Copper(ii) ketimides in sp3 C–H amination

Commercially available benzophenone imine (HN CPh₂) reacts with β-diketiminato copper(ii) tert-butoxide complexes [Cu^II]–O^tBu to form isolable copper(ii) ketimides [Cu^II]–N CPh₂. Structural characterization of the three coordinate copper(ii) ketimide [Me₃NN]Cu–N CPh₂ reveals a short Cu-N_ketimide distance (1.700(2) Å) with a nearly linear Cu–N–C linkage (178.9(2)°). Copper(ii) ketimides [Cu^II]–N CPh₂ readily capture alkyl radicals R˙ (PhCH(˙)Me and Cy˙) to form the corresponding R–N CPh₂ products in a process that competes with N–N coupling of copper(ii) ketimides [Cu^II]–N CPh₂ to form the azine Ph₂C N–N CPh₂. Copper(ii) ketimides [Cu^II]–N CAr₂ serve as intermediates in catalytic sp³ C–H amination of substrates R–H with ketimines HN CAr₂ and ^tBuOO^tBu as oxidant to form N-alkyl ketimines R–N CAr₂. This protocol enables the use of unactivated sp³ C–H bonds to give R–N CAr₂ products easily converted to primary amines R–NH₂via simple acidic deprotection.

Commercially available benzophenone imine (HN CPh₂) reacts with β-diketiminato copper(ii) tert-butoxide complexes [Cu^II]–O^tBu to form isolable copper(ii) ketimides [Cu^II]–N CPh₂ that serve as intermediates in catalytic sp³ C−H amination via radical relay.     

The power of trichlorosilylation: isolable trisilylated allyl anions,allyl radicals,and allenyl anions

Treatment of hexachloropropene (Cl₂C C(Cl)–CCl₃) with Si₂Cl₆ and [nBu₄N]Cl (1 : 4 : 1) in CH₂Cl₂ results in a quantitative conversion to the trisilylated, dichlorinated allyl anion salt [nBu₄N][Cl₂C C(SiCl₃)–C(SiCl₃)₂] ([nBu₄N][1]). Tetrachloroallene Cl₂C C CCl₂ was identified as the first intermediate of the reaction cascade. In the solid state, [1]⁻ adopts approximate C_s symmetry with a dihedral angle between the planes running through the olefinic and carbanionic fragments of [1]⁻ of C C–Si//Si–C–Si = 78.3(1)°. One-electron oxidation of [nBu₄N][1] with SbCl₅ furnishes the distillable blue radical 1˙. The neutral propene Cl₂C C(SiCl₃)–C(SiCl₃)₂H (2) was obtained by (i) protonation of [1]⁻ with HOSO₂CF₃ (HOTf) or (ii) H-atom transfer to 1˙ from 1,4-cyclohexadiene. Quantitative transformation of all three SiCl₃ substituents in 2 to Si(OMe)₃ (2^OMe) or SiMe₃ (2^Me) substituents was achieved by using MeOH/NMe₂Et or MeMgBr in CH₂Cl₂ or THF, respectively. Upon addition of 2 equiv. of tBuLi, 2^Me underwent deprotonation with subsequent LiCl elimination, 1,2-SiMe₃ migration and Cl/Li exchange to afford the allenyl lithium compound Me₃Si(Li)C C C(SiMe₃)₂ (Li[4]), which is an efficient building block for the introduction of Me, SiMe₃, or SnMe₃ (5) groups. The trisilylated, monochlorinated allene Cl₃Si(Cl)C C C(SiCl₃)₂ (6), was obtained from [nBu₄N][1] through Cl⁻-ion abstraction with AlCl₃ and rearrangement in CH₂Cl₂ (1˙ forms as a minor side product, likely because the system AlCl₃/CH₂Cl₂ can also act as a one-electron oxidant).

