Application In Asymmetric Catalysis Research Articles

A Chiral Hexa-amino Cyclotriphosphazene for Enantioselective Recognition of Small Organic Compounds.

Chiral recognition and separation studies are of paramount importance in research in view of their applications in asymmetric catalysis and substrate recognition in biological processes. The efficiencies of these processes are governed by the subtle differences in noncovalent interactions between the host and guest molecules. Hexakis(organoamino)phosphazenes are versatile building blocks for host-guest chemistry for their ability to act as both the donor and the acceptor of H-bonds. Herein, we report an enantiomeric pair of cyclotriphosphazenes [P3N3(NHR*)6], [R* = (R)-(CH(CH3)Ph)] (1-R) and [(S)-(CH(CH3)Ph)] (1-S), with chiral α-methylbenzylamino substituents. The chiral recognition capabilities of its R-enantiomer were further probed for several chiral organic compounds containing a range of functional groups. Among these, a remarkable guest selectivity (ξ) value of 2506 was observed for binol (BOL) in favor of its R-enantiomer. DFT-optimized structures of the host-guest pairs suggest that the multiple noncovalent interactions between the molecules in the two unique types of binding sites at the phosphazenes play a crucial role in the observed high binding selectivities.

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.

Synthesis of Three‐Dimensional Chiral Covalent Organic Frameworks Using Surfactant as Inducer in Water

Comprehensive SummaryChiral covalent organic frameworks (COFs) have shown promising applications in asymmetric catalysis, enantiomer separation and chiral recognition due to their tunable structures and permanent porosity. Currently, synthesis of chiral COFs mainly relies on direct‐ synthesis method which requires asymmetric monomers to polymerize and crystallize with symmetric monomers and post‐synthesis method which has been greatly limited to having complete reactions with the micro‐/meso‐sized pores of COFs. Recently, the synthesis of two‐dimensional COFs by covalent replacement of chiral competitor has been reported. Herein, we present the synthesis of three types of 3D COFs with tunable chirality using chiral amino acid derivative surfactant as inducer in water under ambient conditions. The hydrogen bonds and electrostatic interactions between amino acid derivative surfactant and monomers as well as their precursors facilitate the transfer of the chirality.

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis.

The different configurations of chiral pesticides generally have significant influence on their biological activities. Chiral agrochemicals with high optical purities have become a prominent topic in the research field of new pesticides due to their advantages including lower toxicity, higher efficiency, and reduced residue levels. However, most commercially available pesticides that possess chiral elements are still used in their racemic forms. To date, asymmetric catalysis has emerged as a versatile tool for the enantioselective synthesis of various chiral agrochemicals and novel chiral pesticide active molecules. This perspective provides a comprehensive overview of the applications of diverse asymmetric catalytic approaches in the facile preparation of numerous novel pesticide active molecules, and our own outlook on the future development of this highly active research direction is also presented at the end of this review.

Design of rigid chiral bipyridine-2NO tetradentate ligands: application in asymmetric catalysis

A new class of chiral bipyridine-2NO ligands, which incorporate the advantages of both the bipyridine skeleton and the pyrroloimidazolone-based N-oxide moiety, was developed.

Emerging optically active tetraphenylenes: Advances and challenges in synthesis and applications in asymmetric catalysis and chiral functional materials

Emerging optically active tetraphenylenes: Advances and challenges in synthesis and applications in asymmetric catalysis and chiral functional materials

Chiral Bisphosphoric Acids and Their Applications in Asymmetric Catalysis.

Asymmetric Brønsted acid catalysis has been recognized as a powerful concept for asymmetric synthesis. In the process of pursuing more robust and highly effective chiral Brønsted acid catalysts, chiral bisphosphoric acids have received much attention in the last two decades. Their unique catalytic properties are mainly attributed to the inherent intramolecular hydrogen bonding interactions that could increase the overall acidity and tune the conformation property. Integrating hydrogen bonding into the catalyst design, quite a few structurally unique and effective bisphosphoric acids have been synthesized, which frequently exhibited superior selectivity in a broad range of asymmetric transformations. This review summarizes the status quo of chiral bisphosphoric acid catalysts and their applications in catalyzing asymmetric transformations.

