Laura Falivene

[Pd(IPr*)(cinnamyl)Cl]: An Efficient Pre‐catalyst for the Preparation of Tetra‐ortho‐substituted Biaryls by Suzuki–Miyaura Cross‐Coupling

The bigger the better: The new well-defined [Pd(IPr*)(cin)Cl] pre-catalyst is described. This complex proves to be highly active in the Suzuki-Miyaura cross-coupling for the synthesis of tetra-ortho-substituted biaryls under mild conditions. IPr* is reported as the largest N-heterocyclic carbene (NHC) to date for [Pd(NHC)(cin)Cl] complexes, explaining the high reactivity observed for this complex in this challenging transformation.

SambVca 2. A Web Tool for Analyzing Catalytic Pockets with Topographic Steric Maps

Developing more efficient catalysts remains one of the primary targets of organometallic chemists. To accelerate reaching this goal, effective molecular descriptors and visualization tools can represent a remarkable aid. Here, we present a Web application for analyzing the catalytic pocket of metal complexes using topographic steric maps as a general and unbiased descriptor that is suitable for every class of catalysts. To show the broad applicability of our approach, we first compared the steric map of a series of transition metal complexes presenting popular mono-, di-, and tetracoordinated ligands and three classic zirconocenes. This comparative analysis highlighted similarities and differences between totally unrelated ligands. Then, we focused on a recently developed Fe(II) catalyst that is active in the asymmetric transfer hydrogenation of ketones and imines. Finally, we expand the scope of these tools to rationalize the inversion of enantioselectivity in enzymatic catalysis, achieved by point mutat...

Room-temperature synthesis of tetra-ortho-substituted biaryls by NHC-catalyzed Suzuki-Miyaura couplings

Transition-metal-catalyzed cross couplings have become some of the most powerful and widely used methods to construct C C bonds. Among them, the Suzuki–Miyaura coupling, has emerged as a particularly attractive and practical tool for synthetic organic chemistry. Indeed, over the last decade, several limitations of this methodology have been successfully addressed by using bulky, electron-rich monodentate phosphines or sterically demanding NHC ligands (NHC= N-heterocyclic carbene). One of the few challenges remaining in the Suzuki–Miyaura coupling reaction involves transformations with sterically demanding substrates that lead to tetra-ortho-substituted products. Especially in cases where aryl chlorides are used, the relatively poor nucleophilicity of the arylboron reagents results in diminished catalytic activities. In 2004, Glorius and co-workers showed for the first time that aryl chlorides can indeed be coupled to aryl boronic acids to generate such tetra-orthosubstituted biaryls at elevated temperature (110 8C) by employing a very bulky, yet flexible derivative of their bioxazoline-derived NHC ligands in combination with a Pd metal salt. More recently in 2009 and following the same concept of flexible steric bulk of the NHC ligand, Organ and coworkers used the complex Pd-PEPPSI-IPent as the catalyst for the Suzuki–Miyaura couplings to form bulky tetra-orthosubstituted biaryls at milder conditions (65 8C). Since then, various other ligand systems have been shown to effect similar couplings involving aryl chlorides when appropriate heating is employed. To date, systems that work at room temperature have not been reported for the construction of these important tetra-ortho-substituted biaryl structures by way of the Suzuki–Miyaura coupling. Recently, we have presented a new class of saturated NHC ligands with naphthyl-derived side chains that showed excellent reactivities in a variety of catalytic applications. In related studies, we noticed that a ligand with a cyclooctyl group in position 2 of the naphthalene moieties led to significantly increased reactivity. On the basis of these observations, we now report the application of such NHC ligand systems in the palladium-catalyzed Suzuki–Miyaura couplings to give tetra-ortho substituted biaryls and present conclusive evidence concerning the reasons leading to their superior behavior in these reactions. Reaction of NHC ligands with saturated and unsaturated N-heterocycles incorporating 2or 2,7-cyclooctyl groups on the naphthalene side chains with a Pd ACHTUNGTRENNUNG(cin)Cl dimer (cin =cinnamyl) and appropriate workup gave the four complexes depicted in Table 1 in good yield as single isomers (anti-configured). To explore the effect of these new NHC ligands on biaryl formation in difficult Suzuki–Miyaura couplings, we chose the reaction between 2,4,6-trimethylphenyl chloride and 2,6dimethylphenyl boronic acid (Table 1). Under optimized reaction conditions, the four new catalyst systems were benchmarked against the commercially available, SIPr/IPrmodified congeners (Nolan s catalysts) as well as Organ s Pd-PEPPSI-IPent system, currently the most powerful precatalyst for such transformations. At room temperature, these reference systems resulted in low product yields (Table 1, entries 1–5, GC yields). In entries 4 and 5 in Table 1, we used Organ s previously reported reaction conditions, which deteriorated the reaction outcome. Gratifyingly, all catalysts incorporating the new NHC structures showed higher conversions and yields than the benchmark systems. Among the four substructures tested, anti-C clearly stands out as being particularly effective as it shows both high conversions and yields at room temperature. We then proceeded in evaluating the coupling of a variety of hindered aryl bromides (Table 2) and aryl chlorides (Table 3) employing precatalyst anti-C. As can be seen from the data reported in Table 2, high isolated product yields were normally obtained at room temperature within short reaction times when employing aryl bromides. In entry 2 in Table 2, where the coupling proceeded very slowly at room temperature, slight heating (65 8C) was applied, leading to a [a] L. Wu, E. Drinkel, F. Gaggia, S. Capolicchio, Priv.-Doz. Dr. A. Linden, Prof. Dr. R. Dorta Organisch-chemisches Institut, Universit t Z rich Winterthurerstrasse 190, 8057 Z rich (Switzerland) E-mail : dorta@oci.uzh.ch [b] L. Falivene, Prof. Dr. L. Cavallo Dipartimento di Chimica Universit di Salerno Via Ponte don Melillo, 84084 Fisciano (Italy) [] New Address: School of Biomedical, Biochemical and Chemical Sciences, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009 (Australia) [**] NHC=N-heterocyclic carbene. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201102442.

