M. N. Mihoubi

Bio: M. N. Mihoubi is an academic researcher from Centre national de la recherche scientifique. The author has contributed to research in topics: Halogenation & Allylic rearrangement. The author has an hindex of 2, co-authored 6 publications receiving 41 citations.

Allenyl allylic ethers: synthesis and thermal rearrangements

Abstract: Application of the sequence halogenation/dehydrohalogenation/isomerization to alkenes 1a-g affords allenyl allylic ethers 5a-g. Thermal isomerizations of 5a,d,e proceed by Claisen rearrangement, while 5b,c,f,g are transformed by alternate modes of [2+2]cycloaddition involving biradical intermediates of type 19 to polycyclic structures; the variations in these thermal isomerizations are mainly a function of ring size

A new synthetic route to β-bromoprop-2-ynyl mixed acetals and bromovinyl bis-allyl mixed acetals, precursors of α-methylene-γ-butyrolactones

Abstract: Cohalogenation by N-bromosuccinimide in methanol of β-bromoallenyl ethers (3a–g) or allyl allenyl ethers (8d–f) affords unsaturated halogeno-compounds (5a–g) or (9d–f) which are converted via homolytic carbocyclization into α-methylene-γ-butyrolactones (7a–g).

An Efficient Stereoselective Synthesis Of Botryodiplodin Derivatives

Abstract: Intramolecular Radical Cyclization Of Adducts Arising From Cohalogenation Of Methyl Vinyl Ketone (Nbs/Propargyl Alcohol) Constitutes An Efficient Stereoselective Route To Botryodiplodin Derivatives.

Allenyl Allylic Ethers: Synthesis and Thermal Rearrangements.

Abstract: Application of the sequence halogenation/dehydrohalogenation/isomerization to alkenes 1a-g affords allenyl allylic ethers 5a-g. Thermal isomerizations of 5a,d,e proceed by Claisen rearrangement, while 5b,c,f,g are transformed by alternate modes of [2+2]cycloaddition involving biradical intermediates of type 19 to polycyclic structures; the variations in these thermal isomerizations are mainly a function of ring size

4.2 – Radical Cyclizations and Sequential Radical Reactions

Abstract: Reactions that form rings are the central steps in the synthesis of cyclic organic compounds, and the development of cyclization reactions that are mild and general has been a recurring theme since the emergence of organic synthesis as a discipline. Although they have been recognized only recently, intramolecular addition reactions of radicals (hereafter called cyclizations) are among the most powerful tools at the disposal of the synthetic chemist. These radical cyclization reactions have all the advantages of their bimolecular counterparts, such as predictability and functional group tolerance; furthermore, because of the entropic advantages, cyclization reactions are of much broader scope.

Synthesis of (±)- and (−)-botryodiplodin using stereoselective radical cyclizations of acyclic esters and acetals

Abstract: Three different routes for the stereoselective synthesis of botryodiplodin have been investigated. The intramolecular allylation of acetals proved to be unsatisfactory due to unstable intermediates and poor stereocontrol. Zard intramolecular radical allylation of a 2-iodopropionate derivative allows the development of an expeditious synthesis of racemic botryodiplodin. The relative configuration within the final product was corrected by a deprotonation–reprotonation step. The cyclization of allenyl bromoacetals was investigated next and proved to be satisfactory for the synthesis of racemic and enantiomerically pure botryodiplodin. Good stereocontrol was achieved by cyclizing a gem -dibromide followed by the stereoselective reduction of the thus formed cyclic monobromide.

Design and Synthesis of Highly Potent HIV-1 Protease Inhibitors Containing Tricyclic Fused Ring Systems as Novel P2 Ligands: Structure-Activity Studies, Biological and X-ray Structural Analysis.

Abstract: The design, synthesis, and biological evaluation of a new class of HIV-1 protease inhibitors containing stereochemically defined fused tricyclic polyethers as the P2 ligands and a variety of sulfonamide derivatives as the P2' ligands are described. A number of ring sizes and various substituent effects were investigated to enhance the ligand-backbone interactions in the protease active site. Inhibitors 5c and 5d containing this unprecedented fused 6-5-5 ring system as the P2 ligand, an aminobenzothiazole as the P2' ligand, and a difluorophenylmethyl as the P1 ligand exhibited exceptional enzyme inhibitory potency and maintained excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The umbrella-like P2 ligand for these inhibitors has been synthesized efficiently in an optically active form using a Pauson-Khand cyclization reaction as the key step. The racemic alcohols were resolved efficiently using a lipase catalyzed enzymatic resolution. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insight into the binding properties of these new inhibitors.

Reductive free-radical alkylations and cyclisations mediated by 1-alkylcyclohexa-2,5-diene-1-carboxylic acids

Abstract: A range of 1-alkylcyclohexa-2,5-diene-1-carboxylic acids were prepared by Birch reduction–alkylation of benzoic acid and their efficiency as mediators of alkyl radical chain addition and cyclisation processes was investigated. Reductive alkylations were respectably successful, even with only one or two equivalents of alkene, for secondary, tertiary and benzylic radicals. Reaction of 1-[2-(cyclohex-2-enyloxy)ethyl]cyclohexa-2,5-diene-1-carboxylic acid yielded the product of exo-trig-cyclisation, i.e. 7-oxabicyclo[4.3.0]nonane, in a yield comparable to that obtained from the tributyltin hydride induced cyclisation of 3-(2′-iodoethoxy)cyclohexene. This, together with the isolation of both exo- and endo-cyclisation products from 1-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-ylmethoxy)ethyl]cyclohexa-2,5-diene-1-carboxylic acid established that ring closures could also be satisfactorily mediated with these reagents. Preparations were completely free of metal contaminants and direct reduction of the alkyl radicals, prior to addition or cyclisation, was completely absent. However, the desired products were accompanied by alkylbenzenes, together with by-products from the initiator decompositions, and this complicated work-up. Failure to obtain 1-[2-(prop-2-yn-1-yloxy)cyclohexyl]cyclohexa-2,5-diene-1-carboxylic acid in Birch reductive alkylations with trans-1-iodo-2-(prop-2-yn-1-yloxy)cyclohexane (and the corresponding bromide) indicated a limitation on precursor synthesis. The Birch reduction–alkylation was not of universal applicability and was suppressed for alkyl halides having β-substituents.