Achieving in a straightforward way the synthesis of enantioenriched elaborated three-dimensional molecules related to bioactive natural products remains a long-standing quest in organic synthesis. Enantioselective organocatalysis potentially offers a unique opportunity to solve this problem, especially when combined with complementary modes of activation. Here, we report the sequential association of organocatalytic and superacid activations of simple linear achiral readily available precursors to promote the formation of unique highly elaborated chiral methylene-bridged benzazocanes exhibiting three to five fully-controlled stereocenters. This peculiar backbone, difficult to assemble by standard synthetic approaches, is closely related to bioactive natural and synthetic morphinans and benzomorphans. The formation of a highly reactive chiral 7-membered ring N-acyl iminium superelectrophilic ion, evidenced by low-temperature in situ NMR experiments, triggers a challenging stereoselective Friedel-Crafts-type cyclization.
RESUMEN
Catalytic synthesis of nonracemic P-chiral phosphine derivatives remains a significant challenge. Here we report Cu-catalyzed enantioselective arylation of secondary phosphine oxides with diaryliodonium salts for the synthesis of tertiary phosphine oxides with high enantiomeric excess. The new process is demonstrated on a wide range of substrates and leads to products that are well-established P-chiral catalysts and ligands.
RESUMEN
A method for the direct and rare umpolung of the 3 position of indoles is reported. The activation of N-acetylindole with iron(III) chloride allows the C-H addition of aromatic and heteroaromatic substrates to the C2=C3 double bond of the indole nucleus to generate a quaternary center at C3 and leads regioselectively to 3-arylindolines. Optimization, scope (50 examples), practicability (gram scale, air atmosphere, room temperature), and mechanistic insights of this process are presented. Synthetic transformations of the indoline products into drug-like compounds are also described.
RESUMEN
IRONic electrophilic indoles! The C3-regioselective hydroarylation of N-acetyl indoles with aromatic nucleophiles mediated by FeCl(3) features a rare example of the electrophilic reactivity of the indole core in a Friedel-Crafts reaction. This indole umpolung allows us straightforward access to the tetracyclic benzofuroindoline motif found in the natural product diazonamideâ A, which is a potent antitumor agent.
Asunto(s)
Antineoplásicos/síntesis química , Cloruros/química , Compuestos Férricos/química , Indoles/química , Antineoplásicos/química , Catálisis , Compuestos Heterocíclicos de 4 o más Anillos/síntesis química , Compuestos Heterocíclicos de 4 o más Anillos/química , Indoles/síntesis química , Oxazoles/síntesis química , Oxazoles/química , EstereoisomerismoRESUMEN
Hydrogen bonds can play a prominent role in organometallic catalysis, as shown for the title reaction, in which a counteranion directs the cyclization through the formation of hydrogen bonds that likely involve a proton of the π-allyl/palladium species itself. The reaction allows access to four out of the eight stereoisomers of 2,5-disubstitued 3-hydroxy-tetrahydrofurans and thus fragments of complex natural products.
Asunto(s)
Furanos/química , Paladio/química , Catálisis , Ciclización , Furanos/síntesis química , Enlace de Hidrógeno , Estructura Molecular , Estereoisomerismo , TermodinámicaRESUMEN
Herein, we report a mechanistic exploration of the unusual FeCl3-mediated hydroarylation of N-Ac indoles. Electron density topology analysis of a crystal, in situ IR monitoring, Hammett and Taft studies as well as DFT computations allowed us to determine that activation of acetyl with FeCl3 and of the C2[double bond, length as m-dash]C3 bond with a proton is involved.
RESUMEN
We report the FeCl3-mediated direct addition of electron-rich arenes to the C2-position of electrophilic N-Ac indoles under mild conditions (room temperature, air). No functional group is required on the arene nucleophile: one of its C-H bonds is added to the C2[double bond, length as m-dash]C3 double bond of the indole nucleus in a Friedel-Crafts-type reaction. This dearomatisation process delivered a broad range of C2-arylated indolines.
RESUMEN
The straightforward entry to benzofuroindoline containing natural product-like scaffolds has been achieved by a challenging [3 + 2] oxidative coupling between phenols and indoles. The reaction proceeds by NIS-oxidation of the indole followed by the trapping of the resulting electrophilic intermediate by phenol.