Datensatz

Zusammenfassung

This work describes the successful development of highly efficient and enantioselective organocatalytic approaches to the synthesis of chiral β-substituted ketones, β,β-disubstituted nitroalkanes as well as β-nitroesters. The latter could be efficiently converted to the corresponding β²-amino acids. Inspired by the in vivo enzymatic conjugate reductions with NAD(P)H cofactors, we established biomimetic transfer hydrogenations, for which dihydropyridines and organocatalysts were employed as NAD(P)H and enzyme analogues, respectively.
The asymmetric conjugate reduction of enones was achieved via iminium catalysis using a salt composed of a protonated valine tert-butyl ester and a chiral BINOL phosphate counteranion. The process was particularly well-suited for cyclic α,β-unsaturated ketones. Acyclic enones could also be successfully used, although yielding the products with slightly lower enantioselectivities.
A Jacobsen-type thiourea efficiently catalyzed the transfer hydrogenation of β,β-disubstituted nitroalkenes via hydrogen bonding catalysis. The reaction had a broad substrate scope and a number of aromatic and aliphatic nitroalkenes could be utilized.
Moreover, we successfully established a concise new strategy to enantioenriched β²-amino acids. The key step in this process was a highly enantioselective and efficient thiourea-catalyzed conjugate reduction of β-nitroacrylates to the saturated analogues. The nitroesters were then easily and efficiently converted into the corresponding β²-amino acids. In addition, a convenient synthesis of the required β-nitroacrylates via a Henry reaction-dehydration process was developed.