Methodology in organic synthesis


Synthesis of 3-amino-3,4-dihydro-1H-quinolin-2-ones through regioselective palladium-catalyzed intramolecular cyclization

Tetrahedron Letters2016, 57(14), 1547-1550

In this Letter we explored the regioselective cyclization of 2-bromophenylalanine derivatives to access enantiopure dihydroquinolinones via an intramolecular regioselective Buchwald–Hartwig cyclization using Pd2(dba)3/XPhos as a catalytic system in the presence of BTPP as organic base. This procedure represents a promising strategy for the direct synthesis of bridged Phe-Xaa dipeptides.

 

 

Abstract Tetrahedron letters

Rapid and scalable synthesis of innovative unnatural alpha, beta or gamma-amino acids functionalized with tertiary amines on their side-chains

Organic & Biomolecular Chemistry, 2015, 13(25), 7020-7026

We report a selective ruthenium catalyzed reduction of tertiary amides on the side chain of Fmoc-Gln-OtBu derivatives, leading to innovative unnatural alpha, beta or gamma-amino acids functionalized with tertiary amines. Rapid and scalable, this process allowed us to build a library of basic unnatural amino acids at the gram-scale and directly usable for liquid- or solid-phase peptide synthesis. The diversity of available tertiary amines allows us to modulate the physicochemical properties of the resulting amino acids, such as basicity or hydrophobicity.

 

Graphical abstract

 Highlights :En direct des laboratoires de l'institut de Chimie

Access to 4-Alkylaminopyridazine Derivatives via Nitrogen-Assisted Regioselective Pd-Catalyzed Reactions

Journal of Organic Chemistry, 2014, 79 (21), 10311 - 10322

3-Substituted, 6-substituted, and unsymmetrical 3,6-disubstituted 4-alkylaminopyridazines were prepared from a sequence of three chemo- and regioselective reactions combining amination and palladium-catalyzed cross-coupling reactions, such as reductive dehalogenation and Suzuki–Miyaura reactions. Extension of the methodology to Sonogashira reaction yielded a novel class of 3-substituted pyrrolopyridazines.


Graphical abstract: Access to 4-Alkylaminopyridazine Derivatives via Nitrogen-Assisted Regioselective Pd-Catalyzed Reactions

t-BuXPhos: a highly efficient ligand for Buchwald–Hartwig coupling in water

Green Chemistry, 2014,16, 4170-4178

An efficient and versatile ‘green’ catalytic system for the Buchwald–Hartwig cross-coupling reaction in water is reported. In an aqueous micellar medium, the combination of t-BuXPhos with [(cinnamyl)PdCl]2 showed excellent performance for coupling arylbromides or chlorides with a large set of amines, amides, ureas and carbamates. The method is functional-group tolerant, proceeds smoothly (30 to 50 °C) and provides rapid access to the target compounds in good to excellent isolated yields. When applied to the synthesis of a known NaV1.8 modulator, this method led to a significant improvement of the E-factor in comparison with classical organic synthesis.


Graphical abstract: t-BuXPhos: a highly efficient ligand for Buchwald–Hartwig coupling in water

Highlights :
CNRS - Lettre-Innovation
A. Dureuil, Industrie-Pharma, 2015, 85, p58

Buchwald–Hartwig reactions in water using surfactants

Tetrahedron, 2014,70, 21, 3413-3421

Examination of the scope and limitation of the Buchwald–Hartwig cross-coupling reaction in micellar medium is reported. An array of aryl or heteroaryl halides were coupled to diverse nitrogen coupling partners using a combination of [(allyl)PdCl]2 and cBRIDP to afford the corresponding products in moderate to excellent yields. 30 examples are reported, including polar solid and fairly water-soluble organic substrates/reagents.


Graphical abstract: Buchwald-Hartwig reactions in water using surfactants

Fully Regiocontrolled Polyarylation of Pyridine

Journal Of Organic Chemistry, 2014,79(3), 908-918

Starting from commercially available 2-chloro-3-hydroxypyridine, a new route leading to the first protypical pentaarylpyridine bearing five different substituents is reported. This strategy involves a set of five sequential but fully regiocontrolled Suzuki–Miyaura reactions and highlights the 2-OBn pyridine protecting group as a key intermediate. The 2-OBn group played a double role: (i) it allowed additional bromination at position 5 and (ii) it could afford the reactive OTf species for the last C-arylation step at the less hindered 2 position of the tetraarylpyridine. The photophysical properties of the novel compounds are also described. The synthesized pentaarylpyridine derivative exhibit a large Stokes shift, strong solvatochromism, and quantum yield values up to 0.47; thus, they constitute promising building blocks for the design of environment-sensitive probes.


Graphical abstract: Fully Regiocontrolled Polyarylation of Pyridine

Nucleophilic Substitution of Azide Acting as a Pseudo Leaving Group: One-Step Synthesis of Various Aza Heterocycles

Journal Of Organic Chemistry, 2013,78(22), 11335-11341

The reaction of 3-azidopropanoic acid with the carbodiimide-based coupling reagent DIC leads to a six-membered-ring intermediate acting as a versatile precursor to a diverse set of aza heterocycles, including mono-, bi-, and tricyclic compounds.

Graphical abstract: Nucleophilic Substitution of Azide Acting as a Pseudo Leaving Group: One-Step Synthesis of Various Aza Heterocycles