Alkynyl Fischer Carbene Complexes Research Articles

N‐Tosylhydrazones as [N,N] Synthons in Heterocyclic Chemistry: Synthesis of 3,5‐Disubstituted N‐Alkenyl‐1H‐pyrazoles

AbstractA new mode of reactivity of N‐sulfonylhydrazones towards alkynes is described: ketone‐derived N‐tosylhydrazones (NTHs) bearing α‐H atoms behave as [NN] synthons in their reactions with alkoxy alkynyl Fischer carbene complexes (FCCs) and only the two N atoms are incorporated into the newly formed pyrazole ring. The scope of the reaction, leading to 5‐methoxy‐N‐alkenyl pyrazoles, proved to be wide regarding both partners; thus, a variety of aryl and primary, secondary, and tertiary alkyl substituents are tolerated within the FCC, while aryl alkyl NTHs, symmetric and asymmetric dialkyl NTHs and NTHs derived of cyclic ketones can be also employed. In addition, the reaction can be performed at large scale and applied for late‐stage diversification of natural products. A reasonable reaction mechanism is also proposed, which is supported by deuteration experiments and DFT calculations.

Selective synthesis of trisubstituted pyrroles through the reactions of alkynyl Fischer carbene complexes with oxazolones.

An efficient and simple synthesis of novel trisubstituted 1H-pyrroles 4a-qvia 1,3-dipolar cycloaddition of Δ3-trifluoromethyloxazolones 2a-d with both chromium and tungsten alkynyl Fischer carbene complexes (1a-h) is described. An unexpected and unreported -CF3 group elimination process was observed in the pyrrole structure. Our experimental and theoretical data suggested that the metal fragment may be responsible for this phenomenon. The dipolar cycloaddition proceeded efficiently to produce a single regioisomer, which was unambiguously established through NMR and single-crystal X-ray diffraction studies. Nevertheless, the reaction of alkynyl carbenes bearing an α,β,γ,δ-unsaturated moiety with excess oxazolone 2a produced a polycyclic compound 6 speculatively formed through a cascade reaction involving 1,6-, 1,4- and 1,2-nucleophilic addition steps.

Understanding the Reactivity of Group 6 Metal (M = Cr, W) Alkynyl Fischer Carbene Complexes with Multi‐Reactive Masked Dienes

Group 6 alkynyl Fischer carbene complexes behave as electrophiles with highly reactive masked dienes such as anthrone and 3‐hydroxy‐2‐pyrone, which also can react as bidentate nucleophiles. Both Cr0 and W0 alkynyl carbene complexes require tertiary amines to promote the formation of 1,4‐C‐addition products, but a marked dependence of the reactivity on the metal was observed. Although W0 complexes form exclusively the 1,4‐C‐adducts in the presence of a catalytic amount of base, Cr0 complexes lead to new anthrone‐derived bis‐carbene complexes, obtained by a sequential 1,4‐C‐ and 1,4‐O‐addition process with high diastereoselectivity and only in the presence of an excess of base. DFT computational studies show that the gap between the LUMO of the complex and the HOMO of the anthrone determines the differences in reactivity and that the stability of the intermediate metal allenyls formed after the initial 1,4‐addition is decisive for the outcome of the reaction.

Effect of a κ1-Bonded-M-1,2,3-triazole (M = Co, Ru) on the Structure and Reactivity of Group 6 Alkoxy (Fischer) Carbenes.

The [3 + 2] cycloaddition of two different metal-bound azides, [(Me4cyclam)CoII(N3)]ClO4 and (η5-C5H5)(dppe)RuII(N3), (dppe = Ph2PCH2CH2PPh2) with Cr(0) and W(0) (ethoxy)(alkynyl) Fischer carbenes has been efficiently used for the preparation of polymetallic metal-carbene complexes. The presence of the κ1-bonded metal triazole causes a significant influence on the electronic properties, structure, and reactivity of this new class of Fischer alkoxycarbenes. For the Ru(II) derivatives, their chemical behavior is considerably influenced by the interaction of the (η5-C5H5)(dppe)RuII-triazole moiety with the empty p-carbene orbital that provokes a noticeable decrease in the electrophilicity of the M═C carbon (manifested by the shielding of the 13C NMR chemical shifts). In turn, in the Co(II) derivatives, the incorporation of the (Me4cyclam)CoII moiety diminishes the aromaticity of the triazole ring and has a marked effect on the energy and distribution of the LUSO orbital, mostly resident on the Co(II) fragment. The almost negligible participation of the carbene moiety in the LUSO makes this position unable to react with nucleophiles. The reactions reported in this work constitute the first examples of [3 + 2] cycloaddition of azides and alkynyl Fischer carbene complexes in solution.

