Jérôme Hannedouche

Despite the appeal of the scientific community for alkene hydroamination methodology to straightforwardly access valuable N ‐containing compounds from ubiquitous amines and alkenes, there is still a need to develop sustainable catalysts for the direct addition of simple and free amines with high atom efficiency. We herein report the synthesis and characterization of an array of structurally defined three‐coordinate anilido–imine Fe(II) alkyl complexes that show high catalytic activity and selectivity in the intramolecular hydroamination of unprotected primary amines tethered to unactivated alkenes. The influences of steric and electronic ligand variations on the catalytic efficiency of the process were examined. They led to the development of an anilido–imine Fe(II) catalyst far more active than previously reported β ‐diketiminate Fe(II) catalysts, exhibiting even catalytic activity at room temperature and displaying broader scope.

Despite the central relevance of metal‐catalyzed alkene isomerization in academia and industry and the overarching role of iron in sustainable catalysis, highly efficient iron‐catalyzed positional and geometrical isomerizations of alkenes remain long‐sought‐after goals. Herein, we disclose the development of an easily accessible, well‐defined anilido‐aldimine iron(II) alkyl catalyst that efficiently and selectively performs, for the first time, tunable olefin migration over one and multiple carbon–carbon bonds and configurational alkene isomerization. This singular catalyst behavior also unraveled the implementation of productive regiodivergent and regio‐ and stereoconvergent olefin isomerization processes. Notably, with only 1 equiv. of Cy ₂ NH·BH ₃ (relative to Fe) under mild conditions, these reactions exhibited a broad substrate scope, including (hetero)aryl‐substituted and aliphatic alkenes of different substitution patterns and with diverse functionalities. They also displayed high regio‐ and stereoselectivities. Using experimental and computational approaches, a detailed mechanistic study of the positional isomerization regime suggested a redox‐neutral alkyl‐type mechanism via an isolable iron(II)‐hydride species. This study indicated the stereo‐ and rate‐determining β‐hydride elimination step occurs through a two‐state reactivity resulting in spin acceleration and a stereoselectivity correlated to these spin state changes. This work also elucidated the peculiar and critical role of the anilido‐aldimine skeleton on the reactivity.

Despite the central relevance of metal‐catalyzed alkene isomerization in academia and industry and the overarching role of iron in sustainable catalysis, highly efficient iron‐catalyzed positional and geometrical isomerizations of alkenes remain long‐sought‐after goals. Herein, we disclose the development of an easily accessible, well‐defined anilido‐aldimine iron(II) alkyl catalyst that efficiently and selectively performs, for the first time, tunable olefin migration over one and multiple carbon–carbon bonds and configurational alkene isomerization. This singular catalyst behavior also unraveled the implementation of productive regiodivergent and regio‐ and stereoconvergent olefin isomerization processes. Notably, with only 1 equiv. of Cy ₂ NH·BH ₃ (relative to Fe) under mild conditions, these reactions exhibited a broad substrate scope, including (hetero)aryl‐substituted and aliphatic alkenes of different substitution patterns and with diverse functionalities. They also displayed high regio‐ and stereoselectivities. Using experimental and computational approaches, a detailed mechanistic study of the positional isomerization regime suggested a redox‐neutral alkyl‐type mechanism via an isolable iron(II)‐hydride species. This study indicated the stereo‐ and rate‐determining β‐hydride elimination step occurs through a two‐state reactivity resulting in spin acceleration and a stereoselectivity correlated to these spin state changes. This work also elucidated the peculiar and critical role of the anilido‐aldimine skeleton on the reactivity.

A metal‐free dual photo‐ and organocatalytic decarbonylation of aliphatic aldehydes is described for the first time. On the one hand, a wide range of tertiary aldehydes are smoothly decarbonylated thanks to the combination of thioxanthone as photocatalyst and diphenyl disulfide as organocatalyst. On the other hand, by simply using 4‐CzIPN as photocatalyst instead of thioxanthone, various secondary aldehydes readily undergo decarbonylation in an orthogonal manner, via the in situ formation of 1,4‐dihydropyridines. Both methodologies are compatible with various functional groups and are readily applied to the decarbonylation of complex molecules.

A metal‐free dual photo‐ and organocatalytic decarbonylation of aliphatic aldehydes is described for the first time. On the one hand, a wide range of tertiary aldehydes are smoothly decarbonylated thanks to the combination of thioxanthone as photocatalyst and diphenyl disulfide as organocatalyst. On the other hand, by simply using 4‐CzIPN as photocatalyst instead of thioxanthone, various secondary aldehydes readily undergo decarbonylation in an orthogonal manner, via the in situ formation of 1,4‐dihydropyridines. Both methodologies are compatible with various functional groups and are readily applied to the decarbonylation of complex molecules.

