Rhodium‐Catalyzed Highly Diastereo‐ and Enantioselective Synthesis of a Configurationally Stable S‐Shaped Double Helicene‐Like Molecule

An S‐shaped double helicene‐like molecule (>99 % ee), possessing stable helical chirality, has been synthesized by the rhodium(I)/difluorphos complex‐catalyzed highly diastereo‐ and enantioselective intramolecular double [2+2+2] cycloaddition of a 2‐naphthol‐ and benzene‐linked hexayne. The collision between two terminal naphthalene rings destabilizes the helical chirality of the S‐shaped double helicene‐like molecule, but the introduction of two additional fused benzene rings significantly increases the configurational stability. Thus, no epimerization and racemization were observed even at 100 °C. The enantiopure S‐shaped double helicene‐like molecule forms a trimer through the multiple C?H???π and C?H???O interactions in the solid‐state. The trimers stack to form columnar packing structures, in which neighboring stacks have opposite dipole directions. The accumulation of helical structures in the same direction in the S‐shaped double helicene‐like molecule enhanced the chiroptical properties.     

Rhodium-Catalyzed Enantioselective Synthesis,Structures, and Properties of Single and Double Azahelicene-Like Molecules

The enantioselective synthesis of aza[6] and [7]helicene-like molecules have been achieved by the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed intramolecular [2+2+2] cycloaddition of cyanodiynes. This protocol was successfully applied to the diastereo- and enantioselective synthesis of an S-shaped double aza[6]helicene-like molecule with a high ee value of 89 %. Although no epimerization and racemization were observed in the double carbo[6]helicene-like molecule at 80 °C, epimerization and racemization of the double aza[6]helicene-like molecule proceeded at 80 °C. This double aza[6]helicene-like molecule showed good fluorescent quantum yields and chiroptical responses under both neutral and acidic conditions.     

Structures and Reactivities of Cocrystals Involving Diboronic Acids and Bipyridines: In Situ Linker Reaction and 1D-to-2D Dimensionality Change via Crystal-to-Crystal Photodimerization

Cocrystallizations of diboronic acids [1,3-benzenediboronic acid (1,3-bdba), 1,4-benzenediboronic acid (1,4-bdba) and 4,4’-biphenyldiboronic acid (4,4’-bphdba)] and bipyridines [1,2-bis(4-pyridyl)ethylene (bpe) and 1,2-bis(4-pyridyl)ethane (bpeta)] generated the hydrogen-bonded 1 : 2 cocrystals [(1,4-bdba)(bpe)₂] (1), [(1,4-bdba)(bpeta)₂] (2), [(1,3-bdba)(bpe)₂(H₂O)₂] (3) and [(1,3-bdba)(bpeta)₂(H₂O)] (4), wherein 1,3-bdba involved hydrated assemblies. The linear extended 4,4’-bphdba exhibited the formation of 1 : 1 cocrystals [(4,4'-bphdba)(bpe)] (5) and [(4,4'-bphdba-me)(bpeta)] (6). For 6, a hemiester was generated by an in-situ linker transformation. Single-crystal X-ray diffraction revealed all structures to be sustained by B(O)−H⋅⋅⋅N, B(O)−H⋅⋅⋅O, O_w−H⋅⋅⋅O, O_w−H⋅⋅⋅N, C−H⋅⋅⋅O, C−H⋅⋅⋅N, π⋅⋅⋅π, and C−H⋅⋅⋅π interactions. The cocrystals comprise 1D, 2D, and 3D hydrogen-bonded frameworks with components that display reactivities upon cocrystal formation and within the solids. In 1 and 3, the C=C bonds of the bpe molecules undergo a [2+2] photodimerization. UV radiation of each compound resulted in quantitative conversion of bpe into cyclobutane tpcb. The reactivity involving 1 occurred via 1D-to-2D single-crystal-to-single-crystal (SCSC) transformation. Our work supports the feasibility of the diboronic acids as formidable structural and reactivity building blocks for cocrystal construction.     

Catalytic Enantioselective Synthesis of Helicenes

Helicenes and helicene-like molecules, usually containing multiple ortho-fused aromatic rings, possess unique helical chirality. These compounds have found a wide range of important applications in many research fields, such as asymmetric catalysis, molecular recognition, sensors and responsive switches, circularly polarized luminescence materials and others. However, the catalytic enantioselective synthesis of helicenes was largely underexplored, when compared with the enantioselective synthesis of molecules bearing other stereogenic elements (e.g. central chirality and axial chirality). Since the pioneer work of asymmetric synthesis of helicenes via enantioselective [2+2+2] cycloaddition of triynes by Stará and Starý, last two decades have witnessed the tremendous development in the catalytic enantioselective synthesis of helicenes. In this review, we comprehensively summarized the advances in this field, which include methods enabled by both transition metal catalysis and organocatalysis, and provide our perspective on its future development.     

