Zr-Mediated Cyclization of Alkynes as a Transferable Protocol for Constructing C 2 -Symmetric and Other Chiral Multisubstituted Cyclopentadienyl Ligands

Peer Reviewed

New epoxides, derivatives of pyridine, 2,2′-bipyridine, and 1,10-phenanthroline, were synthesized from the respective α-methylazaarenes. The obtained racemic 2-oxiranyl-azaarenes along with styrene oxide and trans-stilbene oxide were submitted to the ring opening with chiral primary amines as a chiral auxiliary. The most effective reaction was run in the presence of Sc(OTf)3/diisopropylethylamine for 7 days at 80°C, affording a good yield of the amino alcohols. Except for styrene oxide which gave both α- and β-amino alcohols, the reactions led regioselectively to the corresponding diastereomeric β-amino alcohols. The resulting diastereomers were separated, and the configurations of their stereogenic centers were established. The obtained enantiomerically pure 2-pyridinyl- and 6-(2,2′-bipyridinyl)-β-amino alcohols were tentatively tested as chiral ligands in the zinc-catalyzed aldol reaction.

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Chirality is a fundamental characteristic of nature and pervades the world. The chiral materials closely related to our life, especially our health. The thalidomide tragedy, lessons for drug safety and regulation from the late 1950s and the early 1960s, indicated the importance of creating chiral materials in optically pure form. Pasteur was the first to conduct chiral resolution for the preparation of optically active molecules before 1860. Since then, scientists including chemists started to search methods for creating chiral materials like enzyme. After more than one hundred years of efforts, chemists find that the synthetic chiral catalysts (also known as artificial enzymes) catalyzed asymmetric reactions is the door to creating chiral materials. From 1970 to 2001, many efficient and selective catalytic asymmetric reactions and methods have been developed for creating chiral materials. In particular, the successes of catalytic asymmetric hydrogenations and catalytic asymmetric epoxidations and their applications in industrial preparation of chiral drugs enable this research field to won the Nobel Prize for chemistry in 2001. To date, tremendous amount of chiral materials such as chiral pharmaceuticals, chiral agrochemicals, chiral liquid crystals were created in a high selective and efficient manner. We now can create chiral materials like enzymes by using asymmetric catalysis with artificial enzymes as catalysts. The Chinese chemists also made great contributions for creating chiral materials, especially in the past two decades. They developed a series of highly efficient chiral ligands and catalysts including the magical chiral spiro ligands and catalysts, the privileged chiral N , N ￠-dioxides, as well as many original organocatalysts. These catalysts are highly efficient for a wide range of reactions involving asymmetric hydrogenation, asymmetric carbon-carbon bond formations, and asymmetric carbon-heteroatom bond formations, providing chiral alcohols, chiral amines, chiral acids, etc. Many new asymmetric catalytic reactions, new concepts, new strategies were also developed by Chinese chemists, which afforded new methodologies for creating chiral materials. From this century, in order to meet the new demand of mankind on the chiral materials, scientists begin to develop green and sustainable methods for the accurate, powerful and environment-friendly creation of chiral materials. In addition, the creation of chiral materials has been in depth combined with life sciences, environmental sciences, materials science and information sciences, etc. This review focus on the main line of the discovery and development of asymmetric catalysis, in combination with the development in China, to give a brief overview for the journey of creation of chiral materials.