Despite the paramount importance of the Suzuki–Miyaura coupling (SMC) in academia and industry, and the great promise of iron to offer sustainable catalysis, iron‐catalyzed SMC involving sp³‐hybridized partners is still in its infancy. We herein report the development of a versatile, well‐defined electron‐deficient anilido‐aldimine iron(II) catalyst. This catalyst effectively performed C(sp³)−C(sp²) and C(sp³)−C(sp³) SMC of alkyl halide electrophiles and (hetero)aryl boronic ester and alkyl borane nucleophiles respectively, in the presence of a lithium amide base. These couplings operated under mild reaction conditions and displayed wide functional group compatibility including various medicinally relevant N‐, O‐ and S‐based heterocycles. They also tolerated primary, secondary and tertiary alkyl halides (Br, Cl, I), electron‐neutral, ‐rich and ‐poor boronic esters and primary and secondary alkyl boranes. Our methodology could be directly and efficiently applied to synthesize key intermediates relevant to pharmaceuticals and a potential drug candidate. For C(sp³)−C(sp²) couplings, radical probe experiments militated in favor of a carbon‐centered radical derived from the electrophile. At the same time, reactions run with a pre‐formed activated boron nucleophile coupled to competition experiments supported the involvement of neutral, rather than an anionic, (hetero)aryl boronic ester in the key transmetalation step.

Despite the paramount importance of the Suzuki–Miyaura coupling (SMC) in academia and industry, and the great promise of iron to offer sustainable catalysis, iron‐catalyzed SMC involving sp³‐hybridized partners is still in its infancy. We herein report the development of a versatile, well‐defined electron‐deficient anilido‐aldimine iron(II) catalyst. This catalyst effectively performed C(sp³)−C(sp²) and C(sp³)−C(sp³) SMC of alkyl halide electrophiles and (hetero)aryl boronic ester and alkyl borane nucleophiles respectively, in the presence of a lithium amide base. These couplings operated under mild reaction conditions and displayed wide functional group compatibility including various medicinally relevant N‐, O‐ and S‐based heterocycles. They also tolerated primary, secondary and tertiary alkyl halides (Br, Cl, I), electron‐neutral, ‐rich and ‐poor boronic esters and primary and secondary alkyl boranes. Our methodology could be directly and efficiently applied to synthesize key intermediates relevant to pharmaceuticals and a potential drug candidate. For C(sp³)−C(sp²) couplings, radical probe experiments militated in favor of a carbon‐centered radical derived from the electrophile. At the same time, reactions run with a pre‐formed activated boron nucleophile coupled to competition experiments supported the involvement of neutral, rather than an anionic, (hetero)aryl boronic ester in the key transmetalation step.

This review outlines the most noteworthy achievements of the last few years in the renascent field of positional and geometrical isomerization of alkenes using iron catalysis, from a mechanistic perspective. Particular attention will be placed on the developments beyond the seminal contributions of iron carbonyl complexes and on their mechanistic aspects underlying the nature of the active iron species. The relevant literature has been covered until late 2022. magnified image

Five- and six-membered ring lactones and lactams are ubiquitous frameworks in various natural and synthetic molecules and are key building blocks in organic synthesis. Catalytic addition of an O-H or N-H bond across an unactivated C–C double bond is an appealing approach to rapidly access such highly valuable N- and O-containing skeletons in a waste-free and 100% atom efficient process. Herein, we report, for the first time, the efficient and high-yield cyclization of δ/ε-alkenoic acids and N-protected δ-alkenamides catalyzedby practical and easily accessible Lewis acid scandium(III) triflate under thermal and microwave conditions. The selectivity outcome of the reaction of δ/ε-alkenoic acids was dependent on the substitution patterns of the backbone chain and alkene moiety, leading to the exclusive formation of either the corresponding γ/δ-lactones via an O-selective cyclization or the Friedel–Crafts-type product by C-selective cyclization. An uncommon and rarely disclosed O-selective cyclization occurred preferentially or exclusively when N-protected δ-alkenamides were engaged in the reaction. The atom selectivity of the cyclization was unambiguously confirmed by single crystal X-ray crystallography.

Photo‐release of triphenylphosphine from a sulfonamide azobenzene ruthenium–arene complex was exploited to activate Pd^IICl₂ into Pd⁰ catalyst, for the photo‐initiation of Sonogashira cross‐coupling. The transformation was initiated on demand – by using simple white LED strip lights – with a high temporal response and the ability to control reaction rate by changing the irradiation time. Various substrates were successfully applied to this photo‐initiated cross‐coupling, thus illustrating the wide functional‐group tolerance of our photo‐caged catalyst activator, without any need for sophisticated photochemistry apparatus.