Stabilization and Structure of the cis Tautomer of a Free‐Base Porphyrin

Single‐crystal X‐ray analysis of the β‐heptakis(trifluoromethyl)‐meso ‐tetrakis(p ‐fluorophenyl)porphyrin, H₂[(CF₃)₇TpFPP], has revealed the first example of a stable cis tautomer of a free‐base porphyrin, the long‐postulated intermediate of porphyrin tautomerism. The stability of the unique molecule appears to reflect a dual origin: a strongly saddled porphyrin skeleton, which alleviates electrostatic repulsion between the two NH protons, and two polarization‐enhanced, transannular N−H⋅⋅⋅O−H⋅⋅⋅N hydrogen bond chains, each involving a molecule of water. DFT calculations suggest that the observed tautomer has a lower energy than the alternative, doubly hydrated trans tautomer by some 8.3 kcal mol⁻¹. A fascinating prospect thus exists that H₂[(CF₃)₇TpFPP]⋅2 H₂O and cognate structures may act as supramolecular synthons, which, given their chirality, may even be amenable to resolution into optically pure enantiomers.     

Directing Foldamer Self-Assembly with a Cyclopropanoyl Cap

The rational design of self-assembling organic materials is extremely challenging due to the difficulty in precisely predicting solid-state architectures from first principles, especially if synthons are conformationally flexible. A tractable model system to study self-assembly was constructed by appending cyclopropanoyl caps to the N termini of helical α/β-peptide foldamers, designed to form both N−H⋅⋅⋅O and C^α−H⋅⋅⋅O hydrogen bonds, which then rapidly self-assembled to form foldectures (foldamer architectures). Through a combined analytical and computational investigation, cyclopropanoyl capping was observed to markedly enhance self-assembly in recalcitrant substrates and direct the formation of a single intermolecular N−H⋅⋅⋅O/C^α−H⋅⋅⋅O bonding motif in single crystals, regardless of peptide sequence or foldamer conformation. In contrast to previous studies, foldamer constituents of single crystals and foldectures assumed different secondary structures and different molecular packing modes, despite a conserved N−H⋅⋅⋅O/C^α−H⋅⋅⋅O bonding motif. DFT calculations validated the experimental results by showing that the N−H⋅⋅⋅O/C^α−H⋅⋅⋅O interaction created by the cap was sufficiently attractive to influence self-assembly. This versatile strategy to harness secondary noncovalent interactions in the rational design of self-assembling organic materials will allow for the exploration of new substrates and speed up the development of novel applications within this increasingly important class of materials.     

Multivalent C−H⋅⋅⋅Cl/Br−C Interactions Directing the Resolution of Dynamic and Twisted Capsules

In this work, we report a mechanism by which stereoisomeric and twisted capsules P/M- 1 direct their dynamic chirality in the presence of haloalkane guests. The capsule comprises a static, but twisted, cage that is linked to a dynamic tris(2-pyridylmethyl)amine (TPA) lid at its top. From the results of experimental (NMR spectroscopy and X-ray crystallography) and computational (DFT) studies, the TPA lid was shown to assume clockwise (+) and counterclockwise (−) folds with diastereomeric (but racemic) capsules M- 1 (+) and M- 1 (−) interconverting at a rapid rate (ΔG^≠_189K=9.1 kcal mol⁻¹). The relative stability of the capsules was found to be a function of guest(s) residing in their interior (243/262 ų) with small CH₂Cl₂ (61 ų) yielding roughly equal population of diastereomeric inclusion complexes. Larger guests, such as CCl₄ (89 ų) and CBr₄ (108 ų), however, formed M- 1 (−)⊂CX₄ at the expense of M- 1 (+)⊂CX₄ in circa 3:1 ratio. To account for the observation, theory (DFT:M06-2X/6–31+G*) and experiments (¹H NMR spectroscopy) were used to deduce that CX₄ guests become localized inside the twisted cage of the capsule by forming a C−X⋅⋅⋅π halogen bond [N_c=d/(r_H+r_X)=0.91–0.92] with the benzene “floor” while encountering electrostatic repulsions with closer naphthalimide boundaries. At last, the TPA lid used its central methylene hydrogens to establish, within the M- 1 (−)⊂CX₄, three stabilizing C−H⋅⋅⋅X−C interactions with the guest. The same C−H⋅⋅⋅X−C interactions, however, became weaker (or possibly vanished) after the conformational reorganization of the lid and the formation of less stable M- 1 (+)⊂CX₄ complex. On individual basis, C−H⋅⋅⋅X−C intermolecular contacts are weak and hardly detectable in the solution phase. In the case of capsule P/M- 1 , however, these contacts were multivalent and altogether strong enough to direct the host's dynamic chirality.     

