Chiara Costabile

Gold‐ and Platinum‐Catalyzed Cycloisomerization of Enynyl Esters versus Allenenyl Esters: An Experimental and Theoretical Study

Ester-way to heaven: Unexpected formation of bicyclo[3.1.0]hexene 4 was the main focus of combined experimental and theoretical studies on the Au-catalyzed cycloisomerization of branched dienyne 1 (see scheme), which provided better understanding of the mechanistic details governing the cyclization of enynes bearing a propargylic ester group.Experimental and theoretical studies on Au- and Pt-catalyzed cycloisomerization of a branched dienyne with an acetate group at the propargylic position are presented. The peculiar architecture of the dienyne precursor, which has both a 1,6- and a 1,5-enyne skeleton, leads, in the presence of alkynophilic gold catalysts, to mixtures of bicyclic compounds 3, 4, and 5. Formation of unprecedented bicyclo[3.1.0]hexene 5 is the main focus of this study. The effect of the ancillary ligand on the gold center was examined and found to be crucial for formation of 5. Further mechanistic studies, involving cyclization of an enantioenriched dienyne precursor, (18)O-labeling experiments, and DFT calculations, allowed an unprecedented reaction pathway to be proposed. We show that bicyclo[3.1.0]hexene 5 is likely formed by a 1,3-OAc shift/allene-ene cyclization/1,2-OAc shift sequence, as calculated by DFT and supported by Au-catalyzed cyclization of isolated allenenyl acetate 7, which leads to improved selectivity in the formation of 5. Additionally, the possibility of OAc migration from allenyl acetates was supported by a trapping experiment with styrene that afforded the corresponding cyclopropane derivative. This unprecedented generation of a vinyl metal carbene from an allenyl ester supports a facile enynyl ester/allenenyl ester equilibrium. Further examination of the difference in reactivity between enynyl acetates and their corresponding [3,3]-rearranged allenenyl acetates toward Au- and Pt-catalyzed cycloisomerization is also presented.

Identification and Characterization of a New Family of Catalytically Highly Active Imidazolin-2-ylidenes

A new class of easily accessible and stable imidazolin-2-ylidenes has been synthesized where the side chains are comprised of substituted naphthyl units. Introduction of the naphthyl groups generates C 2 -symmetric ( rac) and C s- symmetric ( meso) atropisomers, and interconversion between the isomers is studied in detail both experimentally and computationally. Complete characterization of the carbenes includes rare examples of crystallographically characterized saturated NHC structures. Steric properties of the ligands and an investigation of their stability are also presented. In catalysis, the new ligands show versatility comparable to the most widely used NHCs IMes/SIMes or IPr/SIPr. Excellent catalytic results are obtained when either the NHC salts (ring-opening alkylation of epoxides), NHC-modified palladium compounds (C-C and C-N cross-couplings), or NHC-ruthenium complexes (ring-closing metathesis, RCM) are employed. In several cases, this new ligand family provides catalytic systems of higher reactivity than that observed with previously reported NHC compounds.

The Pivotal Role of Symmetry in the Ruthenium-Catalyzed Ring-Closing Metathesis of Olefins

The synthesis of Ru-based precatalysts with N-heterocyclic carbene (NHC) ligands bearing syn- and anti-methyl groups on the NHC backbone and aryl N-substituents with differing steric bulk was carried out. The catalytic behavior of the monophospine Ru precatalysts (7a, 7b, 8a, and 8b) was compared to the corresponding family of phosphine-free catalysts (9a, 9b, 10a and 10b) in the ring-closing metathesis (RCM) of olefins. These catalysts showed high efficiency in RCM reactions and the syn-isomers 7a and 9a, in particular, proved to be among the most active catalysts in the formation of tetrasubstituted olefins through RCM. DFT studies on the entire RCM catalytic cycle of hindered olefins were performed to rationalize the different behaviors of catalysts with syn- and anti-methyl groups on the NHC backbone. Theoretical results not only disclosed how NHC symmetry influences the overall activity of the catalyst, but also gave relevant and more general indications on the crucial steps of the RCM of olefins.

Probing the Relevance of NHC Ligand Conformations in the Ru‐Catalysed Ring‐Closing Metathesis Reaction

Probing the Relevance of NHC Ligand Conformations in the Ru-Catalysed Ring-Closing Metathesis Reaction Cat power : Judicious backbone substitution of N-heterocyclic carbenes (NHCs) leads to stable Ru metathesis catalysts with frozen NHC conformations. This finding not only permits the isolation of complexes that are among the most active catalysts in the ringclosing metathesis of hindered olefins (see graphic; Ts= p-toluenesulfonyl), but also provides fundamental mechanistic insights on the role of N-aryl substituent conformations on catalyst activity.

