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A rhodium-catalyzed protocol has been established for the enantioselective hydroamination of gem-difluoroallenes with anilines. This strategy shows complete atom-efficiency to access a variety of enantioenriched gem-difluoroallylic amines in excellent branched selectivity (>99:1 for each case), which are important backbones in many biologically active compounds. Mechanistic studies suggest the generation of a gem-difluoro π-allyl rhodium intermediate by an exclusive hydrometalation pathway, which undergoes nucleophilic substitution of amines.

The first highly efficient and practical chiral Brønsted acid catalyzed dynamic kinetic asymmetric hydroamination (DyKAH) of racemic allenes and asymmetric hydroamination of unactivated dienes with both high E/Z selectivity and enantioselectivity are described herein. The transformation proceeds through a new catalytic asymmetric model involving a highly reactive π‐allylic carbocationic intermediate, generated from racemic allenes or dienes through a proton transfer mediated by an activating/directing thiourea group. This method affords expedient access to structurally diverse enantioenriched, potentially bioactive alkenyl‐containing aza‐heterocycles and bicyclic aza‐heterocycles. [ABSTRACT FROM AUTHOR]

A copper-catalyzed hydroamination of styrenes using piv ZPhos as ligand is reported. Enantioselectivities up to 94% are achieved under optimized conditions with aryl and heteroaryl styrenes. A variety of electrophilic O -benzoylhydroxylamines are well tolerated. [ABSTRACT FROM AUTHOR]

Simple chiral proligands have been synthesized from inexpensive chiral starting materials. These amidate and ureate ligands support zirconium complexes that successfully catalyze intramolecular hydroamination with up to 26% ee. Several elements necessary for successful ligand design are highlighted and discussed. In particular, the strict control of metal geometry through multidentate tethered ligands is determined to be an essential aspect of future ligand development. Key words: ureate, amidate, hydroamination, zirconium, enantioselective. On a realise la synthese de proligands chiraux simples a partir de produits de depart chiraux peu couteux. Ces ligands amidates et ureates supportent des complexes du zirconium qui peut catalyseur avec succes des hydroaminations intramoleculaires avec des exces d'enantiomere allant jusqu'a 26 %. On met en evidence et on discute de plusieurs elements necessaires au bon developpement d'un ligand. En particulier, on a determine qu'un aspect essentiel du developpement du futur ligand est le controle strict de la geometrie du metal par le biais de ligands multidentates bien fixes, Mots-cles : ureate, amidate, hydroamination, zirconium, enantioselective. [Traduit par la Redaction], Introduction Hydroamination, the addition of an N-H bond across unsaturated C-C bonds, has shown great promise for the efficient synthesis of amines. (1) Numerous systems exist for this highly desirable [...]

We report of a concise synthesis of (R)‐sitagliptin monophosphate – a drug predominantly applied in the treatment of type 2 diabetes. Utilizing our recently developed RhI‐catalyzed hydroamination of allenes for the stereoselective construction of the inherent chiral amino function, a new approach to (R)‐sitagliptin monophosphate on a 3.5 mmol scale was established. [ABSTRACT FROM AUTHOR]

The precise synthesis of chiral polymers remains a significant challenge in polymer chemistry, particularly for applications in advanced biomedical and electronic materials. The development of degradable polymers is important for eco‐friendly and advanced materials. Here, we introduce a stereo‐controlled degradable polymer via cascade enyne metathesis polymerization and enantioselective acetal synthesis through Pd‐catalyzed asymmetric hydroamination. This approach allows for the creation of chiral acetal‐based polymers with controlled stereochemistry and degradability, highlighting their potential for use in drug delivery and electronic applications. This concept article reviews the background, development, and potential applications of these stereo‐controlled degradable polymers. [ABSTRACT FROM AUTHOR]

A novel approach for asymmetric intramolecular hydroamination, hydroalkoxylation and hydrocarbonation of alkynes using chiral palladium catalysts are described. It was found that a chiral palladium catalyst, derived from [Pd.sub.2][(dba).sub.3].CH[CI.sub.3] and (R,R)-renorphos is highly effective for catalyzing asymmetric intramolecular hydroamination.

The synthesis of 3,3'-bis(trisarylsilyl)-substituted binaphtholate rare earth metal complexes and their application as hydroamination catalysts are reported. The experiments of the anti-Markvnikov addition of n-propylamine to styrene show that the highly active lanthanum catalysts (R)-[La{BInol-Sl(3,5-xylyl)(sub 3)}{E(SiMe3)(sub 2)}(THF)(sub 2)] (E = CH (4a), N (4b)) are the most promising candidates for asymmetric intermolecular hydroamination reactions.

