Chiral Diamine Research Articles

Mechanochemical Organocatalysis: Simple Chiral Primary Diamine‐TfOH‐catalysed Asymmetric Aldol and Robinson Annulation Reactions

AbstractMechanochemical organocatalysis, which integrates mechanochemistry and organocatalysis to provide a metal‐and solvent‐free synthetic method for synthesizing chiral products, has garnered significant interest recently due to its importance in green chemistry. In this study, simple, unmodified commercially available chiral primary diamines with TfOH were employed as catalysts in mechanochemical direct asymmetric aldol and Robinson annulation reactions. This protocol demonstrated high efficiency, atom economy and high stereoselectivity. Notably, direct asymmetric aldol reactions involving unreactive aromatic methyl ketones, which still is a challenge for mechanochemical organocatalysis, proceeded smoothly. Additionally, chiral 3,5‐diaryl‐cyclohexenones were efficiently synthesized using this mechanochemical asymmetric catalytic protocol and afforded high‐to‐excellent enantioselectivities. These findings highlight the potential of mechanochemical organocatalysis for asymmetric catalysis.

Iridium‐Catalyzed Asymmetric Transfer Hydrogenation for Facile Access to Optically Active Dihydrodibenzo‐Fused Azepines

The asymmetric transfer hydrogenation of various dibenzo‐fused azepines including 5H‐dibenzo[b,e][1,4]diazepines, dibenzo[b,f][1,4]thiazepines and 11H‐dibenzo[b,e]azepines using chiral iridium diamine catalysts and HCO2H/NEt3 as the hydrogen source has been accomplished. A rang of chiral 10,11‐dihydro‐5H‐dibenzo[b,e][1,4]diazepines, 10,11‐dihydrodibenzo[b,f][1,4]thiazepine and 6,11‐dihydro‐5H‐dibenzo[b,e]azepines have been prepared in 82‐94% yields with 82‐99% ee. Diversely substituted substrates are suitable for this transformation, and a number of functional groups are tolerated. The enantiocontrol is achieved via judicious choice of catalyst, additive and hydrogen source. The synthetic potential of this reaction is explored through gram‐scale reactions without loss of reactivity and optical purity and further transformations on products.

Enantioselective Synthesis of Planar Chiral Ferrocene Triflones

AbstractA multi‐gram scale synthesis of ferrocenetriflone was optimised from ferrocenesulfonyl fluoride and Me3SiCF3 (Ruppert reagent). Enantioselective deprotolithiations were then optimised using alkyllithiums in the presence of catalytic (+)‐sparteine to afford 2‐substituted ferrocene triflones in 79–84% ee. The use of chiral lithium amides in the presence of in situ traps was also optimised and was found to outperform alkyllithium⋅chiral diamine chelates for the first time in the ferrocene series, with 89–93% ee. Crystallisation of derivatives afforded enantiopure compounds that were engaged in deprotolithiation‐electrophilic trapping sequences, a halogen ‘dance’ reaction and transition metal‐promoted coupling to afford a wide range of variously polysubstituted ferrocene triflones.

Fluorescent Dye-Based Chiral Crystalline Organic Salt Networks for Circularly Polarized Luminescence.

A facile and general strategy is developed herein for the construction of circularly polarized luminescence (CPL) materials with simultaneously high fluorescence quantum efficiency (Φ) and large luminescence dissymmetry factor (glum). The self-assembly of fluorescent dye, disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (CBS), with chiral diamines such as (R,R)/(S,S)-1,2-diaminocyclohexane (R/S-DACH) and R/S-1,2-diaminopropane (R/S-DAP), produces four chiral crystalline organic salt networks (COSNs). These as-synthesized organic salts emit strong blue-color CPL upon excitation, with both high Φ and glum values of up to 79% and 0.022. The well-defined molecular structures and arrangements of CBS are directly observed through single crystal X-ray analysis, offering crucial information regarding the origins of high-efficiency CPL performance. The chirality of amine is effectively transferred to CBS and further amplified to the supramolecular structure by multiple hydrogen bonding and π-π stacking interactions, giving rise to the large glum factors; meanwhile, the fixation and the ordered arrangement of CBS by these multiple interactions empower efficient suppression of molecular motions, facilitating strong fluorescence. This work can inspire the assembly of CPL organic materials with high Φ and glum via charge-assisted hydrogen bonds between fluorescent dyes and chiral inducers. It also offers important insight into the structural origins of supramolecular chirality and CPL performance.

Magnetically Separable Chiral Poly(ionic liquid) Microcapsules Prepared Using Oil-in-Oil Emulsions.

