A Rationally Designed Iron(II) Catalyst for C(sp3)-C(sp2) and C(sp3)-C(sp3) Suzuki-Miyaura Cross-Coupling.

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.

Visible-Light-Initiated Palladium-Catalyzed Cross-coupling by PPh3 Uncaging from an Azobenzene Ruthenium-Arene Complex.

Photo-release of triphenylphosphine from a sulfonamide azobenzene ruthenium-arene complex was exploited to activate PdII Cl2 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.

Experimental and Computational Mechanistic Studies of the ß-Diketiminatoiron(II)-Catalysed Hydroamination of Primary Aminoalkenes.

A comprehensive mechanistic study by means of complementary experimental and computational approaches of the exo-cyclohydroamination of primary aminoalkenes mediated by the recently reported ß-diketiminatoiron(II) complex B is presented. Kinetic analysis of the cyclisation of 2,2-diphenylpent-4-en-1-amine (1 a) catalysed by B revealed a first-order dependence of the rate on both aminoalkene and catalyst concentrations and a primary kinetic isotope effect (KIE) (kH /kD ) of 2.7 (90 °C). Eyring analysis afforded ΔH≠ =22.2 kcal mol-1 , ΔS≠ =-13.4 cal mol-1 K-1 . Plausible mechanistic pathways for competitive avenues of direct intramolecular hydroamination and oxidative amination have been scrutinised computationally. A kinetically challenging proton-assisted concerted N-C/C-H bond-forming non-insertive pathway is seen not to be accessible in the presence of a distinctly faster σ-insertive pathway. This operative pathway involves 1) rapid and reversible syn-migratory 1,2-insertion of the alkene into the Fe-Namido σ bond at the monomer {N^N}FeII amido compound; 2) turnover-limiting Fe-C σ bond aminolysis at the thus generated transient {N^N}FeII alkyl intermediate and 3) regeneration of the catalytically competent {N^N}FeII amido complex, which favours its dimer, likely representing the catalyst resting state, through rapid cycloamine displacement by substrate. The collectively derived mechanistic picture is consonant with all empirical data obtained from stoichiometric, catalytic and kinetics experiments.

Mechanistic Insights into First-row Late Transition Metal-catalysed (formal) Hydroamination of Unactivated Alkenes.

This short review provides a mechanistic overview of the most relevant developments into the area of intra- and intermolecular hydroamination and formal hydroamination of unactivated alkenes (excluding allenes and 1,3-dienes) promoted by first-row late transition metal catalysts involving zinc, copper, iron and cobalt. The different activation strategies and mechanistic disparities encountered with these systems will be highlighted. The relevant literature from 2012 until early 2018 has been covered.

First-Row Late Transition Metals for Catalytic Alkene Hydrofunctionalisation: Recent Advances in C-N, C-O and C-P Bond Formation.

This review provides an outline of the most noteworthy achievements in the area of C-N, C-O and C-P bond formation by hydroamination, hydroalkoxylation, hydrophosphination, hydrophosphonylation or hydrophosphinylation reaction on unactivated alkenes (including 1,2- and 1,3-dienes) promoted by first-row late transition metal catalytic systems based on manganese, iron, cobalt, nickel, copper and zinc. The relevant literature from 2009 until mid-2017 has been covered.

Recent developments in alkene hydro-functionalisation promoted by homogeneous catalysts based on earth abundant elements: formation of C-N, C-O and C-P bond.

This Perspective article provides an overview of the recent advancements in the field of intra- and inter-molecular C-N, C-O and C-P bond formation by hydroamination, hydroalkoxylation, hydrophosphination, hydrophosphonylation or hydrophosphinylation of unactivated alkenes, including allenes, 1,3-dienes and strained alkenes, promoted by (chiral) homogeneous catalysts based on earth abundant elements of the s and p blocks, the first row transition metals and the rare-earth metals. The relevant literature from 2009 until late 2014 has been covered.

Well-defined four-coordinate iron(II) complexes for intramolecular hydroamination of primary aliphatic alkenylamines.