Selective Reduction of CO2 to CH4 by Tandem Hydrosilylation with Mixed Al/B Catalysts

This contribution reports the first example of highly selective reduction of CO2 into CH4 via tandem hydrosilylation with mixed main-group organo-Lewis acid (LA) catalysts [Al(C6F5)3 + B(C6F5)3] {[Al] + [B]}. As shown by this comprehensive experimental and computational study, in this unique tandem catalytic process, [Al] effectively mediates the first step of the overall reduction cycle, namely the fixation of CO2 into HCOOSiEt3 (1) via the LA-mediated C═O activation, while [B] is incapable of promoting the same transformation. On the other hand, [B] is shown to be an excellent catalyst for the subsequent reduction steps 2-4, namely the hydrosilylation of the more basic intermediates [1 to H2C(OSiEt3)2 (2) to H3COSiEt3 (3) and finally to CH4] through the frustrated Lewis pair (FLP)-type Si-H activation. Hence, with the required combination of [Al] and [B], a highly selective hydrosilylative reduction of CO2 system has been developed, achieving high CH4 production yield up to 94%. The remarkably different catalytic behaviors between [Al] and [B] are attributed to the higher overall Lewis acidity of [Al] derived from two conflicting factors (electronic and steric effects), which renders the higher tendency of [Al] to form stable [Al]-substrate (intermediate) adducts with CO2 as well as subsequent intermediates 1, 2, and 3. Overall, the roles of [Al] and [B] are not only complementary but also synergistic in the total reduction of CO2, which render both [Al]-mediated first reduction step and [B]-mediated subsequent steps catalytic.

Organocatalytic conjugate-addition polymerization of linear and cyclic acrylic monomers by N-heterocyclic carbenes: mechanisms of chain initiation, propagation, and termination.

