Etienne Brachet

Pd-Catalyzed Reaction of Sterically Hindered Hydrazones with Aryl Halides: Synthesis of Tetra-Substituted Olefins Related to iso-Combretastatin A4

PdCl(2)(MeCN)(2) in combination with dppp proved to be a powerful and efficient catalyst for the coupling of sterically hindered N-arylsulfonylhydrazones with aryl halides, thus providing a flexible and convergent access to tetrasubstituted olefins related to iso-combretastatin A4 in good yields. This new protocol has been applied successfully to the formal synthesis of biphenylisopropylidene 4-pyridine CYP17 inhibitor, 12b, of biological interest.

Nickel-catalyzed arylation, alkenylation, and alkynylation of unprotected thioglycosides at room temperature.

Unprotected thioglycosides were effective nucleophiles for Ni(0)-catalyzed C-S bond-forming reaction with functionalized (hetero)aryl, alkenyl, and alkynyl halides. The functional-group tolerance on the electrophilic partner was typically high and the anomeric selectivities of the thioglycosides were high in all cases. The efficiency of this general procedure was well-demonstrated by the synthesis of 4-methyl-7-thioumbelliferyl-β-D-cellobioside (MUS-CB).

Palladium-Catalyzed Regioselective Alkynylation of Pyrroles and Azoles under Mild Conditions: Application to the Synthesis of a Dopamine D-4 Receptor Agonist

A mild and general method for the direct alkynylation of azoles such as pyrrole, indole, and 7-azaindole is described here. Using a simple catalytic system such as Pd(OAc)2 (2.5 mol %), P(tBu)2Me·HBF4 (5 mol %), and NaOAc (2 equiv) allowed the regioselective introduction of various alkynyl residues at the C-2 position of pyrroles. Interestingly, C-2 alkynylation was also observed on C-3-substituted indoles, whereas classical C-3 alkynylation was obtained on selected unsubstituted indoles and 7-azaindole. Our methodology has been illustrated by the efficient synthesis of a potential schizophrenia drug (dopamine D-4 inhibitor).

A palladium-catalyzed coupling of 3-chloroquinoxalinones with various nitrogen-containing nucleophiles

An efficient and general palladium-catalyzed coupling of 3-chloro-quinoxalinones with a variety of nitrogen-containing nucleophiles such as (hetero)aromatic and aliphatic amides as well as some challenging weakly nucleophilic nitrogen compounds including lactams, carbamates and NH-containing azoles is described. In all cases, the reactions take place rapidly and cleanly in dioxane using Pd(OAc)2 as a catalyst, Xantphos as a ligand and K2CO3 as a base furnishing the coupling 3-N-substituted quinoxalinone products in good to excellent yields.