In the present study, we report the first silver-dependent enantiodivergent gold-catalysed reaction. The asymmetric intramolecular hydroamination of alkenes catalysed by the combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate can afford both enantiomers of the products by a simple solvent change from toluene to methanol. Such an enantiodivergent reaction is strictly independent of the reaction temperature or of the nature of the catalyst anion and displays the same first-order kinetic rate law with respect to substrate concentration in both solvents. Beyond a simple solvent effect the enantioinversion is controlled by gold-silver chloride adducts which occur only in methanol and allow a dual activation of the reagent. While one single gold atom activates the alkene moiety, the other gold atom forms an oxophilic gold-silver chloride adduct which is likely to interact with the carbamate function. By comparison with toluene, which affords ( S)-enantiomer, this proximal and bimetallic activation would allow an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and lead therefore to the ( R)-enantiomer. [ABSTRACT FROM AUTHOR]

A series of intermolecular enantioselective hydroaminations occurring in high yield and enantioselectivities is described. The studies have shown that the arylamide has served as both a reactive and ancillary ligand.

The first palladium-catalyzed intramolecular asymmetric hydroamination of alkynes is developed. Various optically active nitrogen heterocycles are prepared using readily available aminoalkynes.

Amino alcohols are important ligands for the asymmetric catalytic hydroamination of aminoallenes to form chiral pyrrolidines. Herein, we report the crystal structures of two chiral amino alcohols, D-N-(2-Adamantyl)phenylglycinol and L-N-(2-Adamantyl)diphenylphenylalinol, that function as ligands within transition metal complexes that catalyze the hydroamination of aminoallenes. Both molecules crystallize in the noncentrosymmetric orthorhombic space group P212121. Inter- and intramolecular hydrogen bonding plays an important role in stabilizing each alcohol in the solid state in the absence of a transition metal. The presence of these hydrogen bonds has been verified by single crystal X-ray diffraction and their overall strength determined by computational methods. [ABSTRACT FROM AUTHOR]

The first highly enantioselective Brønsted acid catalyzed intramolecular hydroamination of alkenes enables the efficient construction of a series of chiral (spirocyclic) pyrrolidines with an α-tetrasubstituted carbon stereocenter with excellent functional group tolerance. A unique feature of this strategy is the use of a thiourea group acting as both the activating and the directing group through cooperative multiple hydrogen bonding with a Brønsted acid and the double bond. The utility of this method is highlighted by the facile construction of chiral synthetic intermediates and important structural motifs that are widely found in organic synthesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The development of catalysts for intramolecular asymmetric alkene hydroamination has been investigated extensively over the past two decades, since the hydroamination is a highly atom economical process in which an amine N–H bond is added to an unsaturated carbon–carbon bond leading to the formation of nitrogen heterocycles that are building blocks in numerous biologically and pharmacologically active compounds. The organolanthanide catalysts have been shown to be promising in this area. This perspective highlights the recent progress in the development of organolanthanide catalysts with chiral biaryl-backbones for the asymmetric hydroamination/cyclization of non-activated alkenes. [ABSTRACT FROM AUTHOR]

A new class of chiral zirconium complexes supported by chiral tridentate [O−NO−]-type of ligands derived from amino acids were synthesized and structurally characterized. They catalyzed asymmetric hydroamination/cyclization of primary aminoalkenes to give five- and six-membered N-heterocyclic amines with up to 94% ee. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Calcium complexes supported by chiral 1,2-diamines have been shown to be efficient catalysts for the asymmetric hydroamination of amino-olefin substrates; the calcium complexes [Ca(NNR){N(SiMe3)2}(THF)] (R = tBu, iPr, Ph, 4-C6H4F) give enantioselectivities of up to 26% which marks a significant increase based upon literature precedence. The structure of [Ca(NNPh){N(SiMe3)2}(py)] has been computed with density functional methods. [ABSTRACT FROM AUTHOR]

A facile method for the preparation of highly active and enantioselective yttrium precatalysts for asymmetric hydroamination of gem-disubstituted aminoalkenes, from the combination of YCl3 or YCl3(THF)3.5 with ligand (R)-L1 and n-BuLi is described. [ABSTRACT FROM AUTHOR]

A stereocontrolled degradable polymer was synthesized via living cascade enyne metathesis polymerization. Highly stereodefined N,O‐acetal‐containing enyne monomers were prepared using the Pd‐catalyzed hydroamination of alkoxyallenes and ring‐closing metathesis. The resulting chiral polymer exhibited a narrow dispersity window. Block copolymers were prepared not only by sequentially adding nondegradable and degradable monomers but also by using enantiomerically different monomers to produce stereocontrolled blocks. Owing to the hydrolyzable N,O‐acetal moiety in the backbone structure, the resulting polymer could degrade under acidic conditions generated using various acid concentrations to control the degradation. Additionally, the aza‐Diels–Alder reaction modified the polymer without losing the stereochemistry. [ABSTRACT FROM AUTHOR]

