Carbene Insertion Research Articles

Metal-catalyzed alkyne oxidation/CH functionalization: Effects of oxidant, temperature, and metal catalyst on chemoselectivity.

Gold-catalyzed intermolecular alkyne oxidation has attracted much synthetic attention, but mostly suffering undesired over-oxidation. Recent experiments demonstrated that over-oxidation could be dramatically suppressed in zinc(II)-catalyzed intermolecular alkyne oxidation/CH functionalization. By means of first-principle density functional theory calculations, we explored the mechanism of the M-catalyzed intermolecular alkyne oxidations (M = Zn(OTf)2 and Au+ PR3 ) as well as the effects of oxidants, temperature, and metal catalysts on chemoselectivity, in an effort to disclose the origin of the extraordinary chemoselectivity pertaining to zinc catalysis. Our calculations indicate that the Zn-catalyzed intermolecular alkyne oxidation/CH functionalization proceeds by a Friedel-Crafts alkylation mechanism rather than metal carbene insertion mechanism. The chemoselectivity of CH functionalization against over-oxidation in Zn catalysis, in comparison with gold catalysis, can be jointly controlled by four factors: (1) the use of less nucleophilic N-oxide, (2) the enhanced electrophilicity and carbocationic nature of the carbenic site in the α-oxo metal carbenoid intermediate, (3) enhanced steric repulsion to incoming oxidant exerted by bulky ancillary ligand in the close nearby of the carbenic site to disfavor intermolecular over-oxidation and (4) the large negative value of activation entropy in the intermolecular over-oxidation pathway, that jointly give rise to lower activation free energy for the intramolecular cyclization/CH functionalization pathway than for the intermolecular over-oxidation pathway. © 2018 Wiley Periodicals, Inc.

A comparative study of diaryl carbene insertion reactions at polymer surfaces

A detailed investigation of the reactions of diaryldiazo compounds for the surface modification of several polymers has been conducted. This has revealed that the rate of reaction of diaryldiazo compounds is influenced by their substituents, that the reaction is exothermic, and that the polymer itself exerts an influence on the surface modification. The results are consistent with the formation and insertion of a carbene intermediate at the polymer surface. It was further shown that such surface modified polymers, characterized using surface sensitive techniques, display macroscopic behavior consistent with the presence of the newly introduced surface chemical functionality, characterized using a combination of surface sensitive and bulk analytical techniques. This approach is complementary to directed energy deposition approaches, offers an alternative route to functional polymers, and provide a direct link between surface chemistry and observable macroscopic properties.

Silver-Catalyzed Regio- and Stereoselective Formal Carbene Insertion into Unstrained C−C σ-Bonds of 1,3-Dicarbonyls

SummaryA regio- and stereoselective silver-catalyzed formal carbene insertion into 1,3-dicarbonyls has been developed, using N-nosylhydrazones as diazo surrogates. Two new C−C bonds are constructed at the carbenic carbon center through the selective cleavage of the C−C(=O) σ-bond of acyclic 1,3-dicarbonyls, enabling the preparation of various synthetically useful polysubstituted γ-diketones, γ-ketoesters, and γ-ketoamides in high yields. The in situ formation of a donor-acceptor cyclopropane, via reaction of the enolate of the 1,3-dicarbonyl with an electrophilic silver carbenoid, is proposed as a key process in the catalytic cycle.

