Erwan Le Gall

Three-Component Synthesis of α-Branched Amines under Barbier-like Conditions

An array of alpha-branched amines has been prepared by using an expedient three-component Mannich-type reaction among organic halides, aldehyde derivatives, and amines. The experimental procedure, which is characterized by its simplicity, employs zinc dust for the in situ generation of organozinc reagents. We show that this Barbier-like protocol constitutes a useful entry to diarylmethylamines, 1,2-diarylethylamines, alpha- or beta-amino esters, benzylamines, and beta-arylethylamines.

A straightforward three-component synthesis of alpha-amino esters containing a phenylalanine or a phenylglycine scaffold.

A range of alpha-amino esters has been synthesized in good to high yields using a straightforward three-component reaction among preformed or in situ generated aromatic or benzylic organozinc reagents, primary or secondary amines, and ethyl glyoxylate. The procedure, which is characterized by its simplicity, allows the concise synthesis of esters bearing a phenylglycine or a phenylalanine scaffold.

Synthesis of functionalized 4-phenyl-pyridines via electrochemically prepared organozinc reagents

Abstract The efficient and convenient synthesis of various functionalized 4-phenyl-pyridines 2 is described. The key step of the procedure is the electrochemical formation of aromatic organozinc reagents 1 and their coupling with pyridinium salts. Intermediate 1,4-dihydropyridines are oxidized using mild conditions to provide functionalized 4-phenyl-pyridines in moderate to high overall yields.

Cobalt-catalyzed electrochemical cross-coupling of functionalized phenyl halides with 4-chloroquinoline derivatives

Abstract A novel electrochemical procedure allowing the synthesis of various 4-phenylquinoline derivatives in satisfactory to high yields is described. This method relies on a cobalt-catalyzed cross-coupling reaction of functionalized phenyl halides with 4-chloroquinoline derivatives and is conducted in a one-compartment cell using the sacrificial anode process.

An Electrochemical Nickel-Catalyzed Arylation of 3-Amino-6-Chloropyridazines

3-Amino-6-aryl- and 3-amino-6-heteroarylpyridazines have been obtained in generally good yield using a nickel-catalyzed electrochemical cross-coupling between 3-amino-6-chloropyridazines and aryl or heteroaryl halides at room temperature. Comparative experiments involving classical palladium-catalyzed reactions, such as Suzuki, Stille, or Negishi cross-couplings, reveal that the electrochemical method can constitute a reliable alternative tool for biaryl formation. A possible reaction mechanism is proposed on the basis of electrochemical analyses.

Pure acetonitrile as solvent for the efficient electrochemical conversion of aryl bromides in organozinc species and their coupling reaction with acetyl chloride

Conversion of functionalized aryl bromides in an electrochemical cell fitted with a sacrificial anode and in the presence of cobalt bromide without ligand in acetonitrile as solvent affords the corresponding organozinc species in good yields. Their coupling with acetyl chloride is efficient using a palladium catalyst.

Regio- and Diastereoselective Synthesis of α-Cyanoamines by Anodic Oxidation of 6-Membered α-Silylamines

The electrochemical cyanation of N-benzyl-substituted cyclic six-membered α-silylamines including tetrahydroquinoline and piperidine derivatives was studied. The results of these investigations demonstrate that α-silylamines are valuable precursors for the preparation of the corresponding α-cyanoamines. The TMS group α to the N atom not only governs the chemoselectivity of the iminium formation through a preferential desilylation reaction under the experimental conditions (i.e., amine cation radical desilylation versus deprotonation), it also lowers the oxidation potential of tertiary amines compared to their non-TMS counterparts. Both the stereoselectivity and regioselectivity of the cyanide addition were investigated with 3-methylpiperidine as the model compound. The formation of a single cisdiastereoisomer in which the 2-cyano group is axial and the 5-methyl group is equatorial, indicates that the addition of the cyanide anion onto the iminium species is under stereoelectronic control. In addition, the redox reaction involving the intermediate nitrogen-centered cation radical and the cyanide anions played no role, because the α-silyl radical has such a short lifetime.

Synthesis and cytotoxic evaluation of novel paraconic acid analogs

A novel class of 2,3-tri- and tetrasubstituted γ-butyrolactones analogous to paraconic acids has been synthesized in one step using a straightforward three-component reaction among aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of representative compounds has been evaluated against a panel of human cancer cell lines (KB, HCT116, MCF7, HL60). While most molecules exhibit a low to moderate background activity on both KB and HL60 cancer cell lines, one compound shows increased antiproliferative activities against both cell lines with IC(50) values in the 10(-7)-10(-6)mol/L range. An extended evaluation indicated that this compound also inhibits PC3, SK-OV3, MCF7R and HL60R cell growth in the same fashion.

Nickel-catalyzed reductive coupling of chlorodiphenylphosphine with aryl bromides into functionalized triarylphosphines

Abstract Functionalized triarylphosphines are obtained with good yields in a one-step reaction of an equimolar mixture of chlorodiphenylphosphine and an aromatic bromide in NMP or DMF at 110°C in the presence of zinc dust and a catalytic amount of NiBr 2 (bpy). A possible catalytic pathway is discussed.

An Electrochemical Synthesis of Functionalized Arylpyrimidines from 4-Amino-6-Chloropyrimidines and Aryl Halides

A range of novel 4-amino-6-arylpyrimidines has been prepared under mild conditions by an electrochemical reductive cross-coupling between 4-amino-6-chloro-pyrimidines and functionalized aryl halides. The process, which employs a sacrificial iron anode in conjunction with a nickel(II) catalyst, allows the formation of coupling products in moderate to high yields.