Treatment of hexachloropropene (Cl₂C C(Cl)–CCl₃) with Si₂Cl₆ and [nBu₄N]Cl (1 : 4 : 1) in CH₂Cl₂ results in a quantitative conversion to the trisilylated, dichlorinated allyl anion salt [nBu₄N][Cl₂C C(SiCl₃)–C(SiCl₃)₂] ([nBu₄N][1]).     

Synthesis and electronic structure analysis of the actinide allenylidenes, [{(NR2)3}An(CCCPh2)]− (An = U,Th; R = SiMe3)

The reaction of [AnCl(NR₂)₃] (An = U, Th, R = SiMe₃) with in situ generated lithium-3,3-diphenylcyclopropene results in the formation of [{(NR₂)₃}An(CH C CPh₂)] (An = U, 1; Th, 2) in good yields after work-up. Deprotonation of 1 or 2 with LDA/2.2.2-cryptand results in formation of the anionic allenylidenes, [Li(2.2.2-cryptand)][{(NR₂)₃}An(CCCPh₂)] (An = U, 3; Th, 4). The calculated ¹³C NMR chemical shifts of the C_α, C_β, and C_γ nuclei in 2 and 4 nicely reproduce the experimentally assigned order, and exhibit a characteristic spin–orbit induced downfield shift at C_α due to involvement of the 5f orbitals in the Th–C bonds. Additionally, the bonding analyses for 3 and 4 show a delocalized multi-center character of the ligand π orbitals involving the actinide. While a single–triple–single-bond resonance structure (e.g., An–C C–CPh₂) predominates, the An C C CPh₂ resonance form contributes, as well, more so for 3 than for 4.

The actinide allenylidenes [{(NR₂)₃}An(CCCPh₂)]⁻ (An = U, Th, R = SiMe₃) feature significant ligand-to-metal donation bonding and partial An C double bond character.     

Visible light-induced oxidative N-dealkylation of alkylamines by a luminescent osmium(vi) nitrido complex

N-Dealkylation of amines by metal oxo intermediates (M O) is related to drug detoxification and DNA repair in biological systems. In this study, we report the first example of N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex induced by visible light.

The visible light-induced N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex has been investigated. We provide definitive evidence that these reactions occur via an ET/PT mechanism.

High-valent metal oxo (M O) species play key roles in many chemical and biological oxidation processes.¹ They are versatile oxidants that can perform oxidation of substrates via a variety of pathways, including electron transfer, H-atom transfer, hydride transfer and O-atom transfer. In principle, high-valent metal nitrido (M N) complexes should also function as versatile oxidants similar to M O. Although there have been significant advances in M N oxidation chemistry in recent years, the reactivity of M N is still rather limited in scope compared to M O.² M N is intrinsically less oxidizing than M O due to the stronger electron donating property of the N³⁻ ligand than the O²⁻ ligand. Attempts to increase the oxidizing power of M N by increasing the oxidation state or by using less electron-donating ancillary ligands often led to decomposition of the complexes, mainly due to facile coupling of the nitrido ligands to yield N₂ (2M N → 2M + N₂).³ One appealing strategy to enhance the reactivity of M N is photochemical excitation. We have recently designed an osmium(vi) nitrido complex [Os^VI(N)(L)(CN)₃]⁻ (NO2-OsN, HL = 2-(2-hydroxy-5-nitrophenyl)benzoxazole) that is strongly luminescent in the solid state and in fluid solutions.⁴ It readily absorbs visible light to generate a long-lived and highly oxidizing excited state with a redox potential of ca. 1.4 V. The excited state of this complex also possesses [Os N˙] nitridyl characteristics that enable it to readily abstract H-atoms from inert organic substrates.⁵We report herein the visible-light induced N-dealkylation of various alkylamines by NO2-OsN. Iron oxo species have been used by heme and nonheme enzymes to carry out N-dealkylation reactions of tertiary amines, which are important processes involved in detoxification and DNA repair.⁶ A number of synthetic iron(iv) oxo complexes are also able to carry out such N-dealkylation reactions.⁷ Mechanistic studies using cytochrome P₄₅₀ and synthetic iron oxo complexes indicate that there are two possible mechanisms for N-dealkylation of amines, namely hydrogen-atom transfer (HAT) and electron transfer–proton transfer (ET–PT) (Fig. 1).⁸ In this work we report the first example of N-dealkylation of various aromatic as well as aliphatic tertiary amines by a nitrido complex upon visible light excitation. We also provide unambiguous evidence that these reactions occur via an ET/PT mechanism.Open in a separate windowFig. 1Two possible mechanisms for N-demethylation of tertiary amines by cytochrome P₄₅₀ and synthetic Fe(iv) oxo complexes (P = porphyrin).     