QM–MM Ehrenfest dynamics from first principles: photodissociation of diazirine in aqueous solution

This article describes an implementation of Ehrenfest molecular dynamics based on TDDFT and Gaussian basis sets, optimized for hybrid QM–MM simulations in GPU. The present method makes use of the equations of motion proposed by Chen et al. (J Chem Phys 135:044126, 2011), which, at variance with previous formulations of the Ehrenfest dynamics, takes into account the movement of the localized basis functions, thus improving accuracy and energy conservation. This methodology is used to explore the evolution and the stability of excited state dynamics for two different constructions of the initial excited state, consisting in the linear response TDDFT $$S_1$$ solution, and in the ground state density matrix where the HOMO–LUMO occupancies have been switched, which is a widespread approach to model photoexcitation in electron dynamics simulations. It is found that the second kind of starting state leads to a larger numerical noise and to a poorer stability of the dynamics, aside from “awakening” inner electronic modes that become manifest in the frequency spectrum, and which are absent if the dynamics departs from the linear response TDDFT density matrix. Then, the method is applied to investigate the photodissociation of the diazirine molecule, CH $$_2$$ N $$_2$$ , both in vacuum and in aqueous solution. Diazirine decomposes into carbene and molecular nitrogen upon irradiation with UV light, and for this reason it has been widely adopted to photolabel biomolecules through the insertion of carbenes in the macromolecular surface. Our simulations suggest that the quantum yield of the dissociative reaction experiences a decrease in solution with respect to the gas phase, that can be understood in terms of the vibrational relaxation facilitated by the solvent molecules. Besides, the present results indicate that the isomerization and dissociation mechanism occur fully on the $$S_1$$ excited state.

Rhodium-Catalyzed Regioselective N2 -Alkylation of Benzotriazoles with Diazo Compounds/Enynones via a Nonclassical Pathway.

A novel rhodium-catalyzed highly selective N2 -alkylation of benzotriazoles with diazo compounds/enynones is achieved, providing N2 -alkylated benzotriazoles in good to excellent yields and with excellent N2 selectivities. Importantly, different to traditional carbene insertion into X-H (X=N, O etc) bonds, DFT calculations disclose that this selective N2 -alkylation probably proceeds through a formal 1,3- rather than 1,2-H shift to give the final products.

Voltage-Activated Adhesion through Donor–Acceptor Dendrimers

Previous investigations on voltage-activated adhesives were restricted to aqueous solvents, where current-directed cross-linking competed with water electrolysis. Replacing aqueous would expand applications of electrocuring technology and avoid excessive foaming, but many organic solvents have high ohmic resistances that prevent electrical conduction. These impediments were overcome through internal grafting of ferrocene (Fc) and diazirine (Dz) donor–acceptor pairs on fifth-generation polyamidoamine (G5-PAMAM) dendrimers, forming G5-Fc-Dz cografted conjugates, where Fc internal additives provided an instantaneous conductive hole (+) network toward the redox conversion of diazirine to carbene insertion adhesion in nontoxic organic solvents of DMSO, DMF, and PEG400. Size exclusion chromatography, 1H NMR, and 19F NMR evaluated the formulations before and after electrocuring to quantitate grafting ratios and cross-linked dendrimers. Cyclic voltammetry confirmed the retained redox behavior of grafted Fc and Dz...

Rhodium-Catalyzed B-H Bond Insertion Reactions of Unstabilized Diazo Compounds Generated in Situ from Tosylhydrazones.

Although transition-metal-catalyzed B-H bond insertion of carbenes into stable borane adducts has emerged as a promising method for organoborane synthesis, all the diazo compounds used to date as carbene precursors have had an electron-withdrawing group to stabilize them. Herein, we report a protocol for rhodium-catalyzed B-H bond insertion reactions of unstabilized diazo compounds generated in situ from tosylhydrazones. In addition, by using chiral dirhodium catalysts, we also achieved an asymmetric version of the reaction with good to excellent enantioselectivities (up to 98:2 e.r.). This is the first enantioselective heteroatom-hydrogen bond insertion reaction to use unstabilized diazo compounds as carbene precursors. The protocol exhibited good functional group tolerance and could be carried out on a gram scale. It also enabled one-pot transformation of a carbonyl group to a boryl group enantioselectively. The B-H bond insertion products could be easily transformed into chiral alcohols and other widely used organoboron reagents with enantiomeric fidelity.