Modular Construction of Porous Hydrogen-Bonded Molecular Materials from Melams

Ordered materials with predictable structures and properties can be made by a modular approach, using molecules designed to interact with neighbors and hold them in predetermined positions. Incorporating 4,6-diamino-1,3,5-triazin-2-yl (DAT) groups in modules is an effective way to direct assembly because each DAT group can form multiple N−H⋅⋅⋅N hydrogen bonds according to established patterns. We have found that modules with high densities of N(DAT)₂ groups can be made by base-induced double triazinylations of readily available amines. The resulting modules can form structures held together by remarkably large numbers of hydrogen bonds per molecule. Even simple modules with only 1–3 N(DAT)₂ groups and fewer than 70 non-hydrogen atoms can crystallize to form highly open networks in which each molecule engages in over 20 N−H⋅⋅⋅N hydrogen bonds, and more than 70 % of the volume is available for accommodating guests. In favorable cases, guests can be removed to create rigorously porous crystalline solids analogous to zeolites and metal–organic frameworks.     

Competition Between Intra- and Intermolecular Hydrogen Bonding: o-Anisic Acid⋅⋅⋅Formic Acid Heterodimer

Four conformers of the heterodimer o-anisic acid–formic acid, formed in a supersonic expansion, have been probed by Fourier transform microwave spectroscopy. Two of these forms have the typical double intermolecular hydrogen-bond cyclic structure. The other two show the o-anisic acid moiety bearing a trans-COOH arrangement supported by an intramolecular O−H⋅⋅⋅O bond to the neighbor methoxy group. In these conformers, formic acid interacts with o-anisic acid mainly through an intermolecular O−H⋅⋅⋅O hydrogen bond either to the O−H or to the C=O moieties, reinforced by other weak interactions. Surprisingly, the most abundant conformer in the supersonic expansion is the complex in which the o-anisic acid is in trans arrangement with the formic acid interacting with the O−H group. Such a trans-COOH arrangement in which the intramolecular hydrogen bond dominates over the usually observed double intermolecular hydrogen bond interaction has never been observed previously in an acid–acid dimer.     

Exchanged Metal-Hydrogen Anagostic Bonds and Resonance of Dithiocarbamate and Thioureide Mesomers**

The pressure-induced transformation of plane-square complex nickel(II) bis(N,N-diethyldithiocarbamate) between its soft dithiocarbamate (form I) and thioureide (form II) mesomeres is coupled to the interchange of anagostic Ni⋅⋅⋅H−C interactions from methylene to the methyl group, respectively. At 1.23 GPa, the clearly visible giant anomalous compressibility of the crystal reveals a potential-energy difference of 5.4 kJ mol⁻¹ between the two complex forms. The structural and spectroscopic results, which are supported by quantum-mechanical calculations, connect this solid-state phase transition with the mesomeric transition, and this is accompanied by the conformational transformation of anagostic Ni⋅⋅⋅H−C rearrangement and formation of the charge-assisted S⁻⋅⋅⋅H−C bond under pressure.     

Interactions of Pyridine-Based Organic Cations as Structure-Determining Factors in Perovskite-Related Compounds AxPb(II)yBrz

We have synthesised and characterised 21 new ternary Pb(II) bromides with 16 different pyridine-based organic cations by single crystal XRD measurements. The dominating composition is APbBr₃ with 10 representatives, but also 6 examples for APb₂Br₅ were found. The systematic variation of topological aspects of the organic cations allowed conclusions on the influence of N−H⋅⋅⋅Br hydrogen bridges on the connectivity and bonding situation of the Pb−Br polyhedra. Additionally, it turned out, that further weak ionic interactions can have an influence, if the formation of N−H⋅⋅⋅Br hydrogen bridges is hindered by steric effects. In general, the high versatility of the dominating PbBr₆ octahedra, and in some cases higher or lower coordination numbers, allows conclusions on the parameters that influence pattern and extent of the N−H⋅⋅⋅Br bridges as the strongest structure-determining factor. Type and extent of N−H⋅⋅⋅Br bridges have also an impact on the distortion of the PbBr₆ octahedra ranging from nearly regular PbBr₆ octahedra to 2+2+2 and 1+2+2+1 patterns with significant lone pair activity. Finally, the connectivity mode of the octahedra relates to formation and strength of hydrogen bonds.     

