C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.

Design and Asymmetric Control of Orientational Chirality by Using the Combination of C(sp2)-C(sp) Levers and Achiral N-Protecting Group.

New chiral targets of orientational chirality have been designed and asymmetrically synthesized by taking advantage of N-sulfinyl imine-directed nucleophilic addition/oxidation, Suzuki-Miyaura, and Sonogashira cross-coupling reactions. Orientation of single isomers has been selectively controlled by using aryl/alkynyl levers [C(sp2)-C(sp) axis] and tBuSO2- protecting group on nitrogen as proven by X-ray diffraction analysis. The key structural characteristic of resulting orientational products is shown by remote through-space blocking manner. Seventeen examples of multi-step synthesis were obtained with modest to good chemical yields and complete orientational selectivity.

Study on the Mechanism of Ru-Catalyzed Cyclization of Aromatic Amides with Allylphosphine Oxides.

The mechanism of Ru-catalyzed cyclization of aromatic amides with allylphosphine oxides is studied by density functional theory calculation (DFT). The results show that, first, a 5-membered Ru ring intermediate is formed by N-H and C-H diprotons via the concerted metalation-deprotonation mechanism (CMD) and then the allylphosphine oxide is inserted through the ring-extending reaction to form a 7-membered ring intermediate. Next, reduction elimination is followed via intramolecular hydrogen transfer isomerization. At last, with the assistance of acetic acid, Ru (II) → Ru (IV) → Ru (II) complexes occur from the 7-membered Ru ring intermediate, and the final product is formed by reduction elimination and protonation reaction, while the catalyst is released to participate in the next cycle.

Switchable synthesis of natural-product-like lawsones and indenopyrazoles through regioselective ring-expansion of indantrione.

Lawsones and indenopyrazoles are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules, but their synthesis has always remained challenging as no comprehensive protocol has been outlined to date. Herein, a metal-free, ring-expansion reaction of indantrione with diazomethanes, generated in situ from the N-tosylhydrazones, has been developed for the synthesis of lawsone and indenopyrazole derivatives in acetonitrile and alcohol solvents, respectively. It provides these valuable lawsone and pyrazole skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials. DFT calculations were used to explore the mechanism in different solutions. The synthetic application example also showed the prospects of this method for the preparation of valuable compounds.

Design and synthesis of axially chiral aryl-pyrroloindoles via the strategy of organocatalytic asymmetric (2 + 3) cyclization.

The catalytic asymmetric construction of axially chiral indole-based frameworks is an important area of research due to the unique characteristics of such frameworks. Nevertheless, research in this area is still in its infancy and has some challenges, such as designing and constructing new classes of axially chiral indole-based scaffolds and developing their applications in chiral catalysts, ligands, etc. To overcome these challenges, we present herein the design and atroposelective synthesis of aryl-pyrroloindoles as a new class of axially chiral indole-based scaffolds via the strategy of organocatalytic asymmetric (2 + 3) cyclization between 3-arylindoles and propargylic alcohols. More importantly, this new class of axially chiral scaffolds was derived into phosphines, which served as efficient chiral ligands in palladium-catalyzed asymmetric reactions. Moreover, theoretical calculations provided an in-depth understanding of the reaction mechanism. This work offers a new strategy for constructing axially chiral indole-based scaffolds, which are promising for finding more applications in asymmetric catalysis.

Can a Wanzlick-like equilibrium exist between dicoordinate borylenes and diborenes?

Boron chemistry has experienced tremendous progress in the last few decades, resulting in the isolation of a variety of compounds with remarkable electronic structures and properties. Some examples are the singly Lewis-base-stabilised borylenes, wherein boron has a formal oxidation state of +I, and their dimers featuring a boron-boron double bond, namely diborenes. However, no evidence of a Wanzlick-type equilibrium between borylenes and diborenes, which would open a valuable route to the latter compounds, has been found. In this work, we combine DFT, coupled-cluster, multireference methods, and natural bond orbital/natural resonance theory analyses to investigate the electronic, structural, and kinetic factors controlling the reactivity of the transient CAAC-stabilised cyanoborylene, which spontaneously cyclotetramerises into a butterfly-type, twelve-membered (BCN)4 ring, and the reasons why its dimerisation through the boron atoms is hampered. The computations are also extended to the NHC-stabilised borylene counterparts. We reveal that the borylene ground state multiplicity dictates the preference for self-stabilising cyclooligomerisation over boron-boron dimerisation. Our comparison between NHC- vs. CAAC-stabilised borylenes provides a convincing rationale for why the reduction of the former always gives diborenes while a range of other products is found for the latter. Our findings provide a theoretical background for the rational design of base-stabilised borylenes, which could pave the way for novel synthetic routes to diborenes or alternatively non-dimerising systems for small-molecule activation.

