Steric Bulkiness Research Articles

N-Alkylation of Dopamine and Its Impact on Surface Coating Properties.

Surface coating with dopamine (DA) has received significant attention over the past decade due to its compatibility with other surface coating techniques and versatility, making it applicable to solid surfaces regardless of substrate and shape. Much effort has been made to elucidate the origin of its surface coating capability, and as a result, many important factors affecting the coating properties have been determined. For example, it has been reported that the length of the carbon chain between catechol and amino groups, the attachment of specific functional groups to the catechol ring and amino group, and the replacement of the amino group with another functional group can affect the surface coating properties of DA. Despite these various attempts, there are still many factors that remain unknown. In this study, we investigate the effect of N-alkylation on DA coating. N-Ethyl-DA, N-propyl-DA, and N-isopropyl-DA are newly synthesized through simple organic reactions, and the coating efficiency of DA derivatives is compared with nucleophilicity and steric bulkiness. As a result, the coating efficiency of N-ethyl-DA and N-propyl-DA is lower than for pristine DA and N-methyl-DA, but it is possible to coat solid surfaces with alkyl-functionalized DA. In contrast, the coating with sterically bulky N-isopropyl-DA is almost unsuccessful.

Controlling Reactivity through Spin Manipulation: Steric Bulkiness of Peroxocobalt(III) Complexes.

The intrinsic relationship between spin states and reactivity in peroxocobalt(III) complexes was investigated, specifically focusing on the influence of steric modulation on supporting ligands. Together with the previously reported [CoIII(TBDAP)(O2)]+ (2Tb), which exhibits spin crossover characteristics, two peroxocobalt(III) complexes, [CoIII(MDAP)(O2)]+ (2Me) and [CoIII(ADDAP)(O2)]+ (2Ad), bearing pyridinophane ligands with distinct N-substituents such as methyl and adamantyl groups, were synthesized and characterized. By manipulating the steric bulkiness of the N-substituents, control of spin states in peroxocobalt(III) complexes was demonstrated through various physicochemical analyses. Notably, 2Ad oxidized the nitriles to generate hydroximatocobalt(III) complexes, while 2Me displayed an inability for such oxidation reactions. Furthermore, both 2Ad and 2Tb exhibited similarities in spectroscopic and geometric features, demonstrating spin crossover behavior between S = 0 and S = 1. The steric bulkiness of the adamantyl and tert-butyl group on the axial amines was attributed to inducing a weak ligand field on the cobalt(III) center. Thus, 2Ad and 2Tb are an S = 1 state under the reaction conditions. In contrast, the less bulky methyl group on the amines of 2Me resulted in an S = 0 state. The redox potential of the peroxocobalt(III) complexes was also influenced by the ligand field arising from the steric bulkiness of the N-substituents in the order of 2Me (-0.01 V) < 2Tb (0.29 V) = 2Ad (0.29 V). Theoretical calculations using DFT supported the experimental observations, providing insights into the electronic structure and emphasizing the importance of the spin state of peroxocobalt(III) complexes in nitrile activation.

Dynamic Kinetic Resolution of 2‐Hydroxybiaryl Atropisomers via Lipase‐Catalyzed Enantioselective O‐Acylation

The increasing interest in axially chiral biaryl moieties, which are prevalent in chiral ligands, organocatalysts, and bioactive molecules, has raised the need for developing novel efficient synthetic methods for these types of molecules. In addition to the currently available methods, such as kinetic resolution, desymmetrization and enantio‐ and diastereo‐selective biaryl coupling, we herein report a lipase‐catalyzed dynamic kinetic resolution (DKR) of racemic 2‐hydroxybiaryls through enantioselective O‐acylation. This method features the production of enantiomerically enriched atropisomers (89%–98% ee) in 91%–99% yields from eleven racemates. Notably, the DKR proceeds without any racemization catalyst since in situ‐racemization was achieved by easy rotation about the biaryl axis of the substrates. The enzymatic O‐acylation then furnished conformationally stable biaryl‐containing esters, in which the increased steric bulkiness of the O‐acyl moiety suppresses the rotation, i.e., racemization, under the reaction conditions of 35–50 °C. This experimental study was accompanied by a computational determination of the rotational barrier of substrates and products. The choice of suitable substrates with a significant difference in their rotational barrier compared to that of their products turned out to be the key to an efficient implementation of this method.