This article presents a method for producing chiral ionic liquid-based polyurea microcapsules that can be magnetically separated. The method involves entrapping hydrophilic magnetic nanoparticles within chiral polyurea microspheres. The synthetic process for creating these magnetic polyurea particles involves oil-in-oil (o/o) nano-emulsification of an ionic liquid-modified magnetite nanoparticle (MNPs-IL) and an ionic liquid-based diamine monomer, which comprises a chiral bis(mandelato)borate anion, in a nonpolar organic solvent, toluene, and contains a suitable surfactant. This is followed by an interfacial polycondensation reaction between the isocyanate monomer, polymethylenepolyphenyl isocyanate (PAPI 27), and the chiral diamine monomer, which generates chiral polyurea microcapsules containing magnetic nanoparticles within their cores. The microcapsules generated from the process are then utilized to selectively adsorb either the R or S enantiomer of tryptophan (Trp) from a racemic mixture that is dissolved in water, in order to evaluate their chiral recognition capabilities. During the experiments, the magnetically separable chiral poly(ionic liquid) microcapsules, which incorporated either the R or S isomer of chiral bis(mandelato)borate, exhibited exceptional enantioselective adsorption performance. Thus, the chiral polymeric microcapsules embedded with the R-isomer of the bis(mandelato)borate anion demonstrated significant selectivity for adsorbing L-Trp, yielding a mixture with 70% enantiomeric excess after 96 h. In contrast, microcapsules containing the S-isomer of the bis(mandelato)borate anion preferentially adsorbed D-Trp, achieving an enantiomeric excess of 73% after 48 h.

Chiral Polymeric Diamine Ligands for Iridium-Catalyzed Asymmetric Transfer Hydrogenation.

A series of polymeric chiral diamine ligands are developed by diboron-templated asymmetric reductive couplings, and their iridium complexes Ir-polydiamines are efficient and recyclable catalysts for asymmetric transfer hydrogenation (ATH) of functionalized ketones, affording a series of optically active secondary alcohols in excellent enantioselectivities (up to 99% ee) and unprecedentedly high total TONs (12,000, six cycles). Ir-polydiamine catalysts with longer chains offered higher reactivities, providing a plausible deactivation mechanism and practical solutions of ATH for vitamin B5 and phenylephrine.

Asymmetric Synthesis of Axially Chiral N, N‐1,2‐Pentatomic Heterobiaryl Diamines by an Organocatalytic Arylation Reaction

The utilization of axially chiral biaryl diamines has been widely acknowledged as highly advantageous structures for the advancement of chiral catalysts and ligands. This highlights their extensive range of applications in asymmetric catalysis and synthesis. Herein, we devised a direct arylation reactions of 5‐aminopyrazoles with azonaphthalenes, utilizing chiral phosphoric acid as the catalyst. This method delivers structurally novel atroposelective N, N‐1,2‐azole heteroaryl diamines with high yields (up to >98%) and good to excellent enantiomeric ratios while exhibiting a wide range of substrate compatibility.

Dipeptidic Proline‐Derived Thiourea Organocatalysts for Asymmetric Michael addition Reactions between Aldehydes and Nitroolefins

AbstractThe enantiodivergent synthesis of syn‐Michael adducts can be easily achieved by switching the terminal proline in dipeptidic proline‐thiourea catalysts. In this study, a dipeptidic proline‐derived thiourea organocatalyst was rationally designed and facilely prepared from dipeptidic proline, a chiral diamine as a linker, and isothiocyanate. This asymmetric bifunctional catalyst for Michael addition between aldehydes and nitroolefins provided chiral 4‐nitro aldehyde adducts with yields of up to 99 %, 92 : 8 syn‐diastereoselectivity, and 97 % enantiomeric excess at room temperature.

Octopus[5]arene from Pagoda[5]arene by Macrocycle-to-Macrocycle Conversion.

Macrocycle-to-macrocycle conversion is an effective strategy to construct new macrocyclic arenes with specific structures. Herein, a new class of chiral macrocyclic arene, namely, octopus[5]arenes (Oc5s), cannot be synthesized by the direct approach from the corresponding chiral monomers but can be successfully achieved by a macrocycle-to-macrocycle conversion strategy utilizing racemic pagoda[5]arenes as the starting materials. It was found that enantiomeric Oc5s showed fixed conformations and stable chiral structures and exhibited significant chiral recognition toward chiral diamines.

Chiral vicinal diamines as promising ligands in Pd-catalyzed reductive Heck type cyclizations

Palladium complexes with inexpensive and available vicinal diamines can serve as catalysts for the reductive Heck-type cyclization. o-Bromo-N-(2-phenylallyl)anilides are converted into the corresponding 3-methyl-3-phenylindolines, the analogous cyclization occurred for 2-bromo-4-methylphenyl 2-phenylallyl ether and N-(2-bromophenyl)-2-phenylacrylamides. The use of (1R,2R)-N,N’-dibenzylcyclohexane-1,2-diamine provides up to 35% ee of the indolines; this is the first case of asymmetric induction during the reductive Heck reaction involving diamine complexes.

