Stereoelectronic Properties Research Articles

Non-planar Boron Lewis Acids Taking the Next Step: Development of Tunable Lewis Acids, Lewis Superacids and Bifunctional Catalysts

Although boron Lewis acids commonly adopt a trigonal planar geometry, a number of compounds in which the trivalent boron atom is located in a pyramidal environment have been described. This review will highlight the recent developments of the chemistry and applications of non-planar boron Lewis acids, including a series of non-planar triarylboranes derived from the triptycene core. A thorough analysis of the properties and of the influence of the pyramidalization of boron Lewis acids on their stereoelectronic properties and reactivities is presented based on recent theoretical and experimental studies.1 Non-planar Trialkylboranes2 Non-planar Alkyl and Aryl-Boronates3 Non-planar Triarylboranes and Alkenylboranes3.1 Previous Investigations on Bora Barrelenes and Triptycenes3.2 Recent Work on Boratriptycenes from Our Research Group4 Applications of Non-planar Boranes4.1 Non-planar Alkyl Boranes and Boronates4.2 Non-planar Triarylboranes (Boratriptycenes)5 Other Non-planar Group 13 Lewis Acids6 Further Work and Perspectives

Stereoelectronic Profiling of Acyclic Diamino Carbenes (ADCs).

A library of 14 heterobis(carbene) complexes of the general formula [Au(iPr2-bimy)(ADC)]BF4 (7-20) containing the N-heterocyclic carbene reporter iPr2-bimy and various protic acyclic diaminocarbenes (ADCs) have been prepared to estimate their stereoelectronic properties by 13C NMR spectroscopy and percentage buried volume (%Vbur) determinations. Their preparation was achieved by nucleophilic attack of five secondary amines on six mixed NHC/isocyanide complexes of the type [Au(iPr2-bimy)(CN-R)]BF4 (1-6). Analyses of the iPr2-bimy carbene signals reveal that protic ADCs are stronger donors than classical and expanded-ring NHCs. On the other hand, they are weaker donating compared to NHCs with reduced-heteroatom stabilization. Moreover, stereoelectronic fine-tuning of these ligands is possible by a diverse range of substituents originating from the employed isocyanides and amines.

Controlled Generation of 9‐Boratriptycene by Lewis Adduct Dissociation: Accessing a Non‐Planar Triarylborane

AbstractA highly bent triarylborane, 9‐boratriptycene, was generated in solution by selective protodeboronation of the corresponding tetra‐aryl boron ate complex with the strong Brønsted acid HNTf2. The iptycene core confers enhanced Lewis acidity to 9‐boratriptycene, making it unique in terms of structure and reactivity. We studied the stereoelectronic properties of 9‐boratriptycene by quantifying its association with small N‐ and O‐centered Lewis bases, as well as with sterically hindered phosphines. The resultant Lewis adducts exhibited unique structural, spectroscopic, and photophysical properties. Beyond the high pyramidalization of the 9‐boratriptycene scaffold and its low reorganization energy upon Lewis base coordination, quantum chemical calculations revealed that the absence of π donation from the triptycene aryl rings to the boron vacant pz orbital is one of the main reasons for its high Lewis acidity.

Controlled Generation of 9-Boratriptycene by Lewis Adduct Dissociation: Accessing a Non-Planar Triarylborane.

A highly bent triarylborane, 9-boratriptycene, was generated in solution by selective protodeboronation of the corresponding tetra-aryl boron ate complex with the strong Brønsted acid HNTf2 . The iptycene core confers enhanced Lewis acidity to 9-boratriptycene, making it unique in terms of structure and reactivity. We studied the stereoelectronic properties of 9-boratriptycene by quantifying its association with small N- and O-centered Lewis bases, as well as with sterically hindered phosphines. The resultant Lewis adducts exhibited unique structural, spectroscopic, and photophysical properties. Beyond the high pyramidalization of the 9-boratriptycene scaffold and its low reorganization energy upon Lewis base coordination, quantum chemical calculations revealed that the absence of π donation from the triptycene aryl rings to the boron vacant pz orbital is one of the main reasons for its high Lewis acidity.