Synthesis, characterization and catalytic behaviour of a palladium complex bearing a hydroxy-functionalized N-heterocyclic carbene ligand

The synthesis of a new stable palladium(II) complex (3) featuring an unsymmetrical substituted N-heterocyclic carbene (NHC) ligand with a pendant hydroxy-functionalized group was successfully accomplished via transmetalation of the corresponding bis-NHC silver(I) complex (2). Solid-state structures of both 2 and 3 were determined by single-crystal X-ray diffraction. The catalytic behaviour of 3 in the direct regioselective arylation of furan and thiophene derivatives by using challenging aryl halides was studied, revealing that 3 was capable of promoting these environmentally attractive coupling reactions to afford arylated heterocycles in moderate to good yields.

Activity and stereoselectivity of Ru-based catalyst bearing a fluorinated imidazolinium ligand

AbstractGrubbs II generation catalyst (3), bearing a fluorinated imidazolinium ligand, was investigated in cross metathesis (CM), ring closing metathesis (RCM) and ring opening polymerization metathesis (ROMP) for a variety of substrates. Kinetic studies showed reduced stability of the catalyst in methylene chloride following the first 15 minutes of reaction preventing a higher efficiency despite the very high activity. Beneficial solvent effects on the catalyst stability were observed by performing RCM in C6F6.

Methyl and phenyl substituent effects on the catalytic behavior of NHC ruthenium complexes

New second-generation ruthenium benzylidene and isopropoxybenzylidene catalysts bearing N-heterocyclic carbene (NHC) ligands with o-biphenyl groups at the N-atoms and syn methyl or phenyl groups on the backbone were obtained and their catalytic behaviors were compared to those of analogous N-o-tolyl catalysts in standard ring-closing metathesis (RCM) reactions. A pronounced difference in catalyst efficiency was observed depending on the nature of ortho-N-aryl substituents (methyl or phenyl). Notably, very impressive catalytic performances were exhibited by N-o-biphenyl complexes with a syn dimethyl backbone in the formation of di- and trisubstituted cycloalkenes. To rationalize catalytic results, methyl and phenyl substituent effects on the steric and electronic properties of NHC ligands were assessed through experimental and theoretical investigations involving ruthenium complexes as well as newly developed rhodium derivatives. Despite the different electron donor capacities of the examined carbenes, the steric differences shown by N-o-biphenyl and N-o-tolyl NHCs, although subtle, were found to be the key factor in addressing catalyst behavior.

Synthesis and complexing properties of cyclic benzylopeptoids - a new family of extended macrocyclic peptoids.

An efficient protocol for the solid-phase synthesis of six members of a new class of extended macrocyclic peptoids (based on ortho-, meta- and para-N-(methoxyethyl)aminomethyl phenylacetyl units) is described. Theoretical (DFT) and experimental (NMR) studies on the free and Na+-complexed cyclic trimers (3-5) and tetramers (6-8) demonstrate that annulation of the rigidified peptoids can generate new hosts with the ability to sequestrate one or two sodium cations with the affinities and stoichiometries defined by the macrocycle morphology. Ion transport studies have been also performed in order to better appreciate the factors promoting transmembrane cation translocation.

Influence of the catalyst-nanotube spacing on the synthesis of polymer-functionalized multiwalled carbon nanotubes by “grafting from” approach

Polynorbornene-functionalized multiwalled carbon nanotubes (MWCNTs) were prepared by a “grafting from” approach, on varying the catalyst-MWCNT spacing to evaluate the influence of the starting catalyst-MWCNT distance on the polymerization efficiency. In particular, 2nd generation Grubbs catalysts and Hoveyda-Grubbs catalysts, both active in the ring opening metathesis polymerization of olefins, were grafted on MWCNTs at 8 to 12 atom spacing from the nanotube surface, and the activity of initiators was tested in the 2-norbornene polymerization. According to our results, initiator performances depend (i) on the length of the arm connecting the catalyst to the MWCNTs, being initiators with longer arms more efficient, and (ii) on the class of Ru catalysts, being Hoveyda-Grubbs catalysts surprisingly more active at room temperatures than 2nd generation Grubbs catalysts. High fractions (80–95 wt%) of polymer covalently bound to the nanotubes in the MWCNT-grafted polynobornene obtained composites were achieved.

Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins. Similarly to the natural depsipeptides, the synthetic oligolactam analogues show a correlation between ion transport abilities in artificial liposomes and cytotoxic activity on human cancer cell lines. The reported results demonstrate that the versatile cyclic peptoid scaffold, for its remarkable conformational and complexing properties, can morphologically mimic related natural products and elicit powerful biological activities.