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

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

Synthèse de nouveaux dérivés du 9-hydroxy-parthénolide contenant un noyau -1,2,3-triazole substitué

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Suzuki–Miyaura Reactions of Halospirooxindole Derivatives.

International audienceStarting from 5,5′-dihalo-1′-pentyl-2H-spiro[furo[2,3-b]pyridine-3,3′-indolin]-2′-one, various 5,5′-di(het)aryl-1′-pentyl-2H-spiro[furo[2,3-b]pyridine-3,3′-indolin]-2′-ones were synthesized through palladium-catalysed cross-coupling reactions. A large panel of boronic acids (aryl or heteroaryl) could easily be introduced, leading to a library of new 5- or 5′-monosubstituted and 5,5′-disubstituted 1′-pentyl-2H-spiro[furo[2,3-b]pyridine-3,3′-indolin]-2′-ones