Quantifying the Electronic and Steric Properties of 1,3-Imidazole-Based Mesoionic Carbenes (iMICs)

1,3-Imidazole-based mesoionic carbenes (iMICs) are a very promising class of carbon-donor ligands in synthesis and catalysis. However, a systematic study of the quantification of stereoelectronic properties of iMICs is lacking. This is most likely due to the absence of rational synthetic routes to suitable iMIC compounds. Herein, we report the synthesis of the appropriate phosphinidene (iMICAr)PPh (iMICAr = :CCH(NDipp)2CAr; Ar = Ph (5a), DMP (5b); DMP = 4-Me2NC6H4; Dipp = 2,6-iPr2C6H3), selenium (iMICAr)Se (Ar = Ph (6a), DMP (6b)), and nickel carbonyl compounds (iMICAr)Ni(CO)3 (Ar = Ph (7a), DMP (7b)). The π-accepting property of iMICAr (Ar = Ph (2a), DMP (2b)) has been evaluated by 31P and 77Se NMR spectroscopic analyses of 5 and 6, respectively. The overall donor property of 2 has been assessed by determining the Tolman electronic parameter (TEP) of 7. Studies suggest that iMICAr (2) are stronger σ donors and weaker π acceptors compared to classical N-heterocyclic carbenes (NHCs). The steric profile of iMICAr (2) has been obtained by calculating the percentage buried volume (%Vbur) for (iMICAr)CuX (Ar = Ph, X = I (8a); Ar = DMP, X = Br (8b)).

Sulfonated Phosphine Ligands in the Ruthenium Catalyzed Biphasic Hydrogenation of Unsaturated Hydrocarbons

The hydrogenation of monocyclic aromatic hydrocarbons by ruthenium catalysts has been investigated in the presence of sulfonated monophosphine ligands with different stereoelectronic properties under biphasic conditions. The effects of (i) the number of sulfonate groups, (ii) the steric demand of the ligand and (iii) the σ-donor ability of the phosphorus atom have been investigated in the catalytic reactions. The TEM analysis of the catalytically active systems revealed that in situ formed soluble ruthenium nanoparticles (RuNPs) are responsible for the catalytic turnover. The Ru/sulfonated phosphine system with the properly tuned ligand exhibited high activity (8800 h−1) and selectivity in the hydrogenation of benzene to cyclohexane. Furthermore, the aqueous phase containing RuNPs could be recycled four times without a considerable loss of activity.Graphic

Stereoelectronic Properties of 1,2,4-Triazole-Derived N-heterocyclic Carbenes - A Theoretical Study

Stereoelectronic Properties of 1,2,4-Triazole-Derived N-heterocyclic Carbenes - A Theoretical Study

Chiral Ferrocenyl-Bismuthines containing N/O donor pendant arm: Syntheses and molecular structures

Some new chiral substituted ferrocenyl bismuthines CpFe(2-[Me2NCH(R)]C5H3)BiPhCl where R = H (1) or Me (2) and CpFe(2-[Me2NCH(R)]C5H3)BiPh2 where R = H (3) or Me (4) (Cp = cyclopentadienyl) containing a Rac-2-[(Me2NCH(R)] pendant arm on the ferrocenyl ring were synthesized. Nucleophilic substitution reaction of mono ammonium salt Rac-{[CpFe{2-(Me3N+CH2)C5H3}BiPh2][I−] (5) by o-hydroxyacetaphenone, salicyladehyde, N-methylpiperazine and 4′- aminobenzo-15-crown-5 in acetonitrile gave new ferrocenyl bismuthines [CpFe{2-(RCH2)C5H3}BiPh2] where R = OC6H4-2-C(O)Me (6), OC6H4-2-C(O)H (7), N(CH2CH2)2NMe (8) and NHC6H4-3,4-O-cyclo{(CH2)2-O}4 (9) respectively with N or O containing pendant arm. All the new compounds were characterized by 1H NMR, 13C NMR, FAB+, and High-Resolution Mass Spectrometry. All the compounds presented in this work present planar chirality because of 1,2-disubstituted ferrocene. In the solid-state, the presence of the ferrocenyl group influences the stereoelectronic properties in the molecule and Bi···N or Bi···O hypervalent interaction could not be observed in compounds with BiPh2 fragment while this interaction was observed in compounds with BiPhCl fragment. For compounds (1)-(4), (6)-(8) and (10), NMR spectra obtained at different temperatures show the association and/or dissociation of hypervalent N···Bi coordination in these compounds. Molecular structures of compounds (1), (2) and (10) show distorted pseudo-trigonal bipyramidal geometry (see-saw structure) at bismuth center with intramolecular Bi···N hypervalent interaction while (6) and (7) present a distorted pseudo-trigonal pyramidal geometry and do not show hypervalent Bi···O interaction. Crystal structures of these compounds show that CFc-Bi bond length is shorter than CPh-Bi bond length due to lower group electronegativity of ferrocenyl vs phenyl and bidentate nature of FcN ligand in ferrocenyl bismuthines.

