Chirality transfer in cascade rearrangements of enediynes

La synthèse asymétrique d’aza-hétérocycles (tétrahydro-isoquinoléines et naphtodiazépines) a été réalisée grâce à la mise en œuvre d’un processus faisant intervenir des réactions radicalaires et polaires en cascade à partir des ènediynes portant un centre stéréogène. Ce processus implique successivement : la formation d’un ényne-allène (via une migration-1,3 de proton, une réaction d’un alcyne terminal avec un carbénoïde de cuivre, ou encore une réaction d’homologation de Crabbé)/ la cyclisation de Saito-Myers/ le transfert-1,5 d’un atome d’hydrogène/ la recombinaison du biradical résultant. Les deux dernières étapes élémentaires de ce réarrangement étaient idéalement adaptées à l’application d’une stratégie basée sur le phénomène de mémoire de chiralité. Des études mécanistiques basées sur des expériences de marquage isotopique et des calculs théoriques ont permis de mieux comprendre les paramètres qui contrôlent la régio- et la stéréosélectivité de la réaction. L’ambition de contrôler par cette voie, via une double mémoire de chiralité, deux centres stéréogènes nous a conduits à étudier le transfert de la chiralité axiale d’un motif allénique judicieusement substitué. Cette étude a permis de découvrir une cycloisomérisation originale catalysée par le cuivre (I) conduisant à des fulvènes chiraux via un double transfert de chiralité (centrique-axial-centrique).The asymmetric synthesis of azaheterocycles (tetrahydorisoquinolines and naphthodiazepines) was successfully achieved via the polar/radical cross-over rearrangement of enediynes bearing a stereogenic center. This process involves successively : enyne-allene formation (via 1,3-proton shift, reaction of a terminal alkyne group with carbenoids or Crabbé homologation)/Saito-Myers cyclization/1,5-hydrogen atom transfer/biradical recombination. It was ideally suited to apply a strategy based on the memory of chirality phenomenon. Mechanistic studies based on isotopic labelling and theoretical calculations enabled to go deeper into the understanding of the parameters controlling the regio- and the stereoselectivity of the reaction. The ambition to control two stereogenic centers via double memory of chirality, led us to investigate the transfer of the axial chirality of a designed allenic moiety. This study led to the discovery of an original copper (I)-mediated cycloisomerization leading to chiral fulvenes and proceeding via central-to-axial-to-central double chirality transfer

Copper Carbenoid, Reactant and Catalyst for One-Pot Diazo Ester Coupling Cascade Rearrangement of Enediynes: Formation of Two Contiguous Tetrasubstituted Stereocenters

International audienceThe copper-catalyzed reaction of enediynes with diazo esters leads to cyclic amino esters bearing two contiguous tetrasubstituted stereogenic centers through a one-pot, five-step cascade. Copper iodide catalyzes the formation of an intermediate 3-alkynoate and copper carbenoid promotes its reversible isomerization to the corresponding allenoate. The alkynoate-allenoate equilibrium is completely shifted to the right by the rapid consumption of the allenoate by MyersSaito cyclization. This is followed by 1,5-H atom transfer and recombination of the resulting biradical. Memory of chirality phenomenon explains the high enantioselectivity

Axial-to-central chirality transfer in cyclization processes

International audienceSubstrates, bearing axial chirality, can cyclize intra-or inter-molecularly with concomitant transfer of axial-to-central chirality to produce at least one stereocenter. In order to satisfy a strict definition of axial-to-central chirality transfer, the initial axial chirality must be lost during the cyclization process. Highly functionalized enantiopure carbocycles and heterocycles were prepared using this strategy. The transformations of configurationally stable substrates take place with high regio-and stereo-selectivity. Selected examples involving allenes, biaryls, arylamides and transient axially chiral short-lived species are discussed. Special attention is focused on the mechanistic rationale of the chirality transfer

Copper and iron complexes as visible-light-sensitive photoinitiators of polymerization

International audienceThe utilization of visible lights for the fabrication of polymeric materials is recognized as a promising and environmentally friendly approach. This process relies on the photochemical generation of reactive species (e.g., radicals, radical cations, or cations) from well-designed photoinitiators (PIs) or photoinitiating systems (PISs) to initiate the polymerization reactions of different monomers (acrylates, methacrylates, epoxides, and vinyl ethers). In spite of the fact that metal complexes such as ruthenium- or iridium-based complexes have found applications in organic and polymer synthesis, the search of other low-cost metal-based complexes as PISs is emerging and attracting increasing attentions. Particularly, the concept of the photoredox catalysis has appeared recently as a unique tool for polymer synthesis upon soft conditions (use of light emitting diodes and household lamp). This highlight focuses on recently designed copper and iron complexes as PI catalysts in the application of photoinduced polymerizations (radical, cationic, interpenetrated polymer networks, and thiol-ene) or controlled radical polymerization under visible light irradiatio

Iron Complexes in Visible-Light-Sensitive Photoredox Catalysis: Effect of Ligands on Their Photoinitiation Efficiencies

