Françoise Dumas

High pressure activation in the asymmetric Michael addition of chiral imines to alkyl and aryl crotonates

High pressure-mediated Michael addition of chiral imines derived from 2-methylcyclopentanone, 2-methylcyclohexanone and optically active 1-phenylethylamine, to methyl and phenyl crotonates was investigated. The corresponding adducts were obtained in fair yields and with a high degree of regio-, diastereo- and enantioselectivity.

The origin of the stereoselectivity in the asymmetric Michael reaction using chiral imines/secondary enamines under neutral conditions: a computational investigation

Abstract The diastereoselectivity in the asymmetric Michael reaction using chiral imines/secondary enamines under neutral conditions has been investigated with the help of AM1 calculations. The energetic differences between the two competing transition states involving enamino ketones 7d , 7g and methyl acrylate are in good agreement with the stereoselectivities observed with the corresponding chiral imines, derived from 1-phenylethylamine (de 95%) and from 1-cyclohexylethylamine (de 45%). The calculated transition structures indicate that steric factors govern the π-facial discrimination.

Synthesis, structural analysis and anticonvulsant activity of a ternary Cu(II) mononuclear complex containing 1,10-phenanthroline and the leading antiepileptic drug valproic acid

The synthesis and characterization of the binary complex of copper(II) with the antiepileptic drug valproic acid sodium salt (Valp) and the related ternary complex with 1,10-phenanthroline (phen) are reported, as well as the anticonvulsant properties of the latter. The characterization was carried out by means of elemental analyses, infrared (IR), UV-visible (UV-vis) spectrophotometry and Electron Paramagnetic Resonance (EPR). The X-ray crystal structure of the mononuclear complex bis(2-propylpentanoate)(1,10-phenanthroline)copper(II) [Cu(Valp)(2)phen] is showed for the first time. It crystallized in C2/c space group with unit cell dimensions of a = 14.939(1) A, b = 19.280(1) A, c = 9.726(1) A, beta = 97.27(2) degrees , V = 2778.8(4) A(3) and Z = 8. The carboxylates bond in an asymmetric chelating mode and the copper atom adopts a highly distorted octahedral coordination, characterized by the sum of the angles of 365.9 degrees around Cu(II) and its nearest atoms in the CuN(2)O(2) + O(2) chromophore instead of the expected 360 degrees for a basal square planar geometry found in most Cu(II) complexes. Molecules assemble three by three through slipped pi-pi stacking of the aromatic phen with respectively 3.519 and 3.527 A distances, in a head-to-tail arrangement. Studies of the anticonvulsant properties of this bioligand chelate evidenced its lack of efficacy in preventing MES-induced seizures. Interestingly, complex 4 protected mice against the Minimal Clonic seizures at doses that do not cause Rotorod toxicity, with an ED(50) documenting very potent anticonvulsant activity in this model of seizure, a particularly useful pharmacological profile of activity for the treatment of Petit Mal seizures.

Synthesis and structural determination of new chiral auxiliaries derived from (−)-β-pinene

New chiral auxiliaries, alcohols syn-11a,e and anti-12a,e were readily synthesized in a stereoselective manner from (−)-β-pinene. Their stereochemical determinations have been made on the basis of nOe experiments.

Tricyclic Sesquiterpenes from Marine Origin

The structure elucidation, biosynthesis, and biological activity of marine carbotricyclic sesquiterpene compounds are reviewed from the pioneering results to the end of 2015. Their total syntheses with a particular emphasis on the first syntheses, enantiomeric versions, and syntheses that led to the revision of structures or stereochemistries are summarized. Overall, 284 tricyclic compounds are classified into fused, bridged, and miscellaneous structures based on 54 different skeletal types. Tricyclic sesquiterpenes constitute an important group of natural products. Their structural diversity and biological activities have generated further interest in the field of drug discovery research, although the exact mechanisms of action of these species are not well known. Furthermore, these tricyclic structures, according to their chemical complexity, are a source of inspiration for chemists in the field of total synthesis for the development of innovative methodologies.

A SIMPLE, EFFICIENT ACCESS TO FUNCTIONALIZED PYRROLOBENZAZEPINES RELATED TO THE ABC CORE OF CEPHALOTAXINE

Abstract Tetracyclic nitrile 19a and ester 19b , exhibiting the ABC core of cephalotaxine 1a , were prepared through KH-induced cyclization of thioimides 14a and 14b , respectively. This new ring-closure methodology proved to be particularly efficient: thus nitrile 19a was obtained in only 7 steps with a 17 % overall yield from commercially available, inexpensive safrole 2 .

Asymmetric aza-Michael addition under ultra-high pressure: short bias to polyhydroxylated piperidines

Two polyhydroxylated piperidines have been prepared in short sequences from diacetone gluco- and allofuranose. The key step is a piezo-aza-Michael addition of diphenylmethanamine to enoates bearing a sugar moiety in the γ-position. The combination of ultra-high pressure associated to the presence of readily available sugars chiral pool led to the expected chiral amines in good yields and excellent stereoselectivities.

A comparative study of high pressure versus other activation modes in the asymmetric Michael reaction of chiral imines

The Michael reaction of chiral imines under neutral conditions has emerged as an efficient method for the elaboration of quaternary carbon centers in the alpha position relative to a carbonyl group. It was established early on that this reaction could be accelerated by thermal activation without altering its remarkable features, namely its high regio- and stereoselectivities, Michael adducts being obtained typically in high yield and with 90–98% ee. In this article, a comparative study of high-pressure activation versus thermal, microwave or catalytic activation of this reaction will be reported, highlighting the specificity of each activation mode.

High-pressure and thermally induced asymmetric diels-alder cycloadditions of heterosubstituted dienes to homochiral α,β-didehydro amino acid derivatives

Abstract An amino pentenoate and an unsaturated oxazolone have shown to be suitable homochiral dienophiles to be reacted with electron-rich heterosubstituted dienes. High-pressure and thermal activation have been studied for these cycloadditions. The adducts obtained are polyfunctional building blocks useful for the synthesis of enantiopure cyclohexane amino acids and related products.

A New Route to Trans 2,5-Dialkylpyrrolidines

Benzylic amines 8 react with ketoenoates 7 yielding, after reduction of the primary adducts, 2,5-dialkylpyrrolidines 9 (trans isomer predominating). This reaction has been applied to the synthesis of trans 2-heptyl-5-ethylpyrrolidine, a component of the venom of fire ant (Solenopsis punctaticeps).