Formal carbene insertion into C[dbnd]O double bond: A facile approach to the synthesis of 2H-chromenes

A formal carbene insertion into CO double bonds of 2-hydroxycinnamaldehydes catalyzed by Rh2(esp)2 with Na2CO3 as additive has been disclosed by using aryldiazoacetates as carbene precursors. 2H-chromenes with a quaternary carbon at C-2 position were readily obtained from simple starting materials in good yields with excellent diastereoselectivity under mild reaction conditions in one pot. The reaction mechanism was investigated and proposed as the formation of epoxide intermediate from Rh(II)-associated carbene and (E)-2-hydroxycinnamaldehyde and followed by a cascade epoxide ring-opening procedure in which the (E)-intermediate was converted into the (Z)-intermediate to give (Z)-products.

Correction to Kinetics and Mechanism of Isocyanide-Promoted Carbene Insertion into the Aryl Substituent of an N-Heterocyclic Carbene Ligand in Ruthenium-Based Metathesis Catalysts

Correction to Kinetics and Mechanism of Isocyanide-Promoted Carbene Insertion into the Aryl Substituent of an N-Heterocyclic Carbene Ligand in Ruthenium-Based Metathesis Catalysts

Complexes of [(dadi)Ti(L/X)]m That Reveal Redox Non-Innocence and a Stepwise Carbene Insertion into a Carbon–Carbon Bond

The addition of donors to (dadi)Ti(THF) (1-THF, dadi = [{−CH═N(1,2-C6H4)N(2,6-iPr2–C6H3)}2]n) afforded the adducts [(dadi)Ti(L/X)]m (1-L, m = 0, N2CPh2; m = −1, X = Cl–, N3–, OiPr–, CH3–, neoPe–, CH═CH2–, CCPh–, CCTMS–, H(D)−). In all adducts, the chelate was in the (dadi)4– redox state. For certain anions, evidence for intimate binding of the Li+ counterion was explored spectroscopically. Treatment of 1-THF with PhHCN2, yielded {PhC3H3(-NC6H4-2-NAr)2}Ti(THF) (3, Ar = 2,6-iPr2–C6H3), which contains a cyclopropanated dadi ligand. The mechanism was explored by calculations, and the addition of Ph2CN2 to 3 produced a nacnac derivative, {PhC(CHNC6H4-2-NAr)2}Ti(η2-HNNCPh2) (4, Ar = 2,6-iPr2–C6H3), generated via hydrogen transfer from the cyclopropane.

Au Nanoparticle-Catalyzed Insertion of Carbenes from α-Diazocarbonyl Compounds into Hydrosilanes.

Supported Au nanoparticles on TiO2 catalyze the insertion of carbenes from α-diazocabonyl compounds into hydrosilanes. It is proposed that the transformation involves two modes of catalytic activation: formation of nucleophilic Au carbenes on the surface of nanoparticle via expulsion of N2 and activation of the Si-H bond of hydrosilane on Au nanoparticle, followed by coupling of the chemisorbed species. No external ligands or additives are required, while the process is purely heterogeneous, thus allowing the recycling and reuse of the catalyst.

Carbene Transfer and Carbene Insertion Reactions Catalyzed by a Mixed‐Ligand Copper(I) Complex

The catalytic activity of the mixed‐ligand copper(I) complex [Cu(PPh3)2(κ2‐O,O"‐lact)] (1) {lact = l‐(+)‐lactate} has been investigated in carbene transfer and carbene insertion reactions. Complex 1 catalytically promoted the diastereoselective cyclopropanation of olefins in the presence of ethyl diazoacetate (EDA), under mild conditions, and with a low catalyst loading (1 mol‐%). In the case of internal alkenes, a trans/cis ratio of up to 93:7 was reached. Moreover, compound 1 easily promoted the insertion of the carbene fragment deriving from the decomposition of ethyl diazoacetate into O–H (alcohols and phenols) and N–H (amine) bonds, with formation of the corresponding ethyl 2‐alkoxyacetate, ethyl 2‐phenoxyacetate, and ethyl 2‐aminoacetate derivatives in good to high yields.