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.

Chiral phosphoric acid-catalyzed enantioselective phosphinylation of 3,4-dihydroisoquinolines with diarylphosphine oxides

Chiral phosphorous-containing compounds are playing a more and more significant role in several different research fields. Here, we show a chiral phosphoric acid-catalyzed enantioselective phosphinylation of 3,4-dihydroisoquinolines with diarylphosphine oxides for the efficient and practical construction of a family of chiral α-amino diarylphosphine oxides with a diverse range of functional groups. The phosphine products are suitable for transforming to several kinds of chiral (thio)ureas, which might be employed as chiral ligands or catalysts with potential applications in asymmetric catalysis. Control and NMR tracking experiments show that the reaction proceeds via the tert-butyl 1-(tert-butoxy)-3,4-dihydroiso-quinoline-2(1H)-carboxylate intermediate, followed by C-P bond formation. Furthermore, computational studies elucidated that the hydrogen bonding strength between the phosphonate and isoquinolinium determines the stereoselectivity of the phosphinylation reaction.

Synthesis of Cyclic 1,2‐Bisphosphines by Tandem Michael Addition of 2,3‐Bis(diarylphosphinyl)‐1,3‐butadiene

AbstractA base‐promoted tandem Michael addition of malonates to 2,3‐ bis(diarylphosphinyl)‐1,3‐butadienes was developed for the synthesis of cyclopentyl 1,2‐bisphosphine compounds. This method enables rapid construction of various 1,2‐bis(diarylphosphinyl)cyclopentanes, and features readily accessible reactants, mild conditions and good functional group tolerance. The product could be easily transformed to the corresponding transition metal complexes, which may find broad applications in asymmetric catalysis.

Recent Advances in Asymmetric Catalysis Associated with B(C6F5)3.

The prevalence and significance of asymmetric catalysis in the modern medicinal industry has been witnessed in recent years, which have already been used to manufacture the (S)-Naproxen and the (S)-Propranolol. With matched specificities such as the Lewis acidity and steric bulk, B(C6F5)3 has gained accelerating attention on its application in asymmetric catalysis of Diels-Alder cycloaddition reactions, carbonyl-ene cyclization, and other various reactions, which have been demonstrated by the elegant examples from the most recent literature. Some significant progress in the reaction of indirect activation of substrates through in situ generation of numerous supramolecular catalysts from B(C6F5)3 based on Lewis-acid-assisted Lewis acid (LLA) or Lewis acid assisted Brønsted acid (LBA) strategies or the reaction promoted by cooperative actions of chiral co-catalysts and B(C6F5)3 which played a direct role on the activation of substrates have been demonstrated in this review.

Synthesis of P-stereogenic 1-phosphanorbornane-derived phosphine-phosphite ligands and application in asymmetric catalysis.

A convenient synthesis of enantiopure mixed donor phosphine-phosphite ligands has been developed incorporating P-stereogenic phosphanorbornane and axially chiral bisnaphthols into one ligand structure. The ligands were applied in Pd-catalyzed asymmetric allylic substitution of diphenylallyl acetate, Rh-catalyzed asymmetric hydroformylation of styrene and Rh-catalyzed asymmetric hydrogenation of an acetylated dehydroamino ester. Excellent branched selectivity was observed in the hydroformylation although low ee was found. Moderate ee's of up to 60% in allylic substitution and 50% in hydrogenation were obtained using bisnaphthol-derived ligands.

Catalytic Asymmetric Synthesis of Axially Chiral 3,3'‐Bisindoles by Direct Coupling of Indole Rings

Comprehensive SummaryA new strategy for the enantioselective synthesis of axially chiral 3,3'‐bisindoles was devised by the direct coupling of two indole rings. This strategy makes use of the C3‐umpolung reactivity of 2‐indolylmethanols, which enables the catalytic asymmetric addition reaction of 2‐indolylmethanols with rationally designed 2‐substituted indoles, thus constructing axially chiral 3,3'‐bisindole scaffolds in overall excellent yields (up to 98%) with high enantioselectivities (up to 96 : 4 er). This approach not only has overcome the challenges in constructing axially chiral five‐five‐membered heterobiaryls, but also represents a new application of the C3‐umpolung reactivity of 2‐indolylmethanols in asymmetric catalysis. More importantly, this class of axially chiral 3,3'‐bisindoles can undergo a variety of post‐functionalizations to give axially chiral 3,3'‐bisindole‐based organocatalysts, which have found their preliminary applications in asymmetric catalysis.