A General Protocol toward Oxindoles Bearing C3‐Allylic Quaternary Stereocenter via Domino Reaction: A Concise Synthesis of Heterocycle‐Fused Indoline Alkaloids

Comprehensive SummaryAn efficiently catalytic method toward the synthesis of indolin‐2‐ones featuring an allylic derived C3‐quaternary stereocenter via an intramolecular Heck cyclization/Suzuki coupling of N‐substituted‐N‐(2‐bromophenyl)acrylamides and organoboron reagents was successfully developed by using a 1,3‐bis(2,6‐diisopropylphenyl)acenaphthoimidazol‐2‐ylidene (AnIPr)‐ligated oxazoline palladacycle. It enabled a very broad substrate scope tolerating different functional groups, electronic properties and steric bulkiness. Notably, it revealed a great potential to build diverse heterocycle‐fused indoline alkaloids via the same intermediate 3‐allyl‐1,3‐dimethylindolin‐2‐ one.

Relay catalysis over Pd-catalysts induced by two divergent ligands for cascade bis-alkoxycarbonylation of alkynes

The mono-metal relay catalysis is a good strategy for one-pot multi-step cascade process in which the specific catalysis can be switched upon the ligand exchange to match the requirements for each independent reaction but without mutual interference and quenching problem. Herein, the one-pot cascade bis-alkoxycarbonylation of terminal alkynes was achieved by taking advantages of the mono-metallic (Pd) relay catalysis, wherein the two kinds of divergent di-phosphines of L1 and DTBPMB were involved. In this Pd(OAc)2-L1-DTBPMB system, due to the steric bulkiness of L1 and DTBPMB, the two type of catalysts including Pd(OAc)2-L1 and Pd(OAc)2-DTBPMB co-existed independently and compatibly. Pd(OAc)2-L1 system was only in charge of the first-step carbonylation of alkynes towards the branched α,β-unsaturated esters with gem-positioned double bond. Subsequent, Pd(OAc)2-DTBPMB system took over the carbonylation of the branched α,β-unsaturated esters to afford the target diesters. It was indicated Pd(OAc)2-L1 system was an efficient and stable catalyst which could be recycled upon 15 runs for the first-step carbonylation. Anyway, Pd(OAc)2-DTBPMB system easily underwent deactivation, which degraded the recyclability of the Pd(OAc)2-L1-DTBPMB coupling system for this cascade bis-alkoxycarbonylation.

Activation of H2 using ansa-aminoboranes: solvent effects, dynamics, and spin hyperpolarization.

Spin hyperpolarization generated upon activation of parahydrogen, the spin-0 isomer of H2, by ansa-aminoboranes (AABs) constitutes a rare but interesting example of applied metal-free catalysis in parahydrogen-induced polarization (PHIP). AAB molecular moieties made of light elements would be useful in important areas of NMR, such as chemosensing and the production of hyperpolarized substances, or generally in NMR sensitivity enhancement. At the same time, little is known about the detailed mechanistic aspects of underlying chemical processes. Herein, we present a joint experimental-computational study of the kinetic and thermodynamic aspects of H2 activation by AABs, for the first time providing molecular-level details and results of PHIP experiments with AABs in various solvents. Specifically, a large number of kinetic and thermodynamic parameters are measured experimentally for H2 activation by 2-aminophenylboranes of variable steric bulkiness of the boryl site. A clear correlation between the experimental and DFT-predicted thermochemical parameters is observed. PHIP effects in toluene, dichloromethane, and acetonitrile are characterized and rationalized based on the use of the kinetic and nuclear spin relaxation parameters. Altogether, the obtained results provide valuable information for the further rational design of efficient AAB catalysts for metal-free PHIP based on frustrated Lewis pair (FLP) chemistry.

Catalytic effect of microflow space for supramolecular block co-polymerization of water-soluble porphyrins.

Using microflow space, a catalytic effect was achieved for supramolecular polymerization. With increasing reactivity at the polymer end, the selective connection of active monomers formed new block domains, avoiding fast homo-assembly. Binding of less-reactive monomers at the polymer end overcame steric bulkiness, affording a stable supramolecular diblock copolymer (SdiBCP).