The incorporation of only L-amino acids into DNAencoded proteins imparts a great biological significance to the chirality of amino acids. This importance also translates to compounds synthesized from amino acid components. As with all chiral materials, it is typically more difficult to synthesize amino acids as pure enantiomers rather than as racemic mixtures. One method of utilizing the racemate is to kinetically resolve it into optically pure product and unreacted enantiomer.1 We have explored the polymerization of R-amino acid-Ncarboxyanhydrides (NCAs) to form block copolypeptides for applications as biomedical materials.2 In such materials, the absolute configuration of the amino acid monomers is crucial for both structural development and biological activity.3 To utilize synthetic, racemic amino acids in these materials, we pursued the use of optically active initiators to develop enantioasymmetric polymerizations. We now report the use of chiral pyridinyl oxazoline ligands in nickel initiators to enantioasymmetrically polymerize γ-benzyl-glutamate NCA. Enantioasymmetric ring-opening polymerizations have been developed for many chiral cyclic monomers such as epoxides and episulfides.4 There also have been attempts to prepare optically active polypeptides from racemic NCA mixtures. Interest in this area has arisen from the pharmaceutical value of the optically active products as well as possible relevance to the origins of handedness in biological macromolecules.5 Some of the different chiral initiators used to induce asymmetry in NCA polymerizations include optically active amines6 and polypeptides,7 organoaluminum complexes,8 and chiral nickel carboxylates.9 These initiators generally displayed moderate-to-poor efficiencies and gave complex polymerizations whose propagation steps were poorly understood. All systems gave broad molecular weight distributions and poor control of polymer molecular weights and displayed reasonable enantioselectivities only at very low conversions of monomer. We have developed nickel initiators that allow the controlled polymerization of NCAs.2 Using this methodology, polypeptides can be prepared with defined chain lengths and with narrow molecular weight distributions. A key feature of this system is that all polymer formation occurs with identical nickel-containing reactive species. The straightforward nature of this system provides a superior starting point for the development of an enantioasymmetric polymerization system compared to previous methods used to polymerize NCAs. In particular, asymmetric initiators can be prepared by direct substitution of the achiral 2′,2′bipyridyl (bpy) ligand in our nickel system with a suitable optically active ligand (Figure 1). The choice of a suitable chiral ligand required some consideration. Most common chiral ligands are bidentate, since the chelate structure provides both a rigid environment as well as asymmetry around the metal.1 A large number of chiral chelating ligands are based on bisarylphosphines,10 which unfortunately form ineffective initiators when complexed with nickel due to their poor donating ability, as we have previously shown for PPh3. For this reason, we focused our attention on N-donor ligands that are similar in character to bpy, which forms a very efficient initiator.11 We initially explored diimine and bisoxazoline ligands (e.g., 1-4) (Figure 2), which have been used extensively in metalmediated asymmetric aziridinations,12 Diels-Alder reactions,13 and olefin polymerizations.14 These ligands were found to bind only weakly to zerovalent nickel and were thus also generally ineffective in generating active NCA polymerization initiators. To increase coordinating ability, we decided to study hybrid ligands consisting of pyridine coupled with either a chiral imine or oxazoline group (Figure 3). To test the efficiency of such ligands, we prepared achiral 5 and evaluated its ability to form an active initiator. When 5 was mixed with Ni(COD)2 in tetrahydrofuran (THF), a stable blue complex, 5Ni(COD), was formed. This compound displayed NCA polymerization activity that was virtually identical to that of bpyNiFigure 1. Strategy for formation of chiral nickel NCA polymerization initiators.

The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 % yield and 74 % ee. The strategy involves [Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)‐f‐binaphane as the catalyst, NH4I as the amine source and H2 as the reductant. This is a straightforward and user‐friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 % achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.

Novel SiO 2-supported chromium catalyst bearing new organo-siloxane ligand for ethylene polymerization

C − N axially chiral compounds have recently attracted significant interest among synthetic chemistry community due to their widespread application in pharmaceuticals, advanced materials and organic synthesis. Although the emerging asymmetric Catellani reaction offers great opportunity for their modular and efficient preparation, the only operative chiral NBE strategy to date requires using half stoichiometric amount of chiral NBE and 2,6-disubstituted bromoarenes as electrophiles. We herein report an efficient assembly of C–N axially chiral scaffolds through a distinct chiral ligand strategy. The crucial chiral source, a biimidazoline (BiIM) chiral dinitrogen ligand, is used in relatively low loading and permits the use of less bulky bromoarenes. The method also features the use of feedstock plain NBE, high reactivity, good enantioselectivity, ease of operation and scale-up. Applications in the preparation of chiral optoelectronic material candidates featuring two C–N chiral axes and a chiral ligand for asymmetric C–H activation have also been demonstrated.

Chiral nanostructured materials have emerged to be an influential class of high-performance materials used in areas ranging from enantioselective sensing, separation, and catalysis to optoelectronics. The materials are highly sophisticated and involve chiral metal-organic frameworks, covalent organic frameworks, carbon dots, and quantum dots etc. Owing to properties such as enantioselectivity, reproducibility, and catalytic properties, facilitating their incorporation into multifunctional systems these materials offer remarkable enantiomeic separations, environmental monitoring, and sustainable energy. In the past few years, various synthetic strategies such as chiral ligands, templating techniques, and environmentally friendly synthetic methods have been investigated to achieve improved chiral materials. Great advances have been achieved in chromatographic performance and scalability toward chiral membranes, composite materials, and MOFs- and COFs-based stationary phases. Furthermore, multi-mode platforms combining fluorescence, magnetism, and other recognition approaches show vast potential for label-free real-time enantiomeric detection. Here, we review the interdisciplinary advancement in the area of nanostructured chiral materials focusing on synthetic strategies, characterization, and enantiorecognition performance of common chiral organic compounds and drugs.

Chirality Transfer from Chiral Mesoporous Silica to Perovskite CsPbBr ₃ Nanocrystals: The Role of Chiral Confinement

Cyclopentadienyl (Cp) ligands enable efficient steering of various transition-metal-catalyzed transformations, in particular enantioselective C-H activation. Currently only few chiral Cp ligands are available. Therefore, a conceptually general approach to chiral Cp ligand discovery would be invaluable as it would enable the discovery of applicable Cp ligands and to efficiently and rapidly vary and tune their structures. Herein, we describe the three-step gram-scale synthesis of a structurally diverse and widely applicable chiral Cp ligand collection (JasCp ligands) with highly variable and adjustable structures. Their modular nature and their amenability to rapid structure variation enabled the efficient discovery of ligands for three enantioselective RhIII -catalyzed C-H activation reactions, including one unprecedented transformation. This novel approach should enable the discovery of efficient chiral Cp ligands for various further enantioselective transformations.

