Chiral Isocamphoric Acid: Founding a Large Family of Homochiral Porous Materials

Homochiral metal–organic frameworks (MOFs) are an important class of chiral solids with potential applications in chiral recognition; however, relatively few are available. Of great importance is the availability of low‐cost, racemization‐resistant, and versatile enantiopure building blocks. Among chiral building blocks, d ‐camphoric acid is highly prolific, yet, its trans‐isomer, l ‐isocamphoric acid, has remained unknown in the entire field of solid‐state materials. Its rich yet totally untapped synthetic and structural chemistry has now been investigated through the synthesis of a large family of homochiral metal isocamphorates. The first observation of diastereoisomerism in isostructural MOFs is presented. Isocamphorate has a powerful ability to create framework topologies unexpected from common inorganic building blocks, and isocamphoric acid should allow access to hundreds of new homochiral materials.     

Frozen Dissymmetric Cavities in Resorcinarene‐Based Coordination Capsules

By introducing slight structural modifications to a D₄‐symmetric coordination capsule, we succeeded in isolating the nearly enantiopure capsules (P)‐ and (M)‐ 2 a (BF₄)₄. Chiral guest, dibenzyl 4,4′‐diacetoxy‐6,6′‐dimethyl‐[1,1′‐biphenyl]‐2,2′‐dicarboxylate ( 3 ) was encapsulated within the dissymmetric cavity of 2 a (BF₄)₄, resulting in a high diastereoselectivity of >99 % de. The encapsulated guest was successfully removed from the complex without racemization through precipitation of the empty capsule. CD spectra confirmed that the chirality of the capsule was maintained in THF and 1,4‐dioxane for long periods, whereas a small amount of acetonitrile accelerated racemization of the empty capsule. The activation parameters of the racemization reaction were determined in dichloromethane and 1,2‐dichloroethane, resulting in positive enthalpic contributions and large negative entropic contributions, respectively. Accordingly, the racemization fits a first‐order kinetic model. Mechanically coupled Cu⁺‐2,2′‐bipyridine coordination centers were responsible for the high‐energy barrier of racemization and led to the unique chiral memory of the dissymmetric cavity, which was turned off by the addition of acetonitrile.     

Synthesis,Properties, and Two‐Dimensional Adsorption Characteristics of 5‐Amino[6]hexahelicene

A convergent synthesis of racemic 5‐amino[6]hexahelicene is described. Cross‐coupling reactions are used to assemble a pentacyclic framework, and a metal‐catalyzed ring‐closure comprises the final step. The enantiomers were separated by means of chromatography and the absolute configurations were assigned by comparison of the CD spectra with hexahelicene. The t_1/2 value for racemization at 210 °C was approximately 1 hour. Scanning tunneling microscopy (STM) measurements were carried out on enantiopure and racemic samples of aminohelicene on Au(111) under ultrahigh vacuum (UHV) conditions.     

Strategies for the Synthesis of Chiral Carbon-Bridged Group IV ansa-Metallocenes

This minireview provides a survey of the various synthetic approaches to chiral ansa-metallocenes of Ti, Zr, and Hf containing a carbon-based bridge. The individual strategies to install substitution patterns at either the cyclopentadienyl framework or the bridging unit are highlighted with focus on the progress made towards a direct preparation of single complex stereoisomers. The review further includes the discussion of potential problems such as the formation of undesired diastereomers, the threat of racemization of enantiopure material, and synthetic challenges originating from the synthesis, purification, and isolation of the target complexes. The review has been written with the goal in mind to facilitate the design and synthesis of new chiral ansa-metallocene derivatives for emerging research areas in asymmetric catalysis and organometallic chemistry.     

General Access to Aminobenzyl‐o‐carboranes as a New Class of Carborane Derivatives: Entry to Enantiopure Carborane–Amine Combinations

The convenient synthesis of original aminobenzyl‐o‐carboranes, which represent a new class of nitrogenated carborane derivatives, is described. These novel compounds have been efficiently prepared starting from commercially available aromatic aldehydes and monosubstituted o‐carboranes via carboranyl alcohols and chlorides as intermediates. The key step of this methodology is a selective nucleophilic amination under mild conditions that allows the formation of the expected amines while limiting the partial deboronation of the carborane cluster. This general strategy has been applied to the preparation of a wide variety of aminobenzyl‐o‐carboranes. The extension of this pathway to the synthesis of enantiopure carborane–amine combinations is also described.     