Photochemistry of the Stilbenes in Methanol. Trapping the Common Phantom Singlet State.

A comparative study of the photochemistry of cis- and trans-stilbene in methanol shows that both isomers undergo methanol photoaddition giving similar yields of α-methoxybibenzyl in competition with cis-trans photoisomerization. Methanol addition occurs primarily following torsional relaxation of the lowest excited singlet states of each isomer, 1 c* and 1 t*, to a common twisted singlet excited state intermediate, 1 p*, initially called the phantom singlet state. The addition is consistent with the zwitterionic character of 1 p*. Ether forms by direct 1,2-addition of CH3OH to the central carbon atoms and by 1,1-addition following rearrangement to 1-benzyl-1-phenylcarbene. Use of CD3OD and GC/MS (gas chromatographic/mass spectroscopic) analysis of the ether products revealed that the ratio of carbene/direct addition pathways is higher starting from cis-stilbene. We conclude that 1 p* formed from 1 c* is hotter than 1 p* formed from 1 t*. Surprisingly, except for favoring the carbene pathway, the use of higher energy photons (254 vs 313 nm) does not affect the overall ether quantum yield starting from cis-stilbene but significantly enhances both pathways starting from trans-stilbene. It appears that carbene formation and direct methanol addition to higher trans-stilbene excited state(s) compete with relaxation to S1. Substitution of D for the vinyl Hs of stilbene enhances the direct addition pathway more than 2-fold and strongly suppresses the carbene insertion pathway, revealing a large, kpcd0/ kped2 = 6.3, primary deuterium isotope effect in the carbene rearrangement. The 2-fold increase in the ether quantum yield is due primarily to a 2.75-fold increase in the lifetime of 1 p* on deuterium substitution of the vinyl hydrogens.

Formal Carbene Insertion into C−O or C−N Bond: An Efficient Strategy for the Synthesis of 2‐Substituted 2H‐Chromene Derivatives from Chromene Acetals or Hemiaminal Ethers

AbstractWe report the palladium/Brønsted acid co‐catalyzed formal insertion of carbene into the C−O or C−N bond of 2H‐chromene acetals or hemiaminal ethers. This transformation was initiated by the Brønsted acid‐promoted cleavage of the C−O or C−N bond, followed by modification of the leaving alcohol or amino fragments with palladium carbenes, and reassembly of the modified fragments. A variety of C‐2 functionalized 2H‐chromene derivatives were obtained in moderate yield (43∼75%) with good to excellent diastereoselectivities (up to >95:5 dr) under mild conditions.magnified image

Access to Spiroindolines and Spirodihydrobenzofurans via Pd-Catalyzed Domino Heck Spiroyclization through C-H Activation and Carbene Insertion.

A new palladium-catalyzed domino approach for the synthesis of attractive spirocyclic indolines and dihydrobenzofurans was developed. The reaction proceeds through a sequential intramolecular Heck spirocyclization, remote C-H activation, and diazocarbonyl carbene insertion. Various spiroindolines and spirodihydrobenzofurans containing two quartenary carbon stereocenters were readily obtained in good to excellent yields. A preliminary study of asymmetric spirocyclization using chiral monophosphoramidite as a ligand was also conducted, enabling access to highly valuable chiral spiroindolines with up to 80% ee.

