Application of NMR Spectroscopy for the Detection of Equilibrating E-Z Diastereomers.

Conjugation can lower the energy barrier for unsaturated C-C bond rotations, resulting in a mixture of equilibrating diastereomers at room temperature. Therefore, methods claiming diastereoselective synthesis of conjugated double bonds often require proof that the observed diastereomeric ratio is not because of the diastereomeric equilibration of the product. Variable-temperature (VT) NMR experiments are commonly used to distinguish between the two possibilities. However, the VT technique requires accessories for the NMR spectrometer and more setup time. Here, we show that the rarely used application of 1-D and 2-D nuclear Overhauser effect spectroscopy experiments for the detection of the equilibrating diastereomers is a convenient alternative to the VT technique.

Copper-Catalyzed Coupling of Thioamides and Donor/Acceptor-Substituted Carbenoids: Synthesis of Enamino Esters and Enaminones.

The coupling of thioamides and donor/acceptor-substituted diazocarbonyl compounds is reported for the first time. The present report provides a mild, catalytic method that couples thioamides and donor/acceptor-substituted diazocarbonyl compounds to form enamino esters and enaminones. Unlike traditional methods for the synthesis of enamino esters and enaminones from thioamides, both N-alkyl thioamides and thiocarbamates are suitable substrates in this coupling reaction. Copper(I) bromide catalyzes the reaction and provides enamino esters and enaminones chemo- and diastereoselectively in less time than Rh2(OAc)4 or Ru(PPh3)3Cl2 catalysts.

2,5-Disubstituted pyrrolidines: synthesis by enamine reduction and subsequent regioselective and diastereoselective alkylations.

Methodology for the diastereoselective synthesis of 2,5-disubstituted pyrrolidines by reduction of enamines derived from pyroglutamic acid is reported; the nature of nitrogen protection was found to be critical for the stereochemical control of the reaction outcome. Regioselective manipulation of the C-2 and C-5 substituents is possible, providing access to differently substituted pyrrolidines for a limited number of cases.

2,5-Disubstituted pyrrolidines: versatile regioselective and diastereoselective synthesis by enamine reduction and subsequent alkylation.

A direct and versatile route enabling the regio- and diastereoselective synthesis of 2,5-disubstituted pyrrolidines by reduction of enamines derived from pyroglutamic acid is reported.