Over the past decade, considerable progress on iron-catalyzed C–C bond-forming cross-coupling reactions has been made, leading to the successful development of several new catalytic systems. This ...perspective presents the proposed mechanistic pathways of iron-mediated cross-coupling reactions of organohalides and Grignard reagents and discusses the evidence documented in the literature that distinguishes whether such pathways proceed via single- or double-electron processes. When cross-coupling reactions are conducted in the presence of ligands, there is still much discussion in the literature as to whether the lowest iron oxidation state responsible for catalytic activity is Fe(I) or Fe(II). However, when ligand-free conditions are employed, it has been shown that iron reaches an Fe(I) oxidation state, allowing an Fe(I)/Fe(III) catalytic cycle. Moreover, for cross-couplings using alkyl halide electrophiles, evidence suggests that the reaction proceeds through single-electron steps, with the generation of an alkyl radical. While this topic is still the subject of much debate, it is thought that reactions of alkyl Grignards with aryl and alkenyl electrophiles proceed via a double-electron pathway.
There is a tremendous need to have perennial and continuous access to cost-effective electricity generated from the intermittent energy sources (wind, solar, geothermal, hydropower, wave etc.). This ...will require development of inexpensive and efficient electrical energy storage (EES) devices such as stationary battery for uninterrupted electricity (power storage back up) and load leveling as well as grid energy storage systems 1-6. Magnesium based secondary batteries are a viable 'environmental friendly, non-toxic' alternative compared to the immensely popular Li-ion systems owing to its high volumetric capacity (3833mAh/cc for Mg vs. 2046mAh/cc for Li) for stationary EES applications. Following the successful demonstration of a prototype magnesium cell capable of offering energy density 60Wh/kg in the early 2000, the last decade has witnessed tremendous amount of work dedicated to magnesium battery and its components. The present review is an earnest attempt to collect all of the comprehensive body of research performed in the literature hitherto to develop non-aqueous nucleophilic/non-nucleophilic liquid electrolytes, ionic liquid based polymer as well as solid/gel polymer electrolytes; intercalation/insertion/conversion type cathodes; metallic magnesium and their alloys/intermetallic/composites as anodes; and electronically conductive but chemically and electrochemically inert current collectors for magnesium battery. The limited electrochemical oxidative stability of current generation of electrolytes with inherently slow magnesium-ion diffusion in to electrodes as well as the inability of Mg2+ to reversibly cycle in all but a few materials systems impede the growth of high power and high energy density magnesium cells, analogous to Li-ion systems. Before the successful fabrication of a prototype magnesium battery, optimization of electrolyte performance, the realization of suitable intercalation/insertion cathodes and the identification of alternative alloys, intermetallics, composites and compounds as anodes are highly critical. Exploration of the compatibility of various battery parts including metallic current collectors with currently used organochloro electrolytes sheds light on the electrochemical corrosion of metals such as Cu, Al, stainless steel (SS) toward chlorinated Grignard's salts warranting further investigation for identifying, electrically conducting and electrochemically inert current collectors. Results to date show the preferential selectivity of certain electronically conducting metallic and non-metallic current collectors for rechargeable magnesium batteries owing to its high anodic stability in the present electrolyte. Development of magnesium-ion battery therefore requires an interdisciplinary approach with a sound understanding of organometallic and inorganic chemistry, adequate knowledge of materials chemistry, materials science and engineering, as well as electrochemistry, and a comprehensive knowledge of metallic corrosion principles in basic/acidic electrolytic environments in order that a system with acceptable energy density (150-200Wh/kg) and operational voltage 2-3V can be developed in the near future.
Catalytic enantioselective addition of organometallic nucleophiles to ketones is among the most straightforward approaches to the synthesis of chiral tertiary alcohols. The first such catalytic ...methodologies using the highly reactive organomagnesium reagents, which are the preferred organometallic reagents in terms of cost, availability, atom efficiency, and structural diversity, were developed only during the last five years. This Concept article highlights the fundamental breakthrough that made the development of methodologies for highly enantioselective Cu(I) -catalyzed alkylation of ketones using organomagnesium reagents possible.
Using a palladium catalyst supported by DrewPhos, the alkylation of monochlorosilanes with primary and secondary alkylmagnesium halides is now possible. Arylation with sterically demanding aromatic ...magnesium halides is also enabled. This transformation overcomes the high bond strength of the Si–Cl bond (113 kcal/mol) and is a rare example of a transition-metal catalyzed process involving its activation. Because of the availability of both chlorosilanes and organomagnesium halide reagents, this method allows for the preparation of a wide range of alkyl and aryl silanes.
The scarcity of precious metals has led to the development of sustainable strategies for metal‐catalyzed cross‐coupling reactions. The establishment of new catalytic methods using iron is attractive ...owing to the low cost, abundance, ready availability, and very low toxicity of iron. In the last few years, sustainable methods for iron‐catalyzed cross‐couplings have entered the critical area of pharmaceutical research. Most notably, iron is one of the very few metals that have been successfully field‐tested as highly effective base‐metal catalysts in practical, kilogram‐scale industrial cross‐couplings. In this Minireview, we critically discuss the strategic benefits of using iron catalysts as green and sustainable alternatives to precious metals in cross‐coupling applications for the synthesis of pharmaceuticals. The Minireview provides an essential introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.
