Louis Hamon

Radical cyclizations of 1,4-dihydropyridines. Synthesis of chiral fused nitrogen heterocycles. Synthesis of Lupinine and Epilupinine

Radical cyclizations of 1-(4-iodoalkanoyl)-3-formyl-4-methyl-1,4-dihydropyridines are described and discussed. A regio and diasteroselective reaction is obtained under ultrasonic conditions. An application to the synthesis of lupinine and epilupinine is shown.

Highly Stereoselective trans Addition of π-Type Nucleophiles to a Bicyclic N-Acyliminium Ion – Application to the Synthesis of Indolizidine and Pyrrolizidine Alkaloids

Enantiopure bicyclic 5-ethoxytetrahydropyrrolo[1,2-c]oxazol-3-one 1b was prepared in two steps from the known tosylate 4, which is readily available from (S)-pyroglutamic acid. Trapping of the N-acyliminium ion (I), generated in situ from 1b in the presence of Lewis acid, with various silylated π-type nucleophiles gave rise selectively to trans adducts 2. The usefulness of this stereoselective access to trans-2,5-disubstituted pyrrolidines was illustrated by formal syntheses of 3,5-disubstituted indolizidine toxins, starting from 5-allyltetrahydropyrrolo[1,2-c]oxazol-3-one 2a. Moreover, an enantiodivergent synthesis of the pyrrolizidine alkaloids (+) and (–)-xenovenine was achieved starting from the same chiral building block 2a.

Direct derivatization of glyoxal into chiral templates providing complete discrimination between the aldehyde groups

Abstract Condensation between glyoxal thiophenol and N-substituted ( R )-phenylglycinol led to morpholine derivatives. The totally stereoselective formation of heterocycle 6 gives access to a chiral masked form of glyoxal in which the symmetry features of the dialdehyde have disappeared. The cyclisation is consistent with Baldwin rules for ring closures when applied to different competing pathways. AMI conformational calculations were used in order to rationalize the stereochemical outcome of the reported transformation.

Efficient Preparation of a Highly Strained Eleven-Membered Ring

Two strategies have been explored to build the highly strained eleven-membered ring 2, a potential precursor for the biosynthetic key intermediate of the protoilludane family: an intramolecular Horner-Wadsworth-Emmons olefination and an intramolecular Nozaki-Hiyama-Kishi type-ring closure.

Π-accepting ligands in cuprate reactions

Abstract A Molecular Orbital description of the reductive elimination during alkylation by dialkylcuprates has been used to explain the favourable role of π-accepting ligands such as cyanide or dimethyl maleate.

Unsymmetrical cyano-cuprates as reagents in substitution and addition reactions

Unsymmetrical cyano-cuprates prepared by treating CuCN with RLi, can by used instead of R2CuLi in substitution and addition reactions.

Stereochemistry, part. 62—Acetolysis of triterpenoid p-toluenesulfonates, part 2☆☆☆★★★

Abstract Synthesis of p -toluenesulfonates 8b and 9b and of labelled analogs is described and previous assignements of proton NMR signals for quaternary methyl groups are confirmed. Acetolysis of these p -toluenesulfonates in the presence of NaOAc gave both substitution and elimination products. Substitution could be accounted for by bimolecular processes (SN2 on carbon, S A N on sulfur). Kinetics confirmed the intervention of bimolecular processes for 8b . Elimination products came for a great part from intermediates formed by hydride and/or methyl shifts. All rearranged products could be explained by plain sigmatropic rearrangements or by contact ion pair rearrangements. Attention is drawn to the close resemblance between sigmatropic rearrangements and contact ion pair rearrangements.