Ferrocenyl-substituted nitronyl nitroxide in the design of one-dimensional magnets.

By the reaction of M(hfac)2 (M = Mn(II), Co(II), Cu(II), and Zn(II); hfac is the hexafluoroacetylacetonate anion) and ferrocenyl-substituted nitronyl nitroxide (L), we succeeded in the synthesis of stable heterospin complexes: mononuclear [Zn(hfac)2L], trinuclear {[Cu(hfac)2]3L2} and chain polymer [Mn(hfac)2L]n and [Co(hfac)2L]n. The specific steric bulkiness of the ferrocenyl substituent leads to the formation of trans-type coordination polyhedra in the [Mn(hfac)2L]n and [Co(hfac)2L]n chains. The introduction of the ferrocene substituent leads to an effective weakening of intermolecular or interchain magnetic exchange coupling. Ferrimagnetic ordering was observed for one-dimensional complexes [M(hfac)2L]n (M = Mn(II), Co(II)). [Co(hfac)2L]n exhibits features of single-chain magnet behaviour: slow relaxation of magnetization below 13 K is associated with a high coercive field (54 kOe at 2 K).

BODIPY directed one-dimensional self-assembly of gold nanorods.

The assembly of anisotropic nanomaterials into ordered structures is challenging. Nevertheless, such self-assembled systems are known to have novel physicochemical properties and the presence of a chromophore within the nanoparticle ensemble can enhance the optical properties through plasmon-molecule electronic coupling. Here, we report the end-to-end assembly of gold nanorods into micrometer-long chains using a linear diamino BODIPY derivative. The preferential binding affinity of the amino group and the steric bulkiness of BODIPY directed the longitudinal assembly of gold nanorods. As a result of the linear assembly, the BODIPY chromophores positioned themselves in the plasmonic hotspots, which resulted in efficient plasmon-molecule coupling, thereby imparting photothermal properties to the assembled nanorods. This work thus demonstrates a new approach for the linear assembly of gold nanorods resulting in a plasmon-molecule coupled system, and the synergy between self-assembly and electronic coupling resulted in an efficient system having potential biomedical applications.

A General Protocol toward Synthesis of 3-Methylindoles Using Acenaphthoimidazolyidene-Ligated Oxazoline Palladacycle.

An efficient catalytic strategy toward the synthesis of N-substituted 3-methylindoles from inactive o-dihaloarenes and N-allylamines was developed by using a 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene (AnIPr)-ligated oxazoline palladacycle. It enabled a very broad substrate scope tolerating different functional groups, electronic properties, and steric bulkiness and afforded desired products in good to excellent yields. Importantly, it showed great potential to synthesize several bioactive compounds and key intermediates of natural products in high yields.

Steric effect on the photoreaction of chromium(III) porphyrin complexes with imidazole ligands

The steric effect in the photoreaction and ligand substitution reaction of axially coordinated imidazole ligands in chromium(III) porphyrin complexes was investigated in toluene. Imidazole ligands that have various alkyl substituents at the carbon atom [Formula: see text] to the coordinating nitrogen atom were used. The quantum yield of the photodissociation reaction of the axial imidazole ligand shows a remarkable steric effect. Reflecting the steric bulkiness, the magnitude of the quantum yield is isopropyl &gt; ethyl &gt; methyl &gt; (H). The steric effect also appears in the thermal ligand substitution reactions. The mechanism of the steric effect on reactivity will be discussed in terms of the steric hindrance between the porphyrin ligand and the alkyl substituents of imidazole.

Remote Steric and Electronic Effects of N-Heterocyclic Carbene Ligands on Alkene Reactivity and Regioselectivity toward Hydrocupration Reactions: The Role of Expanded-Ring N-Heterocyclic Carbenes.

