Application of Metathesis Protocols to the Stereocontrolled Synthesis of some Functionalized ß-Amino Esters and Azaheterocycles.

In this account our aim was to give an insight into the application of metathesis protocols (ROM, RCM, RCEYM, CM, RRM) for the synthesis of various azaheterocyclic frameworks. Due to the high biological potential and importance in peptide chemistry and drug design of ß-amino acids our intention is to give a highlight on the synthetic procedures and transformation of these class of compounds with the above-mentioned metathesis strategies with emphasis on selectivity, stereocontrol, substrate-directing effect or functional group tolerance.

Stereocontrolled synthesis of some novel functionalized heterocyclic amino ester and amide derivatives with multiple stereocenters.

The synthesis of some novel functionalized fused-ring ß-amino lactones and lactams with multiple chiral centers has been attempted from readily available strained bicyclic ß-amino acids via a stereocontrolled synthetic route. The key step was ring-rearrangement metathesis of allyl/propargyl esters or N-allylated/N-propargylated amides of (oxa)norbornene ß-amino acids. The RRM transformations [ring-opening metathesis (ROM)/ring-closing metathesis (RCM) or ring-opening metathesis (ROM)/ring-closing enyne metathesis (RCEYM)] have been investigated using some commercially available catalysts. Importantly, the procedure used in this synthetic process does not affect the configurations of the chiral centers. This means that the structure of the starting (oxa)norbornene ß-amino acids predetermines the configuration of the formed products.

Selective Transformation of Norbornadiene into Functionalized Azaheterocycles and ß-Amino Esters with Stereo- and Regiocontrol.

Novel functionalized azaheterocycles with multiple chiral centers have been accessed from readily available norbornene ß-amino acids or ß-lactams across a stereocontrolled synthetic route, based on ring-opening metathesis (ROM) of the staring unsaturated bicyclic amino esters, followed by selective cyclization through ring-closing metathesis (RCM). The RCM transformations have been studied under various experimental conditions to assess the scope of conversion, catalyst, yield, and substrate influence. The structure of the starting norbornene ß-amino acids predetermined the structure of the new azaheterocycles, and the developed synthetic route took place with the conservation of the configuration of the chiral centers.