Porphyrinic Metal-Organic Frameworks As Chemoselective Catalysts

Owing to the designable structure, large surface area, high porosity et al, metal-organic frameworks (MOFs) as heterogeneous catalysts have aroused a lot of interests. By reasonable design of the components (e.g. metal node, ligand and guest), cavity, topology, etc., MOFs can be widely applied in a variety of reactions. With the aid of diffusion-controlment, host-guest recognition, and confinement effect of the coordination space of MOFs, they can display chemoselectivity, including shape-, size-, regio- and enantio-selectivitiy, and even inverted chemeoselectivity compared to conventional molecular catalysts. Considering that various elements such as transition metals and main group elements can be implanted into the central ring of porphyrin, porphyrinic metal-organic frameworks (PMOFs) have emerged as powerful MOF-based heterogeneous catalysts and applied in a variety of reactions, including photocatalysis, electrocatalysis, CO2 conversion, carbene insertion, etc. Our group has recently worked on the design and synthesis PMOFs based on noble metals (e.g. Ru, Rh, Ir, Pd, and Pt). Catalytic results show that our PMOFs can induce selective X-H (X = Si, N) insertion reaction. Figure 1

Electrospun Gelatin Membrane Cross-Linked by a Bis(diarylcarbene) for Oil/Water Separation: A New Strategy To Prepare Porous Organic Polymers

Porous organic polymers (POPs) as absorbing materials have attracted increasing attention. Here, we report a new approach to prepare these polymers for selective oil absorption from oil/water mixtures. Perfluoroalkylbis(diaryldiazomethane) was synthesized and used to modify the surface of an electrospun gelatin membrane by a carbene insertion reaction, not only to immobilize the porous network morphology by cross-linking but also to introduce perfluoroalkyl groups for oil/water separation. The membrane was characterized to show its surface and bulk properties, as well as its performance for absorption capacity, selectivity, and renewability. This approach offers a new horizon in the preparation of POPs for oil/water separation.

Double rings made with heme

Biocatalysis Cyclic organic structures with adjacent three-carbon rings—bicyclobutanes—are useful starting materials for chemical and materials synthesis owing to their extreme ring strain. Constructing these molecules is a challenging task for organic chemists, especially if a single stereoisomer is desired. Chen et al. engineered a heme-containing enzyme to catalyze sequential carbene insertion reactions using an alkyne substrate. Starting with an enzyme that could only catalyze a single carbene insertion, a series of mutations led to variants that catalyzed efficient, stereoselective production of bicyclobutanes. By using a less reactive alkyne substrate and screening more variants with active site mutations, the authors found enzymes that stop at either enantiomer of the intermediate cyclopropene. Science , this issue p. [71][1] [1]: /lookup/doi/10.1126/science.aar4239

Enzymatic construction of highly strained carbocycles.

Small carbocycles are structurally rigid and possess high intrinsic energy due to their ring strain. These features lead to broad applications but also create challenges for their construction. We report the engineering of hemeproteins that catalyze the formation of chiral bicyclobutanes, one of the most strained four-membered systems, via successive carbene addition to unsaturated carbon-carbon bonds. Enzymes that produce cyclopropenes, putative intermediates to the bicyclobutanes, were also identified. These genetically encoded proteins are readily optimized by directed evolution, function in Escherichia coli, and act on structurally diverse substrates with high efficiency and selectivity, providing an effective route to many chiral strained structures. This biotransformation is easily performed at preparative scale, and the resulting strained carbocycles can be derivatized, opening myriad potential applications.

Mechanism of the Selective Fe-Catalyzed Arene Carbon–Hydrogen Bond Functionalization

The complete chemoselective functionalization of aromatic C(sp2)–H bonds of benzene and alkyl benzenes by carbene insertion from ethyl diazoacetate was unknown until the recent discovery of an iron-based catalytic system toward such transformation. A Fe(II) complex bearing the pytacn ligand (pytacn = L1 = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane) transferred the CHCO2Et unit exclusively to the C(sp2)–H bond. The cycloheptatriene compound commonly observed through Buchner reaction or, when employing alkyl benzenes, the corresponding derivatives from C(sp3)–H functionalization are not formed. We herein present a combined experimental and computational mechanistic study to explain this exceptional selectivity. Our computational study reveals that the key step is the formation of an enol-like substrate, which is the precursor of the final insertion products. Experimental evidences based on substrate probes and isotopic labeling experiments in favor of this mechanistic interpretation are provided.