RESUMO
The first asymmetric synthesis of α-allyl-α-aryl α-amino acids by means of a three-component coupling of α-iminoesters, Grignard reagents, and cinnamyl acetate is reported. Notably, the enolate from the tandem process provides a much higher level of reactivity and selectivity than the same enolate generated via direct deprotonation, presumably due to differences in the solvation/aggregation state. A novel method for removal of a homoallylic amine protecting group delivers the free amine congeners. The α-allyl group offers a means to generate further valuable α-amino acid structures as exemplified by ring closing metathesis to generate a higher ring homologue of α-aryl-proline.
Assuntos
Aminoácidos/síntese química , Iminas/química , Prolina/análogos & derivados , Prolina/síntese química , Alquilação , Aminoácidos/química , Ácidos Carboxílicos , Catálise , Técnicas de Química Combinatória , Ésteres , Estrutura Molecular , Prolina/química , EstereoisomerismoRESUMO
Mechanism studies of a mild palladium-catalyzed decarboxylation of aromatic carboxylic acids are described. In particular, reaction orders and activation parameters for the two stages of the transformation were determined. These studies guided development of a catalytic system capable of turnover. Further evidence reinforces that the second stage, protonation of the arylpalladium intermediate, is the rate-determining step of the reaction. The first step, decarboxylative palladation, is proposed to occur through an intramolecular electrophilic palladation pathway, which is supported by computational and mechanism studies. In contrast to the reverse reaction (C-H insertion), the data support an electrophilic aromatic substitution mechanism involving a stepwise intramolecular protonation sequence for the protodepalladation portion of the reaction.
Assuntos
Ácidos Carboxílicos/química , Éteres/síntese química , Compostos Organometálicos/química , Paládio/química , Catálise , Descarboxilação , Éteres/química , Cinética , Estrutura Molecular , Compostos Organometálicos/síntese química , Teoria QuânticaRESUMO
The synthesis of alpha,alpha-disubstituted alpha-amino acids by means of a three component coupling is reported. The coupling occurs through umpolung addition of organometallic reagents to the nitrogen of alpha-iminoesters. The resulting enolate intermediates subsequently react with electrophiles (aldehydes, imines, alpha,beta-unsaturated nitro, alkyl halides, acyl cyanides) to form a quaternary center. Tethering of the electrophile and nucleophile components provides cyclic alpha,alpha-disubstituted alpha-amino acid derivatives.
Assuntos
Aminoácidos/síntese química , Ésteres/química , Iminas/química , Compostos Organometálicos/química , Aminoácidos/química , Estrutura MolecularRESUMO
Alpha-iminoesters are useful precursors to substituted alpha-amino acid derivatives and are utilized in a number of organic transformations. As a consequence of the adjacent ester functionality, these imines are more reactive relative to other types of imines. While a significant body of work has focused on nucleophilic additions to the imine carbon (C-alkylation), a second pathway that involves nucleophilic reaction at the nitrogen (N-alkylation) is much less explored. This tutorial review highlights work that has exploited this unusual alpha-iminoester reactivity mode.
Assuntos
Ésteres/química , Iminas/química , Nitrogênio/química , Compostos Organometálicos/química , Alquilação , Boro/química , Cobre/química , Titânio/químicaRESUMO
A palladium-catalyzed aromatic decarboxylation reaction has been developed. With electron-rich aromatic acids, the reaction proceeds efficiently under fairly mild conditions in good yields. The method was useful with complex functionalized substrates containing hindered carboxylic acids.