Effect of Combined Application of Hydrofluoric and Phosphoric Acids and Active Irrigation with a Microbrush on Shear Bond Strength of Lithium Disilicate Ceramics to Enamel.

Background: This study assessed the effect of combined application of hydrofluoric (HF) acid and phosphoric acid (PA) and active irrigation (AI) with a microbrush on shear bond strength (SBS) of lithium disilicate (LDS) ceramics to enamel. Materials and Methods: This in vitro study was conducted on 40 extracted teeth that received enamel preparation with a #12 cylindrical bur. Forty IPS e.max LT rods (3mm diameter, 6mm height) were fabricated and randomly assigned to four groups (n = 10) for surface treatment with 5% HF (group 1), 5% HF and AI with a microbrush for 20 seconds (group 2), 5% HF and 32% PA (group 3), and 5% HF and 32% PA plus AI with a microbrush for 20 seconds (group 4). Silane and Choice 2 cement were used for bonding rods to enamel. The SBS was measured by a universal testing machine. Data were analyzed by two-way analysis of variance (ANOVA), Bonferroni, and Chi-square tests (alpha = 0.05). Results: Group 4 had the highest SBS, and group 1 had the lowest SBS (P < 0.05). Group 2 had a significantly higher SBS than group 1, and group 4 had a significantly higher SBS than group 3. AI with a microbrush significantly increased the SBS (P < 0.05), but the application of PA caused no significant change in SBS (P > 0.05). The interaction effect of PA and AI on SBS was not significant (P > 0.05). Conclusion: The application of PA in addition to 5% HF acid caused no significant change in the SBS of LDS ceramic to enamel. However, AI with a microbrush significantly increased the SBS.

Combinatorial Ligand Assisted Simultaneous Control of Axial and Central Chirality in Highly Stereoselective C-H Allylation.

The significance of stereoselective C-H bond functionalization thrives on its direct application potential to pharmaceuticals or complex chiral molecule synthesis. Complication arises when there are multiple stereogenic elements such as a center and an axis of chirality to control. Over the years cooperative assistance of multiple chiral ligands has been applied to control only chiral centers. In this work, we harness the essence of cooperative ligand approach to control two different stereogenic elements in the same molecule by atroposelective allylation to synthesize axially chiral biaryls from its racemic precursor. The crucial roles played by chiral phosphoric acid and chiral amino acid ligand in concert helped us to obtain one major stereoisomer out of four distinct possibilities.

Diversity-Oriented Catalytic Asymmetric Dearomatization of Indoles with o-Quinone Diimides.

Herein, the first diversity-oriented catalytic asymmetric dearomatization of indoles with o-quinone diimides (o-QDIs) is reported. The catalytic asymmetric dearomatization (CADA) of indoles is one of the research focuses in terms of the structural and biological importance of dearomatized indole derivatives. Although great achievements have been made in target-oriented CADA reactions, diversity-oriented CADA reactions are regarded as more challenging and remain elusive due to the lack of synthons featuring multiple reaction sites and the difficulty in precise control of chemo-, regio-, and enantio-selectivity. In this work, o-QDIs are employed as a versatile building block, enabling the chemo-divergent dearomative arylation and [4 + 2] cycloaddition reactions of indoles. Under the catalysis of chiral phosphoric acid and mild conditions, various indolenines, furoindolines/pyrroloindolines, and six-membered-ring fused indolines are collectively prepared in good yields with excellent enantioselectivities. This diversity-oriented synthesis protocol enriches the o-quinone chemistry and offers new opportunities for CADA reactions.

Enantioselective Alkynylation of 2-Aryl-3H-indol-3-ones via Cooperative Catalysis of Copper/Chiral Phosphoric Acid.

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)-CPA catalysis is described. The strategy of the alkynylation of 2-aryl-3H-indol-3-one directly to chiral propargylic amines containing indolin-3-one moiety in good yields and enantioselectivities. Moreover, gram-scale synthesis of chiral propargylamines based C2-quaternary indolin-3-ones was performed. The synthetic applications were confirmed by transformations of the products with no decrease in the yield and enantioselectivity.

Asymmetric (4+n) Cycloadditions of Indolyldimethanols for the Synthesis of Enantioenriched Indole-Fused Rings.

