Photo-induced copper-catalyzed alkynylation and amination of remote unactivated C(sp3)-H bonds

A method for remote radical C–H alkynylation and amination of diverse aliphatic alcohols has been developed. The reaction features a copper nucleophile complex formed in situ as a photocatalyst, which reduces the silicon-tethered aliphatic iodide to an alkyl radical to initiate 1,n-hydrogen atom transfer. Unactivated secondary and tertiary C–H bonds at β, γ, and δ positions can be functionalized in a predictable manner.

Remote C−H alkynylation and amination of aliphatic alcohols.     

Ultra-small cobalt nanoparticles from molecularly-defined Co–salen complexes for catalytic synthesis of amines

We report the synthesis of in situ generated cobalt nanoparticles from molecularly defined complexes as efficient and selective catalysts for reductive amination reactions. In the presence of ammonia and hydrogen, cobalt–salen complexes such as cobalt(ii)–N,N′-bis(salicylidene)-1,2-phenylenediamine produce ultra-small (2–4 nm) cobalt-nanoparticles embedded in a carbon–nitrogen framework. The resulting materials constitute stable, reusable and magnetically separable catalysts, which enable the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds and ammonia. The isolated nanoparticles also represent excellent catalysts for the synthesis of primary, secondary as well as tertiary amines including biologically relevant N-methyl amines.

We report the synthesis of in situ generated cobalt nanoparticles from molecularly defined complexes as efficient and selective catalysts for reductive amination reactions.     

Synthesis of N-aryl amines enabled by photocatalytic dehydrogenation

Catalytic dehydrogenation (CD) via visible-light photoredox catalysis provides an efficient route for the synthesis of aromatic compounds. However, access to N-aryl amines, which are widely utilized synthetic moieties, via visible-light-induced CD remains a significant challenge, because of the difficulty in controlling the reactivity of amines under photocatalytic conditions. Here, the visible-light-induced photocatalytic synthesis of N-aryl amines was achieved by the CD of allylic amines. The unusual strategy using C₆F₅I as an hydrogen-atom acceptor enables the mild and controlled CD of amines bearing various functional groups and activated C–H bonds, suppressing side-reaction of the reactive N-aryl amine products. Thorough mechanistic studies suggest the involvement of single-electron and hydrogen-atom transfers in a well-defined order to provide a synergistic effect in the control of the reactivity. Notably, the back-electron transfer process prevents the desired product from further reacting under oxidative conditions.

The synergy of SET, HAT, and BET enables a visible-light induced catalytic dehydrogenation for the synthesis of N-aryl amines.     

Single-molecule junctions of multinuclear organometallic wires: long-range carrier transport brought about by metal–metal interaction

Here, we report multinuclear organometallic molecular wires having (2,5-diethynylthiophene)diyl-Ru(dppe)₂ repeating units. Despite the molecular dimensions of 2–4 nm the multinuclear wires show high conductance (up to 10⁻² to 10⁻³G₀) at the single-molecule level with small attenuation factors (β) as revealed by STM-break junction measurements. The high performance can be attributed to the efficient energy alignment between the Fermi level of the metal electrodes and the HOMO levels of the multinuclear molecular wires as revealed by DFT–NEGF calculations. Electrochemical and DFT studies reveal that the strong Ru–Ru interaction through the bridging ligands raises the HOMO levels to access the Fermi level, leading to high conductance and small β values.

Multinuclear organometallic molecular wires having (diethynylthiophene)diyl-Ru(dppe)₂ repeating units show high conductance with small attenuation factors. The strong Ru–Ru interaction is the key for the long-range carrier transport.     