ChemInform Abstract: Synthesis of Novel Polysubstituted N‐Benzyl‐1H‐pyrroles via a Cascade Reaction of Alkynyl Fischer Carbenes with α‐Imino Glycine Methyl Esters.

ChemInformVolume 47, Issue 16 Heterocyclic Compounds ChemInform Abstract: Synthesis of Novel Polysubstituted N-Benzyl-1H-pyrroles via a Cascade Reaction of Alkynyl Fischer Carbenes with α-Imino Glycine Methyl Esters. Fabiola N. de la Cruz, Fabiola N. de la Cruz Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorJulio Lopez, Julio Lopez Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorJ. Oscar C. Jimenez-Halla, J. Oscar C. Jimenez-Halla Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorMarcos Flores-Alamo, Marcos Flores-Alamo Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorJoaquin Tamariz, Joaquin Tamariz Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorFrancisco Delgado, Francisco Delgado Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorMiguel A. Vazquez, Miguel A. Vazquez Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this author Fabiola N. de la Cruz, Fabiola N. de la Cruz Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorJulio Lopez, Julio Lopez Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorJ. Oscar C. Jimenez-Halla, J. Oscar C. Jimenez-Halla Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorMarcos Flores-Alamo, Marcos Flores-Alamo Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorJoaquin Tamariz, Joaquin Tamariz Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorFrancisco Delgado, Francisco Delgado Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this authorMiguel A. Vazquez, Miguel A. Vazquez Dep. Quim., Univ. Guanajuato, 36050 Guanajuato, Mex.Search for more papers by this author First published: 29 March 2016 https://doi.org/10.1002/chin.201616127Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume47, Issue16March, 2016 RelatedInformation

Mono- and bimetallic zwitterionic chromium(0) and tungsten(0) allenyls.

A series of stable chiral (racemic), formally neutral, zwitterionic mono- and bimetallic M(CO)5[C(OEt)═C═CR(NHC)] (M = Cr, W) σ-allenyls are ready available by the addition of N-heterocyclic carbenes (NHCs) to Cr(0) and W(0) alkynyl Fischer carbene complexes. Different classes of NHCs, (e.g., 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene, and their six- and seven-membered analogues and 1,3-bis(dimethyl)imidazol-2-ylidene) were employed as nucleophiles in these C-C bond-forming reactions yielding the novel complexes in essentially quantitative yields. A systematic experimental and computational study of the electronic properties of the Cr- and W-allenyls shows that their UV-vis spectra are directly influenced by the structure of the heterocyclic moiety derived from the NHC (ring size, substituents on the N atoms) and by the nature of the metal fragment (Cr/W). The electron-releasing nature of these complexes allows them to participate in electron-transfer reactions in the ground state, leading to a type of charged α,β-unsaturated Fischer carbenes that incorporate an NHC fragment in their structure.

Synthesis of novel polysubstituted N-benzyl-1H-pyrroles via a cascade reaction of alkynyl Fischer carbenes with α-imino glycine methyl esters.

An efficient and simple synthesis of novel and densely substituted N-benzyl-1H-pyrroles 6a-r is described by a 1,4-addition/isomerization/ring closure/demetalation cascade process of alkynyl Fischer carbene complexes 1a-f and 2a and α-imino glycine methyl esters 3a, b, d, g, h, and k promoted with LDA.

Triazolyl Alkoxy Fischer Carbene Complexes in Conjugation with Ferrocene/Pyrene as Sensory Units: Multifunctional Chemosensors for Lead(II), Copper(II), and Zinc(II) Ions

The regioselective 1,3-dipolar cycloaddition reaction of alkoxy alkynyl Fischer carbene complex 1 with azidomethyl ferrocene 2 and with azidomethyl pyrene 4 under solvent-free conditions yielded the triazolyl Fischer carbene complexes 3 (C27H21O6N3FeW) and 5 (C33H21O6N3W), respectively. The cation complexation properties of these receptors have been systematically studied using electrochemical and spectroscopic techniques. The exceptional structural feature existing in these receptors is the presence of a Fischer carbene moiety, connected to the ferrocene or pyrene moiety through a 1,2,3-triazole ring. Receptor 3 contains a redox-active ferrocene moiety and is highly selective toward Pb2+ ion, whereas receptor 5, having a fluorescent pyrene unit, selectively recognizes Zn2+ and Cu2+ ions. The binding ability of receptor 3 can be inferred either from the redox shift (the anodic shift ΔE1/2 = 55 mV) or the highly visual output response for Pb2+ ion. Receptor 5 displays considerable chelation-enhanced fluore...