Multistimuli‐Responsive Luminescent Porous Organic Polymers with Chiroptical Properties and Acid‐Induced Degradation

Comprehensive SummaryPorous organic polymers (POPs) have attracted great attention in past decades. Although diverse functional POPs have been developed, multistimuli‐responsive POPs with excellent aggregate‐state luminescence together with good chiroptical properties have rarely been reported. Herein, two pairs of Salen‐type enantiomeric POPs with multistimuli‐responsive luminescence and chiral features were designed and synthesized by facile polycondensation reactions between polyfunctional aggregation‐induced emission luminogen (AIEgen)‐containing salicylaldehyde derivatives and chiral diamines. With Salen units in polymer backbones as tetradentate ligands, a series of POP‐metal complexes were further prepared. The obtained POPs and metal complexes show good porosity, high thermal stability, and obvious circular dichroism signals. Moreover, benefiting from the coexistence of AIEgen and Salen units in polymer structures, these POPs exhibit excellent luminescence performance in aggregate states and tunable fluorescence behaviors in response to external stimuli of Zn2+ ion, mechanical forces, organic solvent, and acids. Due to the dynamic feature of Schiff base C=N bonds, the present POPs can efficiently undergo hydrolysis reactions under strong acidic conditions to reproduce the AIEgen‐ containing monomers, and such an acid‐induced degradation process can be directly visualized and dynamically monitored via fluorescence variation. These properties collectively make the POPs candidate materials for applications in heterogeneous asymmetric catalysis, fluorescence sensing, biomedicine, etc.

Organocatalytic Atroposelective Construction of Pentatomic Heterobiaryl Diamines through Arylation of 5-Aminoisoxazoles with Azonaphthalenes.

An efficient catalytic asymmetric Michael-type reaction of azonaphthalenes with 5-aminoisoxazoles has been developed. The reaction was based on the utilization of a chiral phosphoric acid as the catalyst, delivering a large panel of axially chiral heterobiaryl diamines in generally good yields with excellent enantioselectivities. The gram-scale reaction and postmodification of the chiral product demonstrated their potentials in the synthesis of chiral catalysts and ligands. This approach not only provides a useful method for the construction of pentatomic heterobiaryl scaffolds but also offers new members to the axially chiral diamine family with promising applications in synthetic and medicinal chemistry.

Synthesis of Chiral 2‐Oxazolidinones by Ruthenium‐Catalyzed Asymmetric Transfer Hydrogenation of 2‐Oxazolones

AbstractAn asymmetric transfer hydrogenation of 2‐oxazolones in the presence of a chiral diamine ruthenium catalyst with potassium formate as a hydrogen source and potassium carbonate as an additive in 2,2,2‐trifluoroethanol is described. A series of chiral 2‐oxazolidinones were obtained with 29%–95% yields and 86%–>99% ee's. Furthermore, gram‐scale synthesis of chiral 2‐oxazolidinone and its downstream derivatizations demonstrate the practicality of this method.

Synthesis, X-ray crystallographic, Hirshfeld, DFT study and interactions with TNFα receptors of chiral bisimines and diamines holding thiophene spacers

This paper outlines a facile synthesis of chiral bisimines R,R-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl)methanimine) R,R-BI-1, S,S-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl)methanimine) S,S-BI-2 and their reduced products R,R-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl)methanamine) R,R-DA-1, S,S-(Thiophene-2,5-diyl)bis(N-(1-phenylethyl) methanamine) S,S-DA-2 holding thiophene spacers. The new derivatives were suitably characterized by microanalysis, standard spectroscopic techniques (1H, 13C NMR, FTIR, UV–visible absorption). Single crystal X-ray diffraction (SCXRD) method was used to study the supramolecular structures of R,R-BI-1 and S,S-BI-2, sustained primarily by CH…π intermolecular contacts which are well supported by molecular electrostatic potential (MESP). Quantification of short contacts existing in the crystal packing of these molecules was accomplished by Hirshfeld surface and fingerprint plots calculations. The geometry of all the molecules has been optimized by using a density functional theory calculation and the theoretical data were compared well with the experimental outcomes. Further, the calculated HOMO-LUMO band gaps for R,R-BI-1,S,S-BI-2,R,R-DA-1 andS,S-DA-2 (4.05–5.30 eV) suggests their non-conducting nature. Moreover, virtual screening of these nitrogenous compounds has been performed by molecular docking study to propose their potentials as biologically relevant molecules.