Cu-Catalyzed Radical Addition and Oxidation Cascade: Unsymmetrical Trimerization of Indole to Access Isotriazatruxene.

Herein we describe a Cu-catalyzed radical addition and oxidation cascade reaction for the chemo/regioselective synthesis of unsymmetrical indole trimers (isotriazatruxenes, i-TATs) from easily available starting materials. The i-TATs exhibited blue fluorescence in various solvents with different fluorescence intensities and showed good structural expansibility. A wider range of products could be used in optoelectronic materials by developing suitable derivatives.

Catalytic Synthesis of Atropisomeric o-Terphenyls with 1,2-Diaxes via Axial-to-Axial Diastereoinduction.

Herein, we report a modular and convergent strategy for the assembly of atropisomeric o-terphenyls with 1,2-diaxes via palladium/chiral norbornene cooperative catalysis and axial-to-axial diastereoinduction. Readily available aryl iodides, 2,6-substituted aryl bromides, and potassium aryl trifluoroborates are used as the building blocks, laying the foundation for diversity-oriented synthesis of these scaffolds (46 examples). Other features include the unique axial-to-axial diastereoinduction mode, construction of two axes in a single operation, and step economy. DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process. Synthetic utilities of this method in preparation of atropisomeric oligophenyls, chiral catalysts, and ligands are demonstrated.

Regio- and Enantioselective (3+3) Cycloaddition of Nitrones with 2-Indolylmethanols Enabled by Cooperative Organocatalysis.

The regio- and enantioselective (3+3) cycloaddition of nitrones with 2-indolylmethanols was accomplished by the cooperative catalysis of hexafluoroisopropanol (HFIP) and chiral phosphoric acid (CPA). Using this approach, a series of indole-fused six-membered heterocycles were synthesized in high yields (up to 98 %), with excellent enantioselectivities (up to 96 % ee) and exclusive regiospecificity. This approach enabled not only the first organocatalytic asymmetric (3+3) cycloaddition of nitrones but also the first C3-nucleophilic asymmetric (3+3) cycloaddition of 2-indolylmethanols. More importantly, theoretical calculations elucidated the role of the cocatalyst HFIP in helping CPA control the reactivity and enantioselectivity of the reaction, demonstrating a new mode of cooperative catalysis.

NBO/NRT Two-State Theory of Bond-Shift Spectral Excitation.

We show that natural bond orbital (NBO) and natural resonance theory (NRT) analysis methods provide both optimized Lewis-structural bonding descriptors for ground-state electronic properties as well as suitable building blocks for idealized "diabatic" two-state models of the associated spectroscopic excitations. Specifically, in the framework of single-determinant Hartree-Fock or density functional methods for a resonance-stabilized molecule or supramolecular complex, we employ NBO/NRT descriptors of the ground-state determinant to develop a qualitative picture of the associated charge-transfer excitation that dominates the valence region of the electronic spectrum. We illustrate the procedure for the elementary bond shifts of SN2-type halide exchange reaction as well as the more complex bond shifts in a series of conjugated cyanine dyes. In each case, we show how NBO-based descriptors of resonance-type 3-center, 4-electron (3c/4e) interactions provide simple estimates of spectroscopic excitation energy, bond orders, and other vibronic details of the excited-state PES that anticipate important features of the full multi-configuration description. The deep 3c/4e connections to measurable spectral properties also provide evidence for NBO-based estimates of ground-state donor-acceptor stabilization energies (sometimes criticized as "too large" compared to alternative analysis methods) that are also found to be of proper magnitude to provide useful estimates of excitation energies and structure-dependent spectral shifts.

Insights into 2-Indolylmethanol-Involved Cycloadditions: Origins of Regioselectivity and Enantioselectivity.