Despite the growing interest in iron catalysis and hydroamination reactions, iron-catalyzed hydroamination of unprotected primary aliphatic amines and unactivated alkenes has not been reported to date. Herein, a novel well-defined four-coordinate ß-diketiminatoiron(II) alkyl complex is shown to be an excellent precatalyst for the highly selective cyclohydroamination of primary aliphatic alkenylamines at mild temperatures (70-90 °C). Both empirical kinetic analyses and the reactivity of an isolated iron(II) amidoalkene dimer, [LFe(NHCH2 CPh2 CH2 CHCH2 )]2 favor a stepwise σ-insertive mechanism that entails migratory insertion of the pendant alkene into an iron-amido bond associated with a rate-determining aminolysis step.

Cationic Group-IV pincer-type complexes for polymerization and hydroamination catalysis.

Neutral Zr(IV) and Hf(IV) dimethyl complexes stabilized by unsymmetrical dianionic {N,C,N'} pincer ligands have been prepared from their corresponding bis-amido complexes upon treatment with AlMe3. Their structure consists of a central ó-bonded aryl donor group (C) capable of forming robust M-C bonds with the metal center, enforced by the synergic effect of both the coordination of peripheral donor groups (N) and the chelating rigid structure of the {N,C,N} ligand framework. Such a combination translates into systems having a unique balance between stability and reactivity. These Zr(IV) and Hf(IV) dimethyl complexes were converted in situ into cationic species [M(IV){N⁻,C⁻,N}Me][B(C6F5)4] which are active catalysts for the room temperature (r.t.) intramolecular hydroamination/cyclization of primary and secondary aminoalkenes as well as for the high temperature ethylene-1-octene copolymerizations.

Cationic Group-IV pincer-type complexes for polymerization and hydroamination catalysis.

Neutral Zr(IV) and Hf(IV) dimethyl complexes stabilized by unsymmetrical dianionic {N,C,N'} pincer ligands have been prepared from their corresponding bis-amido complexes upon treatment with AlMe3. Their structure consists of a central σ-bonded aryl donor group (C) capable of forming robust M-C bonds with the metal center, enforced by the synergic effect of both the coordination of peripheral donor groups (N) and the chelating rigid structure of the {N,C,N} ligand framework. Such a combination translates into systems having a unique balance between stability and reactivity. These Zr(IV) and Hf(IV) dimethyl complexes were converted in situ into cationic species [M(IV){N(-),C(-),N}Me][B(C6F5)4] which are active catalysts for the room temperature (r.t.) intramolecular hydroamination/cyclization of primary and secondary aminoalkenes as well as for the high temperature ethylene-1-octene copolymerizations.

Asymmetric hydroamination: a survey of the most recent developments.

Asymmetric hydroamination allows the direct and selective formation of a new C-N bond as a simple procedure towards valuable scalemic synthons. Huge efforts have recently been made to overcome the challenges associated with this transformation. This non-comprehensive Concept article aims at pointing out the most recent and original progresses, offering nearby developments, and addressing the next challenges.

29Si-1H IMPACT HMBC: a suitable tool for analyzing silylated derivatives.

A modified version of the IMPACT heteronuclear multiple bond correlation (HMBC) has allowed the characterization of an organosilane and a tetrasilylated yttrium complex. With the help of this sequence, an average gain in sensitivity close to 2 has been obtained compared with the standard HMBC experiment for disilanes as well as for yttrium complexes containing silylated ligands. This modified version of this long-range correlation experiment opens the way for following kinetics in the range of a fraction of a minute and to study by NMR low concentrated samples and low abundant nuclei.

LiCl-effect on asymmetric intramolecular hydroamination catalyzed by binaphthylamido yttrium complexes.

Chiral alkyl or amido yttrium complexes were prepared from N-silyl- or N-cyclopentyl-substituted binaphthylamido ligands. According to the synthetic procedure, these complexes could be obtained in their neutral form or as heterobimetallic complexes in the presence of 1 equiv. LiCl. These new species were characterized by IR and NMR spectroscopies, elemental analyses and some of them by X-ray diffraction studies. Their efficiency as catalysts for the asymmetric intramolecular hydroamination was then evaluated with several substrates towards the synthesis of two pyrrolidines and a piperidine derivative. A cooperative effect between the lithium and the yttrium atoms was undoubtedly revealed. LiCl-containing complexes afforded indeed higher enantioselectivities than their salt-free counterparts and according to the structure of the chiral ligand, they were also the most active species.

