RESUMO
[Reaction: see text] The stereoselective preparation of (E)- or (Z)-trisubstituted alpha,beta-unsaturated esters in three steps from N-protected glycine is presented. The key step in the synthesis is the highly selective enol tosylation of gamma-amino beta-keto esters. The enol tosylates are stable, crystalline compounds that undergo smooth and effective Suzuki-Miyaura coupling reaction with a variety of aryl boronic acids.
Assuntos
Aldeídos/química , Ésteres/síntese química , Glicina/química , Cetonas/química , Compostos de Tosil/química , Ésteres/química , Estrutura Molecular , Estereoisomerismo , Ácido gama-Aminobutírico/químicaRESUMO
A general method for the enantioselective hydrogenation of protected allylic amine derivatives is described. This procedure relies on the generation of a cationic ruthenium complex with the axially chiral ligand (-)-TMBTP. The utility is highlighted by the highly enantioselective hydrogenation of a diene substrate that can then be elaborated to prepare Telcagepant, a compound currently in Phase III clinical trials. The scope of the hydrogenation reaction was studied, and a variety of substituted allylic amine derivatives could be hydrogenated with enantiomeric ratios of 92:8 or higher.
Assuntos
Compostos Alílicos/química , Aminas/química , Azepinas/síntese química , Caprolactama/síntese química , Catálise , Hidrogenação , Imidazóis/síntese química , Estrutura Molecular , EstereoisomerismoRESUMO
An expedient, five step synthesis of caprolactam 1 is reported starting from natural L-homoserine. The key step is a chemoselective reductive cyclization of alpha,beta-unsaturated nitrile 10 mediated by Raney-Co type metals. This hydrogenation is extensively investigated in order to account for the observed product distribution and yields.
Assuntos
Cobalto/química , Nitrilas/química , Aldeídos/síntese química , Aldeídos/química , Caprolactama/química , Ciclização , Homosserina/síntese química , Homosserina/química , Isomerismo , Metionina/química , Estrutura Molecular , Oxirredução , TemperaturaRESUMO
[reaction: see text] Herein we demonstrate functionalized enol tosylates to be robust substrates that undergo Suzuki-Miyaura, Sonogashira, and Stille cross-coupling reactions to provide stereodefined trisubstituted unsaturated esters.