To gain insights into 2-indolylmethanol-involved reactions and to understand the origins of regioselectivity and enantioselectivity, theoretical investigations on the reaction mechanisms of three representative cycloadditions of 2-indolylmethanols have been carried out. In Ir-catalyzed regioselective (3 + 3) cycloaddition, it was found that the great difference between the energy barriers of the first initiating steps of the two pathways played a key role in determining the observed high regioselectivity and the C3-nucleophilicity of 2-indolylmethanol in this reaction. In chiral phosphoric acid (CPA)-catalyzed regioselective and enantioselective (3 + 3) and (3 + 4) cycloadditions, it was discovered that the great difference between the energy barriers of the transition states corresponding to the (R)- and (S)-configurations led to the observed high enantioselectivity of the products. In the presence of CPA, the C3-nucleophilicity of 2-indolylmethanol increased, resulting in exclusive regioselectivity. It was discovered that the electronic nature is not a decisive factor for the observed C3-regioselectivity in the delocalized cation of 2-indolylmethanol, and the steric factor should play a crucial role in the observed C3-regioselectivity. This study offers insights into the mechanisms of 2-indolylmethanol-involved reactions, which will give an in-depth understanding of the chemistry of 2-indolylmethanols and advance the development of this research field.

Atroposelective Access to Oxindole-Based Axially Chiral Styrenes via the Strategy of Catalytic Kinetic Resolution.

Atroposelective synthesis of axially chiral molecules has attracted substantial attention from chemists because of the importance of such molecules. However, catalytic asymmetric synthesis of axially chiral styrenes or vinyl arenes is underdeveloped and challenging due to the low rotational barrier and weak configurational stability of such molecules. Therefore, the development of powerful strategies for the catalytic atroposelective synthesis of axially chiral styrenes or vinyl arenes is of great importance. In this work, we have accomplished the first atroposelective access to oxindole-based axially chiral styrenes by the strategy of catalytic kinetic resolution, and this strategy offered two kinds of oxindole-based axially chiral styrene derivatives in good diastereoselectivities (up to 94:6 dr) and excellent enantioselectivities (up to 98% ee) with high selectivity factors (S up to 106). This strategy not only provides easy access to oxindole-based axially chiral styrenes but also offers a robust method for synthesizing bisamide derivatives bearing both axial and central chirality. More importantly, this strategy has added a new class of members to the atropisomeric family, especially to the family of axially chiral styrenes.

Thermal Conductivity Estimation of Diverse Liquid Aliphatic Oxygen-Containing Organic Compounds Using the Quantitative Structure-Property Relationship Method.

Thermal conductivity is an essential thermodynamic data in chemical engineering applications. Liquid aliphatic oxygen-containing organic compounds are important organic intermediates and raw materials. As a result, estimating thermal conductivity of liquid aliphatic oxygen-containing organic compounds is of significance in industry production. In this study, the genetic function approximation method was applied to screen descriptors and develop a 6-descriptor linear quantitative structure-property relationship model. The entire data set of these compounds covering 1064 thermal conductivity values was divided into 694-member training set, 298-member test set, and 72-member prediction set. The average absolute relative deviation of the training set, test set, and prediction set were 4.14, 4.41, and 4.16%, respectively. Model validation and Y-randomization test proved that the developed model has goodness-of-fit, predictive power, and robustness. In addition, the applicability domain of the developed model was visualized by the Williams plot. This study can provide a convenient method to estimate the thermal conductivity for researchers in chemical engineering production.

Recent Advances of Sulfonylation Reactions in Water.

BACKGROUND: The sulfonyl groups are general structural moieties present in agrochemicals, pharmaceuticals, and natural products. Recently, many efforts have been focused on developing efficient procedures for preparation of organic sulfones. MATERIALS AND METHODS: Water, a proton source, is considered one of the most ideal and promising solvents in organic synthesis for its easy availability, low cost, nontoxic and nonflammable characteristics. From the green and sustainable point of view, more and more reactions are designed proceeding in water. OBJECTIVE: The review focuses on recent advances of sulfonylation reactions proceeding in water. Sulfonylation reactions using sodium sulfinates, sulfonyl hydrazides, sulfinic acids, and sulfonyl chlorides as sulfonating agents were introduced in detail. RESULTS AND DISCUSSION: In this review, sulfonylation reactions proceeding in water developed in recent four yields were presented. Sulfonylation reactions using water as solvent have attracted more and more attention because water is one of the most ideal and promising solvents in organic synthesis for its facile availability, low cost, nontoxic and nonflammable properties. CONCLUSION: Numerous sulfonating agents such as sodium sulfinates, sulfonyl hydrazides, sulfinic acid, sulfonyl chlorides and disulfides are efficient for sulfonylation reactions which proceed in water.

