16501-24-9

Laser flash photolysis studies (LFP) of O,S-diethylmonothiodiazomalonate (1) and S,S-dietrryldithiodiazomalonate (2) in 1,1,2-trichlorotrifluoroethane (Freon-113) were consistent with the trapping of an intermediate with λmax = 425 nm, attributed, in the LFP of 1, to that of ylide 10, formed from the reaction of singlet O,S-carboethoxythioethoxycarbene (9) with pyridine. The deduced lifetime of both singlet O,S-dicarboethoxycarbene (9) and S,S-dicarbothioethoxycarbene (13) are essentially the same in Freon-113, but compared to dicarbomethoxycarbene 14, the lifetimes of 9 and 13 were found to be about six times shorter. The LFP studies, in addition to calculations at the B3LYP/6-31 G* level of theory, provide an explanation for the effect of sulfur perturbation that shortens the carbene lifetimes, as well as an explanation for the exclusive migration of the SEt group to ultimately form 5 upon light (300 nm) induced nitrogen extrusion and Wolff rearrangement of 1 in EtOH.

2-Carboxyethanethioic S-esters (RSCOCH2COOH) and propanebis(thioic) S,S'-diesters (RSCOCH2COSR) were easily prepared in high yields by the direct condensation of malonic acid with thiols in the presence of ethyl polyphosphate (PPE).

A series of novel l-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-β-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R)-phenibut in high yield.

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.