Organocatalytic Dynamic Kinetic Resolution Enabled Asymmetric Synthesis of Phosphorus-Containing Chiral Helicenes

The catalytic asymmetric synthesis of phosphorus-containing helicenes remains a formidable challenge, presumably due to the lack of rational design of substrates, right choice of reactions together with highly effective catalysis systems. Herein, we disclosed an efficient and practical DKR-involving (dynamic kinetic resolution) cascade strategy toward synthesizing a novel family of phosphorus-installing helicenes by peptide-mimic phosphonium salt (PPS) catalysis. The sequential process of PPS-catalyzed phospha-Michael attack and copper salt-facilitated aromatization led to the formation of unprecedented phosphorus-containing oxa[5]helicene scaffolds. A wide variety of substrates bearing an assortment of functional groups were compatible with this protocol, furnishing the expected helical compounds in high yields and excellent stereoselectivities. Additionally, the helical products could be conveniently elaborated to promising phosphine ligands with perfectly retained helical chirality, which turned out to be highly efficient chiral ligands in transition metal-catalyzed reactions. These findings not only expand the current library of phosphorus-containing helicenes but also offer insights to explore other challenging scaffolds with molecular chirality.     

Catalytic Kinetic Resolution of Biaryl Compounds

Biaryl compounds with axial chirality are very common in synthetic chemistry, especially in catalysis. Axially chiral biaryls are important due to their biological activities and extensive applications in asymmetric catalysis. Thus the development of efficient enantioselective methods for their synthesis has attracted considerable attention. This Minireview discusses the progress made in catalytic kinetic resolution of biaryl compounds and chronicles significant advances made recently in catalytic kinetic resolution of biaryl scaffolds.     

Enantioselective Alkynylation of 2‐Trifluoroacetyl Imidazoles Catalyzed by Bis‐Cyclometalated Rhodium(III) Complexes Containing Pinene‐Derived Ligands

Chiral rhodium(III) complexes containing two cyclometalating 2‐phenyl‐5,6‐(S,S)‐pinenopyridine ligands and two additional acetonitriles are introduced as excellent catalysts for the highly enantioselective alkynylation of 2‐trifluoroacetyl imidazoles. Whereas the ligand‐based chirality permits the straightforward synthesis of the complexes in a diastereomerically and enantiomerically pure fashion, the metal‐centered chirality is responsible for the asymmetric induction over the course of the catalysis. For comparison, the analogous iridium congeners provide only low enantioselectivity, and previously reported benzoxazole‐ and benzothiazole‐based catalysts do not show any catalytic activity for this reaction under standard reaction conditions.     

Organocatalytic Enantioselective Synthesis of Axially Chiral N,N′-Bisindoles

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N′-bisindoles via chiral phosphoric acid-catalyzed formal (3+2) cycloadditions of indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various axially chiral N,N′-bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiral N,N′-bisindoles exhibited some degree of cytotoxicity toward cancer cells and was derived into axially chiral phosphine ligands with high catalytic activity. This study provides a new strategy for enantioselective synthesis of axially chiral N,N′-bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.     

Development of Ar‐BINMOL‐Derived Atropisomeric Ligands with Matched Axial and sp3 Central Chirality for Catalytic Asymmetric Transformations

Recently, academic chemists have renewed their interest in the development of 1,1′‐binaphthalene‐2,2′‐diol (BINOL)‐derived chiral ligands. Six years ago, a working hypothesis, that the chirality matching of hybrid chirality on a ligand could probably lead to high levels of stereoselective induction, prompted us to use the axial chirality of BINOL derivatives to generate new stereogenic centers within the same molecule with high stereoselectivity, obtaining as a result sterically favorable ligands for applications in asymmetric catalysis. This Personal Account describes our laboratory's efforts toward the development of a novel class of BINOL‐derived atropisomers bearing both axial and sp³ central chirality, the so‐called Ar‐BINMOLs, for asymmetric synthesis. Furthermore, on the basis of the successful application of Ar‐BINMOLs and their derivatives in asymmetric catalysis, the search for highly efficient and enantioselective processes also compelled us to give special attention to the BINOL‐derived multifunctional ligands with multiple stereogenic centers for use in catalytic asymmetric reactions.