International audienceThe novel role of metal-based complexes as photoinitiator catalysts fits well into the concept of green chemistry, as it realizes the activation of polymer synthesis processes by visible light that are abundant in the solar light and allows the marked reduction of photoinitiator amount in the systems. In the present paper, a series of iron complexes (FeC_x) with various ligands have been proposed as new photoinitiator catalysts to initiate the cationic polymerization of epoxides or the free radical polymerization of acrylates upon a near-UV or visible-light LED exposure. The ligands play an important role on the light absorption properties and the photoinitiation ability of the iron complexes. In combination with one or two additives, FeC_x are capable to efficiently generate radicals, cations, and radical cations through an oxidative or a reductive path. Two of the newly developed FeC_x-based photoinitiating systems exhibited comparable photoinitiation efficiency with the commercial Type I photoinitiator bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (BAPO). Owing to the photocatalytic effect, remarkable photoinitiation efficiencies have been achieved by using very low concentration of iron complexes (0.02 wt %) in the systems. The involved photochemical mechanisms have been studied using electron spin resonance spin trapping, steady state photolysis, cyclic voltammetry, and laser flash photolysis technique

Memory of Chirality in Cascade Rearrangements of Enediynes

International audienceThe cascade rearrangement of chiral enediynes 1c-e, involving successively 1,3-proton shift, Saito-Myers cyclization, 1,5-hydrogen atom transfer, and intramolecular coupling of the resulting biradical, proceeded at 80 degrees C to form tri- and tetracyclic heterocycles possessing a quaternary stereogenic center with a very high level of memory of chirality

The carbazole-bound ferrocenium salt as a specific cationic photoinitiator upon near-UV and visible LEDs (365–405 nm)

International audienceA carbazole-bound ferrocenium salt [i.e., (η6-Carbazole) (η5-cyclopentadienyl) iron hexafluorophosphate—FS] is proposed as an efficient photoinitiator for the cationic ring-opening polymerization of epoxides under air upon the exposure to a near-UV LED at 385 nm or a visible LED at 405 nm. When using this ferrocenium salt FS (0.2 wt%)/diphenyliodonium hexafluorophosphate or FS (0.2 wt%)/diphenyliodonium hexafluorophosphate/N-vinylcarbazole, final epoxide conversions of 55–66 % can be obtained after 800 s of irradiation at 385 or 405 nm. Reference cationic photoinitiators (i.e., diphenyliodonium hexafluorophosphate; 9-(4-hydroxyethoxyphenyl) thianthrenium hexafluorophosphate and triphenylsulfonium hexafluorophosphate) are unable to initiate the epoxide polymerization under the same conditions. The photochemical mechanisms for the formation of the initiating species are studied using steady-state photolysis, cyclic voltammetry, laser flash photolysis and electron spin resonance spin-trapping techniques. Molecular orbital calculations help to describe the absorption properties and the initiation step. The performance attained when using FS alone is really promising for applications under soft near-UV or visible light-emitting diode irradiation

An efficient and recyclable hybrid nanocatalyst to promote enantioselective radical cascade rearrangements of enediynes

International audienceMesoporous silica grafted with a tertiary amine was used as a basic nanocatalyst to promote in confined medium the enantioselective cascade rearrangement of enediynes based on the phenomenon of memory of chirality; the multi-substrates recyclable catalytic reagent could easily be recovered by simple filtration, and reused without any decrease in activity even when changing the solvent

Theoretical Study To Explain How Chirality Is Stored and Evolves throughout the Radical Cascade Rearrangement of Enyne-allenes

This article reports a theoretical study to explain how the intrinsic property of chirality is retained throughout the radical cascade rearrangement of an enantiopure chiral enyne-allene (bearing one stereogenic center) selected as a model for this family of reactions. Calculations at the MRPT2/6-31G­(d)//CASSCF­(10,10)/6-31G­(d) level of theory were used to determine the entire reaction pathway which includes singlet state diradicals and closed-shell species. The cascade process involves three elementary steps, i.e., by chronological order: Myers–Saito cycloaromatization (M-S), intramolecular hydrogen atom transfer (HAT), and recombination of the resulting biradical. The enantiospecificity of the reaction results from a double transmission of the stereochemical information, from the original center to an axis and eventually from this axis to the final center. The first two steps lead to a transient diradical intermediate which retains the chirality via the conversion of the original static chirogenic element into a dynamic one, i.e., a center into an axis. The only available routes to the final closed-shell tetracyclic product imply rotations around two σ bonds (σ­(C–C) and σ­(C–N), bonds β and α respectively). The theoretical calculations confirmed that the formation of the enantiomerically pure product proceeds via the nonracemizing rotation around the σ­(C–C) pivot. They ruled out any rotation around the second σ­(C–N) pivot. The high level of configurational memory in this rearrangement relies on the steric impediment to the rotation around the C–N bond in the chiral native conformation of the diradical intermediate produced from tandem M-S/1,5-HAT

Mechanistic Investigation of Enediyne-Connected Amino Ester Rearrangement. Theoretical Rationale for the Exclusive Preference for 1,6- or 1,5-Hydrogen Atom Transfer Depending on the Substrate. A Potential Route to Chiral Naphthoazepines

Memory of chirality (MOC) and deuterium-labeling studies were used to demonstrate that the cascade rearrangement of enediyne-connected amino esters <b>1a</b> and <b>1b</b> evolved through exclusive 1,5- or 1,6-hydrogen atom transfer, subsequent to 1,3-proton shift and Saito–Myers cyclization, depending on the structure of the starting material. These results were independently confirmed by DFT theoretical calculations performed on model monoradicals. These calculations clearly demonstrate that in the alanine series, 1,5-hydrogen shift is kinetically favored over 1,6-hydrogen shift because of its greater exergonicity. In the valine series, the bulk of the substituent at the nitrogen atom has a major influence on the fate of the reaction. <i>N</i>-Tosylation increases the barrier to 1,5-hydrogen shift to the benefit of 1,6-hydrogen shift. The ready availability of 1,6-hydrogen atom transfer was explored as a potential route for the enantioselective synthesis of naphthoazepines