Polyvinylpyridine-Supported Palladium Nanoparticles: A Valuable Catalyst for the Synthesis of Alkynyl Ketones via Acyl Sonogashira Reactions

Palladium nanoparticles (NP) immobilized on metal scavengers (Smopex®-234, Smopex®-111, PVPy, 1% w/w) have been tested in the acyl Sonogashira reactions between terminal acetylenes and acid chlorides. Pd/PVPy resulted especially effective in the synthesis of alkynyl ketones with different stereoelectronic properties, even working with a very low amount of palladium (0.2 mol%). Preliminary tests seem to indicate that Pd/PVPy could act as a reservoir of very active palladium NP which are partially released during the reaction and then recaptured from the resin at the end of the process, thus ensuring the possibility of reuse of the catalyst.

Thiol Michael-Type Reactions of Optically Active Mercapto-Acids in Aqueous Medium

Defined chemical reactions in a physiological environment are a prerequisite for the in situ synthesis of implant materials potentially serving as matrix for drug delivery systems, tissue fillers or surgical glues. ‘Click’ reactions like thiol Michael-type reactions have been successfully employed as bioorthogonal reaction. However, due to the individual stereo-electronic and physical properties of specific substrates, an exact understanding their chemical reactivity is required if they are to be used for in-situ biomaterial synthesis. The chiral (S)-2-mercapto-carboxylic acid analogues of L-phenylalanine (SH-Phe) and L-leucine (SH-Leu) which are subunits of certain collagenase sensitive synthetic peptides, were explored for their potential for in-situ biomaterial formation via the thiol Michael-type reaction. In model reactions were investigated the kinetics, the specificity and influence of stereochemistry of this reaction. We could show that only reactions involving SH-Leu yielded the expected thiol-Michael product. The inability of SH-Phe to react was attributed to the steric hindrance of the bulky phenyl group. In aqueous media, successful reaction using SH-Leu is thought to proceed via the sodium salt formed in-situ by the addition of NaOH solution, which was intented to aid the solubility of the mercapto-acid in water. Fast reaction rates and complete acrylate/maleimide conversion were only realized at pH 7.2 or higher suggesting the possible use of SH-Leu under physiological conditions for thiol Michael-type reactions. This method of in-situ formed alkali salts could be used as a fast approach to screen mercapto-acids for thio Michael-type reactions without the synthesis of their corresponding esters.

Structure and redox stability of [Au(III)(X^N^X)PR3] complexes (X = C or N) in aqueous solution: The role of phosphine auxiliary ligand

The choice of the auxiliary ligand in Au(III) complexes is of paramount importance in tuning their reactivity and biological activity. Tertiary phosphines are one of the most used auxiliary ligands in gold compounds, due to their stereo-electronic properties that confer stability and lipophilicity to these metallodrugs. The redox stability of [Au(III)(C^N^C)PR3]+ (A) (C^N^C = 2,6-diphenylpyridine) and [Au(III)(N^N^N)PR3]3+ (N^N^N = 2,2′:6′,2″-terpyridine) (B) complexes (where R is the phosphine substituent groups with different steric and electronic properties) was herein investigated for a set of 41 phosphines, using the predicted standard reduction potential (εo) for Au(III)/Au(I) electrochemical system as reference. For the complexes A, εo spread over 829 mV and all values were negative, whereas for the complexes B εo were positive and covered a narrower range of 507 mV. The phosphines with high buried volume (%Vbur ≥ 32%) decrease the complex stability despite being strong σ-donors. Both steric and electronic properties were used as molecular descriptors to build quantitative structure-property relationships (QSPR), which showed that the %Vbur plays the major role on the redox stability of the studied Au(III) complexes. For complexes B where the phosphine affects both Au(III) and Au(I) forms, the steric impact is more pronounced on the Au(I) reduced species. The electron-donating ability of phosphines is also important and plays a greater role on the redox stability of complexes B than complexes A. These outcomes are certainly useful to predict the redox stability of Au(III) complexes which, in turn, should affect their chemical reactivity against biological targets.

Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids.