Catalytic asymmetric construction of chiral indole-fused rings has become an important issue in the chemical community because of the significance of such scaffolds. In this work, we have accomplished the first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3-indolyldimethanols by using indoles and 2-naphthols as suitable reaction partners under the catalysis of chiral phosphoric acids, constructing enantioenriched indole-fused six-membered and seven-membered rings in high yields with excellent enantioselectivities. In addition, this approach is used to realize the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which are found to show promising anticancer activity. More importantly, theoretical calculations of the reaction pathways and activation mode offer an in-depth understanding of this class of indolylmethanols. This work not only settles the challenges in realizing catalytic asymmetric cycloadditions of indolyldimethanols but also provides a powerful strategy for the construction of enantioenriched indole-fused rings.

Direct Regioselective Dehydrogenation of α-Substituted Cyclic Ketones.

We disclose a highly regioselective, catalytic one-step dehydrogenation of α-substituted cyclic ketones in the presence of 2,3-dichlorobenzo-5,6-dicyano-1,4-benzoquinone (DDQ). The high regioselectivity originates from a phosphoric acid-catalyzed enolization, selectively affording the thermodynamically preferred enol, followed by the subsequent oxidation event. Our method provides reliable access to several α-aryl and α-alkyl substituted α,ß-unsaturated ketones.

Brønsted Acid Catalysis-Controlling the Competition between Monomeric versus Dimeric Reaction Pathways Enhances Stereoselectivities.

Chiral phosphoric acids (CPA) have become a privileged catalyst type in organocatalysis, but the selection of the optimum catalyst is still challenging. So far hidden competing reaction pathways may limit the maximum stereoselectivities and the potential of prediction models. In CPA-catalyzed transfer hydrogenation of imines, we identified for many systems two reaction pathways with inverse stereoselectivity, featuring as active catalyst either one CPA or a hydrogen bond bridged dimer. NMR measurements and DFT calculations revealed the dimeric intermediate and a stronger substrate activation via cooperativity. Both pathways are separable: Low temperatures and high catalysts loadings favor the dimeric pathway (ee up to -98 %), while low temperatures with reduced catalyst loading favor the monomeric pathway and give significantly enhanced ee (92-99 % ee; prior 68-86 % at higher temperatures). Thus, a broad impact is expected on CPA catalysis regarding reaction optimization and prediction.

Asymmetric aza-Friedel-Crafts Reaction of Cyclic Ketimines with 5-Aminopyrazole Derivatives: Expedient Access to Pyrazole-Based C2-quaternary Indolin-3-Ones.

A chiral phosphoric acid-catalyzed enantioselective aza-Friedel-Crafts reaction of 5-aminopyrazole derivatives with cyclic ketimines attached to a neutral functional group is reported. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 5-aminopyrazole-based C2-quaternary indolin-3-ones was performed, with no decrease in the yield and enantioselectivity.

Design, Synthesis and Actual Applications of the Polymers Containing Acidic P-OH Fragments: Part 2-Sidechain Phosphorus-Containing Polyacids.

Macromolecules containing acidic fragments in side-groups­polyacids­occupy a special place among synthetic polymers. Properties and applications of polyacids are directly related to the chemical structure of macromolecules: the nature of the acidic groups, polymer backbone, and spacers between the main chain and acidic groups. The chemical nature of the phosphorus results in the diversity of acidic >P(O)OH fragments in sidechain phosphorus-containing polyacids (PCPAs) that can be derivatives of phosphoric or phosphinic acids. Sidechain PCPAs have many similarities with other polyacids. However, due to the relatively high acidity of −P(O)(OH)2 fragment, bone and mineral affinity, and biocompatibility, sidechain PCPAs have immense potential for diverse applications. Synthetic approaches to sidechain PCPAs also have their own specifics. All these issues are discussed in the present review.

Multifunctional Organocatalysts - Singly-Linked and Macrocyclic Bisphosphoric Acids for Asymmetric Phase-Transfer and Brønsted-Acid Catalysis.

The linking of phosphoric acids via covalent or mechanical bonds has proven to be a successful strategy for the design of novel organocatalysts. Here, we present the first systematic investigation of singly-linked and macrocyclic bisphosphoric acids, including their synthesis and their application in phase-transfer and Brønsted acid catalysis. We found that the novel bisphosphoric acids show dramatically increased enantioselectivities in comparison to their monophosphoric acid analogues. However, the nature, length and number of linkers has a profound influence on the enantioselectivities. In the asymmetric dearomative fluorination via phase-transfer catalysis, bisphosphoric acids with a single, rigid bisalkyne-linker give the best results with moderate to good enantiomeric excesses. In contrast, bisphosphoric acids with flexible linkers give excellent enantioselectivities in the transfer-hydrogenation of quinolines via cooperative Brønsted acid catalysis. In the latter case, sufficiently long linkers are needed for high stereoselectivities, as found experimentally and supported by DFT calculations.

