RESUMO
anti-Selective catalytic asymmetric nitroaldol reactions of α-keto esters promoted by a heterogeneous Nd/Na heterobimetallic catalyst exhibited a significant, unexpected disparity in enantioselection that was solvent-dependent. This phenomenon exclusively occurred when the stereogenic center of a diamide ligand had the smallest substituent (Me group, derived from l-Ala), which behaved uniquely in comparison with other structurally similar ligands to provide antipodal products under otherwise identical conditions.
RESUMO
A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.
Assuntos
Álcoois/síntese química , Ésteres/química , Furanos/química , Cetonas/química , Nitrocompostos/química , Catálise , Ésteres/síntese química , Neodímio/química , Nitrocompostos/síntese química , Quinazolinas/síntese química , Sódio/química , Solventes/química , Estereoisomerismo , Triazóis/síntese químicaRESUMO
A highly anti-selective catalytic asymmetric nitroaldol reaction of trifluoromethyl ketones based on Nd/Na and Pr/Na heterobimetallic catalysts was developed. These catalysts function as heterogeneous catalysts to engage nitroethane and a range of trifluoromethyl ketones in a stereoselective assembly to afford CF3-appended vic-nitroalkanols that could be readily converted to enantioenriched vic-amino alcohols, which are privileged structural motifs in medicinal chemistry.
Assuntos
Amino Álcoois/química , Catálise , Cetonas , Estrutura Molecular , Sódio , EstereoisomerismoRESUMO
An asymmetric total synthesis of ent-pyripyropeneâ A was achieved by a convergent synthetic route. We used our originally developed Ti(III) -catalyzed radical cyclization to construct an AB-ring portion that consisted of a trans-decalin skeleton with five contiguous stereogenic centers. The coupling between the AB-ring and the DE-ring portions, and a subsequent C-ring cyclization, led to the total synthesis of ent-pyripyropeneâ A. An evaluation of the insecticidal activity of ent-pyripyropeneâ A against two aphid species revealed that ent-pyripyropeneâ A was 35-175 times less active than naturally occurring pyripyropeneâ A. This result indicated that the biological target of pyripyropeneâ A recognizes the absolute configuration of pyripyropeneâ A.