Short Enantioselective Total Synthesis of Tatanan A and 3-epi-Tatanan A Using Assembly-Line Synthesis

Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly-line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio- and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate-controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps

Versatile C(sp2)−C(sp3) ligand couplings of sulfoxides for the enantioselective synthesis of diarylalkanes

The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98% yield and greater than 99.5% enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds, traditionally synthesised via transition metal-catalysed cross-couplings, which circumvents common issues associated with proto-demetalation and β-hydride elimination

Enantiospecific sp(2)-sp(3) coupling of secondary and tertiary boronic esters

The cross-coupling of boronic acids and related derivatives with sp² electrophiles (the Suzuki–Miyaura reaction) is one of the most powerful C–C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures

Synthèse asymétrique d'alcaloïdes de la famille des Lythraceae

Ce travail de thèse est dédié à la synthèse de la (+)-vertine et de la (+)-lythrine. Ces deux alcaloïdes possèdent des activités biologiques et physiologiques importantes. Entre autres, ils contribuent à augmenter le taux de glucose dans le sang, diminue de façon significative la pression sanguine. Il n'existe à notre connaissance, aucune synthèse de ces alcaloïdes décrite dans la littérature. La première synthèse totale de la (+)-vertine et de la (+)-lythrine est reportée. Toutes les réactions conduisant à la formation d'un nouveau centre asymétrique ont lieu avec une très bonne ou complète stéréosélectivité, à savoir : 1-La condensation asymétrique de la pelletiérine 2-La réduction diastéréoselective de la fonction cétone 3-La réaction de métathèse par fermeture du cycle. De plus, nous avons reporté le premier exemple de métathèse par fermeture de cycle pour former une lactone a, ß-insaturée à 12 chainons avec une Z sélectivité

Microfluidique-pour-la-photochimie

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Palladium-Catalyzed Cross-Coupling of Gem-Bromofluoroalkenes with Alkylboronic Acids for the Synthesis of Alkylated Monofluoroalkenes

Monofluoroalkenes are versatile fluorinated synthons in organic synthesis, medicinal chemistry and materials science. In light of the importance of alkyl-substituted monofluoroalkenes efficient synthesis of these moieties still represents a synthetic challenge. Herein, we described a mild and efficient methodology to obtain monofluoroalkenes through a stereospecific palladium-catalyzed alkylation of gem-bromofluoroalkenes with primary and strained secondary alkylboronic acids under mild conditions. This novel strategy gives access to a wide range of functionalized tri- and tetrasubstituted monofluoroalkenes in high yield, with good functional group tolerance, independently from the gem-bromofluoroalkenes geometry