Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia.

Exhaustive Michael-type alkylations of amines and ammonia with azoalkenes (generated from α-halohydrazones) were demonstrated as an efficient approach to poly(hydrazonomethyl)amines - a novel class of polynitrogen ligands. An intramolecular cyclotrimerization of C=N bonds in tris(hydrazonomethyl)amine to the respective 1,4,6,10-tetraazaadamantane derivative was demonstrated.

Divergent Reactivity of In Situ Generated Metal Azides: Reaction with N,N-Bis(oxy)enamines as a Case Study.

Metal azides generated in situ by ion exchange exhibit divergent reactivity in reaction with cyclic N-alkoxy,N-siloxy-enamines. Depending on the nature of metal and the [M]/N ratio, addition of the azide ion to the C,C-double bond proceeds with regioselective cleavage of either exo- or endo-cyclic N-O bond leading to cyclic or open-chain α-azidooxime derivatives, respectively. Mechanistic studies in combination with solvent state FTIR spectroscopy and DFT calculations revealed that covalently bound metal azides (Co, Cu, Zn) transfer N anion to the C,C-double bond through a Lewis acid-assisted S ' substitution of trialkylsilyloxy-group.

Synthesis of PDE IV inhibitors. First asymmetric synthesis of two of GlaxoSmithKline's highly potent Rolipram analogues.

Asymmetric syntheses of two of GlaxoSmithKline’s highly potent phosphodiesterase IV inhibitors CMPI 1 and CMPO 2 have been accomplished from nitroethane and simple precursors in 8 and 7 steps, respectively. The suggested synthetic strategy involves as a key stage the silylation of enantiopure six-membered cyclic nitronates. In vitro studies of PDE IVB1 inhibition revealed a significant difference in the activity of CMPI 1 and CMPO 2 enantiomers.