Biphasic electrochemical peptide synthesis

The large amount of waste derived from coupling reagents is a serious drawback of peptide synthesis from a green chemistry viewpoint. To overcome this issue, we report an electrochemical peptide synthesis in a biphasic system. Anodic oxidation of triphenylphosphine (Ph₃P) generates a phosphine radical cation, which serves as the coupling reagent to activate carboxylic acids, and produces triphenylphosphine oxide (Ph₃P O) as a stoichiometric byproduct. In combination with a soluble tag-assisted liquid-phase peptide synthesis, the selective recovery of desired peptides and Ph₃P O was achieved. Given that methods to reduce Ph₃P O to Ph₃P have been reported, Ph₃P O could be a recyclable byproduct unlike byproducts from typical coupling reagents. Moreover, a commercial peptide active pharmaceutical ingredient (API), leuprorelin, was successfully synthesized without the use of traditional coupling reagents.

The large amount of waste derived from coupling reagents is a serious drawback of peptide synthesis from a green chemistry viewpoint.     

SuFEx-enabled,chemoselective synthesis of triflates,triflamides and triflimidates

Sulfur(vi) Fluoride Exchange (SuFEx) chemistry has emerged as a next-generation click reaction, designed to assemble functional molecules quickly and modularly. Here, we report the ex situ generation of trifluoromethanesulfonyl fluoride (CF₃SO₂F) gas in a two chamber system, and its use as a new SuFEx handle to efficiently synthesize triflates and triflamides. This broadly tolerated protocol lends itself to peptide modification or to telescoping into coupling reactions. Moreover, redesigning the S^VI–F connector with a S O → S NR replacement furnished the analogous triflimidoyl fluorides as SuFEx electrophiles, which were engaged in the synthesis of rarely reported triflimidate esters. Notably, experiments showed H₂O to be the key towards achieving chemoselective trifluoromethanesulfonation of phenols vs. amine groups, a phenomenon best explained—using ab initio metadynamics simulations—by a hydrogen bonded termolecular transition state for the CF₃SO₂F triflylation of amines.

Triflyl fluoride gas (CF₃SO₂F) and its aza analogues are reported as new SuFEx activators. These S^VI–F reagents react efficiently with a variety of nucleophiles, yet the presence of water grants complete chemoselectivity to phenols.     

On 1,3-phosphaazaallenes and their diverse reactivity

1,3-Phosphaazaallenes are heteroallenes of the type RP C NR′ and little is known about their reactivity. In here we describe the straightforward synthesis of ArPCNR (Ar = Mes*, 2,4,6-tBu-C₆H₂; ^MesTer, 2.6-(2,4,6-Me₃C₆H₂)–C₆H₃; ^DipTer, 2.6-(2,6-iPr₂C₆H₂)–C₆H₃; R = tBu; Xyl, 2,6-Me₂C₆H₃) starting from phospha-Wittig reagents ArPPMe₃ and isonitriles CNR. It is further shown that ArPCNtBu are thermally labile with respect to the loss of iso-butene and it is shown that the cyanophosphines ArP(H)CN are synthetically feasible and form the corresponding phosphanitrilium borates with B(C₆F₅)₃, whereas deprotonation of ^DipTerP(H)CN was shown to give an isolable cyanidophosphide. Lastly, the reactivity of ArPCNR towards Pier''s borane was investigated, showing hydroboration of the C N bond in Mes*PCNtBu to give a hetero-butadiene, while with ^DipTerPCNXyl the formation of the Lewis acid–base adduct with a B–P linkage was observed.