The remote groups in N-heterocyclic carbene (NHC) ligands have a significant influence on metal-catalyzed reactions. We examine how remote bulkiness, electronic groups, and expanded-ring NHCs (ER-NHCs) influence alkene reactivity and regioselectivity toward hydrocupration using density functional theory calculations. The impact of remote steric bulkiness on the Cu-H insertion rate is analyzed, revealing a strong correlation between the steric substituent constant and rate ratio, where a bulky group increases the rate due to reduced steric effects in the transition state (TS). The steric properties of the examined catalysts (with a remote group R2 = CPh3, CHPh2, CH2Ph, CH3, and H) and their corresponding TSs are found to be modulated greatly by the remote steric substitution group and the ring size of the NHC ligand. Enhanced bulkiness enhances the nucleophilic Cu-H moiety. The remote electronic groups have a smaller impact on insertion barrier compared to that of steric hindrance. Furthermore, ER-NHC exploration indicates that NHCs with over five-membered rings have a significantly negative influence on the reaction rate. Finally, with a highly bulky group (R2 = CPh3), anti-Markovnikov insertion preference is attributed to high interaction energy and improved steric properties. Overall, our findings here provide valuable insights for the development of a more effective catalyst in metal-catalyzed reactions.

Synthesis of Zwitterionic CsPbBr3 Nanocrystals with Controlled Anisotropy using Surface-Selective Ligand Pairs.

Mechanistic studies of the morphology of lead halide perovskite nanocrystals (LHP-NCs) are hampered by a lack of generalizable suitable synthetic strategies and ligand systems. Here, the synthesis of zwitterionic CsPbBr3 NCs is presented with controlled anisotropy using a proposed "surface-selective ligand pairs" strategy. Such a strategy provides a platform to systematically study the binding affinity of capping ligand pairs and the resulting LHP morphologies. By using zwitterionic ligands (ZwL) with varying structures, majority ZwL-capped LHP NCs with controlled morphology are obtained, including anisotropic nanoplatelets and nanorods, for the first time. Combining experiments with density functional theory calculations, factors that govern the ligand binding on the different surface facets of LHP-NCs are revealed, including the steric bulkiness of the ligand, the number of binding sites, and the charge distance between binding moieties. This study provides guidance for the further exploration of anisotropic LHP-NCs.

Dehydrogenative Annulation of Silylated 1H-Indoles with Alkynes via Silyl Migration.

We investigated the dehydrogenative annulation of silylated 1H-indole derivatives with alkynes to synthesize a silole-fused indole. The addition of the in situ generated silylium ion to alkynes was followed by the sila-Friedel-Crafts reaction via silyl migration, realizing regioselective dehydrogenative annulation controlled by the steric bulkiness of a base. The optical properties of the obtained siloloindoles indicated fluorescence of which the intensity depends on the location of the fused silole.

A Metal‐Organic Framework Incorporating Eight Different Size Rare‐Earth Metal Elements: Toward Multifunctionality À La Carte

AbstractMulti‐metallic multivariate (MTV) rare earth (RE) metal−organic frameworks (MOFs) are of interest for the development of multifunctional materials, however examples with more than three RE cations are rare and obstructed by compositional segregation during synthesis. Herein, this work demonstrates the synthesis of a multi‐metallic MTV RE MOF incorporating two, four, six, or eight different RE ions with different sizes and in nearly equimolar amounts and no compositional segregation. The MOFs are formed by a combination of RE cations (La, Ce, Eu, Gd, Tb, Dy, Y, and Yb) and a 1,7‐di(4‐carboxyphenyl)‐1,7‐dicarba‐closo‐dodecaborane (mCB‐L) linker. The steric bulkiness and acidity of mCB‐L is crucial for the incorporation of different size RE ions into the MOF structure. Demonstration of the incorporation of all RE cations is performed via compositional and structural characterization. The more complex MTV MOF, including all eight RE ions (mCB‐8RE), are also characterized using optical, thermal, and magnetic techniques. Element‐selective X‐ray absorption spectroscopy and X‐ray Magnetic Circular Dichroism measurements allow us to characterize spectroscopically each of the eight RE ions and determine their magnetic moments. This work paves the way for the investigation of MTV MOFs with the possibility to combine RE ions à la carte for diverse applications.