Iodine Clathrated: A Solid-State Analogue of the Iodine–Starch Complex

Co-crystallizing iodine with a simple dicationic salt (1,8-diammoniumoctane chloride) results in the clathration of the iodine (I₂) molecules inside trigonal and hexagonal helical channels of the crystal lattice with 72 wt % overall I₂ loading. The I₂ inside the bigger trigonal channel forms a I−I⋅⋅⋅I−I⋅⋅⋅I−I halogen-bonded infinite helical chain, while the I₂ in the smaller hexagonal channel is disordered. In both channels the I₂ interaction with the channel wall happens through I−I⋅⋅⋅Cl⁻ halogen bonds. The helical channels in the crystal lattice are constructed via the strong charge-assisted H₂N⁺H⋅⋅⋅Cl⁻ hydrogen bonds between the dications and the chloride anions. The structure shows a marked similarity with the well-known starch–I₂ system, and thus may provide insight for the yet unresolved structure of the I₂ in the helical starch channel.     

Synthesis,Structural Characterization,and Reductive Cleavage of an Oxygen-Containing Naphthyl Macrocycle

A small macrocycle comprising ether-bridged naphthyl units was prepared in a two-step synthesis. Single-crystal X-ray diffraction of two polymorphs are reported, one of which showed multiple C−H⋅⋅⋅π_naphthyl interactions of a solvent molecule in the cavity of the macrocycle. Chemical reduction led to C−O bond cleavages accompanied by a Z/E isomerization. The resulting twofold negatively charged (E)-1,2-bis(2-naphthyl)ethylene fragment was isolated as its potassium salts. Electronic characterization revealed a singlet ground state, and a marked distortion of the central ethylene unit was observed upon electron uptake.     

Control of Axial Chirality by Planar Chirality Based on Optically Active [2.2]Paracyclophane

Optically active X-shaped molecules based on the planar chiral [2.2]paracyclophane building block were prepared, in which di(methoxy)terphenyl units were stacked on the central benzene rings. At 25 °C, anisolyl rings freely rotate in solution, while in the crystal form, they are fixed by intramolecular CH–π interactions, thereby leading to the expression of the axial chirality, i.e., propeller chirality was exhibited by the planar chiral [2.2]paracyclophane moiety. The X-shaped molecule exhibited good circularly polarized luminescence (CPL) profiles with moderate Φ_PL and a large g_lum value in the order of 10⁻³ at 25 °C, in solution. In contrast, at −120 °C, dual CPL emission with opposite signs was observed. According to the theoretical studies, the rotary motion of the anisolyl units is suppressed in the excited states, and so emission from two isomers could be observed. These results demonstrate that the axial chirality was controlled by the planar chirality, leading ultimately to propeller chirality.     

An Experimental Exploration of C−H⋅⋅⋅X Hydrogen Bond in [CHCl3−X(CH3)2] Complexes (X=O,S, and Se)

Among the conglomeration of hydrogen bond donors, the C−H group is prevalent in chemistry and biology. In the present work, CHCl₃ has been selected as the hydrogen bond donor and are X(CH₃)₂ are the hydrogen bond acceptors. Formation of C−H⋅⋅⋅X hydrogen bond under the matrix isolation condition is confirmed by the observation of red-shift in the C−H stretching frequency of CHCl₃ and comparison with the simulated spectra. Stabilisation energy of all the three complexes is almost equal although the observed red-shift for the C−H⋅⋅⋅O complex is less compared to the C−H⋅⋅⋅S/Se complexes. The nature and origin of the hydrogen bond have been delineated using Natural Bond Orbital, Atoms in Molecules, Non-Covalent Interaction analyses, and Energy Decomposition Analysis. Charge transfer is found to be proportional to the observed red-shift. This work provides the first impression of C−H⋅⋅⋅Se hydrogen bond and its comparison with C−H⋅⋅⋅O/S hydrogen bond interaction under experimental condition.     