BINOL as a chiral element in mechanically interlocked molecules.

In this minireview we present the use of the axially chiral 1,1'-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in mechanically interlocked molecules (MIMs). We describe the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and their use in stereoselective chemosensing. Given the growing importance of mechanically interlocked molecules and the key advantages of the privileged chiral BINOL backbone, we believe that this research area will continue to grow and deliver many useful applications in the future.

Enantio- and Regioselective Construction of 1,4-Diamines via Cascade Hydroamination of Methylene Cyclopropanes.

Despite the widespread existence of chiral 1,4-diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long-standing challenge. Here, we report a Cu-catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4-diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4-diamine structures. The desired products could be easily transformed into chiral 1,4-diamines and chiral NH2 -Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring-opening and cascade hydroamination sequence.

Enantio‐ and Regioselective Construction of 1,4‐Diamines via Cascade Hydroamination of Methylene Cyclopropanes

AbstractDespite the widespread existence of chiral 1,4‐diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long‐standing challenge. Here, we report a Cu‐catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4‐diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4‐diamine structures. The desired products could be easily transformed into chiral 1,4‐diamines and chiral NH2‐Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring‐opening and cascade hydroamination sequence.

Simple Double Hetero[5]helicenes Realize Highly Efficient and Narrowband Circularly Polarized Organic Light-Emitting Diodes

Simple Double Hetero[5]helicenes Realize Highly Efficient and Narrowband Circularly Polarized Organic Light-Emitting Diodes

Organocatalytic Atroposelective Synthesis of N−N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation

AbstractThe first highly atroposelective construction of N−N axially chiral indole scaffolds was established via a new strategy of de novo ring formation. This strategy makes use of the organocatalytic asymmetric Paal–Knorr reaction of well‐designedN‐aminoindoles with 1,4‐diketones, thus affordingN‐pyrrolylindoles in high yields and with excellent atroposelectivities (up to 98 % yield, 96 % ee). In addition, this strategy is applicable for the atroposelective synthesis of N−N axially chiral bispyrroles (up to 98 % yield, 97 % ee). More importantly, such N−N axially chiral heterocycles can be converted into chiral organocatalysts with applications in asymmetric catalysis, and some molecules display potent anticancer activity. This work not only provides a new strategy for the atroposelective synthesis of N−N axially chiral molecules but also offers new members of the N−N atropisomer family with promising applications in synthetic and medicinal chemistry.

Organocatalytic Atroposelective Synthesis of N-N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation.

The first highly atroposelective construction of N-N axially chiral indole scaffolds was established via a new strategy of de novo ring formation. This strategy makes use of the organocatalytic asymmetric Paal-Knorr reaction of well-designed N-aminoindoles with 1,4-diketones, thus affording N-pyrrolylindoles in high yields and with excellent atroposelectivities (up to 98 % yield, 96 % ee). In addition, this strategy is applicable for the atroposelective synthesis of N-N axially chiral bispyrroles (up to 98 % yield, 97 % ee). More importantly, such N-N axially chiral heterocycles can be converted into chiral organocatalysts with applications in asymmetric catalysis, and some molecules display potent anticancer activity. This work not only provides a new strategy for the atroposelective synthesis of N-N axially chiral molecules but also offers new members of the N-N atropisomer family with promising applications in synthetic and medicinal chemistry.

New tertiary amine-derived C2-symmetric chiral pyridine-N,N′-dioxide ligands and their applications in asymmetric catalysis

Developing efficient methods for preparing privileged chiral ligands is an important endeavor in synthetic chemistry.