First enantiopure calix[6]aza-cryptand: synthesis and chiral recognition properties towards neutral molecules

The synthesis of the first enantiopure calix[6]aza-cryptand was achieved in five steps from the known 1,3,5-tris-O-methylated calix[6]arene. A ¹H NMR spectroscopic study has shown that the chiral tren cap constrains the calixarene core in a straight cone conformation ideal for host–guest chemistry applications. As a result, the tetra-protonated derivative displays remarkable host properties towards polar neutral molecules and enantioselective recognition processes have been evidenced with chiral guests.     

Lipase‐Catalyzed Dynamic Kinetic Resolution of C1‐ and C2‐Symmetric Racemic Axially Chiral 2,2′‐Dihydroxy‐1,1′‐biaryls

We have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C₁‐ and C₂‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis.     

Synthesis of Enantiopure C3‐Symmetric Triangular Molecules

An asymmetric synthesis of C ₃‐symmetric triangular macrocycles is reported. 1‐Methylsulfonyl‐4‐(4‐vinylphenyl)‐1,2,3‐triazole undergoes a rhodium(II)‐catalyzed cyclotrimerization to establish an enantiopure C ₃‐symmetric triangular macrocycle motif. This method can be applied to the synthesis of an enantiopure hydrocarbon, which owes its chirality to asymmetric distribution of H/D atoms on the benzene rings.     

Asymmetric Synthesis of Fluorinated Isoindolinones through Palladium‐Catalyzed Carbonylative Amination of Enantioenriched Benzylic Carbamates

The asymmetric synthesis of fluorinated isoindolinones has been achieved by a palladium‐catalyzed aminocarbonylation reaction of the corresponding α‐fluoroalkyl o‐iodobenzylamines. A base‐mediated anti β‐hydride elimination process was suggested to explain the partial erosion of the optical purity observed in some cases. This mechanistic rationale enabled the minimization of this partial racemization by fine‐tuning the pK_a of the base.     

Near‐Enantiopure Trimerization of 9‐Ethynylphenanthrene on a Chiral Metal Surface

Enantioselectivity in heterogeneous catalysis strongly depends on the chirality transfer between catalyst surface and all reactants, intermediates, and the product along the reaction pathway. Herein we report the first enantioselective on‐surface synthesis of molecular structures from an initial racemic mixture and without the need of enantiopure modifier molecules. The reaction consists of a trimerization via an unidentified bonding motif of prochiral 9‐ethynylphenanthrene (9‐EP) upon annealing to 500 K on the chiral Pd₃‐terminated PdGa{111} surfaces into essentially enantiopure, homochiral 9‐EP propellers. The observed behavior strongly contrasts the reaction of 9‐EP on the chiral Pd₁‐terminated PdGa{111} surfaces, where 9‐EP monomers that are in nearly enantiopure configuration, dimerize without enantiomeric excess. Our findings demonstrate strong chiral recognition and a significant ensemble effect in the PdGa system, hence highlighting the huge potential of chiral intermetallic compounds for enantioselective synthesis and underlining the importance to control the catalytically active sites at the atomic level.     

Chiral M3L2 Self‐Assembled Capsules through Metal Coordination of Enantiopure Ligating Benzocyclotrimers: NMR Spectroscopic and ESI Mass Spectrometric Investigation