A Dynamic Kinetic Resolution Approach to Axially Chiral Diaryl Ethers by Catalytic Atroposelective Transfer Hydrogenation.

Diaryl ethers are widespread in biologically active compounds, ligands and catalysts. It is known that the diaryl ether skeleton may exhibit atropisomerism when both aryl rings are unsymmetrically substituted with bulky groups. Despite recent advances, only very few catalytic asymmetric methods have been developed to construct such axially chiral compounds. We describe herein a dynamic kinetic resolution approach to axially chiral diaryl ethers via a Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes with anilines. The desired diaryl ethers could be obtained in moderate to good chemical yields (up to 79 %) and high enantioselectivities (up to 95 % ee) under standard reaction conditions. Such structural motifs are interesting precursors for further transformations and may have potential applications in the synthesis of chiral ligands or catalysts.

Short-term effect of adhesive system on clinical performance of bulk fill composite: randomized clinical trial

Aim: Although bulk fill composites have been widely used as restorative material, there is no consensus regarding the best clinical protocol in terms of composite technique and adhesive system. Therefore, this clinical trial evaluated the clinical performance of bulk fill composites for class I restorations under different protocols. Methods: A randomized clinical trial including 155 class I restorations was conducted using different adhesive systems: conventional technique (phosphoric acid + conventional three-step adhesive system) (Group 1, 2 and 3); or self-etching adhesive system (Groups 4, 5 and 6). Control groups 1 and 4 were restored with conventional composite; groups 2 and 5 with low viscosity bulk fill and conventional composite as occlusal coverage; groups 3 and 6 with high viscosity bulk fill. The FDI criteria was used for clinical evaluation at baseline and after 6 months. Results: All groups showed good clinical performance. At baseline, the adhesive system did not affect postoperative hypersensitivity. After 6 months, group 5 showed a significant reduction in color and translucency; group 6 a reduction in terms of anatomical form and for postoperative sensitivity and an improvement in patient satisfaction (p<0.05). Considering the same restorative technique, the use of the self-etching adhesive system showed a significant decrease in color and translucency (p<0.05). Conclusion: All groups showed favorable clinical performance, and promising results were found for the conventional adhesive system and high viscosity bulk fill protocol

Unusual Enantiodivergence in Chiral Brønsted Acid-Catalyzed Asymmetric Allylation with ß-Alkenyl Allylic Boronates.

We report herein a rare example of enantiodivergent aldehyde addition with ß-alkenyl allylic boronates via chiral Brønsted acid catalysis. 2,6-Di-9-anthracenyl-substituted chiral phosphoric acid-catalyzed asymmetric allylation using ß-vinyl substituted allylic boronate gave alcohols with R absolute configuration. The sense of asymmetric induction of the catalyst in these reactions is opposite to those in prior reports. Moreover, in the presence of the same acid catalyst, the reactions with ß-2-propenyl substituted allylic boronate generated homoallylic alcohol products with S absolute configuration. Unusual substrate-catalyst C-H⋅⋅⋅π interactions in the favoured reaction transition state were identified as the origins of observed enantiodivergence through DFT computational studies.

Sterically Demanding Flexible Phosphoric Acids for Constructing Efficient and Multi-Purpose Asymmetric Organocatalysts.

Herein, we present a novel approach for various asymmetric transformations of cyclic enones. The combination of readily accessible chiral diamines and sterically demanding flexible phosphoric acids resulted in a simple and highly tunable catalyst framework. The careful optimization of the catalyst components led to the identification of a particularly powerful and multi-purpose organocatalyst, which was successfully applied for asymmetric epoxidations, aziridinations, aza-Michael-initiated cyclizations, as well as for a novel Robinson-like Michael-initiated ring closure/aldol cyclization. High catalytic activities and excellent stereocontrol was observed for all four reaction types, indicating the excellent versatility of our catalytic system. Furthermore, a simple change in the diamine's configuration provided easy access to both product antipodes in all cases.

Hydrogen Atom Transfer Driven Enantioselective Minisci Reaction of Alcohols.

Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α-amino radical coupling partners. We report a substantial evolution of the enantioselective Minisci reaction that enables α-hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through the direct oxidative coupling of two C-H bonds on simple alcohol and pyridine partners through a hydrogen atom transfer (HAT)-driven approach: a challenging process to achieve due to the numerous side reactions that can occur. Our approach is highly regioselective as well as highly enantioselective. Dicumyl peroxide, upon irradiation with 390 nm light, serves as both HAT reagent and oxidant whilst selectivity is controlled by use of a chiral phosphoric acid catalyst. Computational and experimental evidence provide mechanistic insight as to the origin of selectivity, revealing a stereodetermining deprotonation step distinct from the analogous reaction of amide-containing substrates.