3D-QSAR assisted design, synthesis and pharmacological evaluation of novel substituted benzamides as procaspase-3 activators and anticancer agents

Novel substituted benzamides were designed using 3D-QSAR analysis, synthesized and screened using in vitro procaspase-3 kinase activation and MTT assays. For the rational design of the novel compounds, we performed 3D-QSAR study and generated statistically validated CoMFA (q2 = 0.736, r2cv = 0.729) and CoMSIA (q2 = 0.751, r2cv = 0.716) models. Generated contour maps using CoMFA and CoMSIA analysis suggested the requirement of steric bulkiness (aromatic ring) along with small electron-withdrawing groups (-Cl, -diCl, -F) for the design of novel compounds. CoMSIA, HBA, and HBD contour maps also suggested the requirement of functional groups (amide and hydrazide) for hydrogen bonding interactions. A total of 40 novel substituted benzamides were designed, and generated 3D-QSAR models were used for prediction of their activity prior to synthesis. ADMET prediction study was also carried out for the selection of better compounds with no toxicity and better physicochemical parameters for the synthesis. Finally, we synthesised and characterised a total of 10 substituted benzamide derivatives. Synthesized compounds were screened for their anticancer activities, in which compound 14c showed IC50 value of 3.13 µM and 6.01 µM against HT-29 and MDA-MB-231, respectively, compound 7c exhibited excellent anticancer activity with an IC50 value of 3.76 µM and 5/63 µM against HT-29 and MDA-MB-231, respectively. Furthermore, a procaspase-3 kinase activation assay was performed, in which both these compounds (7c, EC50 = 3.12 µM, 12b, EC50 = 2.93 µM and 14C EC50 =2.93) demonstrated activation of enzymatic potency and revealed that the anticancer activity of these compounds may be due to activation of the procaspase-3 enzyme. In vitro screening assays confirmed and validated the computational design of novel benzamide derivatives. Compounds 14c and 7c are our lead compounds for further development as anticancer agents based on the induction of apoptosis through procaspase-3 activation.

Expanding the Role of Dimeric Species: On-Cycle Involvement, Improved Stability, and Control of Stereo-Specificity. A Case Study of Atom-Economic Catalytic Hydrothiolation

A common assumption that dimeric metal complexes in many catalytic systems represent a resting state and are not directly involved in catalytic processes was revised in a combined experimental and theoretical study. On-cycle participation of dimeric metal complexes, rather than typically assumed off-cycle involvement, was revealed, and advantageous performance in terms of improved selectivity was observed. The conceptual rationalization for the participation of dimeric species in the catalytic cycle was developed. The Pd-catalyzed hydrothiolation process (where strong Pd–S binding is well established and a persistent opinion for the inactive/poisoning role of dimeric species is presumed) was evaluated as a challenging system to test the concept. Activation of an (NHC)Pd(Cl)(acac) precatalyst (NHC─N-heterocyclic carbene and acac─acetylacetonate) under the reaction conditions produced monomeric (NHC)Pd(SPh)2 or dimeric (NHC)2Pd2(SPh)4 species depending on the steric bulkiness of the NHC ligand. Dimeric complexes possessed higher selectivity and tolerated disulfide impurities in contrast to monomeric complexes. Quantum chemical modeling suggested that dimeric catalysis proceeds through the opening of only one (μ-SPh)–Pd bridging bond with retention of the dimeric structure. The second bridging bond is maintained, which prevents the monomerization of the complex. Catalytically active species were detected in a hydrothiolation reaction by high-resolution mass spectrometry and NMR spectroscopy. Proving the opportunity for productive homogeneous catalysis via strongly coordinated dimeric metal species opens new opportunities for catalyst design in the increased nuclearity dimension.

Efficient and stable tripodal Phosphine-Controlled Pd-Catalyst for anti-Markovnikov hydroaminocarbonylation of alkenes with aromatic amines

