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.

Synthesis of functionalised isochromans: epoxides as aldehyde surrogates in hexafluoroisopropanol.

The oxa-Pictet-Spengler reaction is arguably the most straightforward and modular way to construct the privileged isochroman motif, but its scope is largely limited to benzaldehyde derivatives and to electron-rich ß-phenylethanols that lack substitution along the aliphatic chain. Here we describe a variant of this reaction starting from an epoxide, rather than an aldehyde, that greatly expands the scope and rate of the reaction (<1 h, 20 °C). Besides facilitating the initial Meinwald rearrangement, the use of hexafluoroisopropanol (HFIP) as a solvent expands the electrophile scope to include partners equivalent to ketones, aliphatic aldehydes, and phenylacetyl aldehydes, and the nucleophile scope to include modestly electronically deactivated and highly substituted ß-phenylethanols. The products could be easily further derivatised in the same pot by subsequent ring-opening, reductions, and intra- and intermolecular Friedel-Crafts reactions, also in HFIP. Finally, owing to the high pharmacological relevance of the isochroman motif, the synthesis of drug analogues was demonstrated.

The Rational Design of Reducing Organophotoredox Catalysts Unlocks Proton-Coupled Electron-Transfer and Atom Transfer Radical Polymerization Mechanisms.

Photocatalysis has become a prominent tool in the arsenal of organic chemists to develop and (re)imagine transformations. However, only a handful of versatile organic photocatalysts (PCs) are available, hampering the discovery of new reactivities. Here, we report the design and complete physicochemical characterization of 9-aryl dihydroacridines (9ADA) and 12-aryl dihydrobenzoacridines (12ADBA) as strong reducing organic PCs. Punctual structural variations modulate their molecular orbital distributions and unlock locally or charge-transfer (CT) excited states. The PCs presenting a locally excited state showed better performances in photoredox defunctionalization processes (yields up to 92%), whereas the PCs featuring a CT excited state produced promising results in atom transfer radical polymerization under visible light (up to 1.21 D, and 98% I*). Unlike all the PC classes reported so far, 9ADA and 12ADBA feature a free NH group that enables a catalytic multisite proton-coupled electron transfer (MS-PCET) mechanism. This manifold allows the reduction of redox-inert substrates including aryl, alkyl halides, azides, phosphate and ammonium salts (Ered up to -2.83 vs SCE) under single-photon excitation. We anticipate that these new PCs will open new mechanistic manifolds in the field of photocatalysis by allowing access to previously inaccessible radical intermediates under one-photon excitation.

Synthesis of Unprotected ß-Arylethylamines by Iron(II)-Catalyzed 1,2-Aminoarylation of Alkenes in Hexafluoroisopropanol.

ß-Arylethylamines are prevalent structural motifs in molecules exhibiting biological activity. Here we report a sequential one-pot protocol for the 1,2-aminoarylation of alkenes with hydroxylammonium triflate salts and (hetero)arenes. Unlike existing methods, this reaction provides a direct entry to unprotected ß-arylethylamines with remarkable functional group tolerance, allowing key drug-oriented functional groups to be installed in a two-step process. The use of hexafluoroisopropanol as a solvent in combination with an iron(II) catalyst proved essential to reaching high-value nitrogen-containing molecules.

Electrochemical Umpolung C-H Functionalization of Oxindoles.

Herein, we present a general electrochemical method to access unsymmetrical 3,3-disubstituted oxindoles by direct C-H functionalization where the oxindole fragment behaves as an electrophile. This Umpolung approach does not rely on stoichiometric oxidants and proceeds under mild, environmentally benign conditions. Importantly, it enables the functionalization of these scaffolds through C-O, and by extension to C-C or even C-N bond formation.

Electrochemical Rearrangement of 3-Hydroxyoxindoles into Benzoxazinones.

We report an unexpected rearrangement of 3-hydroxyoxindoles into benzoxazinones using electrochemistry. Our reaction employs mild and environmentally friendly conditions, and the benzoxazinone products are obtained in moderate to excellent yields. Mechanistic experiments suggest that a peroxide intermediate is likely involved.

Exploring the Limits of π-Acid Catalysis Using Strongly Electrophilic Main Group Metal Complexes: The Case of Zinc and Aluminium.

The catalytic activity of cationic NHC-ZnII and NHC-AlIII (NHC=N-heterocyclic carbene) complexes in reactions that require the electrophilic activation of soft C-C π bonds has been studied. The former proved able to act as a soft π-Lewis acid in a variety of transformations. The benefit of the bulky IPr NHC ligand was demonstrated by comparison with simple ZnX2 salts. The tested NHC-AlIII catalyst is not able to activate C-C π bonds but simple AlX2 + ions were found potent in some cases.

Synthesis of Medium-Sized Carbocycles by Gallium-Catalyzed Tandem Carbonyl-Olefin Metathesis/Transfer Hydrogenation.

The first examples of a catalytic tandem process involving a ring-closing carbonyl-olefin metathesis and a transfer hydrogenation are described. 1,4-Cyclohexadiene has been used as an H2 surrogate to reduce the cyclic alkenes formed after the metathesis step. The same cationic gallium(III) complex, [IPr·GaCl2][SbF6], performs the two steps with functional group tolerance. This stereoselective reaction leads to 1,2-cis-disubstituted cyclopentanes and various cyclohexanes. DFT computations support an unexpected mechanism involving activation of 1,4-cyclohexadiene by superelectrophilic gallium(III) dimers.

Synthesis of 3-Substituted 3-Bromo-1-phenylallenes from Alkynylcycloheptatrienes.

A new method has been developed for the preparation of 3-bromo-1-phenylallenes from 7-alkynylcycloheptatrienes and N-bromosuccinimide. Trisubstituted bromoallenes were obtained at room temperature in moderate to excellent yields. Functionalization of the carbon-bromine bond via Pd- or Cu-catalyzed cross-coupling reactions easily provided substituted allenes.

Iron-Catalyzed Reductive Ethylation of Imines with Ethanol.

The borrowing hydrogen strategy has been applied to the ethylation of imines with an air-stable iron complex as precatalyst. This approach opens new perspectives in this area as it enables the synthesis of unsymmetric tertiary amines from readily available substrates and ethanol as a C2 building block. A variety of imines bearing electron-rich aryl or alkyl groups at the nitrogen atom could be efficiently reductively alkylated without the need for molecular hydrogen. The mechanism of this reaction, which shows complete selectivity for ethanol over other alcohols, has been studied experimentally and by means of DFT computations.

Revealing the Activity of π-Acid Catalysts using a 7-Alkynyl Cycloheptatriene.

A compound that isomerizes into distinct products depending on the particular Lewis acid or Brønsted acid catalyst used is disclosed. One product can only be obtained with the softest π-acids, such as Au, Pt, Ga, or In complexes. Another is formed only with harder π-acids incorporating Ag or Cu salts. The formation of the third category requires even harder π-acids or protons. This simple benchmark reaction allows for prediction of the category of transformations that can be catalyzed by a new complex. It also informs whether protons have been unintentionally generated in the reaction mixture.

Acid-catalysed intramolecular addition of ß-ketoesters to 1,3-dienes.

1,3-Dienyl ß-keto esters are cyclised into bicyclolactones using the Bi(OTf)3/TfOH catalytic system. This reaction represents a rare case of simultaneous C-C and C-O bond formation at positions 1 and 3 of a 1,3-diene. Application to the synthesis of ramulosin is presented.