Synthesis of 2,3-Disubstituted Pyrroles Initiated by 1,4-Addition of Chelated Enolates onto Alkynyl Carbene Complexes

Chelated glycine ester enolates, which have been found to be good nucleophiles, e.g., for Michael additions, undergo 1,4-addtition toward alkynyl Fischer carbene complexes. Instead of the expected unsaturated carbene amino acid derivatives, 2,3-disubstituted pyrroles are formed, probably by a domino process initiated by the 1,4-addition. Subsequent 1,3-H-shift, 1,2-addition, and reductive elimination during workup finalized the reaction cascade.

Addition of Oxime Derivatives to Alkynyl Fischer Carbene Complexes

The addition of oxime derivatives to alkynyl Fischer carbene complexes has been explored through a combined experimental and computational approach. Up to four different heterocycles with diverse regiochemistry and ring size were found, depending on the starting ketone. The reaction mechanism was studied by DFT methods.

Regioselective and Stepwise [8 + 2] Cycloaddition Reaction between Alkynyl–Fischer Carbene Complexes and Tropothione

The formal [8 + 2] cycloaddition reaction between alkynyl Fischer carbene complexes and tropothione leads to the regioselective formation of novel 3aH-cyclohepta[b]thiophene carbene complexes. Computational DFT calculations indicate that the process proceeds stepwise via antiaromatic zwitterionic intermediates.

ChemInform Abstract: [1,5]‐Hydride Transfer/Cyclization of ortho‐Amino Alkynyl Fischer Carbene Complexes: A Useful Tool for the Synthesis of Quinoline Derivatives.

An efficient method for the synthesis of compounds containing a quinoline moiety by using o-aminophenyl alkynyl Fischer carbene complexes as starting materials is described. The reaction is based on a cascade process involving [1,5]-hydride transfer/cyclization to afford new alkenylcarbene complexes with quinoline moiety 2. The reaction of alkenyl complexes 2 with unsaturated substrates such as electron-poor alkynes afford furo[2',3'-3,4]cyclopenta[1,2-c]quinolinone derivatives 6 and (1,2-dihydroquinolin-3-ylvinyl)-malonates 12 when propiolic aldehydes and propiolates are used, respectively. The reactivity of the alkenylcarbene complexes was also studied by using 1,3-dienes to afford cyclohepta[c]quinolinones 17 when Danishefsky's diene is used and 3-pirimidinylquinoline derivatives 21 when 4-amino-1-azadienes are employed.

Photochemically Driven Addition of Iminyl Radicals to Alkynyl Fischer Carbene Complexes

Nitrogen-centered radicals, generated by the action of UV light, are capable of reacting with alkynyl Fischer carbene complexes in two ways, 1,2- and 1,4-addition. Our results constitute the first reported example of a photochemically driven reaction of this kind.

Highly Regioselective [3 + 2] Annulation of Azomethine Imines with 1-Alkynyl Fischer Carbene Complexes to Functionalized N,N-Bicyclic Pyrazolidin-3-ones

The highly regioselective [3 + 2] cycloaddition of azomethine imines to 1-alkynyl Fischer carbene complexes has been successfully realized under mild conditions. Oxidative demetalation of the newly formed pyrazolo-pyrazolone carbene complexes with pyridine-N-oxide or ceric ammonium nitrate efficiently afforded pyrazolo-pyrazolone derivatives as well as cycloprop-2-enone and trisubstituted 1H-pyrazoles in some cases, providing a novel route to versatile functionalized N,N-bicyclic pyrazolidin-3-ones.

ChemInform Abstract: Competitive Pathways in the Reaction of Lithium Oxy‐ortho‐quinodimethanes and Fischer Alkoxy Alkynyl Carbene Complexes: Synthesis of Highly Functionalized Seven‐Membered Benzocarbocycles.

AbstractReaction of in situ generated 1‐oxy‐ortho‐quinodimethanes with alkoxy alkynyl Fischer carbene complexes can provide four different cycloadducts depending on the substrate structure and on the reaction solvent used.

1,5]‐Hydride Transfer/Cyclization of ortho‐Amino Alkynyl Fischer Carbene Complexes: A Useful Tool for the Synthesis of Quinoline Derivatives

AbstractAn efficient method for the synthesis of compounds containing a quinoline moiety by using o‐aminophenyl alkynyl Fischer carbene complexes as starting materials is described. The reaction is based on a cascade process involving [1,5]‐hydride transfer/cyclization to afford new alkenylcarbene complexes with quinoline moiety 2. The reaction of alkenyl complexes 2 with unsaturated substrates such as electron‐poor alkynes afford furo[2′,3′‐3,4]cyclopenta[1,2‐c]quinolinone derivatives 6 and (1,2‐dihydroquinolin‐3‐ylvinyl)malonates 12 when propiolic aldehydes and propiolates are used, respectively. The reactivity of the alkenylcarbene complexes was also studied by using 1,3‐dienes to afford cyclohepta[c]quinolinones 17 when Danishefsky's diene is used and 3‐pirimidinylquinoline derivatives 21 when 4‐amino‐1‐azadienes are employed.