Direct cyanation, hydrocyanation, dicyanation and cyanofunctionalization of alkynes.

In this review, direct cyanation, hydrocyanation, dicyanation, cyanofunctionalization and other cyanation reactions of alkynes were highlighted. Firstly, the use of nitriles and development of cyanation was simply introduced. After presenting the natural properties of alkynes, cyanation reactions of alkynes were classified and introduced in detail. Transition metal catalysed direct cyanation and hydrocyanation of alkynes gave alkynyl cyanides and alkenyl nitriles in good yields. Dicyanation of alkynes produced 1,2-dicyano adducts. Cyanofunctionalization of alkynes afforded functional cyanated compounds. Thiocyanation and selenocyanation yielded the expected functional vinylthiocyanates and vinylselenocyanates. A plausible reaction mechanism is presented if available.

A Strategy for Synthesizing Axially Chiral Naphthyl-Indoles: Catalytic Asymmetric Addition Reactions of Racemic Substrates.

A new strategy for enantioselective synthesis of axially chiral naphthyl-indoles has been established through catalytic asymmetric addition reactions of racemic naphthyl-indoles with bulky electrophiles. Under chiral phosphoric acid catalysis, azodicarboxylates and o-hydroxybenzyl alcohols served as bulky but reactive electrophiles that were attacked by C2-unsubstituted naphthyl-indoles, which underwent a dynamic kinetic resolution to afford two series of axially chiral naphthyl-indoles in good yields (up to 98 %) and high enantioselectivities (up to 98:2 er).

Organocatalytic [4 + 2] cyclizations of para-quinone methide derivatives with isocyanates.

The first [4 + 2] cyclizations of para-quinone methide derivatives with isocyanates have been established under the catalysis of Brønsted acids or Brønsted bases, which efficiently constructed benzoxazin-2-one frameworks in generally high yields (up to 95%). This reaction will not only enrich the research contents of para-quinone methide-involved cyclization reactions but also provide a useful method for constructing biologically important benzoxazin-2-one frameworks.

What Is the Nature of Supramolecular Bonding? Comprehensive NBO/NRT Picture of Halogen and Pnicogen Bonding in RPH2···IF/FI Complexes (R = CH3, OH, CF3, CN, NO2).

We employ a variety of natural bond orbital (NBO) and natural resonance theory (NRT) tools to comprehensively investigate the nature of halogen and pnicogen bonding interactions in RPH2···IF/FI binary complexes (R = CH3, OH, CF3, CN, and NO2) and the tuning effects of R-substituents. Though such interactions are commonly attributed to "sigma-hole"-type electrostatic effects, we show that they exhibit profound similarities and analogies to the resonance-type 3-center, 4-electron (3c/4e) donor-acceptor interactions of hydrogen bonding, where classical-type "electrostatics" are known to play only a secondary modulating role. The general 3c/4e resonance perspective corresponds to a continuous range of interatomic A···B bond orders (bAB), spanning both the stronger "covalent" interactions of the molecular domain (say, bAB ≥ ½) and the weaker interactions (bAB ˂ ½, often misleadingly termed "noncovalent") that underlie supramolecular complexation phenomena. We show how a unified NBO/NRT-based description of hydrogen, halogen, pnicogen, and related bonding yields an improved predictive utility and intuitive understanding of empirical trends in binding energies, structural geometry, and other measurable properties that are expected to be manifested in all such supramolecular interaction phenomena.

Catalytic Asymmetric (4+3) Cyclizations of In Situ Generated ortho-Quinone Methides with 2-Indolylmethanols.

The first catalytic asymmetric (4+3) cyclization of in situ generated ortho-quinone methides with 2-indolylmethanols has been established, which constructed seven-membered heterocycles in high yields (up to 95 %) and excellent enantioselectivity (up to 98 %). This approach not only represents the first catalytic asymmetric (4+3) cyclization of o-hydroxybenzyl alcohols, but also enabled an unprecedented catalytic asymmetric (4+3) cyclization of 2-indolylmethanols. In addition, a scarcely reported catalytic asymmetric (4+3) cyclization of para-quinone methide derivatives was accomplished.