Iron-Catalyzed Allylic C(sp3)-H Silylation: Spin-Crossover-Efficiency-Determined Chemoselectivity.

The nuanced role of spin effects remains a critical gap in designing proficient open-shell catalysts. This study elucidates an iron-catalyzed allylic C(sp3)-H silylation/alkyne hydrosilylation reaction, in which the spin state of the open-shell iron catalyst dictates the reaction kinetics and pathway. Specifically, spin crossover led to alkyne hydrosilylation, whereas spin conservation resulted in a novel allylic C(sp3)-H silylation reaction. This chemoselectivity, governed by the spin-crossover efficiency, reveals an unexpected dimension in spin effects and a first in the realm of transition-metal-catalyzed in situ silylation of allylic C(sp3)-H bonds, which had been previously inhibited by the heightened reactivity of alkenes in hydrosilylation reactions. Furthermore, this spin crossover can either accelerate or hinder the reaction at different stages within a single catalytic reaction, a phenomenon scarcely documented. Moreover, we identify a substrate-assisted C-H activation mechanism, a departure from known ligand-assisted processes, offering a fresh perspective on C-H activation strategies.

[Effect of sodium alginate-g-deferoxamine/chitosan microspheres on osteogenic differentiation of rat bone mesenchymal stem cells].

PURPOSE: To explore the effect of sodium alginate-g-deferoxamine/chitosan (SA-g-DFO/CS) microspheres on proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). METHODS: A kind of SA-g-DFO/CS microsphere was developed through electrostatic interaction between porous chitosan microspheres and sodium alginate chemically grafted on the surface of DFO. Its morphology, porosity rate, pore size and sustained release of DFO in vitro were examined. Rat BMSCs were isolated and co-cultured with microspheres in osteogenic differentiation medium. MTT assay was used to study the influence of cell proliferation, and Calcein-AM/PI staining was used to observe the cell viability. Alkaline phosphatase (ALP) activity assay was conducted. PCR was used to detect the expression of genes related to angiogenesis and osteogenesis. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: The SA-g-DFO/CS porous microspheres were successfully prepared with a sustained re6lease of DFO. Compared with SA/CS microspheres, the SA-g-DFO/CS microspheres were conducive to cell proliferation and differentiation, with the increases in expression level of ALP, related angiogenesis genes HIF-1α, VEGF and osteogenesis genes COLI, OCN. CONCLUSIONS: The SA-g-DFO/CS porous microspheres can provide a new choice for the development of alveolar bone regeneration.

Iron-Catalyzed Stereoconvergent 1,4-Hydrosilylation of Conjugated Dienes.

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.

Iron-Catalyzed Alkene Hydroalumination.

Hydroalumination of olefins generally gives thermodynamically controlled anti-Markovnikov addition selectivity in literatures. In this paper, a highly Markovnikov hydroalumination of aromatic terminal alkenes was realized to prepare various new benzylaluminum complexes by using the well-defined 2,9-diaryl-1,10-phenanthroline modified iron complex as the catalyst and commercially available DIBAL-H as the aluminum hydride reagent. This is the first ironcatalyzed alkene hydroalumination, and the regioselectivity observed in this study is different from the related reactions reported in the literatures.

Iron-catalysed hydroalumination of internal alkynes.

Although research on iron-catalysed reactions has recently achieved significant progress, the activity and selectivity of iron catalysts are generally inferior to those of noble-metal catalysts. The development of new iron-catalysed reactions, especially those in which iron catalysts exhibit superior activity or selectivity to other catalysts, is the key to promote iron catalysis. Herein, we report the first protocol for iron-catalysed hydroalumination of internal alkynes. Specifically, in the presence of iron catalysts bearing 2,9-diaryl-1,10-phenanthroline ligands, internal alkynes were stereo- and regioselectively hydroaluminated with the commercially available reagent diisobutylaluminum hydride. Compared with other metal-catalysed alkyne hydroalumination reactions reported in the literature, the iron-catalysed protocol has the following advantages: unusual amino-group-directed regioselectivity, a wide substrate scope, good functional group tolerance, high selectivity, and mild reaction conditions. The alkenylaluminum products prepared in this way could undergo a diverse array of transformations, and were used for the synthesis of bioactive compounds. The current study expands the scope of iron catalysis, provides a new efficient access to alkenylaluminum, discloses the origin of the superiority of iron catalysts, and thus may inspire further studies in related fields.

Phenanthroline-imine ligands for iron-catalyzed alkene hydrosilylation.