     

Turning on Asymmetric Catalysis of Achiral Metal-Organic Frameworks by Imparting Chiral Microenvironment

The development of heterogeneous asymmetric catalysts has attracted increasing interest in synthetic chemistry but mostly relies on the immobilization of homogeneous chiral catalysts. Herein, a series of chiral metal–organic frameworks (MOFs) have been fabricated by anchoring similar chiral hydroxylated molecules (catalytically inactive) with different lengths onto Zr-oxo clusters in achiral PCN-222(Cu). The resulting chiral MOFs exhibit regulated enantioselectivity up to 83 % ee in the asymmetric ring-opening of cyclohexene oxide. The chiral molecules furnished onto the catalytic Lewis sites in the MOF create multilevel microenvironment, including the hydrogen interaction between the substrate and the chiral −OH group, the steric hindrance endowed by the benzene ring on the chiral molecules, and the proximity between the catalytic sites and chiral molecules confined in the MOF pores, which play crucial roles and synergistically promote chiral catalysis. This work nicely achieves heterogeneous enantioselective catalysis by chiral microenvironment modulation around Lewis acid sites.     

固有手性杯芳烃的研究

固有手性杯芳烃是指在杯芳烃三维骨架上引入数个非手性基团使之不再具有对称面或反转中心而呈现出整体手性。本文综述了固有手性杯芳烃的合成、光学拆分及其在手性识别和不对称催化领域的应用。     

Enantioselective Synthesis of Azahelicenes through Organocatalyzed Multicomponent Reactions

We have developed an efficient modular asymmetric synthesis of azahelicenes through an organocatalyzed asymmetric multicomponent reaction from readily available polycyclic aromatic amines, aldehydes, and (di)enamides, by employing a central-to-helical chirality conversion strategy. A series of aza[5]- and aza[4]helicenes bearing various substituents were readily afforded through this one-pot sequential enantioselective Povarov reaction/oxidative aromatization process, with good yields and high enantioselectivities. The fruitful and diverse derivatizations of the chiral azahelicene products demonstrated the potential of this method, and a preliminary application of the azahelicene derivative as a chiral organocatalyst was showcased. The photophysical and chiroptical properties of these azahelicenes, particularly the acid/base-triggered switching of these properties, were also well studied, which may find potential applications in the development of novel organic optoelectronic materials.     

固有手性杯芳烃的研究

固有手性杯芳烃是指在杯芳烃三维骨架上引入数个非手性基团使之不再具有对称面或反转中心而呈现出整体手性。本文综述了固有手性杯芳烃的合成、光学拆分及其在手性识别和不对称催化领域的应用。     

Expansion of the Concept of Nonlinear Effects in Catalytic Reactions Beyond Asymmetric Catalysis

The observation and investigation of nonlinear effects in catalytic reactions provides valuable mechanistic insight. However, the applicability of this method was, until now, limited to molecules possessing chirality and therefore to asymmetric synthesis. The concept of nonlinear effects is expanded to catalytic reactions beyond asymmetric catalysis by using derivatives instead of enantiomers and by considering rates instead of enantiomeric excess. Additionally, its systematic application to investigate the mechanism of catalytic reactions is presented. By exceeding the limitation to asymmetric reactions, the study of nonlinear effects can become a general tool to elucidate reaction mechanisms.     

Development of Asymmetric Reactions Catalyzed by Chiral Organotin‐Alkoxide Reagents

Asymmetric catalysis under almost‐neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)‐BINOL‐derived chiral tin‐dibromide reagent that possesses a bulky aryl group at the 3 or 3′ position as the chiral pre‐catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three‐component Mannich‐type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N‐nitroso aldol reaction of unsaturated lactones with nitrosoarenes.     

Enantioselective Hydrogenation of Acetophenone over Cinchonidine-Stabilized and Supported Rhodium Clusters

Because of the importance of the chirality in chemicals in everyday, the synthesis of enantiomerically pure chiral compounds has become an important academic and commercial advantage. In asymmetric synthesis field, enantioselective catalysis has been the most challenging subject over the past decades. Among the numerous enantioselective heterogeneous catalysts, the rhodium is always an unsuccessful example under favorable reaction conditions with only 20%-30% enantiomeric excess (e.e.)^[1].And almost all of papers about heterogeneous enantioselective catalysis have reported that rhodium is not suitable for heterogeneous enantioselective hydrogenation^[1-3].     

Asymmetric Ion‐Pairing Catalysis

Charged intermediates and reagents are ubiquitous in organic transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small molecules has emerged as a powerful strategy for catalytic, enantioselective synthesis. This review describes developments in the burgeoning field of asymmetric ion‐pairing catalysis with an emphasis on the insights that have been gleaned into the structural and mechanistic features that contribute to high asymmetric induction.     

Asymmetric Catalysis on the Nanoscale: The Organocatalytic Approach to Helicenes

The first asymmetric organocatalytic synthesis of helicenes is reported. A novel SPINOL‐derived phosphoric acid, bearing extended π‐substituents, catalyzes the asymmetric synthesis of helicenes through an enantioselective Fischer indole reaction. A variety of azahelicenes and diazahelicenes could be obtained with good to excellent yields and enantioselectivities.     