The combination of phospha-Wittig reagents with isonitriles affords 1,3-phosphaazaallenes and their diverse reactivity has been studied in detail.     

Crystallization induced room-temperature phosphorescence and chiral photoluminescence properties of phosphoramides

We report the design and synthesis of a series of room temperature phosphorescent phosphoramides TPTZPO, TPTZPS, and TPTZPSe with a donor (phenothiazine)–acceptor (P = X, X = O, S, and Se) architecture. All the compounds show structureless fluorescence with a nanosecond lifetime in dilute solutions. However, these compounds show dual fluorescence and room temperature phosphorescence (RTP) in the solid state. Both the intensity and energy of luminescence depend on the heteroatom attached to the phosphorus center. For example, compound TPTZPO with the P O unit exhibits fluorescence at a higher energy region than TPTZPS and TPTZPSe with the P S and P Se groups, respectively. Crystalline samples of TPTZPO, TPTZPS, and TPTZPSe show stronger RTP than the amorphous powder of respective compounds. Detailed steady-state, time-resolved photoluminescence and computational studies established that the ³n–π* state dominated by the phenothiazine moiety is the emissive state of these compounds. Although TPTZPS and TPTZPSe crystallized in the chiral space group, only TPTZPSe showed chiroptical properties in the solid state. The luminescence dissymmetry factor (g_lum) value of TPTZPS is small and below the detection limit, and a CPL spectrum could not be observed for this compound.

The crystallization-induced room temperature phosphorescence and CPL of phosphoramides are reported. The nonplanar phenothiazine and the tetrahedral geometry of phosphorus curbed the non-radiative deactivation pathways, which led to improved RTP.     

Ir/f-Ampha complex catalyzed asymmetric sequential hydrogenation of enones: a general access to chiral alcohols with two contiguous chiral centers

A general and highly efficient method for asymmetric sequential hydrogenation of α,β-unsaturated ketones has been developed by using an iridium/f-Ampha complex as the catalyst, furnishing corresponding chiral alcohols with two contiguous stereocenters in high yields with excellent diastereo- and enantioselectivities (up to 99% yield, >20 : 1 dr and >99% ee). Control experiments indicated that the C C and C O bonds of the enones were hydrogenated sequentially, and the final stereoselectivities were determined by the dynamic kinetic resolution of ketones. Moreover, DFT calculations revealed that an outer sphere pathway was involved in both reduction of C C and C O bonds of enones. The synthetic utility of this method was demonstrated by a gram-scale reaction with very low catalyst loading (S/C = 20 000) and a concise synthetic route to key chiral intermediates of the antiasthmatic drug CP-199,330.

A general and efficient method for asymmetric sequential hydrogenation of α,β-unsaturated ketones has been developed. A dynamic kinetic resolution and an outer sphere pathway were involved in this transformation.     

Catalytic asymmetric synthesis of spirocyclobutyl oxindoles and beyond via [2+2] cycloaddition and sequential transformations

Efficient asymmetric synthesis of a collection of small molecules with structural diversity is highly important to drug discovery. Herein, three distinct types of chiral cyclic compounds were accessible by enantioselective catalysis and sequential transformations. Highly regio- and enantioselective [2+2] cycloaddition of (E)-alkenyloxindoles with the internal C C bond of N-allenamides was achieved with N,N′-dioxide/Ni(OTf)₂ as the catalyst. Various optically active spirocyclobutyl oxindole derivatives were obtained under mild conditions. Moreover, formal [4+2] cycloaddition products occurring at the terminal C C bond of N-allenamides, dihydropyran-fused indoles, were afforded by a stereospecific sequential transformation with the assistance of a catalytic amount of Cu(OTf)₂. In contrast, performing the conversion under air led to the formation of γ-lactones via the water-involved deprotection and rearrangement process. Experimental studies and DFT calculations were performed to probe the reaction mechanism.