The tripodal phosphine [L1, 1,1,1-tris(diphenylphosphino-methyl)ethane] was applied to control the activity, regioselectivity, and stability of the involved Pd-catalyst in anti-Markovnikov hydroaminocarbonylation of alkenes with aromatic amines for the synthesis of linear-amides. Due to the unique characters of L1 in terms of the steric bulkiness, the switching-coordination mode from tripodal phosphine to bidental one, and the robustness against moisture and oxygen, L1 conferred to Pd-catalyst with the high activity, good regioselectivity, and excellent stability for this carbonylation, leading to 44 ∼ 87 % yields of the target amides with L/B of greater than 80/20. The in situ high-pressure FT-IR analysis and the DFT calculations verified that L1 not only promoted the formation and stability of PdII-H active species (ν ca. 1932 cm−1) but also facilitated the anti-Markovnikov’s addition of alkenes with PdII-H bond due to the favorable energy level of linear intermediate (B-1). In addition, since L1 can coordinate to Pd(II)-center as a bidental chelator as fulfill catalysis and then coordinate to Pd(0)-center as an tripodal pincer, Pd-catalyst was protected timely by L1 against metal-deposition (Pd0-black precipitation) to guarantee its stability for recycling uses for 5 runs without activity loss.

Room Temperature Fluoranthene Synthesis through Cationic Rh(I)/H8-BINAP-Catalyzed [2 + 2 + 2] Cycloaddition: Unexpected Acceleration due to Noncovalent Interactions

The fluoranthene skeleton is a structure often found in natural products and fluorescent materials, and thus developing an operationally simple method for diversity-oriented fluoranthene synthesis is an important research topic in organic synthesis. However, existing synthetic methods require harsh reaction conditions or limited substrate applicability or both. Here, we report the room temperature synthesis of substituted fluoranthenes and azafluoranthenes through the cationic Rh(I)/H8-BINAP complex-catalyzed [2 + 2 + 2] cycloaddition using 1,8-dialkynylnaphthalenes. DFT calculations reveal that the H8-BINAP ligand stabilizes the intermediates, allowing the room temperature reaction. Among the substrates examined, 1,8-bis(phenylethynyl)naphthalene and diarylacetylenes show high reactivity, contrary to the reactivity predicted by their steric bulkiness. Theoretical and experimental mechanistic studies have demonstrated that the noncovalent interactions of the phenyl groups on both the substrates and the ligand accelerate the present sterically demanding reactions by stabilizing the transition states rather than inducing steric repulsions.

Formation of lignin alkyl-O-alkyl ether structures via 1,6-addition of aliphatic alcohols to β-O-4-aryl ether quinone methides.

Quinone methides (QMs) are formed as the intermediates during lignin biosynthesis and chemical transformation; the chemical structure of the resulting lignin can then be significantly modified via the corresponding aromatization. Herein, the structure-reactivity relationship of β-O-4-aryl ether QMs (GS-QM, GG-QM and GH-QM, which are 3-monomethoxylated QMs carrying syringyl, guaiacyl and p-hydroxyphenyl β-etherified aromatic rings, respectively) was investigated to clarify the formation of alkyl-O-alkyl ether structures in lignin. The structural features of these QMs were characterized by NMR spectroscopy, and their alcohol-addition experiment was well performed at 25 °C to generate alkyl-O-alkyl/β-O-4 products. The preferential conformation of GS-QM contains a stable directional intramolecular H-bond between γ-OH hydrogen and β-phenoxy oxygen, which makes the β-phenoxy group locate on the same side with γ-OH. In contrast, the β-phenoxy groups in both GG- and GH-QM conformations are distant from the γ-OH; thus, the stable intermolecular H-bond is associated with the γ-OH hydrogen. Based on UV spectroscopy, the addition of methanol and ethanol occurs in QMs with a half-life of 1.7-2.1 and 12.8-19.3 minutes, respectively. With the same nucleophile, these QMs react faster in the order GH-QM > GG-QM > GS-QM. However, the reaction rate appears to be more influenced by the type of nucleophile than by the β-etherified aromatic ring. Furthermore, the NMR spectra of products indicate that the steric bulkiness of both the β-etherified aromatic ring and nucleophile contributes to the erythro-preferential formation of adducts from QMs. Moreover, the effect is more pronounced for the β-etherified aromatic ring of QMs than the nucleophiles. The structure-reactivity relationship study demonstrates that the competition effect between H-bonds and steric hindrance determines the approaching direction and the accessibility of nucleophiles to planar QMs, resulting in stereo-differentiating formation of adducts. This model experiment may provide implications for the biosynthetic route and structural information of the alkyl-O-alkyl ether structure in lignin. Its results can also be further utilized to design innovative extraction methods of organosolv lignins for subsequent selective depolymerization or material preparation.