The synthesis of enantiopure (+)‐benzotricamphor syn‐ 5 , an important chiral C₃‐symmetric rigid building block for supramolecular applications, was studied in detail to reduce the number of steps and to increase the diastereoselectivity and overall yield. The new synthetic procedure allowed larger amounts of syn‐ 5 to be obtained and used for the preparation of new derivatives, such as the corresponding tris‐trifluoromethanesulfonate syn‐ 12 , which was efficiently transformed into (+)‐benzotribornenetrinitrile syn‐ 1 and (+)‐benzotribornenetris(ethynyl‐4‐pyridine) syn‐ 2 . The previously reported (+)‐benzotricamphortrioxime syn‐ 6 was transformed into tris‐nitrile syn‐ 3 by Beckman reaction. Compounds syn‐ 1 – 3 were employed as multidentate ligands for silver(I) and platinum(II) centres in apolar solvents. The linear coordination geometry of Ag^I and square‐planar geometry of cis‐chelated Pt^II in combination with the chiral tripodal ligands syn‐ 1 – 3 led to the formation of chiral enantiopure capsules with M₃L₂ stoichiometry, as confirmed by 2D NMR NOESY and DOSY experiments as well as ESI mass spectrometry.     

Preparation of Enantiomerically Pure Compounds Employing Anodic Oxidations of Carboxylic Acids – A Late Review of Research Done in the 1980ies

There are widely unknown enantiopure building blocks and non‐conventional transformations described in this old work that could become useful in today's diversity‐oriented organic synthesis world. Coupling and mixed couplings of functionalized CF₃‐substituted chiral radicals by Kolbe electrolysis of carboxylic acids lead to hexafluoro‐hexane‐2,5‐diol and to butyro‐ and valerolactone derivatives with functional‐group relationships that normally require components with reactivity umpolung. Oxidative decarboxylation of amino‐acid and peptide derivatives by Hofer‐Moest electrolyses provide entry into the synthetic use of chiral acyliminium‐ion intermediates. Chiral oxazoline and thioazoline building blocks (from serine, threonine, and cysteine) are accessible for substitutions and cycloadditions. The stereochemical course of oxidative CO₂H replacement in serine by nucleophilically introduced groups with retention of configuration is discussed.     

Chemoenzymatic syntheses of new optically active C2-symmetrical macrocyclic polyazacyclophanes

The syntheses of new C₂-symmetrical optically active macrocyclic polyazacyclophanes have been achieved from a common synthetic precursor, which has been prepared in enantiopure form by means of a chemoenzymatic pathway. The effect of the aromatic spacer on the flexibility of the systems is also discussed.     

Asymmetric Conjugate Addition of Unmodified Cyclic Ketones to Nitroolefins Using Aminophosphonate as the Organocatalyst

本文设计合成了光学纯吡咯烷基磷酸酯,并成功地应用于酮类底物与b-硝基芳基乙烯衍生物的不对称催化Michael加成反应中。在20 mol %催化剂用量下,以10 mol %三氟乙酸作为添加物,无溶剂条件下,0 oC反应7-24小时,Michael加成产物的收率最高达96%,非对映选择性最高可达97:3,ee值最高可达90%。     

Total Synthesis of Enantiopure Pyrrhoxanthin: Alternative Methods for the Stereoselective Preparation of 4‐Alkylidenebutenolides

A new stereocontrolled total synthesis of the configurationally labile C₃₇‐norcarotenoid pyrrhoxanthin in enantiopure form has been completed. A highly stereoselective Horner–Wadsworth–Emmons (HWE) condensation of a C₁₇‐allylphosphonate and a C₂₀‐aldehyde was used as the last conjunctive step. Both a Sonogashira reaction to form the C₁₇‐phosphonate and the final HWE condensation proved to be compatible with the sensitive C7–C10 enyne E configuration. Regioselective (5‐exo‐dig) silver‐promoted lactonization reactions of three alternative pent‐2‐en‐4‐ynoic acid precursors with increased complexity, including a fully functionalized C₂₀‐fragment, were explored for the preparation of the γ‐alkylidenebutenolide fragment. This survey extends the existing methodologies for the preparation of oxygen‐containing carotenoids (xanthophylls) and streamlines the synthesis of additional members of the C₃₇‐norcarotenoid butenolide family of natural products.     

A Synthetic High‐Spin Oxoiron(IV) Complex: Generation,Spectroscopic Characterization,and Reactivity

High versus low : The high‐yield generation of a synthetic high‐spin oxoiron(IV) complex, [Fe^IV(O)(TMG₃tren)]²⁺ (see picture, TMG₃tren = 1,1,1‐tris{2‐[N2‐(1,1,3,3‐tetramethylguanidino)]ethyl}amine), has been achieved by using the very bulky tetradentate TMG₃tren ligand, in order to both sterically protect the oxoiron(IV) moiety and enforce a trigonal bipyramidal geometry at the iron center, for which an S=2 ground state is favored.

