RESUMO
The vinylation of various nucleophiles with acetylene at a maximum pressure of 1.5 bar is achieved by organocatalysis with easily accessible phosphines like tri-n-butylphosphine. A detailed mechanistic investigation by quantum-chemical and experimental methods supports a nucleophilic activation of acetylene by the phosphine catalyst. At 140 °C and typically 5 mol % catalyst loading, cyclic amides, oxazolidinones, ureas, unsaturated cyclic amines, and alcohols were successfully vinylated. Furthermore, the in situ generation of a vinyl phosphonium species can also be utilized in Wittig-type functionalization of aldehydes.
RESUMO
The reaction of cyclic amides with acetylene under low pressure, using ruthenium-phosphine catalysts, afforded a broad variety of N-vinylated amides including (azabicyclic) lactams, oxazolidinones, benzoisoxazolones, isoindolinones, quinoxalinones, oxazinanones, cyclic urea derivatives (imidazolidinones), nucleobases (thymine), amino acid anhydrides and thiazolidinone.
RESUMO
A greatly improved process has been developed for synthesis of the glutarate derivative 2, a key intermediate required for Pfizer's drug candoxatril. The cationic (R,R)-Me-DuPHOS-Rh catalyst was found to allow highly efficient and enantioselective hydrogenation of a unique carboxylate substrate (5) to afford the desired product in >99% ee and high yield (95%). The robust nature of the process was validated on a 12 kg reaction scale. A novel mechanism for the hydrogenation process is proposed. Through use of a labile eta(6)-benzene-Rh-Me-DuPHOS complex, the postulated catalytic intermediates have been synthesized by independent means. Detailed spectroscopic analyses of these intermediates corroborate the mechanistic hypotheses. Interconversion of these key catalytic intermediates has been demonstrated.