Enantioselective Assembly of α, β‐Diamine Acid Derivatives via Three‐Component Reaction of α‐H Diazoacetates with Sulfonamides and Imines

AbstractAn asymmetric three‐component reaction of α‐H diazoacetate with sulfonamide and imine has been developed under the co‐catalyzation of Rh2(OAc)4 and a chiral phosphoric acid (CPA), which proceed through Mannich‐type interception of transient ammonium ylide. The reaction offers a convenient access to α, β‐diamine acid derivatives with two adjacent chiral centers in 59%‐74% yields with 91%‐99% ee and 92:8 to>95:5 dr. Moreover, the generated products could be easily converted to free chiral diamines and other useful chiral motifs.

Asymmetric hydrogenation of isoquinolines with chiral cationic ruthenium diamine catalysts

A general asymmetric hydrogenation of isoquinolines catalyzed by chiral cationic ruthenium catalysts has been investigated. A wide range of isoquinoline derivatives, including 1-substituted, 3-substituted, 1,3-disubstituted and 3,4-disubstituted isoquinolines, were efficiently hydrogenated to give chiral tetrahydroisoquinolines with up to 92 % ee and >20:1 dr. It was found that the ruthenium catalyst bearing a non-coordinating BArF anion resulted in high enantioselectivity. Preliminary mechanistic studies revealed that the isoquinoline is reduced via a stepwise pathway, including 1,2-hydride addition, isomerization, and 2,3-hydride addition.

Asymmetric [4 + 2], [6 + 2], and [6 + 4] Cycloadditions of Isomeric Formyl Cycloheptatrienes Catalyzed by a Chiral Diamine Catalyst.

Novel asymmetric aminocatalytic cycloadditions are described between formyl cycloheptatrienes and 6,6-dimethylfulvene that lead to [4 + 2], [6 + 2], and [4 + 6] cycloadducts. The unprecedented reaction course is dependent on the position of the formyl functionality in the cycloheptatriene core, and each formyl cycloheptatriene isomer displays a distinct reactivity pattern. The formyl cycloheptatriene isomers are activated by a chiral primary diamine catalyst, and the activation mode is dependent on the position of the formyl functionality relative to the cycloheptatriene core. The [4 + 2] and [6 + 2] cycloadducts are formed via rare iminocatalytic inverse electron-demand cycloadditions, while the [4 + 6] cycloadduct is formed by a normal electron-demand cycloaddition. The reactivity displayed by the different formyl cycloheptatrienes was investigated by DFT calculations. These computational studies account for the different reaction paths for the three isomeric formyl cycloheptatrienes. The aminocatalytic [4 + 2], [6 + 2], and [4 + 6] cycloadditions proceed by stepwise processes, and the interplay between conjugation, substrate distortion, and dispersive interactions between the fulvene and aminocatalyst mainly defines the outcome of each cycloaddition.

Regio- and Enantioselective Macrocyclization from Dynamic Imine Formation: Chemo- and Enantioselective Fluorescent Recognition of Lysine.

The dynamic covalent chemistry of imines is utilized to conduct a regioselective as well as enantioselective synthesis of an unsymmetric (C1) chiral macrocycle from the reaction of an unsymmetric (C1) chiral dialdehyde, (S)-4, that contains a salicylaldehyde unit and a benzaldehyde unit, with lysine, an unsymmetric (C1) chiral diamine. The enantioselectivity is further enhanced in the presence of Zn2+. Compound (S)-4 in combination with Zn2+ is found to be a highly chemoselective as well as enantioselective fluorescent probe for lysine. It can be used to detect specific enantiomers of this amino acid.

Asymmetric Hydrogenation of Tetrapyridine‐Type N‐Heteroarenes Using Phosphine‐Free Ruthenium Diamine Catalysts†

Comprehensive SummaryChiral ruthenium‐catalyzed enantioselective hydrogenation of tetrapyridine‐type N‐heteroarenes was firstly developed. The partial reduction of adjacent tetraheteroaromatic substrates proceeded smoothly in the presence of phosphine‐free chiral cationic ruthenium diamine complexes, affording unprecedented high reactivity, enantioselecitivity and diastereoselectivity (up to 93% yield, >99% ee and 92 : 8 dr). The potential application of chiral tetradentate pyridine‐amine products as chiral ligands has been demonstrated in the Cu‐catalyzed asymmetric Friedel–Crafts alkylation reaction between indoles and nitroalkenes.

Heterocyclic Merging of Stereochemically Diverse Chiral Piperazines and Morpholines with Indazoles.

We report a heterocyclic merging approach to construct novel indazolo-piperazines and indazolo-morpholines. Starting from chiral diamines and amino alcohols, novel regiochemically (1,3 and 1,4) and stereochemically diverse (relative and absolute) cohorts of indazolo-piperazines and indazolo-morpholines were obtained within six or seven steps. The key transformations involved are a Smiles rearrangement to generate the indazole core structure and a late-stage Michael addition to build the piperazine and morpholine heterocycles. We further explored additional vector diversity by incorporating substitutions on the indazole aromatic ring, generating a total of 20 unique, enantiomerically pure heterocyclic scaffolds.