The Shape of the Simplest Non-proteinogenic Amino Acid α-Aminoisobutyric Acid (Aib)

The simplest non-proteinogenic amino acid α-aminoisobutyric acid (Aib), an analogue of glycine and alanine, has been vaporized by laser ablation and probed by high-resolution Fourier transform microwave spectroscopic techniques. Comparison of the experimental rotational and ¹⁴N nuclear quadrupole constants with that predicted ab initio has allowed the identification of three conformers of Aib exhibiting three types of hydrogen-bond interactions I (NH⋅⋅⋅O=C, cis-COOH), II (OH⋅⋅⋅N, trans-COOH), and III (N−H⋅⋅⋅O−H, cis-COOH) within the amino acid backbone. The observation of conformer III, not detected previously for related proteinogenic amino acids with a nonpolar side chain in a supersonic expansion, indicates that the presence of the methyl groups should restrict the conformational relaxation from conformer Aib-III to Aib-I. For conformer Aib-II, the rotational spectra of the ¹³C isotopomers reveal a tunneling motion arising from the two equivalent methyl groups in the molecule. The observation of a single spectrum at the midpoint between those predicted for the two ¹³C of the methyl groups has been explained by considering a double-minimum potential function with a low-energy interconversion barrier for a large amplitude internal motion. This singular fact has been corroborated by the anomalous centrifugal distortion effects determined in conformer Aib-II.     

Mapping C−H⋅⋅⋅M Interactions in Confined Spaces: (α-ICyDMe)Au,Ag, Cu Complexes Reveal “Contra-electrostatic H Bonds” Masquerading as Anagostic Interactions**

What happens when a C−H bond is forced to interact with unpaired pairs of electrons at a positively charged metal? Such interactions can be considered as “contra-electrostatic” H-bonds, which combine the familiar orbital interaction pattern characteristic for the covalent contribution to the conventional H-bonding with an unusual contra-electrostatic component. While electrostatics is strongly stabilizing component in the conventional C−H⋅⋅⋅X bonds where X is an electronegative main group element, it is destabilizing in the C−H⋅⋅⋅M contacts when M is Au(I), Ag(I), or Cu(I) of NHC−M−Cl systems. Such remarkable C−H⋅⋅⋅M interaction became experimentally accessible within (α-ICyD^Me)MCl, NHC-Metal complexes embedded into cyclodextrins. Computational analysis of the model systems suggests that the overall interaction energies are relatively insensitive to moderate variations in the directionality of interaction between a C−H bond and the metal center, indicating stereoelectronic promiscuity of fully filled set of d-orbitals. A combination of experimental and computational data demonstrates that metal encapsulation inside the cyclodextrin cavity forces the C−H bond to point toward the metal, and reveals a still attractive “contra-electrostatic” H-bonding interaction.     

Cobalt(II)-Catalyzed [4+2] Annulation of Picolinamides with Alkynes via C−H Bond Activation

A cobalt(II)-catalyzed [4+2] annulation of picolinamides with alkynes via C−H bond activation has been developed. The operationally simple annulation reaction allows for the synthesis of acyl-substituted 1H-benzoquinoline bearing multiple aromatic rings (up to 96 % yield) without co-oxidant or other oxidation factors under mild conditions. Several control experiments were carried out. This practical [4+2] annulation provides an efficient route to access highly functionalized compounds.     

A Convergent,Modular Approach to Trifluoromethyl-Bearing 5-Membered Rings via Catalytic C(sp3)−H Activation

Trifluoromethyl-bearing 5-membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp³)−H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF₃-α-alkyl carbene insertion into C(sp³)−H bonds of a broad range of substrates to access 7 types of CF₃-bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C−H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to the synthesis of chiral CF₃ analogues of bioactive molecules. Ruthenium α-CF₃-α-alkyl carbene complexes underwent stoichiometric reactions to give C−H insertion products, lending evidence for the involvement of metal α-CF₃-α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra-carbene C−H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C−H insertion reactions.     

N-Heterocyclic Carbene-Catalyzed Asymmetric C−O Bond Construction Between Benzoic Acid and o-Phthalaldehyde: Mechanism and Origin of Stereoselectivity

A computational study was contributed to explore the origin of stereoselectivity of NHC-mediated cyclization reaction between benzoic acid and o-phthalaldehyde for asymmetric construction of phthalidyl ester. The most energetically favorable pathway mainly includes the following steps: (1) nucleophilic attack on carbonyl carbon of o-phthalaldehyde by catalyst NHC, (2) formation of Breslow intermediate, (3) oxidation by DQ, (4) asymmetric formation of dual C−O bonds, and (5) dissociation of catalyst with the product. The C−O bond formation was testified as the stereoselectivity-determining step, the R-configurational pathway is more energetically favorable than the S-configurational one. The non-covalent interaction (NCI) and atom-in-molecule (AIM) analyses were performed to reveal that the O−H ⋅⋅⋅ O and C−H ⋅⋅⋅ O hydrogen-bond interactions are the key factors for controlling the stereoselectivity. The detailed mechanism and origin of stereoselectivity give useful insights for understanding organocatalytic reactions for asymmetric construction of C−O bond.