Iron-catalyzed organic reactions have been attracting increasing research interest but still have serious limitations on activity, selectivity, functional group tolerance, and stability relative to those of precious metal catalysts. Progress in this area will require two key developments: new ligands that can impart new reactivity to iron catalysts and elucidation of the mechanisms of iron catalysis. Herein, we report the development of novel 2-imino-9-aryl-1,10-phenanthrolinyl iron complexes that catalyze both anti-Markovnikov hydrosilylation of terminal alkenes and 1,2-anti-Markovnikov hydrosilylation of various conjugated dienes. Specifically, we achieved the first examples of highly 1,2-anti-Markovnikov hydrosilylation reactions of aryl-substituted 1,3-dienes and 1,1-dialkyl 1,3-dienes with these newly developed iron catalysts. Mechanistic studies suggest that the reactions may involve an Fe(0)-Fe(ii) catalytic cycle and that the extremely crowded environment around the iron center hinders chelating coordination between the diene and the iron atom, thus driving migration of the hydride from the silane to the less-hindered, terminal end of the conjugated diene and ultimately leading to the observed 1,2-anti-Markovnikov selectivity. Our findings, which have expanded the types of iron catalysts available for hydrosilylation reactions and deepened our understanding of the mechanism of iron catalysis, may inspire the development of new iron catalysts and iron-catalyzed reactions.

Iron-Catalyzed Vinylzincation of Terminal Alkynes.

Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C-H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.

Iron-Catalyzed Regiodivergent Alkyne Hydrosilylation.

Although tremendous effort has been devoted to the development of methods for iron catalysis, few of the catalysts reported to date exhibit clear superiority to other metal catalysts, and the mechanisms of most iron catalysis remain unclear. Herein, we report that iron complexes bearing 2,9-diaryl-1,10-phenanthroline ligands exhibit not only unprecedented catalytic activity but also unusual ligand-controlled divergent regioselectivity in hydrosilylation reactions of various alkynes. The hydrosilylation protocol described herein provides a highly efficient method for preparing useful di- and trisubstituted olefins on a relatively large scale under mild conditions, and its use markedly improved the synthetic efficiency of a number of bioactive compounds. Mechanistic studies based on control experiments and density functional theory calculations were performed to understand the catalytic pathway and the observed regioselectivity.

Iron-Catalyzed Dihydrosilylation of Alkynes: Efficient Access to Geminal Bis(silanes).

Geminal bis(silanes) are versatile synthetic building blocks owing to their stability and propensity to undergo a variety of transformations. However, the scarcity of catalytic methods for their synthesis limits their structural diversity and thus their utility for further applications. Herein we report a new method for synthesis of geminal bis(silanes) by means of iron-catalyzed dihydrosilylation of alkynes. Iron catalysts were distinctly superior to the other tested catalysts, which clearly demonstrates that novel reactivity can be found by using iron catalysts. This method features 100% atom economy, regiospecificity, mild reaction conditions, and readily available starting materials. Using this method, we prepared a new type of geminal bis(silane) with secondary silane moieties, the Si-H bonds of which can easily undergo various transformations, facilitating the synthetic applications of these compounds. Preliminary mechanistic studies demonstrated that the reaction proceeds via two iron-catalyzed hydrosilylation reactions, the first generating ß-( E)-vinylsilanes and the second producing geminal bis(silanes).

Ligands with 1,10-phenanthroline scaffold for highly regioselective iron-catalyzed alkene hydrosilylation.

Transition-metal-catalyzed alkene hydrosilylation is one of the most important homogeneous catalytic reactions, and the development of methods that use base metals, especially iron, as catalysts for this transformation is a growing area of research. However, the limited number of ligand scaffolds applicable for base-metal-catalyzed alkene hydrosilylation has seriously hindered advances in this area. Herein, we report the use of 1,10-phenanthroline ligands in base-metal catalysts for alkene hydrosilylation. In particular, iron catalysts with 2,9-diaryl-1,10-phenanthroline ligands exhibit unexpected reactivity and selectivity for hydrosilylation of alkenes, including unique benzylic selectivity with internal alkenes, Markovnikov selectivity with terminal styrenes and 1,3-dienes, and excellent activity toward aliphatic terminal alkenes. According to the mechanistic studies, the unusual benzylic selectivity of this hydrosilylation initiates from π-π interaction between the phenyl of the alkene and the phenanthroline of the ligand. This ligand scaffold and its unique catalytic model will open possibilities for base-metal-catalyzed hydrosilylation reactions.