Three distinct types of chiral cyclic compounds were accessible by catalytic asymmetric synthesis of spirocyclobutyl oxindoles via [2+2] cycloaddition and sequential transformations.     

Water-stable hydrazone-linked porous organic cages

Although porous organic cages (POCs), particularly imine-linked (C N) ones, have advanced significantly over the last few decades, the reversible nature of imine linkages makes them prone to hydrolysis and structural collapse, severely limiting their applications under moist or water conditions. Herein, seven water-stable hydrazone-linked (C N–N) POCs are prepared through a simple coupling of the same supramolecular tetraformylresorcin[4]arene cavitand with different dihydrazide linkers. Their structures are all determined by single-crystal X-ray crystallography, demonstrating rich structural diversity from the [2 + 4] lantern, [3 + 6] triangular prism, and unprecedented [4 + 8] square prism to the extra-large [6 + 12] octahedron. In addition, they respectively exhibit tunable window diameters and cavity volumes ranging from about 5.4 to 11.1 nm and 580 to 6800 ų. Moreover, their application in the water environment for pollutant removal was explored, indicating that they can effectively eliminate various types of contaminants from water, including radionuclide waste, toxic heavy metal ions, and organic micropollutants. This work demonstrates a convenient method for rationally constructing versatile robust POCs and presents their great application potentialities in water medium.

A convenient method for constructing water-stable hydrazone-linked porous organic cages (POCs) with tunable structures has been reported, and such POCs can be used as robust adsorbents for effective removal of various pollutants from water.     

Highly regioselective and diastereodivergent aminomethylative annulation of dienyl alcohols enabled by a hydrogen-bonding assisting effect

A ligand-controlled palladium-catalyzed highly regioselective and diastereodivergent aminomethylative annulation of dienyl alcohols with aminals has been established, which allows for producing either cis- or trans-disubstituted isochromans in good yields with complete regioselectivity and good to excellent diastereoselectivity. Moreover, the chiral cis-products were also obtained in good yields with up to 94% ee by using a chiral phosphinamide as the ligand. Mechanistic studies revealed that the hydroxyl group plays a key role in facilitating the Pd-catalyzed Heck insertion regioselectively taking place across the internal C C bond of conjugated dienes.

An efficient hydrogen-bonding assisted directing strategy has been identified, which enables the Pd-catalyzed highly regioselective and diastereodivergent 3,4-difunctionalized aminomethylative annulation of dienyl alcohols with aminals.     

Correlating axial and equatorial ligand field effects to the single-molecule magnet performances of a family of dysprosium bis-methanediide complexes

Treatment of the new methanediide–methanide complex [Dy(SCS)(SCSH)(THF)] (1Dy, SCS = {C(PPh₂S)₂}²⁻) with alkali metal alkyls and auxillary ethers produces the bis-methanediide complexes [Dy(SCS)₂][Dy(SCS)₂(K(DME)₂)₂] (2Dy), [Dy(SCS)₂][Na(DME)₃] (3Dy) and [Dy(SCS)₂][K(2,2,2-cryptand)] (4Dy). For further comparisons, the bis-methanediide complex [Dy(NCN)₂][K(DB18C6)(THF)(toluene)] (5Dy, NCN = {C(PPh₂NSiMe₃)₂}²⁻, DB18C6 = dibenzo-18-crown-6 ether) was prepared. Magnetic susceptibility experiments reveal slow relaxation of the magnetisation for 2Dy–5Dy, with open magnetic hysteresis up to 14, 12, 15, and 12 K, respectively (∼14 Oe s⁻¹). Fitting the alternating current magnetic susceptibility data for 2Dy–5Dy gives energy barriers to magnetic relaxation (U_eff) of 1069(129)/1160(21), 1015(32), 1109(70), and 757(39) K, respectively, thus 2Dy–4Dy join a privileged group of SMMs with U_eff values of ∼1000 K and greater with magnetic hysteresis at temperatures >10 K. These structurally similar Dy-components permit systematic correlation of the effects of axial and equatorial ligand fields on single-molecule magnet performance. For 2Dy–4Dy, the Dy-components can be grouped into 2Dy–cation/4Dy and 2Dy–anion/3Dy, where the former have almost linear C Dy C units with short average Dy C distances, and the latter have more bent C Dy C units with longer average Dy C bonds. Both U_eff and hysteresis temperature are superior for the former pair compared to the latter pair as predicted, supporting the hypothesis that a more linear axial ligand field with shorter M–L distances produces enhanced SMM properties. Comparison with 5Dy demonstrates unusually clear-cut examples of: (i) weakening the equatorial ligand field results in enhancement of the SMM performance of a monometallic system; (ii) a positive correlation between U_eff barrier and axial linearity in structurally comparable systems.