With an iron hand: Iron is one of the very few metals that have been successfully used as highly effective base‐metal catalysts in practical, kilogram‐scale industrial cross‐couplings. The Minireview provides an introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.
Herein we disclose an iron‐catalyzed cross‐coupling reaction of propargyl ethers with Grignard reagents. The reaction was demonstrated to be stereospecific and allows for a facile preparation of ...optically active allenes via efficient chirality transfer. Various tri‐ and tetrasubstituted fluoroalkyl allenes can be obtained in good to excellent yields. In addition, an iron‐catalyzed cross‐coupling of Grignard reagents with α‐alkynyl oxetanes and tetrahydrofurans is disclosed herein, which constitutes a straightforward approach towards fully substituted β‐ or γ‐allenols, respectively.
A method for facile synthesis of highly substituted allenols and fluoroalkyl allenes via iron‐catalyzed cross‐coupling reaction of propargyl ethers with Grignard reagents is disclosed. Various tri‐ and tetrasubstituted fluoroalkyl allenes and β‐/γ‐allenols were obtained in good to excellent yields. The reaction was demonstrated to be stereospecific occurring with syn‐SN2′ displacement of the methoxy group by the Grignard reagent.
Simple, commercially available Grignard reagents have been used as highly efficient precatalysts for the hydroboration of a wide range of aldehydes and ketones. The reaction employs very low catalyst ...loadings (aldehydes: 0.05 mol%, ketones: 0.5 mol%), and proceeds rapidly (aldehydes: 10 min, ketones: 20 min) under neat condition at room temperature. The Grignard reagent catalyst demonstrated good substrate scope, functional group tolerance, and high chemoselectivity in the carbonyl hydroboration. DFT calculations were performed to investigate the possible reaction mechanism. In contrast to the traditional stoichiometric use of Grignard reagents, this newly developed protocol provides a catalytic application of these reagents for molecular transformations.
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•Grignard reagents have been employed as efficient precatalysts for various carbonyl hydroboration.•The Grignard reagent catalyst shows a high functional group tolerance and high chemoselectivity.•In contrast to the traditional stoichiometric use of Grignard reagents, this protocol provides a catalytic application.
The asymmetric catalytic addition of linear Grignard reagents to ketones has been a long‐standing challenge in organic synthesis. Herein, a novel family of PNP ligands (W‐Phos) was designed and ...applied in copper‐catalyzed asymmetric addition of linear Grignard reagents to aryl alkyl ketones, allowing facile access to versatile chiral tertiary alcohols in good to high yields with excellent enantioselectivities (up to 94 % yield, 96 % ee). The process can also be used to synthesize chiral allylic tertiary alcohols from more challenging α,β‐unsaturated ketones. Notably, the potential utility of this method is demonstrated in the gram‐scale synthesis and modification of various densely functionalized medicinally relevant molecules.
A novel family of PNP ligands (W‐Phos) was designed and applied in the copper‐catalyzed asymmetric addition of linear Grignard reagents to ketones, allowing ready access to versatile chiral tertiary alcohols in high yields and with excellent enantioselectivities.
Catalytic asymmetric addition of reactive Grignard reagents to ketimines poses a considerable challenge. Herein, a PNP-type W-Phos ligand developed recently by our group showed a unique effect toward ...this end, paving the way to a Cu(I)-catalyzed asymmetric alkylation reaction of N-sulfonyl ketimines, delivering optically active α-tertiary amines in high enantioselectivities. This catalytic protocol shows an unprecedented substrate scope with more than 80 examples, not only compatible with benzo five- and six-membered cyclic N-sulfonyl ketimines but also suitable for geometrically unstable (E or Z) acyclic N-sulfonyl ketimines. The application potential of the protocol is featured by the extensive presence of α-tertiary amines in natural products and pharmaceutical compounds and also demonstrated by downstream transformations with maintenance of the enantioselectivity.
The identification of two nickel(II) precatalysts for the preparation of 2-substituted 1,3-dienes by a Kumada cross-coupling between vinyl magnesium bromide and vinyl phosphates is described. This ...is noteworthy as engaging only one vinyl derivative in a transition-metal-catalyzed cross-coupling reaction is already reputedly challenging. Salient features of this method are its operational simplicity, the mild reaction conditions, the low catalyst loadings, the short reaction times, its scalability, and the use of stoichiometric quantities of each coupling partner. The tolerance of the two nickel catalysts to an important number of reactive functional groups and their compatibility with structurally complex molecular architectures has been extensively delineated. A Negishi variant of the reaction has been developed for even more sensitive organic functions such as ester or nitrile. Several other conjugated 1,3-dienes with various substitution patterns have been prepared by combining commercial alkenyl Grignard reagents and/or readily available alkenyl enol phosphates. Proper choice of the nickel catalyst and the reaction temperature gave access to a variety of different olefin isomers with high levels of stereocontrol. Overall, this approach affords conjugated dienes that would not be accessible otherwise and therefore provides a valuable complement to existing methods.
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