This contribution presents a full account of experimental and theoretical/computational investigations into the mechanisms of chain initiation, propagation, and termination of the recently discovered N-heterocyclic carbene (NHC)-mediated organocatalytic conjugate-addition polymerization of acrylic monomers. The current study specifically focuses on three commonly used NHCs of vastly different nucleophilicity, 1,3-di-tert-butylimidazolin-2-ylidene (I(t)Bu), 1,3-dimesitylimidazolin-2-ylidene (IMes), and 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene (TPT), and two representative acrylic monomers, the linear methyl methacrylate (MMA) and its cyclic analog, biomass-derived renewable γ-methyl-α-methylene-γ-butyrolactone (MMBL). For MMA, there exhibits an exquisite selectivity of the NHC structure for the three types of reactions it promotes: enamine formation (single-monomer addition) by IMes, dimerization (tail-to-tail) by TPT, and polymerization by I(t)Bu. For MMBL, all three NHCs promote no dimerization but polymerization, with the polymerization activity being highly sensitive to the NHC structure and the solvent polarity. Thus, I(t)Bu is the most active catalyst of the series and converts quantitatively 1000-3000 equiv of MMBL in 1 min or 10,000 equiv in 5 min at room temperature to MMBL-based bioplastics with a narrow range of molecular weights of M(n) = 70-85 kg/mol, regardless of the [MMBL]/[I(t)Bu] ratio employed. The I(t)Bu-catalyzed MMBL polymerization reaches an exceptionally high turnover frequency up to 122 s(-1) and a high initiator efficiency value up to 1600%. Unique chain-termination mechanisms have been revealed, accounting for the production of relative high-molecular-weight linear polymers and the catalytic nature of this NHC-mediated conjugate-addition polymerization. Computational studies have provided mechanistic insights into reactivity and selectivity between two competing pathways for each NHC-monomer zwitterionic adduct, namely enamine formation/dimerization through proton transfer vs polymerization through conjugate addition, and mapped out extensive energy profiles for chain initiation, propagation, and termination steps, thereby satisfactorily explaining the experimental observations.

π-Face donation from the aromatic N-substituent of N-heterocyclic carbene ligands to metal and its role in catalysis.

In this work, we calculate the redox potential in a series of Ir and Ru complexes bearing a N-heterocyclic carbene (NHC) ligand presenting different Y groups in the para position of the aromatic N-substituent. The calculated redox potentials excellently correlate with the experimental ΔE(1/2) potentials, offering a handle to rationalize the experimental findings. Analysis of the HOMO of the complexes before oxidation suggests that electron-donating Y groups destabilize the metal centered HOMO. Energy decomposition of the metal-NHC interaction indicates that electron-donating Y groups reinforce this interaction in the oxidized complexes. Analysis of the electron density in the reduced and oxidized states of representative complexes indicates a clear donation from the C(ipso) of the N-substituents to an empty d orbital on the metal. In case of the Ru complexes, this mechanism involves the Ru-alkylidene moiety. All of these results suggest that electron-donating Y groups render the aromatic N-substituent able to donate more density to electron-deficient metals through the C(ipso) atom. This conclusion suggests that electron-donating Y groups could stabilize higher oxidation states during catalysis. To test this hypothesis, we investigated the effect of differently donating Y groups in model reactions of Ru-catalyzed olefin metathesis and Pd-catalyzed C-C cross-coupling. Consistent with the experimental results, calculations indicate an easier reaction pathway if the N-substituent of the NHC ligand presents an electron-donating Y group.

How does the addition of steric hindrance to a typical N-heterocyclic carbene ligand affect catalytic activity in olefin metathesis?

Density functional theory (DFT) calculations were used to predict and rationalize the effect of the modification of the structure of the prototype 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) N-heterocyclic carbene (NHC) ligand. The modification consists in the substitution of the methyl groups of ortho isopropyl substituent with phenyl groups, and here we plan to describe how such significant changes affect the metal environment and therefore the related catalytic behaviour. Bearing in mind that there is a significant structural difference between both ligands in different olefin metathesis reactions, here by means of DFT we characterize where the NHC ligand plays a more active role and where it is a simple spectator, or at least its modification does not significantly change its catalytic role/performance.

