RESUMO
The catalytic asymmetric Friedel-Crafts/protonation of indoles and pyrroles with α-substituted nitroalkenes to give the corresponding adducts in a highly anti-selective manner was achieved by an imidazoline-aminophenol (L2)-Cu complex. The anti-adducts could be successfully transformed to biochemically important α-substituted ß-heteroarylalkylamines.
Assuntos
Alcenos/química , Aminas/síntese química , Compostos Heterocíclicos/química , Hidrocarbonetos Aromáticos/química , Nitrocompostos/química , Aminas/química , Catálise , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , Prótons , EstereoisomerismoRESUMO
A four-step synthetic route to fully substituted chiral tetrahydro-ß-carbolines (THBCs) is described. Starting from the (R,S,S)-Friedel-Crafts/Henry adduct obtained from three-component coupling of an indole, nitroalkene, and aldehyde catalyzed by imidazoline-aminophenol-CuOTf, the (1S,3S,4R)-THBCs were readily synthesized in a three-step operation including reduction of the nitro-functionality and Pictet-Spengler cyclization.
Assuntos
Alcaloides/síntese química , Carbolinas/síntese química , Neurotoxinas/síntese química , Alcenos/química , Aminofenóis/química , Catálise , Cobre/química , Ciclização , Imidazolinas/química , Estrutura Molecular , EstereoisomerismoAssuntos
Alcenos/química , Técnicas de Química Combinatória , Iminas/química , Níquel/química , Nitrocompostos/química , Alcenos/síntese química , Catálise , Técnicas de Química Combinatória/métodos , Ciclização , Iminas/síntese química , Modelos Moleculares , Nitrocompostos/síntese química , EstereoisomerismoRESUMO
The novel C(2)-symmetric bis(imidazolidine)pyridine (PyBidine) ligand was easily synthesized in a single condensation of 2,6-pyridyl aldehyde and optically active (S,S)-diphenylethylenediamine. In the C(2)-symmetric PyBidine-Cu(OTf)(2) complex, imidazolidine rings act as "chiral fences" to shield the first and third quadrants. Use of the PyBidine-Cu(OTf)(2) complex as a catalyst enabled the highly endo-selective reaction of imino esters and nitroalkenes to give the adducts in up to 99% ee.
Assuntos
Imidazolidinas/síntese química , Piridinas/síntese química , Catálise , EstereoisomerismoRESUMO
Catalytic asymmetric Friedel-Crafts reaction of pyrrole with nitroalkenes was smoothly catalyzed by newly synthesized nitro-substituted imidazoline-aminophenol (1b)-Cu complex to give the adduct with up to 92% ee.
Assuntos
Alcenos/química , Compostos Heterocíclicos/química , Imidazolinas/química , Compostos Organometálicos/química , Catálise , Pirróis/químicaRESUMO
A library of imidazoline-aminophenol ligands was synthesized on solid supports. After immobilization of chiral chloromethylimidazolines 1 and 2 onto the polystyrylsulfonyl chloride, nucleophilic substitution with (R)- or (S)-phenylethylamine (3 and 4) provided four combinations of polymer-supported imidazoline-amine ligands. Further reductive alkylation using salicylaldehydes 7-10 provided a series of imidazoline-aminophenol ligands (L9-L24). Analysis by solid-phase catalysis/circular dichroism high-throughput screening of a copper-catalyzed Henry reaction revealed that ligand L25, comprising a (S,S)-diphenylethylenediamine-derived imidazoline, (S)-phenylethylamine, and dibromophenol, was highly efficient, thus providing the adduct of nitromethane and benzaldehyde in 95 % ee. The combination of stereogenic centers was crucial in promoting the highly stereoselective reactions. The unique reaction sphere of L25 was also examined in a Friedel-Crafts alkylation of indole and nitroalkene to give the adduct in up to 83 % ee.