The unique stereoelectronic properties of sp2-iminosugars enable their participation in glycosylation reactions, thereby behaving as true carbohydrate chemical mimics. Among sp2-iminosugar conjugates, the sp2-iminosugar glycolipids (sp2-IGLs) have shown a variety of interesting pharmacological properties ranging from glycosidase inhibition to antiproliferative, antiparasitic, and anti-inflammatory activities. Developing strategies compatible with molecular diversity-oriented strategies for structure–activity relationship studies was therefore highly wanted. Here we show that a reaction sequence consisting in stereoselective C-allylation followed by thiol-ene “click” coupling provides a very convenient access to α-C-glycoside sp2-IGLs. Both the glycone moiety and the aglycone tail can be modified by using sp2-iminosugar precursors with different configurational profiles (d-gluco or d-galacto in this work) and varied thiols, as well as by oxidation of the sulfide adducts (to the corresponding sulfones in this work). A series of derivatives was prepared in this manner and their glycosidase inhibitory, antiproliferative and antileishmanial activities were evaluated in different settings. The results confirm that the inhibition of glycosidases, particularly α-glucosidase, and the antitumor/leishmanicidal activities are unrelated. The data are also consistent with the two later activities arising from the ability of the sp2-IGLs to interfere in the immune system response in a cell line and cell context dependent manner.

Trifluoromethylated Proline Surrogates as Part of "Pro-Pro" Turn-Inducing Templates.

Proline is often found as a turn inducer in peptide or protein domains. Exploitation of its restricted conformational freedom led to the development of the d-Pro-l-Pro (corresponding to (R)-Pro-(S)-Pro) segment as a "templating" unit, frequently used in the design of β-hairpin peptidomimetics, in which conformational stability is, however, inherently linked to the cis-trans isomerization of the prolyl amide bonds. In this context, the stereoelectronic properties of the CF3 group can aid in conformational control. Herein, the impact of α-trifluoromethylated proline analogues is examined for the design of enhanced β-turn inducers. A theoretical conformational study permitted the dipeptide (R)-Pro-(R)-TfmOxa (TfmOxa: 2-trifluoromethyloxazolidine-2-carboxylic acid) to be selected as a template with an increased trans-cis rotational energy barrier. NMR spectroscopic analysis of the Ac-(R)-Pro-(R)-TfmOxa-(S)-Val-OtBu β-turn model, obtained through an original synthetic pathway, validated the prevalence of a major trans-trans conformer and indicated the presence of an internal hydrogen bond. Altogether, it was shown that the (R)-Pro-(R)-TfmOxa template fulfilled all crucial β-turn-inducer criteria.

Evaluating stereoelectronic properties of bulky dialkylterphenyl phosphine ligands

The stereoelectronic properties of a series of sterically hindered phosphines containing a terphenyl substituent, PR2Ar’ (R = alkyl; Ar’ = C6H3-2,6-Ar2), have been evaluated by various methods. Their σ-donating capacity has been assessed on the basis of the carbon monoxide stretching frequencies in benchmark iridium [IrCl(CO)2(PR2Ar’)] and rhodium [Rh(acac)(CO)2(PR2Ar’)] (acac = acetylacetonate) complexes, as well as by measuring 31P–77Se scalar coupling constants (1JSeP) for the corresponding phosphine selenides (Se=PR2Ar’). In turn, the steric profile of terphenyl phosphines has been gauged by calculating Tolman Cone Angle (TCA), ligand shielding (G) and percent buried volume (%VBur) parameters. These calculations have been carried out from both X-ray diffraction and DFT-optimized structures. We have also examined several of the widely used biaryl phosphines for comparative purposes.

Stable Lewis Base Adducts of Tetrahalodiboranes: Synthetic Methods and Structural Diversity.

A series of 22 new bis(phosphine), bis(carbene), and bis(isonitrile) tetrahalodiborane adducts has been synthesized, either by direct adduct formation with highly sensitive B2 X4 precursors (X=Cl, Br, I) or by ligand exchange at stable B2 X4 (SMe2 )2 precursors (X=Cl, Br) with labile dimethylsulfide ligands. The isolated compounds have been fully characterized using NMR spectroscopy, elemental analysis, and, for 20 of these compounds, single-crystal X-ray diffraction, revealing an unexpected variation in the bonding motifs. In addition to the classical B2 X4 L2 diborane(4) bis-adducts, certain more sterically demanding carbene ligands induce a halide displacement which led to the first halide-bridged monocationic diboron species, [B2 X3 L2 ]A (A=BCl4 , Br, I). Furthermore, low-temperature 1:1 reactions of B2 Cl4 with sterically demanding N-heterocyclic carbenes led to the formation of kinetically unstable mono-adducts, one of which was structurally characterized. A comparison of the NMR spectra and structural data of new and literature-known bis-adducts shows several trends pertaining to the nature of the halides and the stereoelectronic properties of the Lewis bases employed.