     

A Quintuple [6]Helicene with a Corannulene Core as a C5‐Symmetric Propeller‐Shaped π‐System

The synthesis and structural analysis of a quintuple [6]helicene with a corannulene core is reported. The compound was synthesized from corannulene in three steps including a five‐fold intramolecular direct arylation. X‐ray crystallographic analysis revealed a C₅‐symmetric propeller‐shaped structure and one‐dimensional alignment in the solid state. The enantiomers of the quintuple [6]helicene were successfully separated by HPLC, and the chirality of the two fractions was identified by CD spectroscopy. A kinetic study yielded a racemization barrier of 34.2 kcal mol^?1, which is slightly lower than that of pristine [6]helicene. DFT calculations indicate a rapid bowl‐to‐bowl inversion of the corannulene moiety and a step‐by‐step chiral inversion pathway for the five [6]helicene moieties.     

A pseudo‐cage complex of silver(I) with tripodal tetraamine having benzyl end groups, {tris[2‐(benzylamino)ethyl]amine‐κ4N}silver(I) perchlorate

The synthesis and crystal structure of {tris­[2‐(benzyl­amino)­ethyl]­amine‐κ⁴N}silver(I) perchlorate, [Ag(C₂₇H₃₆N₄)]ClO₄ or [Ag(bz₃tren)]ClO₄ {bz₃tren is tris­[2‐(benzyl­amino)­ethyl]­amine or N,N′,N′′‐tri­benzyl­tris(2‐amino­ethyl)­amine} are reported. The Ag atom is coordinated to four N atoms of the tren unit and is located 0.604 (3) Å out of the trigonal plane described by the three secondary amine N atoms, away from the bridgehead N atom. Edge‐to‐face π–π interactions between the aromatic end groups, and weak interactions between Ag and arene, allow the formation of a pseudo‐cage complex.     

Stereoretentive N-Arylation of Amino Acid Esters with Cyclohexanones Utilizing a Continuous-Flow System

The N-arylation of chiral amino acid esters with minimal racemization is a challenging transformation because of the sensitivity of the α-stereocenter. A versatile synthetic method was developed to prepare N-arylated amino acid esters using cyclohexanones as aryl sources under continuous-flow conditions. The designed flow system, which consists of a coil reactor and a packed-bed reactor containing a Pd(OH)₂/C catalyst, efficiently afforded the desired N-arylated amino acids without significant racemization, accompanied by only small amounts of easily removable co-products (i. e., H₂O and alkanes). The efficiency and robustness of this method allowed for the continuous synthesis of the desired product in very high yield and enantiopurity with high space-time yield (74.1 g L⁻¹ h⁻¹) and turnover frequency (5.9 h⁻¹) for at least 3 days.     

Asymmetric chemoenzymatic synthesis of ramatroban using lipases and oxidoreductases

A chemoenzymatic asymmetric route for the preparation of enantiopure (R)-ramatroban has been developed for the first time. The action of lipases and oxidoreductases has been independently studied, and both were found as excellent biocatalysts for the production of adequate chiral intermediates under very mild reaction conditions. CAL-B efficiently catalyzed the resolution of (±)-2,3,4,9-tetrahydro-1H-carbazol-3-ol that was acylated with high stereocontrol. On the other hand, ADH-A mediated bioreduction of 4,9-dihydro-1H-carbazol-3(2H)-one provided an alternative access to the same enantiopure alcohol previously obtained through lipase-catalyzed resolution, a useful synthetic building block in the synthesis of ramatroban. Inversion of the absolute configuration of (S)-2,3,4,9-tetrahydro-1H-carbazol-3-ol has been identified as a key point in the synthetic route, optimizing this process to avoid racemization of the azide intermediate, finally yielding (R)-ramatroban in enantiopure form by the formation of the corresponding amine and the convenient functionalization of both exocyclic and indole nitrogen atoms.