Reversible OH-bond activation and amphoterism by metal–ligand cooperativity of calix[4]pyrrolato aluminate

Most p-block metal amides irreversibly react with metal alkoxides when subjected to alcohols, making reversible transformations with OH-substrates a challenging task. Herein, we describe how the combination of a Lewis acidic square-planar-coordinated aluminum(iii) center with metal–ligand cooperativity leverages unconventional reactivity toward protic substrates. Calix[4]pyrrolato aluminate performs OH-bond activation of primary, secondary, and tertiary aliphatic and aromatic alcohols, which can be fully reversed under reduced pressure. The products exhibit a new form of metal–ligand cooperative amphoterism and undergo counterintuitive substitution reactions of a polar covalent Al–O bond by a dative Al–N bond. A comprehensive mechanistic picture of all processes is buttressed by isolation of intermediates, spectroscopy, and computation. This study delineates how structural constraints can invert thermodynamics for seemingly simple addition reactions and invert common trends in bond energies.

The combination of structural constraint and metal–ligand cooperativity in calix[4]pyrrolato aluminate inverts common trends of bond energies and enables reversible OH-bond activation.     

Mimicking transition metals in borrowing hydrogen from alcohols

Borrowing hydrogen from alcohols, storing it on a catalyst and subsequent transfer of the hydrogen from the catalyst to an in situ generated imine is the hallmark of a transition metal mediated catalytic N-alkylation of amines. However, such a borrowing hydrogen mechanism with a transition metal free catalytic system which stores hydrogen molecules in the catalyst backbone is yet to be established. Herein, we demonstrate that a phenalenyl ligand can imitate the role of transition metals in storing and transferring hydrogen molecules leading to borrowing hydrogen mediated alkylation of anilines by alcohols including a wide range of substrate scope. A close inspection of the mechanistic pathway by characterizing several intermediates through various spectroscopic techniques, deuterium labelling experiments, and DFT study concluded that the phenalenyl radical based backbone sequentially adds H⁺, H˙ and an electron through a dearomatization process which are subsequently used as reducing equivalents to the C–N double bond in a catalytic fashion.

An efficient method is developed for harvesting hydrogen, its storage and catalytic transfer by an odd alternant hydrocarbon. The strategy is reminiscent of transition metals in borrowing hydrogen mediated processes.     

Iron-catalyzed α-C–H functionalization of π-bonds: cross-dehydrogenative coupling and mechanistic insights

The deprotonation of propargylic C–H bonds for subsequent functionalization typically requires stoichiometric metal alkyl or amide reagents. In addition to the undesirable generation of stoichiometric metallic waste, these conditions limit the functional group compatibility and versatility of this functionalization strategy and often result in regioisomeric mixtures. In this article, we report the use of dicarbonyl cyclopentadienyliron(ii) complexes for the generation of propargylic anion equivalents toward the direct electrophilic functionalization of propargylic C–H bonds under mild, catalytic conditions. This technology was applied to the direct conversion of C–H bonds to C–C bonds for the synthesis of several functionalized scaffolds through a one-pot cross dehydrogenative coupling reaction with tetrahydroisoquinoline and related privileged heterocyclic scaffolds. A series of NMR studies and deuterium-labelling experiments indicated that the deprotonation of the propargylic C–H bond was the rate-determining step when a Cp*Fe(CO)₂-based catalyst system was employed.

[Cp*Fe(CO)₂]⁺ facilitates the α-deprotonation of unsaturated C–C bond for propargylic and allylic C–H functionalization. Mechanistic studies reveal insights into the superior performance of the electron-rich and hindered ligand on iron.     

Catalytic asymmetric multiple dearomatizations of phenols enabled by a cascade 1,8-addition and Diels–Alder reaction

A direct catalytic asymmetric multiple dearomatization reaction of phenols was disclosed, which provides expedient access to a series of architecturally complex polycyclic compounds bearing four stereogenic centers in high enantiopurity. The key to achieve such a transformation is the combination of a dearomative 1,8-addition of β-naphthols to para-quinone methides generated in situ from propargylic alcohols and a subsequent intramolecular dearomative Diels–Alder reaction. Noteworthily, this protocol enrichs not only the diversity of dearomatized products but also the toolbox of dearomatization strategies.

The first chiral phosphoric acid catalyzed asymmetric multiple dearomatizations of phenols for the synthesis of bridged polycyclic compounds are reported.     