The study of key aspects for the heterogenization of chiral homogeneous catalysts is addressed in this work. Two different heterogenization routes were evaluated. On the one hand, the immobilization of a tartaric acid derivative (Sharpless catalyst) was accomplished by following a two-step synthesis methodology. In the first step, the mesoporous support SBA-15 was functionalized with different percentages of mercaptopropyl-(trimethoxy)-silane (MPTMS) through a co-condensation method, obtaining very high degrees of MPTMS incorporation. In the second step, the chiral moiety is anchored onto the previously organically modified silica by means of a thiotransesterification reaction. On the other hand, the second route consisted of the formation of mesoporous structure and chiral ligand immobilization in the walls, simultaneously, in only one step. In this case, the chiral organic functionality was incorporated into the wall silica framework, since the built-organic complex is a bis-silane, obtaining a chiral PMO. Finally, once characterized, the synthesized materials were proved in an asymmetric catalytic test in order to study their enantioselective properties. The chosen reaction was the thioanisole enantioselective sulfoxidation, using cumene hydroperoxide as an oxidant. The materials synthesized by the multi-step method reached 40% enantiomeric excess (ee), while the synthesized one-pot chiral PMO materials reached up to 50% ee. Thereby, materials with the chiral Sharpless ligand incorporated into the three dimensional silica framework were successfully accomplished, as well as its ability to induce higher chirality in the enantiomeric tested reaction than the conventional methods of chiral ligand heterogenization onto a silica framework.

In this work, we have successfully synthesized a new family of chiral Schiff base–phosphine ligands derived from chiral binaphthol (BINOL) and chiral primary amine. The controllable synthesis of a novel hexadentate and tetradentate N,O,P ligand that contains both axial and sp3-central chirality from axial BINOL and sp3-central primary amine led to the establishment of an efficient multifunctional N,O,P ligand for copper-catalyzed conjugate addition of an organozinc reagent. In the asymmetric conjugate reaction of organozinc reagents to enones, the polymer-like bimetallic multinuclear Cu-Zn complex constructed in situ was found to be substrate-selective and a highly excellent catalyst for diethylzinc reagents in terms of enantioselectivity (up to >99 % ee). More importantly, the chirality matching between different chiral sources, C2-axial binaphthol and sp3-central chiral phosphine, was crucial to the enantioselective induction in this reaction. The experimental results indicated that our chiral ligand (R,S,S)-L1- and (R,S)-L4-based bimetallic complex catalyst system exhibited the highest catalytic performance to date in terms of enantioselectivity and conversion even in the presence of 0.005 mol % of catalyst (S/C = 20 000, turnover number (TON) = 17,600). We also studied the tandem silylation or acylation of enantiomerically enriched zinc enolates that formed in situ from copper-L4-complex-catalyzed conjugate addition, which resulted in the high-yield synthesis of chiral silyl enol ethers and enoacetates, respectively. Furthermore, the specialized structure of the present multifunctional N,O,P ligand L1 or L4, and the corresponding mechanistic study of the copper catalyst system were investigated by 31P NMR spectroscopy, circular dichroism (CD), and UV/Vis absorption.

A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig rearrangement and subsequent catalyst dissociation for an overall N to C-2 alkyl migration. The scope and degree of stereoretention were studied, and both experimental and theoretical investigations were performed to support an unprecedented aza-Wittig rearrangement–rearomatization sequence. A catalytic enantioselective version starting with racemic starting material and chiral phosphite catalyst was also established following our understanding of the stereoretentive process. This method provides efficient access to tertiary and quaternary stereogenic centers in pyridine systems, which are prevalent in drugs, bioactive natural products, chiral ligands, and catalysts.

Two generally applicable routes for the synthesis of chiral amino alcohols embodying the bispidine framework have been developed. In linear route A the bispidine framework is built up successively from chiral primary amines via intermediate formation of a piperidinone and a bispidinone. In convergent route B an achiral bispidine is formed first and then the N-substituents are introduced by reaction of the nitrogen bases with chiral electrophiles. In order to determine if the bispidine core and its N-substituents can influence the steric course of enantioselective transformations, bispidine amino alcohols built up by these two routes were investigated as chiral ligands in the enantioselectively catalyzed addition of diethylzinc to aldehydes and chalcone. In general, tridentate ligands containing one chiral amino alcohol fragment and a second amino substituent without a stereogenic center were more efficient than tetradentate ligands with two amino alcohol structural units. With the best ligands the enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes proceeded with 83-98% ee and the nickel-catalyzed addition of diethylzinc to chalcone was achieved with up to 85% ee.