Multicomponent Synthesis of Unsymmetrical Unsaturated N‐Heterocyclic Carbene Precursors and Their Related Transition‐Metal Complexes

A low-cost, modular, and easily scalable multicomponent procedure affording access in good yields and excellent selectivity (up to 93%) to a wide range of (a)chiral unsymmetrical 1-aryl-3-cycloalkyl-imidazolium salts is disclosed. Electronic and steric properties of the corresponding unsymmetrical unsaturated N-heterocyclic carbene (U2-NHC) ligands were evaluated and evidenced strong electron donor ability, high steric discrimination, and modular steric demand.

Exploring Electronic and Steric Effects on the Insertion and Polymerization Reactivity of Phosphinesulfonato PdII Catalysts

Thirteen different symmetric and asymmetric phosphinesulfonato palladium complexes ([{((X)1-Cl)-μ-M}n], M=Na, Li, 1=(X) (P^O)PdMe) were prepared (see Figure 1). The solid-state structures of the corresponding pyridine or lutidine complexes were determined for ((MeO)2)1-py, ((iPrO)2)1-lut, ((MeO,Me2))1-lut, ((MeO)3)1-lut, (CF3) 1-lut, and (Ph)1-lut. The reactivities of the catalysts (X) 1, obtained after chloride abstraction with AgBF4 , toward methyl acrylate (MA) were quantified through determination of the rate constants for the first and the consecutive MA insertion and the analysis of β-H and other decomposition products through NMR spectroscopy. Differences in the homo- and copolymerization of ethylene and MA regarding catalyst activity and stability over time, polymer molecular weight, and polar co-monomer incorporation were investigated. DFT calculations were performed on the main insertion steps for both monomers to rationalize the effect of the ligand substitution patterns on the polymerization behaviors of the complexes. Full analysis of the data revealed that: 1) electron-deficient catalysts polymerize with higher activity, but fast deactivation is also observed; 2) the double ortho-substituted catalysts ((MeO)2)1 and ((MeO)3)1 allow very high degrees of MA incorporation at low MA concentrations in the copolymerization; and 3) steric shielding leads to a pronounced increase in polymer molecular weight in the copolymerization. The catalyst properties induced by a given P-aryl (alkyl) moiety were combined effectively in catalysts with two different non-chelating aryl moieties, such as (cHexO/(MeO)2)1, which led to copolymers with significantly increased molecular weights compared to the prototypical (MeO)1.

Proton-Transfer Polymerization by N-Heterocyclic Carbenes: Monomer and Catalyst Scopes and Mechanism for Converting Dimethacrylates into Unsaturated Polyesters

This contribution presents a full account of experimental and theoretical/computational investigations into the N-heterocyclic carbene (NHC)-catalyzed proton-transfer polymerization (HTP) that converts common dimethacrylates (DMAs) containing no protic groups into unsaturated polyesters. This new HTP proceeds through the step-growth propagation cycles via enamine intermediates, consisting of the proposed conjugate addition-proton transfer-NHC release fundamental steps. This study examines the monomer and catalyst scopes as well as the fundamental steps involved in the overall HTP mechanism. DMAs having six different types of linkages connecting the two methacrylates have been polymerized into the corresponding unsaturated polyesters. The most intriguing unsaturated polyester of the series is that based on the biomass-derived furfuryl dimethacrylate, which showed a unique self-curing ability. Four MeO- and Cl-substituted TPT (1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene) derivatives as methanol insertion products, (Rx)TPT(MeO/H) (R = MeO, Cl; x = 2, 3), and two free carbenes (catalysts), (OMe2)TPT and (OMe3)TPT, have been synthesized, while (OMe2)TPT(MeO/H) and (OMe2)TPT have also been structurally characterized. The structure/reactivity relationship study revealed that (OMe2)TPT, being both a strong nucleophile and a good leaving group, exhibits the highest HTP activity and also produced the polyester with the highest Mn, while the Cl-substituted TPT derivatives are least active and efficient. Computational studies have provided mechanistic insights into the tail-to-tail dimerization coupling step as a suitable model for the propagation cycle of the HTP. The extensive energy profile was mapped out, and the experimentally observed unicity of the TPT-based catalysts was satisfactorily explained with the thermodynamic formation of key spirocyclic species.