Organocatalytic asymmetric domino Michael-Henry reaction for the synthesis of substituted bicyclo[3.2.1]octan-2-ones

The first organocatalytic asymmetric reaction between 1,4-cyclohexanedione and nitroalkenes have been studied, affording bicyclo[3.2.1]octane derivatives containing four continuous stereogenic centres. The products were obtained through a domino Michael-Henry process as a single diastereoisomer with excellent enantioselectivities

Organocatalytic asymmetric domino Michael–Henry reaction for the synthesis of substituted bicyclo[3.2.1]octan-2-ones

This paper was submitted for publication in the journal "Chemical Communications" and the definitive version can be found at: http://dx.doi.org/10.1039/c3cc39165eThe first organocatalytic asymmetric reaction between 1,4-cyclohexanedione and nitroalkenes have been studied, affording bicyclo[3.2.1]octane derivatives containing four continuous stereogenic centres. The products were obtained through a domino Michael-Henry process as a single diastereoisomer with excellent enantioselectivities

New organocatalysts and applications in asymmetric organic transformations

Nowadays, organocatalysis constitutes the third pillar of asymmetric catalysis, alongside transition metal catalysis and biocatalysis. The definition of organocatalysis is the use of low molecular weight organic molecules as catalysts in organic transformations.The goals of this thesis were on one hand, to synthesize novel organocatalysts based on natural aminoacids and evaluate their activity in known asymmetric transformations, and on the other hand, to exploit organocatalysis in general in order to accomplish unprecedented asymmetric reactions.In the context of synthesizing novel organocatalysts, we synthesized primary amine-thioureas based on di-tert-butyl aspartate and a chiral 1,2-diamine and we studied their catalytic activity in the asymmetric Michael reaction between ketones and nitroalkenes or nitrodienes. Σhe primary amine-thiourea consisting of di-tert-butyl aspartate and (1R, 2R)-diphenylethylene-1,2-diamine, was found to be a very powerful organocatalyst exhibiting remarkable results in the asymmetric Michael addition of methyl ketones to nitroalkenes or nitrodienes. The aforementioned organocatalyst was employed in the key-step of the asymmetric synthesis of the commercially available drug Baclofen.In addition, organocatalysts known in the literature were employed in order to develop unprecedented asymmetric transformations, such as the domino Michael-Henry reaction between 1,4-cyclohexanedione and nitroalkenes and the asymmetric Mannich addition of 2-chloro-1,3-dicarbonyl compounds or nitroalkanes to oxindole derived ketimines.Furthermore, a segment of this thesis focused on the synthesis of proline derivatives properly modified for immobilization on carbon nanotubes, in order to evaluate their catalytic activity in asymmetric aldol reactions

A Reliable Enantioselective Route to Mono-Protected N1-Cbz Piperazic Acid Building Block

The chiral N1-Cbz, N2-H derivative of the piperazic acid monomer is a valuable building block in the total synthesis of natural products, comprising this nonproteinogenic amino acid. In that context, we wish to report an improved synthetic protocol for the synthesis of both (3R)- and (3S)-piperazic acids bearing the carboxybenzyl protecting group (Cbz) selectively at the N1 position. Our method builds on previously reported protocols, circumventing their potential shortcomings, and optimizing the ultimate selective deprotection at the N2 position, thus, offering an efficient and reproducible pathway to suitably modified piperazates in high optical purity