Late stage C―H activation of a privileged scaffold; synthesis of a library of benzodiazepines

A library of over twenty 5-(2-arylphenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-ones has been formed by a microwave-mediated late-stage palladium-catalysed arylation of 1,4-benzodiazepines using diaryliodonium salts. This can also be applied to nordazepam (7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one), the active metabolite of diazepam, and subsequent N-alkylation and/or H/D exchange allows further diversification towards elaborated pharmaceuticals and their 3,3'-deuterated analogues

α-Halogenoacetamides: versatile and efficient tools for the synthesis of complex aza-heterocycles

International audienceThis review provides an overview of the applications of α-halogenoacetamides in domino and cycloaddition reactions. α-Halogenoacetamides are versatile building blocks that can lead to a wide variety of complex aza-heterocycles of biological interest when engaged in domino and/or cycloaddition reactions. The reactivity and the reaction conditions involved for these species (solvent, base, etc.) are closely related to the substituent onto the nitrogen atom of the amide: N-alkyl α-halogenoacetamides usually act as formal 1,3-dipoles in domino processes whereas N-alkoxy derivatives often react as real 1,3-dipoles via the formation of aza-oxyallyl cation species. This important modulation of the reactivity of these compounds opens the way to a large panel of reactions and therefore to a large diversity of aza-heterocycles

2,3‐Epoxyamide‐alcohols in Domino Reactions: En Route to Molecular Diversity

International audienceThe synthesis of polycyclic γ‐ and δ‐lactams bearing up to four contiguous fully controlled stereocenters is presented. For that purpose, we developed an original approach based on the use of 2,3‐epoxyamides in domino reactions by taking advantage of the nucleophilic nitrogen atom and electrophilic epoxide. In reaction with enol ethers bearing gem bis‐electrophiles on the double bond as Michael acceptors, four different reaction pathways were observed. They all started with a domino oxa‐Michael/aza‐Michael/epoxide opening sequence and depending on substrates engaged could be followed either by a lactonization or a hemiketalization/retro‐aldol cascade. Thus, four original fully‐substituted piperidine‐ or pyrrolidine‐2‐one scaffolds were selectively synthesized in good to high yields. Moreover, these polycyclic lactams were obtained in high stereo‐ and chemo‐selectively highlighting the efficiency and molecular diversity offered by this new methodology that should offer various synthetic opportunities in the future