Studies on equatorial donor and C Dy C angle variation effects on energy barriers to the slow relaxation of magnetisation are reported.     

Hydridotetrylene [Ar*EH] (E = Ge,Sn, Pb) coordination at tantalum,tungsten, and zirconium

In a reaction of tantalocene trihydride with the low valent aryl tin cation [Ar*Sn(C₆H₆)][Al(OC{CF₃}₃)₄] (1a) the hydridostannylene complex [Cp₂TaH₂–Sn(H)Ar*][Al(OC{CF₃}₃)₄] (2) was synthesized. Hydride bridged adducts [Cp₂WH₂EAr*][Al(OC{CF₃}₃)₄] (E = Sn 3a, Pb 3b) were isolated as products of the reaction between Cp₂WH₂ and cations [Ar*E(C₆H₆)][Al(OC{CF₃}₃)₄] (E = Sn 1a, Pb 1b). The tin adduct 3a exhibits a proton migration to give the hydridostannylene complex [Cp₂W(H) Sn(H)Ar*][Al(OC{CF₃}₃)₄] 4a. The cationic complex 4a is deprotonated at the tin atom in reaction with base ^MeNHC at 80 °C to give a hydrido-tungstenostannylene [Cp₂W(H)SnAr*] 5a. Reprotonation of metallostannylene 5a with acid [H(Et₂O)₂][BAr^F] provides an alternative route to hydridotetrylene coordination. Complex 4a adds hydride to give the dihydrostannyl complex [Cp₂W(H)–SnH₂Ar*] (7). With styrene 4a shows formation of a hydrostannylation product [Cp₂W(H) Sn(CH₂CH₂Ph)Ar*][Al(OC{CF₃}₃)₄] (8). The lead adduct 3b was deprotonated with ^MeNHC to give plumbylene 5b [Cp₂W(H)PbAr*]. Protonation of 5b with [H(Et₂O)₂][Al(OC{CF₃}₃)₄] at −40 °C followed by low temperature NMR spectroscopy indicates a hydridoplumbylene intermediate [Cp₂W(H) Pb(H)Ar*]⁺ (4b). Hydrido-tungstenotetrylenes of elements Ge (5c), Sn (5a) and Pb (5b) were also synthesized reacting the salt [Cp₂W(H)Li]₄ with organotetrylene halides. The metallogermylene [Cp₂W(H)GeAr*] (5c) shows an isomerization via 1,2-H-migration to give the hydridogermylene [Cp₂W Ge(H)Ar*] (9), which is accelerated by addition of AIBN. 9 is at rt photochemically transferred back to 5c under light of a mercury vapor lamp. Zirconocene dihydride [Cp₂ZrH₂]₂ reacts with tin cation 1a to give the trinuclear hydridostannylene adduct 10 [({Cp₂Zr}₂{μ-H})(μ-H)₂μ-Sn(H)Ar*][Al(OC{CF₃}₃)₄]. Deprotonation of 10 was carried out using benzyl potassium to give neutral [({Cp₂Zr}₂{μ-H})(μ-H)μ-Sn(H)Ar*] (11). 11 was also obtained from the reaction of low valent tin hydride [Ar*SnH]₂ with two equivalents of [Cp₂ZrH₂]₂. The trihydride Ar*SnH₃ reacts with half of an equivalent of [Cp₂ZrH₂]₂ under evolution of hydrogen and formation of a dihydrostannyl complex 13 [Cp₂Zr(μ-H)SnH₂Ar*]₂ and with further equivalents of Ar*SnH₃ to give bis(hydridostannylene) complex [Cp₂Zr{Sn(H)Ar*}₂].