General and selective synthesis of primary amines using Ni-based homogeneous catalysts

The development of base metal catalysts for industrially relevant amination and hydrogenation reactions by applying abundant and atom economical reagents continues to be important for the cost-effective and sustainable synthesis of amines which represent highly essential chemicals. In particular, the synthesis of primary amines is of central importance because these compounds serve as key precursors and central intermediates to produce value-added fine and bulk chemicals as well as pharmaceuticals, agrochemicals and materials. Here we report a Ni-triphos complex as the first Ni-based homogeneous catalyst for both reductive amination of carbonyl compounds with ammonia and hydrogenation of nitroarenes to prepare all kinds of primary amines. Remarkably, this Ni-complex enabled the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic linear and branched primary amines as well as aromatic primary amines starting from inexpensive and easily accessible carbonyl compounds (aldehydes and ketones) and nitroarenes using ammonia and molecular hydrogen. This Ni-catalyzed reductive amination methodology has been applied for the amination of more complex pharmaceuticals and steroid derivatives. Detailed DFT computations have been performed for the Ni-triphos based reductive amination reaction, and they revealed that the overall reaction has an inner-sphere mechanism with H₂ metathesis as the rate-determining step.

A Ni-triphos based homogeneous catalyst enabled the synthesis of all kinds of primary amines by reductive amination of carbonyl compounds with ammonia and hydrogenation of nitroarenes.     

Ti-catalyzed ring-opening oxidative amination of methylenecyclopropanes with diazenes

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py₃TiCl₂(NR) complexes is reported. This reaction selectively generates branched α-methylene imines as opposed to linear α,β-unsaturated imines, which are difficult to access via other methods. Products can be isolated as the imine or hydrolyzed to the corresponding ketone in good yields. Mechanistic investigation via density functional theory suggests that the regioselectivity of these products results from a Curtin–Hammett kinetic scenario, where reversible β-carbon elimination of a spirocyclic [2 + 2] azatitanacyclobutene intermediate is followed by selectivity-determining β-hydrogen elimination of the resulting metallacycle. Further functionalizations of these branched α-methylene imine products are explored, demonstrating their utility as building blocks.

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py₃TiCl₂(NR) complexes is reported.     

The precise editing of surface sites on a molecular-like gold catalyst for modulating regioselectivity

It is extremely difficult to precisely edit a surface site on a typical nanoparticle catalyst without changing other parts of the catalyst. This precludes a full understanding of which site primarily determines the catalytic properties. Here, we couple experimental data collection with theoretical analysis to correlate rich structural information relating to atomically precise gold clusters with the catalytic performance for the click reaction of phenylacetylene and benzyl azide. We also identify a specific surface site that is capable of achieving high regioselectivity. We further conduct site-specific editing on a thiolate-protected gold cluster by peeling off two monomeric RS–Au–SR motifs and replacing them with two Ph₂P–CH₂–PPh₂ staples. We demonstrate that the surface Au–Ph₂P–CH₂–PPh₂–Au motifs enable extraordinary regioselectivity for the click reaction of alkyne and azide. The editing strategy for the surface motifs allows us to exploit previously inaccessible individual active sites and elucidate which site can explicitly govern the reaction outcome.

Editing surface motifs on gold cluster catalysts achieves high regioselectivity for the click reactions of azides and alkynes.     

Direct observation of the evolving metal–support interaction of individual cobalt nanoparticles at the titania and silica interface

Understanding the metal–support interaction (MSI) is crucial to comprehend how the catalyst support affects performance and whether this interaction can be exploited in order to design new catalysts with enhanced properties. Spatially resolved soft X-ray absorption spectroscopy (XAS) in combination with Atomic Force Microscopy (AFM) and Scanning Helium Ion-Milling Microscopy (SHIM) has been applied to visualise and characterise the behaviour of individual cobalt nanoparticles (CoNPs) supported on two-dimensional substrates (SiO_xSi(100) (x < 2) and rutile TiO₂(110)) after undergoing reduction–oxidation–reduction (ROR). The behaviour of the Co species is observed to be strongly dependent on the type of support. For SiO_xSi a weaker MSI between Co and the support allows a complete reduction of CoNPs although they migrate and agglomerate. In contrast, a stronger MSI of CoNPs on TiO₂ leads to only a partial reduction under H₂ at 773 K (as observed from Co L₃-edge XAS data) due to enhanced TiO₂ binding of surface-exposed cobalt. SHIM data revealed that the interaction of the CoNPs is so strong on TiO₂, that they are seen to spread at and below the surface and even to migrate up to ∼40 nm away. These results allow us to better understand deactivation phenomena and additionally demonstrate a new understanding concerning the nature of the MSI for Co/TiO₂ and suggest that there is scope for careful control of the post-synthetic thermal treatment for the tuning of this interaction and ultimately the catalytic performance.