Asymmetric Intramolecular Hydroalkoxylation of 2-Vinylbenzyl Alcohols with Chiral Boro-Phosphates.

Asymmetric intramolecular hydroalkoxylation of alkenes represents a very important approach to access optically active cyclic ethers. It was found that B(C6 F5 )3 could catalyze the cyclization of 2-vinylbenzyl alcohols with only 0.05 mol % catalyst loading, affording the desired product in high yields. To accomplish the asymmetric reaction, a novel type of chiral boro-phosphates was developed by treating chiral phosphoric acid with Piers' borane, in which the oxygen atom of P=O and the boron atom act as Lewis base and acid centers, respectively. A highly enantioselective hydroalkoxylation was successfully realized to give optically active 1,3-dihydroisobenzofuran derivatives in 78-99 % yields with 60-97 % ee's, in which an activation of O-H bond of alcohols by the boro-phosphate species is hypothesized.

Organocatalytic Atroposelective Synthesis of N-N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation.

The first highly atroposelective construction of N-N axially chiral indole scaffolds was established via a new strategy of de novo ring formation. This strategy makes use of the organocatalytic asymmetric Paal-Knorr reaction of well-designed N-aminoindoles with 1,4-diketones, thus affording N-pyrrolylindoles in high yields and with excellent atroposelectivities (up to 98 % yield, 96 % ee). In addition, this strategy is applicable for the atroposelective synthesis of N-N axially chiral bispyrroles (up to 98 % yield, 97 % ee). More importantly, such N-N axially chiral heterocycles can be converted into chiral organocatalysts with applications in asymmetric catalysis, and some molecules display potent anticancer activity. This work not only provides a new strategy for the atroposelective synthesis of N-N axially chiral molecules but also offers new members of the N-N atropisomer family with promising applications in synthetic and medicinal chemistry.

Chiral Phosphoric Acid Catalyzed Conversion of Epoxides into Thiiranes: Mechanism, Stereochemical Model, and New Catalyst Design.

Computations and experiments leading to new chiral phosphoric acids (CPAs) for epoxide thionations are reported. Density functional theory calculations reveal the mechanism and origin of the enantioselectivity of such CPA-catalyzed epoxide thionations. The calculated mechanistic information was used to design new efficient CPAs that were tested experimentally and found to be highly effective. Bulky ortho-substituents on the 3,3'-aryl groups of the CPA are important to restrict the position of the epoxide in the key transition states for the enantioselectivity-determining step. Larger para-substituents significantly improve the enantioselectivity of the reaction.

Sterically Demanding Flexible Phosphoric Acids for Constructing Efficient and Multi-Purpose Asymmetric Organocatalysts.

Herein, we present a novel approach for various asymmetric transformations of cyclic enones. The combination of readily accessible chiral diamines and sterically demanding flexible phosphoric acids resulted in a simple and highly tunable catalyst framework. The careful optimization of the catalyst components led to the identification of a particularly powerful and multi-purpose organocatalyst, which was successfully applied for asymmetric epoxidations, aziridinations, aza-Michael-initiated cyclizations, as well as for a novel Robinson-like Michael-initiated ring closure/aldol cyclization. High catalytic activities and excellent stereocontrol was observed for all four reaction types, indicating the excellent versatility of our catalytic system. Furthermore, a simple change in the diamine's configuration provided easy access to both product antipodes in all cases.

Chiral Phosphoric Acids as Versatile Tools for Organocatalytic Asymmetric Transfer Hydrogenations.

Herein, recent developments in the field of organocatalytic asymmetric transfer hydrogenation (ATH) of C=N, C=O and C=C double bonds using chiral phosphoric acid catalysis are reviewed. This still rapidly growing area of asymmetric catalysis relies on metal-free catalysts in combination with biomimetic hydrogen sources. Chiral phosphoric acids have proven to be extremely versatile tools in this area, providing highly active and enantioselective alternatives for the asymmetric reduction of α,ß-unsaturated carbonyl compounds, imines and various heterocycles. Eventually, such transformations are more and more often used in multicomponent/cascade reactions, which undoubtedly shows their great synthetic potential and the bright future of organocatalytic asymmetric transfer hydrogenations.