Exploration of the Copper-Catalyzed Sydnone and Sydnonimine-Alkyne Cycloaddition Reactions by High-Throughput Experimentation.

The reactivity of sydnones and sydnonimines toward terminal alkynes under copper catalysis has been explored using High-Throughput-Experimentation. A large panel of ligands and reaction conditions have been tested to optimize the copper-catalyzed sydnone click reaction discovered by our group ten years ago. This screening approach led to the identification of new ligands, which boosted the catalytic properties of copper and allowed the discovery of a new copper-catalyzed click-and-release reaction involving sydnonimines. This reaction allowed chemoselective ligation of terminal alkynes with sydnonimines and, simultaneously, the release of an isocyanate fragment molecule that can be used for further transformations.

NDIPhos as a platform for chiral supramolecular ligands in rhodium-catalyzed enantioselective hydrogenation.

Chiral naphthalene diimide ligands (NDIPhos) were exploited in rhodium-catalyzed enantioselective hydrogenation. The key feature of these ligands is their ability to self-assemble via π-π interactions to mimic bidentate ligands, offering a complementary method to traditional supramolecular strategies. This concept was further substantiated by computations with the composite electronic-structure method r2SCAN-3c.

Macrolactonization Reactions Driven by a Pentafluorobenzoyl Group*.

Macrolactones constitute a privileged class of natural and synthetic products with a broad range of applications in the fine chemicals and pharmaceutical industry. Despite all the progress made towards their synthesis, notably from seco-acids, a macrolactonization promoter system that is effective, selective, flexible, readily available, and, insofar as possible, compatible with manifold functional groups is still lacking. Herein, we describe a strategy that relies on the formation of a mixed anhydride incorporating a pentafluorophenyl group which, due to its high electronic activation enables a convenient access to macrolactones, macrodiolides and esters with a broad versatility. Kinetic studies and DFT computations were performed to rationalize the reactivity of the pentafluorophenyl group in macrolactonization reactions.

Modular Synthesis of 9,10-Dihydroacridines through an ortho-C Alkenylation/Hydroarylation Sequence between Anilines and Aryl Alkynes in Hexafluoroisopropanol.

9,10-Dihydroacridines are frequently encountered as key scaffolds in OLEDs. However, accessing those compounds from feedstock precursors typically requires multiple steps. Herein, a modular one-pot synthesis of 9,10-dihydroacridine frameworks is achieved through a reaction sequence featuring a selective ortho-C alkenylation of diarylamines with aryl alkynes followed by an intramolecular hydroarylation of the olefin formed as an intermediate. This transformation was accomplished by virtue of the combination of hexafluoroisopropanol and triflimide as a catalyst that triggers the whole process.

Hexafluoroisopropanol-Promoted Haloamidation and Halolactonization of Unactivated Alkenes.

Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for post-modifications. In principle, one of the simplest ways to build these frameworks is the haloamination of alkenes. While progress has been made in this field, notably with the development of enantioselective versions, this reaction is still fraught with limitations in terms of reactivity. Besides, a major question remaining is to understand the mechanism at work. The formation of a haliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Reported here is an efficient metal- and oxidant-free protocol to achieve the haloamidation of olefins, promoted by hexafluoroisopropanol, along with a DFT investigation of the mechanism. These findings should guide the future development of more complex transformations in the field of halofunctionalization.

Photooxygenation of 2-propargylfurans: a path to structurally diverse nitrogen-containing 5-membered rings.

The photooxygenation of 2-propargylfurans enabled access to original nitrogen-containing cyclopentenones and related compounds in a one-pot fashion. By employing readily-available substrates such as furans and amines, we succeeded in achieving a high degree of molecular complexity. Relying on the introduction of an alkyne moiety and tailored substrates, this transformation reveals a new facet for reaction sequences featuring the photooxygenation of furans.

Synthesis of Cyclopenta[ b]piperazinones via an Azaoxyallyl Cation.

A new and efficient reaction sequence between 2-furylcarbinols, anilines, and α-haloamides has been developed to afford highly functionalized cyclopenta[ b]piperazinones. This transformation was accomplished through an aza-Piancatelli cyclization/azaoxyallyl cation trapping with a complete control of the diastereoselectivity.