Yannick Landais

Radical and Radical–Ionic Multicomponent Processes

All in one pot! Radical, radical-ionic, and radical-organometallic MCR are highly convergent processes, representing a useful pathway to molecular and structural diversity (see scheme). This concept article highlights recent developments in the field and shows the potential of the strategy for the economical elaboration of various kinds of organic substrates.Progress in multicomponent reactions (MCRs) based on ionic and organometallic processes has recently allowed the synthesis, with high efficiency, of large collections of drug-like molecules. In contrast, MCRs based on cascade radical reactions appear to have attracted, so far, much less interest. This concept article highlights the latest progress in the field and underlines the potential of such an approach. The collected examples demonstrate that radical and radical-ionic MCRs are highly convergent processes leading to useful structural diversity.

Free-Radical Carboalkynylation and Carboalkenylation of Olefins

Free-radical three-component carboalkynylation and -alkenylation of olefins have been developed. These involve the addition, across the double bond of an unactivated olefin, of a radical species α- to an electron-withdrawing group and an alkenyl or alkynyl moiety, derived from the corresponding sulfones.

On the chemical fixation of supercritical carbon dioxide with epoxides catalyzed by ionic salts: an in situ FTIR and Raman study

A series of ionic salts have been investigated to catalyze the coupling reaction between epoxide and carbon dioxide at T = 80 °C and P = 8 MPa. Among them, we focused particularly on tetrabutylammonium, imidazolium and guanidinium salts. The kinetics of the synthesis was monitored in situ using both FTIR and Raman spectroscopy. For a given reaction time, the best yields were obtained with 1,5,7-triaza-bicyclo[4.4.0]dec-5-enium bromide (TBD·HBr) and 1-methyl-3-methylimidazolium iodide (MMImI) and both have not been investigated in detail in the literature before. Thanks to this catalyst screening, we have verified how some functional groups of the catalyst can activate the epoxide and the CO2 molecule enabling us to go further in the mechanism comprehension of this reaction. Due to its easier and less expensive synthesis than other ionic liquids, we focused more particularly on TBD·HBr that also offers a good conversion rate even at low pressure (80 °C and 1 MPa).

Ruthenium dioxide in fluoro acid medium: I. A new agent in the biaryl oxidative coupling. Application to the synthesis of non phenolic bisbenzocyclooctadiene lignan lactones.

Abstract Ruthenium (IV) dioxide dihydrate in fluoro acid medium was found to be a very efficient agent for the oxidative coupling of non phenolic lignans and their derivatives, and this method was applied to the total synthesis of (+/-)-neoisostegane 2a and (+/-)-steganolide A 2b. This procedure was also used to obtain the first stereospecific synthesis of a cis-bisbenzocyclooctadiene lactone, the (+/-)-deoxyschizandrin 17, of which, was afforded by a short reduction sequence.

Le tétrakis (trifluoroacétate) de ruthénium(IV), nouveau catalyseur a température ambiante du couplage biarylique oxydant non phénolique -première synthèse totale biomimétique du néoisostégane-

Resume In situ generated Ruthenium(IV) tetrakis (trifluoroacetate) -a new organometallic reagent- was used in intramolecular non-phenolic oxydative biaryl coupling of dibenzylbutanolides, and an application to the first total synthesis of neoisostegane was performed.

Synthesis of fused piperidinones through a radical-ionic cascade.

Azabicyclo[4.3.0]nonanes were assembled, from chiral allylsilanes possessing an oxime moiety, using a stereocontrolled formal [2 + 2 + 2] radical-ionic process. The cascade involves the addition of an alpha-iodoester to the less substituted end of the enoxime which is then followed by a 5-exo-trig cyclization onto the aldoxime function, producing an alkoxyaminyl radical species which finally lactamizes to afford the titled piperidinone. High levels of stereoinduction were observed, demonstrating the ability of a silicon group located at the allylic position to efficiently control the stereochemistry of the two newly created stereogenic centers. When the radical cascade was extended to ketoximes, the resulting sterically hindered alkoxyaminyl radical did not react further with the initiator Et3B to produce the expected nucleophilic amidoborane complex. In sharp contrast, this long-lived radical recombined with the initial alpha-stabilized ester radical to produce a cyclopentane incorporating two ester fragments.

Ruthenium dioxide in fluoro acid medium III. Application to the synthesis of aporphinic, homoaporphinic and dibenzazocinic alkaloids. Studies towards the preparation of azafluoranthenic skeleton.☆

Abstract Intramolecular oxidative couplings of phenylalkyltetrahydroisoquinoline precursors in aporphinic and homoaporphinic alkaloids by using RuO2,2H2O in fluoro acidic media were performed. A comparative study of our reagent with TTFA has been made with different precursors. The procedure was also extended to the synthesis of one dibenzazocinic alkaloid. Then, we attempted to synthetize the azafluoranthenic ring, using phenolic and non phenolic isoquinoline precursors.

Synthesis of diarylbutanes from cordigerines and reinvestigation of their oxidative couplings in deoxyschizandrins. - An unusual formation of phenyltetralin lignans -

Abstract Dibenzylbutanolide lignans including cordigerines were synthetized and transformed in the corresponding diarylbutane lignans which were submitted to non-phenolic oxidative coupling conditions by using RuO2 or Tl2O3 in trifluoroacetic medium to give deoxyschizandrins. A concurrently aryl-benzyl coupling leads to the formation of the corresponding phenyltetralin of which the structure was confirmed by total synthesis.

Free-radical carbo-alkenylation of enamides and ene-carbamates.

The addition of xanthates and vinyldisulfones across the double bond of enamides and ene-carbamates provides access to the corresponding three-component adducts in good to excellent yields with a high level of diastereocontrol in cyclic systems. This strategy illustrates a complementary reactivity for these versatile olefins and extends their scope of application.

Ruthenium(IV) tetrakis(trifluoroacetate), a new oxidizing agent. III. An efficient access to the aporphine and homoaporphine skeletons and their structural studies.

Abstract The title reagent -RUTFA- couples efficiently phenylalkyltetrahydroisoquinolines, and the syntheses of glaucine, thalicsimidine and homoglaucine were carried out. The stereostructures of the aporphine and homoaporphine skeletons were determined by using PMR at 500 MHz.