Understanding the metal–support interaction (MSI) is crucial to comprehend how the catalyst support affects performance and whether this interaction can be exploited in order to design new catalysts with enhanced properties.     

C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

Selective functionalization of ubiquitous unactivated C–H bonds is a continuous quest for synthetic organic chemists. In addition to transition metal catalysis, which typically operates under a two-electron manifold, a recent renaissance in the radical approach relying on the hydrogen atom transfer (HAT) process has led to tremendous growth in the area. Despite several challenges, protocols proceeding via HAT are highly sought after as they allow for relatively easy activation of inert C–H bonds under mild conditions leading to a broader scope and higher functional group tolerance and sometimes complementary reactivity over methods relying on traditional transition metal catalysis. A number of methods operating via heteroatom-based HAT have been extensively reported over the past few years, while methods employing more challenging carbon analogues have been less explored. Recent developments of mild methodologies for generation of various carbon-centered radical species enabled their utilization in the HAT process, which, in turn, led to the development of remote C(sp³)–H functionalization reactions of alcohols, amines, amides and related compounds. This review covers mostly recent advances in C–H functionalization reactions involving the HAT step to carbon-centered radicals.

Intramolecular and intermolecular HAT to C-centered radicals enables selective C–H functionalization of organic molecules.     

Catalytic (3 + 2) annulation of donor–acceptor aminocyclopropane monoesters and indoles

The efficient catalytic activation of donor–acceptor aminocyclopropanes lacking the commonly used diester acceptor is reported here in a (3 + 2) dearomative annulation with indoles. Bench-stable tosyl-protected aminocyclopropyl esters were converted into cycloadducts in 46–95% yields and up to 95 : 5 diastereomeric ratio using catalytic amounts of triethylsilyl triflimide. Tricyclic indoline frameworks containing four stereogenic centers including all-carbon quaternary centers were obtained.

A catalytic dearomatization of indoles with D–A aminocyclopropane monoesters for the synthesis of highly substituted indolines.     

Allylic C(sp3)–H alkylation via synergistic organo- and photoredox catalyzed radical addition to imines

A new catalytic method for the direct alkylation of allylic C(sp³)–H bonds from unactivated alkenes via synergistic organo- and photoredox catalysis is described. The transformation achieves an efficient, redox-neutral synthesis of homoallylamines with broad functional group tolerance, under very mild reaction conditions. Mechanistic investigations indicate that the reaction proceeds through the N-centered radical intermediate which is generated by the allylic radical addition to the imine.

A new catalytic method for the direct alkylation of allylic C(sp³)–H bonds from unactivated alkenes via synergistic organo- and photoredox catalysis is described.     

Mechanistic insights into copper-catalyzed aerobic oxidative coupling of N–N bonds

Catalytic N–N coupling is a valuable transformation for chemical synthesis and energy conversion. Here, mechanistic studies are presented for two related copper-catalyzed oxidative aerobic N–N coupling reactions, one involving the synthesis of a pharmaceutically relevant triazole and the other relevant to the oxidative conversion of ammonia to hydrazine. Analysis of catalytic and stoichiometric N–N coupling reactions support an “oxidase”-type catalytic mechanism with two redox half-reactions: (1) aerobic oxidation of a Cu^I catalyst and (2) Cu^II-promoted N–N coupling. Both reactions feature turnover-limiting oxidation of Cu^I by O₂, and this step is inhibited by the N–H substrate(s). The results highlight the unexpected facility of the N–N coupling step and establish a foundation for development of improved catalysts for these transformations.