Understanding Factors that Control the Structural (Dis)Assembly of Sulphur-Bridged Bimetallic Sites

Bimetallic structures of the general type [M2(µ-S)2] are omnipresent in nature, for biological function [M2(µ-S)2] sites interconvert between electronically distinct, but isostructural, forms. Different from structure-function relationships, the current understanding of the mechanism of formation and persistence of [M2(µ-S)2] sites is poorly developed. This work reports on bimetallic model compounds of nickel that interconvert between functional structures [Ni2(µ-S)2]+/2+ and isomeric congeners [2{κ-S–Ni}]2+/+, S = Aryl-S−, in which the nickel ions are geometrically independent. Interconversion of the two sets of structures was studied quantitatively by UV–VIS absorption spectroscopy and cyclic voltammetry. Assembly of the [Ni2(µ-S)2]+ core from [2{κ-S–Ni}]+ is thermodynamically and kinetically highly preferred over the disassembly of [Ni2(µ-S)2]2+ into [2{κ-S–Ni}]2+. Labile Ni-η2/3-bonding to aromatic π-systems of the primary thiophenol ligand is critical for modeling (dis)assembly processes. A phosphine coligand mimics the role of anionic donors present in natural sites that saturate metal coordination. Three parameters have been identified as critical for structure formation and persistence. These are, first, the stereoelectronic properties of the metals ions, second, the steric demand of the coligand, and, third, the properties of the dative bond between nickel and coligand. The energies of transition states connecting functional and precursor forms have been found to depend on these parameters.

General Cyclopropane Assembly by Enantioselective Transfer of a Redox‐Active Carbene to Aliphatic Olefins

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. The redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect allowed the asymmetric cyclopropanation of various olefins, including unfunctionalized aliphatic alkenes, that enables the three-step total synthesis of (-)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons.

General Cyclopropane Assembly by Enantioselective Transfer of a Redox‐Active Carbene to Aliphatic Olefins

AbstractAsymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. The redox‐active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect allowed the asymmetric cyclopropanation of various olefins, including unfunctionalized aliphatic alkenes, that enables the three‐step total synthesis of (−)‐dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single‐carbon chirons.

Transition metal-catalyzed hydrosilylation of polybutadiene – The effect of substituents at silicon on efficiency of silylfunctionalization process

Herein we present the results of our studies on the hydrosilylation of polybutadiene with alkyl, aryl and alkoxysilanes in the presence of platinum and rhodium complexes. In order to select the most efficient catalytic system, which, under optimal conditions, would smoothly promote incorporation of the above-mentioned organosilicon modifiers into polybutadienes of various structures via hydrosilylation, the real-time in-situ FT-IR spectroscopy was used. The silyl-functionalized polymeric products were characterized by NMR analysis and gel permeation chromatography (GPC). It was demonstrated that the stereo-electronic properties of substituents directly bonded to the HSi moiety play a crucial role in formation of desired products, as well as affect the time required for total conversion of organosilicon reagents. Partially modified polymers containing pendant alkoxy groups can be applied as additives to rubber compounds to enhance dispersion of inorganic particles in the polymer matrix, as well as to promote formation of organic-inorganic hybrid materials.

Regression analysis of properties of [Au(IPr)(CHR2)] complexes.

New [Au(IPr)(CHR2)] complexes have been synthesised through protonolysis reactions of [Au(IPr)(OH)] with moderately acidic substrates, CH2R2. An array of spectroscopic (IR and NMR), structural (X-ray), electronic (DFT) and experimental (reactivity) parameters was collected to quantify the variation in stereoelectronic properties of these new and previously reported [Au(IPr)(CHR2)] complexes. Variation of the R substituents on the carbanion ligands (CHR2-) was found to have a crucial impact on parameters characterising the resulting gold complexes. A regression analysis of both experimental and modelled parameters, guided by network analysis techniques, produced linear models that supported trends within the [Au(IPr)(CHR2)] complexes.