A versatile approach for the immobilization of amines via copper-free “click” reaction between azido self-assembled monolayer and alkynyl Fischer carbene complex. Application to the detection of staphylococcal enterotoxin A antibody

A copper-free “click” reaction between an azido-terminated self-assembled monolayer (SAM) chemisorbed on planar gold-coated glass sensors and an alkynyl Fischer carbene complex yielded functionalized surfaces onto which facile and swift grafting of amine-containing molecules was achieved via aminolysis of the Fischer carbene moieties. The course of this process was conveniently monitored by Polarization-Modulation Infrared Reflection-Absorption Spectroscopy (PM-IRRAS), contact angle measurements and X-ray photoelectron spectroscopy (XPS). A study of the parameters involved in the covalent grafting of the model protein bovine serum albumin (BSA) to the Fischer carbene modified SAM was carried out. As an application, the bacterial toxin staphylococcal enterotoxin A (SEA) produced by some pathogenic strains of Staphylococcus aureus was immobilized on the gold chips and immunocapture of a polyclonal antibody raised against SEA was detected by PM-IRRAS so as to ultimately construct an optical immunosensor for the detection of this toxin in food samples.

Competitive Pathways in the Reaction of Lithium Oxy‐ortho‐quinodimethanes and Fischer Alkoxy Alkynyl Carbene Complexes: Synthesis of Highly Functionalised Seven‐Membered Benzocarbocycles

Up to four different outcomes have been found for the reaction between 1-oxy-ortho-quinodimethanes (oQDMs) and alkoxy alkynyl Fischer carbene complexes (FCCs). The product formed depends on the structure of both reagents and on the reaction solvent. The pathways can be topologically classified as a [4C+2C], a [3(2C+O)+3C], and two different [4C+3C] processes and, in all these sequences, 1-oxy-oQDMs behave as enolates or as vinylogous enolates. The reaction of Choy and Yang's unsubstituted oQDM 1 with tungsten alkynyl FCCs is solvent controlled; thus, selective formation of benzocycloheptenones can be achieved in THF, whereas exclusive synthesis of benzocycloheptene ketals is reached in diethyl ether. On the other hand, THF is the solvent of choice to form benzocycloheptene ketals when an alkyl or aryl group is placed at position 1 of the oQDM in its reaction with tungsten carbene complexes; however, a pyranylidene carbene complex is formed when a chromium carbene complex is used. Alternatively, the presence of bulky alkoxy groups in the FCC component favours a Diels-Alder aromatisation sequence, which leads to 1-naphthyl FCCs. Furthermore, the isolation and the characterisation of several deuterated compounds by labelling experiments have provided some insight into the reaction pathways, and mechanisms consistent with those findings have been established and several reaction intermediates have been identified.

Regioselective 1,3-Dipolar Cycloaddition Reaction of Azides with Alkoxy Alkynyl Fischer Carbene Complexes

Solvent-free conditions at moderate temperature promote regioselective 1,3-dipolar cycloaddition reactions between alkoxy alkynyl Fischer carbene complexes with a wide range of organic azides.

Multiple reactivities of dithranol towards 1-alkynyl Fischer carbene complexes (CO) 5M [dbnd]C(OEt)C [tbnd]CPh (M = Cr, W) – Efficient chemical synthesis of aromatic polyketides

Reactions of anti-psoriasis drug dithranol with 1-alkynyl Fischer carbene complexes (CO) 5M C(OEt)C CPh (M = Cr, W) were investigated under controlled conditions in which triethylamine-promoted C-addition, O-addition, electrophilic aromatic substitution, and cyclization consecutively occurred at up to five positions of dithranol. A remarkable solvent effect led to selective formation of polyphenolic organic and organometallic mono- and triscarbene complexes which were efficiently demetalated to the potentially bioactive aromatic polyketides with pyridine- N-oxide. All the organic and organometallic products were characterized by methods including X-ray single crystal structural determinations. These results have revealed the novel multiple reactivities of dithranol which might be associated to its clinical side effect, providing a new synthetic methodology to functionalize dithranol for medical purposes, and chemically synthesize aromatic polyketides.