Catalytic, enantioselective intramolecular hydroamination of primary amines tethered to di- and trisubstituted alkenes.

The in situ preparation of chiral amido alkyl ate yttrium complexes from an array of chiral N-benzyl-like-substituted binaphthyldiamines is reported. These chiral heteroleptic complexes are shown to be efficient catalysts for the enantioselective intramolecular hydroamination of primary amines tethered to sterically demanding alkenes at high reaction temperatures. Fine tuning of their chiral environment allowed up to 77% ee to be reached for the cyclization of aminoalkenes bearing 1,2-dialkyl-substituted carbon-carbon double bonds. These chiral complexes also demonstrate the ability to promote the cyclization of amine-tethered trisubstituted alkenes in up to 55% ee, as the first report of the formation of enantioenriched quaternary centers by an hydroamination reaction.

Well-defined and easily accessible yttrium complexes for enantioselective cyclisation of amines tethered to 1,2-di-substituted alkenes.

A straightforward in situ preparation of new chiral amido alkyl ate yttrium complexes is described. They catalysed the enantioselective cyclisation of 1,2-dialkyl-substituted aminopentenes in up to 77% ee, a significant value for this challenging transformation. Complex [(R)-L(0)][Y(CH(2)TMS)(2).Li(THF)(4)] undergoes C-H bond activation resulting in the formation of an original dimeric heterobimetallic yttrium complex which also acts as an active precatalyst.

Convenient method for the rapid generation of highly active and enantioselective yttrium catalysts for asymmetric hydroamination.

A facile method for the preparation of highly active and enantioselective yttrium precatalysts for asymmetric hydroamination of gem-disubstituted aminoalkenes, from the combination of YCl(3) or YCl(3)(THF)(3.5) with ligand (R)- and n-BuLi is described.

Asymmetric hydroamination of non-activated carbon-carbon multiple bonds.

The catalysed enantioselective formation of carbon-nitrogen bonds by the hydroamination reaction is reviewed. All examples deal with substrates containing non-activated carbon-carbon multiple bonds which are transformed either via intramolecular or intermolecular reactions. Structurally different complexes already provided nitrogen containing compounds/heterocycles with high enantioselectivities.

Asymmetric catalysis for the construction of quaternary carbon centres: nucleophilic addition on ketones and ketimines.

There is a growing need in organic synthesis for efficient methodologies for the asymmetric synthesis of quaternary carbon centres. One of the most attractive and straightforward methods focuses on the use of asymmetric catalysis for the addition of various types of nucleophiles on prochiral ketones and ketimines. A view of the literature from this growing area of research will be presented in this review, with an emphasis on the pioneer works and milestones brought by the main players in this field.

"Tethered" Ru(II) catalysts for asymmetric transfer hydrogenation of ketones.

Stereochemically well-defined ruthenium(II) catalysts have been applied to the asymmetric transfer hydrogenation of a series of ketones. In one case, statistical experimental design was employed to optimize the enantiomeric excess of the product. In the case of the TsDPEN-based systems, the replacement of trans-1,2-diphenyl substitution with cis-, or deletion of one of the phenyl groups, results in significant deterioration of the enantiomeric excess. A new method is described for the synthesis of tethered amino alcohol-containing catalysts.

A new class of "tethered" ruthenium(II) catalyst for asymmetric transfer hydrogenation reactions.

Ruthenium dimer 4 is converted directly to monomeric asymmetric transfer hydrogenation catalyst 2 under the conditions employed for ketone reduction. Using 0.25 mol % of either 4 or 0.5 mol % of 2 in formic acid/triethylamine, it is possible to achieve ketone reduction in quantitative conversion and with ee's as high as 98%. Complex 2 is a robust "single-reagent" catalyst which offers significant scope for modification toward specific substrates. The synthesis and applications of an analogous complex derived from (1R,2S)-norephedrine are also described.