Low valent cations of tin and lead were used to form hydridotetrylene coordination compounds. The mobility of the hydrogen substituent was investigated in deprotonation equilibria as well as in 1,2-H-shift reactions.     

Generation of a transient base-stabilised arylalumylene for the facile deconstruction of aromatic molecules

While a stable base-free arylalumylene bearing a sterically encumbered terphenyl substituent has been reported previously, we herein report that our attempts to form a base-stabilised arylalumylene bearing a relatively small terphenyl substituent and an N-heterocyclic carbene base led instead to a “masked” dialumene (LRAl AlRL), self-stabilised by one peripheral aromatic group. Intriguingly, examining the behavior of this species or its transient dialumene formed from reducing the diiodoarylalane in aromatic solvents under different conditions reveals that they both decouple into the desired base-stabilised arylalumylene. This transient acyclic, dicoordinate alumylene is highly reactive, deconstructing benzene and toluene to furnish dialuminium derivatives of pentalene, providing the first example of a neutral Al^I compound able to deconstruct these less reactive arenes. Computational insights were also gained on the dialumene dissociation and on the mechanism of arene deconstruction by alumylene.

Attempts to form a base-stabilised arylalumylene by reducing an NHC-coordinated diiodoterphenylalane led to a masked dialumene. Reactivity studies showed it decouples to initially aimed arylalumylene, which easily deconstructs less reactive arenes.     

Scaffold-based [Fe]-hydrogenase model: H2 activation initiates Fe(0)-hydride extrusion and non-biomimetic hydride transfer

We report the synthesis and reactivity of a model of [Fe]-hydrogenase derived from an anthracene-based scaffold that includes the endogenous, organometallic acyl(methylene) donor. In comparison to other non-scaffolded acyl-containing complexes, the complex described herein retains molecularly well-defined chemistry upon addition of multiple equivalents of exogenous base. Clean deprotonation of the acyl(methylene) C–H bond with a phenolate base results in the formation of a dimeric motif that contains a new Fe–C(methine) bond resulting from coordination of the deprotonated methylene unit to an adjacent iron center. This effective second carbanion in the ligand framework was demonstrated to drive heterolytic H₂ activation across the Fe(ii) center. However, this process results in reductive elimination and liberation of the ligand to extrude a lower-valent Fe–carbonyl complex. Through a series of isotopic labelling experiments, structural characterization (XRD, XAS), and spectroscopic characterization (IR, NMR, EXAFS), a mechanistic pathway is presented for H₂/hydride-induced loss of the organometallic acyl unit (i.e. pyCH₂–C O → pyCH₃+C O). The known reduced hydride species [HFe(CO)₄]⁻ and [HFe₃(CO)₁₁]⁻ have been observed as products by ¹H/²H NMR and IR spectroscopies, as well as independent syntheses of PNP[HFe(CO)₄]. The former species (i.e. [HFe(CO)₄]⁻) is deduced to be the actual hydride transfer agent in the hydride transfer reaction (nominally catalyzed by the title compound) to a biomimetic substrate ([^TolIm](BAr^F) = fluorinated imidazolium as hydride acceptor). This work provides mechanistic insight into the reasons for lack of functional biomimetic behavior (hydride transfer) in acyl(methylene)pyridine based mimics of [Fe]-hydrogenase.