In the background is featured Ginkakuji (Silver Pavilion), a Zen temple along Kyoto′s eastern mountains (Higashiyama) in Japan. In the foreground is featured a chemistry sketch based on the Yin and Yang symbol. As many possible dualities (such as light and dark, fire and water…) are thought of as physical manifestations of the duality symbolised by Yin and Yang, parallels can be drawn with organic chemistry and the gold(I)‐catalysed asymmetric hydroamination of alkenes. An enantiodivergent reaction is possible depending on the presence of silver. Whereas a gold‐catalysed hydroamination reaction afforded (S)‐product in toluene, the use of methanol led to an enantioinversion and the generation of (R)‐product through solvation of silver and bimetallic activation of the amino‐alkene reagent. For more information see the Full Paper by F. Agbossou‐Niedercorn, C. Michon and co‐workers on page 10777 ff. [ABSTRACT FROM AUTHOR]

Enantiomerically pure amines are crucial intermediates for a wide range of pharmaceuticals, natural products, and bioactive compounds. Asymmetric intermolecular hydroamination of alkenes is one of the most atom-economical methods for the synthesis of chiral amines. However, the direct stereoselective hydroamination of alkenes remains a significant challenge. Herein, we developed a novel fully biocatalytic system to enable the direct stereoselective hydroamination of aryl alkenes to produce chiral amines. The process involves sequential alkene asymmetric hydration catalyzed by a hydratase (HD), followed by in situ oxidation of alcohol into ketone by two enantiocomplementary alcohol dehydrogenases (ADHs), and finally, enantioselective transformation of ketone into enantiomerically pure amine by a ω-transaminase (TA). The addition of lactate dehydrogenase (LDH) facilitated the connection between alcohol oxidation and pyruvate reduction, making the cascade reaction redox self-sufficient and driving the process towards the desired target product. In vitro cascade biocatalysis for asymmetric hydroamination of 4-hydroxystyrenes 1a–f was first investigated by using the combined enzymes (HD/ADHs/LDH/TA) with trace amounts of NAD+ (0.05 mM) and pyridoxal-5′-phosphate (PLP) (0.1 mM), affording both enantiomers of amines 4a–f in 30–90% conversions and >99% ee. Furthermore, whole-cell-based cascade biocatalysis was achieved by using the constructed recombinant Escherichia coli cells co-expressing the five enzymes without additional NAD+ cofactor; (R)- and (S)-amines 4a–f could be obtained in 35–93% conversions and >99% ee. Finally, the preparative experiments were demonstrated by using the whole-cell biocatalyst E. coli (RFM-ERR-CB) and E. coli (RFC-ERR-CB) with substrate 1a, affording (S)-4a and (R)-4a in 54.8% and 59.2% yields and >99% ee. This research achievement provides a highly selective, highly atom-economical, green and sustainable method for synthesizing chiral amines from alkenes via formal alkene asymmetric hydroamination. [ABSTRACT FROM AUTHOR]

New chiral zirconium systems catalyze the asymmetric hydroamination/cyclization of primary aminoalkenes affording five- and six-membered N-heterocyclic amines with up to 94% e.e. [ABSTRACT FROM AUTHOR]

Enantioenriched pyrrolidines and derivatives are ubiquitous substructures in compounds of importance to medicinal and biological chemistry. Herein, we report an efficient cobalt-catalyzed intramolecular asymmetric hydroamination reaction that produces chiral pyrrolidines with good to excellent yield and enantiocontrol. Compared with previously reported radical-involved methodologies for enantioenriched pyrrolidines, these conditions feature two elegant versatilities, enabling (1) the use of cobalt-catalyzed hydrogen atom transfer (HAT) to generate organocobalt intermediates that bring radical reaction to organometallic chemistry, and (2) enantioselective intramolecular C–N bond forging through an SN2-like displacement involving dynamic kinetic resolution (DKR). This approach provides a new alternative and efficient methodology for enantioselective radical-involved C–N bond construction that can be used in the synthesis of both chiral pyrrolidines and homologous nitrogen heterocycles. [ABSTRACT FROM AUTHOR]

Kinetic and spectroscopic studies are performed on the enantioselective copper(I) hydride-catalyzed hydroamination of styrene. [ABSTRACT FROM AUTHOR]

The thiourea moiety in the substrates acts as both the activating and directing group through cooperative multiple hydrogen bonding with the Broensted acid and the double bond. [ABSTRACT FROM AUTHOR]