Laurent Commeiras

Pandanus amaryllifolius produces structurally unique alkaloids, including pandanusines A and B and pandamarine, featuring rare diazaspirocyclic γ-lactam frameworks. Herein, we report concise total syntheses of these three natural products based on a modular copper(I)-catalyzed reaction. Readily accessible γ-hydroxy-γ-lactams were prepared from iodoacrylic acids, terminal alkynes, and primary amines and subsequently transformed through N-acyliminium ion intermediates to construct diazaspirocyclic backbones. This strategy enabled the synthesis of (±)-pandanusine B in four steps (40% overall yield) and (±)-pandanusine A in five steps (26.5% overall yield) after optimization of the protecting group strategy. The methodology was further extended to the total synthesis of the more complex alkaloid pandamarine. These results demonstrate the synthetic potential of γ-hydroxy-γ-lactams as versatile precursors for the rapid construction of architecturally complex alkaloid scaffolds. Furthermore, the absolute configurations of both HPLC-separated enantiomers of pandanusine A and B were unambiguously determined through a combination of vibrational and electronic circular dichroism analyses and DFT and TD-DFT calculations.

This review highlights enantioselective strategies for preparing (N,O)- (N,N)- and (N,S)-spiroketal skeleton, which are key structural units found in many natural products and pharmacologically active substances. The strategies are mainly based on metallo-, organo- or Lewis acid-catalyzed cycloaddition or annulation reactions.

We describe an operationally simple, good-yielding, two-step cascade process to convert biscyclopropanes 1 into high-value benzocyclobutene building blocks 3. This study highlights the novel reactivity of our "in-house" donor-acceptor cyclopropane, achieving complete diastereoselectivity and regioselectivity transfer.

The synthesis and the studies of optical and electronic properties of new bis‐indenone‐fused tetraazaanthracene isomers as electron accepting materials are reported. TD‐DFT calculations have been also undertaken and corroborate experiments. Organic field effect transistors demonstrated unipolar n‐type characteristics and average electron mobility values.

A single-crystal-to-single-crystal solid-state reaction of vinylogous donor-acceptor cyclopropanes is documented. The enantiospecific synthesis of new products, distinct from those obtained in solution, is achieved for the target compounds. Photopolymerization occurred upon X-ray exposure to the crystals. Notably, in one case, this reactivity exhibits selectivity since an ordered arrangement of polymers and unreacted cocrystallized monomeric conformers has been observed. Structural characterization of the complete transformation monitored through single-crystal X-ray diffraction and supported by molecular dynamics simulations sheds light on the subtle role of crystal packing in the reaction process. Moreover, the X-ray diffraction (XRD)-resolved structure of a donor-acceptor cyclopropane intermediate reveals an elongation in bond length that corroborates the existence of the so-called "push-pull effect".

The molecular complexity of recently reported cobalt(III) polycyclic complexes, resulting from an intramolecular formal (2 + 2 + 3) cycloaddition reaction on an enediyne containing a lactone moiety, has prompted us to computationally review the mechanisms of cobalt cycloaddition reactions with γ-alkylidenebutenolide or γ-alkylidenebuterolactam as 2π partners. Computed mechanisms are compared, leading to either cobalt(III)- or cobalt(I)-spiro complexes depending of both the nature of the reaction (intra- vs. intermolecular pathway) and the nature of the 2π partner (γ-alkylidenebutenolide vs. γ-alkylidenebuterolactam). These proposed mechanisms are supported by experiments, allowing us to report the synthesis and characterization of the predicted compounds.

As the attempts to control malaria through chemotherapy strategies are restricted, we have prepared a small library of 3-substituted-isoindolinones from (Z)-3-benzylideneisobenzofuran-1(3H)-ones in one-pot fashion under ultrasound irradiation. The one-pot reaction was scalable and efficiently produced the desired products (1a–m) in high yields in a short reaction time. Evaluation of their in vitro antiplasmodium assay against the 3D7 (chloroquine-sensitive) and FCR3 (chloroquine-resistant) strains of Plasmodium falciparum demonstrated that they displayed moderate to strong antiplasmodium activities (the IC₅₀ values ranging from 4.21–34.80 μM) and low resistance indices. The in silico prediction of ADME and physicochemical properties showed that the synthesized compounds met the drug-likeliness requirements and featured low toxicity effects. Based on the evaluation of the antiplasmodium profiles, 3-substituted-isoindolinone derivatives of 1a, 1d, 1h, and 1l may become potential antiplasmodium candidates.

An access to functionalised eight‐membered carbocyclic ring compounds was developed by simply stirring an unusual vinylogous Donor‐Acceptor Cyclopropane (DAC) in boilingo‐xylene. Both experimental and computational studies were performed to explain the diastereoselectivity/regioselectivity transfer observed and to provide an overall picture of the mechanism. magnified image

The first intermolecular organocatalytic enantioselective addition of indoles to prochiral 5-membered cyclic N- acyliminium ions, generated from 5-hydroxy-alpha,beta-unsaturated pyrrolidin-2-ones, is reported hereinafter. The reaction proceeds smoothly with a range of 5-hydroxy-5-substituted-alpha,beta-unsaturated pyrrolidin-2-ones and indoles using BINOL-derived phosphoric acid catalyst to afford alpha,beta-unsaturated lactams embedding a tetrasubstituted stereogenic center in high yields and enantioselectivities.

Functionalized isoindolin-1-ones have been prepared in short reaction time and excellent yields from 3-alkylidenephtalides and primary amines under ultrasonic irradiation.