Recent developments in asymmetric multicomponent reactions

Multicomponent reactions (MCRs) receive increasing attention because they address both diversity and complexity in organic synthesis. Thus, in principle diverse sets of relatively complex structures can be generated from simple starting materials in a single reaction step. The ever increasing need for optically pure compounds for pharmaceutical and agricultural applications as well as for catalysis promotes the development of asymmetric multicomponent reactions. In recent years, asymmetric multicomponent reactions have been applied to the total synthesis of various enantiopure natural products and commercial drugs, reducing the number of required reaction steps significantly. Although many developments in diastereoselective MCRs have been reported, the field of catalytic enantioselective MCRs has just started to blossom. This critical review describes developments in both diastereoselective and catalytic enantioselective multicomponent reactions since 2004. Significantly broadened scopes, new techniques, more environmentally benign methods and entirely novel MCRs reflect the increasingly inventive paths that synthetic chemist follow in this field. Until recently, enantioselective transition metal-catalyzed MCRs represented the majority of catalytic enantioselective MCRs. However, metal contamination is highly undesirable for drug synthesis. The emergence of organocatalysis greatly influences the quest for new asymmetric MCRs.     

Design and Catalytic Asymmetric Construction of Axially Chiral 3,3′‐Bisindole Skeletons

The first catalytic asymmetric construction of 3,3′‐bisindole skeletons bearing both axial and central chirality has been established by organocatalytic asymmetric addition reactions of 2‐substituted 3,3′‐bisindoles with 3‐indolylmethanols (up to 98 % yield, all >95:5 d.r., >99 % ee). This reaction also represents the first highly enantioselective construction of axially chiral 3,3′‐bisindole skeletons, and utilizes the strategy of introducing a bulky group to the ortho‐position of prochiral 3,3′‐bisindoles. This reaction not only provides a good example for simultaneously controlling axial and central chirality in one operation, but also serves as a new strategy for catalytic enantioselective construction of axially chiral 3,3′‐bisindole backbones from prochiral substrates.     

Simple N-sulfinyl-based chiral sulfur-olefin ligands for rhodium-catalyzed asymmetric 1,4-additions

A variety of N-sulfinyl-based chiral sulfur-olefin ligands has been successfully developed for the first time for rhodium-catalyzed highly efficient and enantioselective 1,4-additions. The ease of synthesis and needless consideration of the carbon chirality makes this novel type of ligands attractive for asymmetric catalysis.     

手性亚磷酰胺配体及其在不对称催化中的应用

由于结构稳定、合成简便、修饰容易、效果独特等优点,手性亚磷酰胺配体在近十几年得到了迅速的发展,大量基于不同骨架的配体被开发出来,并被成功地应用于多种不对称催化反应中.主要综述了该类配体在不对称共轭加成和烯丙基取代反应中的研究进展,同时也简单介绍了该类配体在其它不对称催化反应中的最新应用.     

A Green and Wide-Scope Approach for Chiroptical Sensing of Organic Molecules through Biomimetic Recognition in Water

Optical chirality sensing has attracted a lot of interest due to its potential in high-throughput screening in chirality analysis. A molecular sensor is required to convert the chirality of analytes into optical signals. Although many molecular sensors have been reported, sensors with wide substrate scope remain to be developed. Herein, we report that the amide naphthotube-based chirality sensors have an unprecedented wide scope for chiroptical sensing of organic molecules. The substrates include, but are not limited to common organic products in asymmetric catalysis, chiral molecules with inert groups or remote functional groups from their chiral centers, natural products and their derivatives, and chiral drugs. The effective chirality sensing is based on biomimetic recognition in water and on effective chirality transfer through guest-induced formation of a chiral conformation of the sensors. Furthermore, the sensors can be used in real-time monitoring on reaction kinetics in water and in determining absolute configurations and ee values of the products in asymmetric catalysis.     

Asymmetric Synthesis of Multi-Substituted Tetrahydrofurans via Palladium/Rhodium Synergistic Catalyzed [3+2] Decarboxylative Cycloaddition of Vinylethylene Carbonates

Unlike the comprehensive development of tandem multi-metallic catalysis, bimetallic synergistic catalysis has been challenging to achieve high stereoselectivity with the generation of multi-stereogenic centers. Herein, an efficient synergistic catalysis for the diastereo- and enantioselective synthesis of multi-substituted tetrahydrofuran derivatives has been developed. Under mild reaction conditions, a series of target molecules with three consecutive stereocenters were synthesized by a palladium(0)/rhodium(III) bimetal-catalyzed asymmetric decarboxylative [3+2]-cycloaddition of vinylethylene carbonates with α,β-unsaturated carbonyl compounds. The corresponding adducts were obtained with moderate to high yields (67 %∼98 %) and excellent stereoselectivities (>20 : 1 d.r., up to 99 % ee).