Mechanistic studies provide valuable insights into Cu-catalyzed N–N coupling reactions relevant to energy conversion and pharmaceutical synthesis.     

Catalysis using transition metal complexes featuring main group metal and metalloid compounds as supporting ligands

Recent development in catalytic application of transition metal complexes having an M–E bond (E = main group metal or metalloid element), which is stabilized by a multidentate ligand, is summarized. Main group metal and metalloid supporting ligands furnish unusual electronic and steric environments and molecular functions to transition metals, which are not easily available with standard organic supporting ligands such as phosphines and amines. These characteristics often realize remarkable catalytic activity, unique product selectivity, and new molecular transformations. This perspective demonstrates the promising utility of main group metal and metalloid compounds as a new class of supporting ligands for transition metal catalysts in synthetic chemistry.

Recent development in catalytic application of transition metal complexes having an M–E bond (E = main group metal or metalloid element), which is stabilized by a multidentate ligand, is summarized.     

Plasmonic O2 dissociation and spillover expedite selective oxidation of primary C–H bonds

Manipulating O₂ activation via nanosynthetic chemistry is critical in many oxidation reactions central to environmental remediation and chemical synthesis. Based on a carefully designed plasmonic Ru/TiO_2−x catalyst, we first report a room-temperature O₂ dissociation and spillover mechanism that expedites the “dream reaction” of selective primary C–H bond activation. Under visible light, surface plasmons excited in the negatively charged Ru nanoparticles decay into hot electrons, triggering spontaneous O₂ dissociation to reactive atomic ˙O. Acceptor-like oxygen vacancies confined at the Ru–TiO₂ interface free Ru from oxygen-poisoning by kinetically boosting the spillover of ˙O from Ru to TiO₂. Evidenced by an exclusive isotopic O-transfer from ¹⁸O₂ to oxygenated products, ˙O displays a synergistic action with native ˙O₂⁻ on TiO₂ that oxidizes toluene and related alkyl aromatics to aromatic acids with extremely high selectivity. We believe the intelligent catalyst design for desirable O₂ activation will contribute viable routes for synthesizing industrially important organic compounds.

Room-temperature O₂ dissociation and spillover, as driven by plasmonic Ru on oxygen-deficient TiO₂, expedite the selective oxidation of primary C–H bonds in alkyl aromatics for synthesizing industrially important organic compounds.     

A general method for site-selective Csp3–S bond formation via cooperative catalysis

Herein, we report a copper-catalysed site-selective thiolation of Csp³–H bonds of aliphatic amines. The method features a broad substrate scope and good functional group compatibility. Primary, secondary, and tertiary C–H bonds can be converted into C–S bonds with a high efficiency. The late-stage modification of biologically active compounds by this method was also demonstrated. Furthermore, the one-pot preparation of pyrrolidine or piperidine compounds via a domino process was achieved.

A copper-catalyzed site-selective thiolation of Csp³–H bonds of aliphatic amines was developed. The method features a broad substrate scope and good functional group tolerance.     

Iron porphyrin catalysed light driven C–H bond amination and alkene aziridination with organic azides

Visible light driven nitrene transfer and insertion reactions of organic azides are an attractive strategy for the design of C–N bond formation reactions under mild reaction conditions, the challenge being lack of selectivity as a free nitrene reactive intermediate is usually involved. Herein is described an iron(iii) porphyrin catalysed sp³ C–H amination and alkene aziridination with selectivity by using organic azides as the nitrogen source under blue LED light (469 nm) irradiation. The photochemical reactions display chemo- and regio-selectivity and are effective for the late-stage functionalization of natural and bioactive compounds with complexity. Mechanistic studies revealed that iron porphyrin plays a dual role as a photosensitizer and as a catalyst giving rise to a reactive iron–nitrene intermediate for subsequent C–N bond formation.

An iron(iii) porphyrin catalysed sp³ C–H amination and alkene aziridination with broad substrate scope under mild conditions is conducted, with selectivity through the use of organic azides as the nitrogen source under blue LED light irradiation.