We report the synthesis and reactivity of a model of [Fe]-hydrogenase derived from an anthracene-based scaffold that includes the endogenous, organometallic acyl(methylene) donor.     

A visible-light activated [2 + 2] cycloaddition reaction enables pinpointing carbon–carbon double bonds in lipids

The precise location of C C bonds in bioactive molecules is critical for a deep understanding of the relationship between their structures and biological roles. However, the traditional ultraviolet light-based approaches exhibited great limitations. Here, we discovered a new type of visible-light activated [2 + 2] cycloaddition of carbonyl with C C bonds. We found that carbonyl in anthraquinone showed great reactivities towards C C bonds in lipids to form oxetanes under the irradiation of visible-light. Combined with tandem mass spectrometry, this site-specific dissociation of oxetane enabled precisely locating the C C bonds in various kinds of monounsaturated and polyunsaturated lipids. The proof-of-concept applicability of this new type of [2 + 2] photocycloaddition was validated in the global identification of unsaturated lipids in a complex human serum sample. 86 monounsaturated and polyunsaturated lipids were identified with definitive positions of C C bonds, including phospholipids and fatty acids even with up to 6 C C bonds. This study provides new insights into both the photocycloaddition reactions and the structural lipidomics.

A new visible-light activated [2 + 2] cycloaddition reaction was discovered and enabled pinpointing carbon–carbon double bonds in lipids.     

Metalation-induced denitrogenative reductive coupling of isocyanides on a silylene-bridged nickel cluster

The denitrogenative reductive coupling of two molecules of CN^tBu to afford a disilylketenimine with an aza-disilacyclobutane skeleton was achieved on a multinuclear silylene-bridged Ni cluster framework in the absence of any strong reducing reagents. During this reaction, sequential cleavage of a C N bond and formation of a C C bond involving two molecules of CN^tBu were achieved on a nickel cluster surrounded by four silylene moieties. First, the cleavage of the C N bond of one molecule of CN^tBu provided a silylene-supported carbide and an N^tBu moiety on the dinuclear nickel skeleton. Further metalation induced coupling between the carbide moiety and an additional molecule of CN^tBu on the pentanuclear nickel-cluster framework to form a moiety via formation of a C C bond. Thermolysis of this pentanuclear cluster produced a disilylketenimine with an aza-disilacyclobutane skeleton in 58% yield.

The denitrogenative reductive coupling of two molecules of CN^tBu was achieved on a multinuclear silylene-bridged Ni cluster framework, and two possible intermediary Ni clusters were isolated.     

Engineered modular heterocyclic-diamidines for sequence-specific recognition of mixed AT/GC base pairs at the DNA minor groove

This report describes a breakthrough in a project to design minor groove binders to recognize any sequence of DNA. A key goal is to invent synthetic chemistry for compound preparation to recognize an adjacent GG sequence that has been difficult to target. After trying several unsuccessful compound designs, an N-alkyl-benzodiimidazole structure was selected to provide two H-bond acceptors for the adjacent GG-NH groups. Flanking thiophenes provide a preorganized structure with strong affinity, DB2831, and the structure is terminated by phenyl-amidines. The binding experimental results for DB2831 with a target AAAGGTTT sequence were successful and include a high ΔT_m, biosensor SPR with a K_D of 4 nM, a similar K_D from fluorescence titrations and supporting competition mass spectrometry. MD analysis of DB2831 bound to an AAAGGTTT site reveals that the two unprotonated N of the benzodiimidazole group form strong H-bonds (based on distance) with the two central G-NH while the central –CH of the benzodiimidazole is close to the –C O of a C base. These three interactions account for the strong preference of DB2831 for a -GG- sequence. Surprisingly, a complex with one dynamic, interfacial water is favored with 75% occupancy.

This report describes a breakthrough in a project to design minor groove binders to recognize any sequence of DNA.