超分子亚胺离子催化的新途径

发展了一种新的超分子亚胺离子催化的策略. 为了提高传统亚胺离子催化的效率并且提供一种新的不对称催化方法,最近发展了一种致力于活化亚胺离子的新催化概念,即超分子亚胺离子催化. 为了扩展该策略的应用范围,在此进一步发展了该方法,使之拓展到可以同时对亚胺离子和亲核体进行双活化的超分子亚胺离子催化方法. 这种新的方法可以显著提高催化剂的活性,使之前应用传统方法比较惰性的反应变得具有良好的反应性. 报道的方法可以用于提高一些比较惰性反应的反应活性,也可以为设计一些新反应提供一种思路.     

Hydrogen‐Bond‐Mediated Asymmetric Catalysis

The utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric organocatalysis. Significant advances have been made in the recent past in this emerging field. Due to space constraints, this Focus Review summarizes only the key aspects with an emphasis on catalysis based on chiral ureas and thioureas, diols, and phosphoric acids. The examples provided neatly demonstrate that chiral ureas and thioureas, diols, and phosphoric acids display effective and unique activation modes of catalysis for a broad spectrum of asymmetric organic transformations, including single‐step and multiple‐step cascade reactions. These functionalities, which have the ability to afford efficient H‐bond activation of electrophiles including C?O, C?N, aziridines, and epoxides, have established their status as “privileged” functional groups in the design of organocatalysts.     

Rationally Designed Multifunctional Supramolecular Iminium Catalysis: Direct Vinylogous Michael Addition of Unmodified Linear Dienol Substrates

The development of a direct vinylogous Michael addition of linear nucleophilic substrates is a long‐standing challenge because of the poor reactivity and the considerable difficulty in controlling regioselectivity. By employing a rationally designed multifunctional supramolecular iminium catalysis strategy, the first direct vinylogous Michael addition of unmodified linear substrates to α,β‐unsaturated aldehydes, to afford chiral 1,7‐dioxo compounds with good yields and excellent regio‐ as well as enantioselectivity, has been developed.     

Stacking and Electrostatic Interactions Drive the Stereoselectivity of Silylium‐Ion Asymmetric Counteranion‐Directed Catalysis

Computational analysis shows that the enantioselectivity of asymmetric Lewis‐acid organocatalysis of the Diels–Alder cycloaddition of cyclopentadiene to cinnamates arises from stacking interactions that favor the addition of the diene to the more hindered face of the dienophile, while electrostatic interactions control the diastereoselectivity by selectively stabilizing the endo transition state. These results not only explain the stereoselectivity of these silylium‐ion‐ACDC reactions but should also guide the development of more effective ion‐pairing asymmetric organocatalysts.     

Design and Assembly of a Chiral Metallosalen‐Based Octahedral Coordination Cage for Supramolecular Asymmetric Catalysis

Supramolecular containers featuring both high catalytic activity and high enantioselectivity represent a design challenge of practical importance. Herein, it is demonstrated that a chiral octahedral coordination cage can be constructed by using twelve enantiopure Mn(salen)‐derived dicarboxylic acids as linear linkers and six Zn₄‐p‐tert‐butylsulfonylcalix[4]arene clusters as tetravalent four‐connected vertices. The porous cage features a large hydrophobic cavity (≈3944 ų) decorated with catalytically active metallosalen species and is shown to be an efficient and recyclable asymmetric catalyst for the oxidative kinetic resolution of racemic secondary alcohols and the epoxidation of olefins with up to >99 % enantiomeric excess. The cage architecture not only prevents intermolecular deactivation and stabilizes the Mn(salen) catalysts but also encapsulates substrates and concentrates reactants in the cavity, resulting in enhanced reactivity and enantioselectivity relative to the free metallosalen catalyst.     

Supramolecular Coordination Cages for Asymmetric Catalysis

Inspired by the high efficiency and specificity of enzymes in living systems, the development of artificial catalysts intrinsic to the key features of enzyme has emerged as an active field. Recent advances in supramolecular chemistry have shown that supramolecular coordination cages, built from non-covalent coordination bonds, offer a diverse platform for enzyme mimics. Their inherent confined cavity, analogous to the binding pocket of an enzyme, and the facile tunability of building blocks are essential for substrate recognition, transition-state stabilization, and product release. In particular, the combination of chirality with supramolecular coordination cages will undoubtedly create an asymmetric microenvironment for promoting enantioselective transformation, thus providing not only a way to make synthetically useful asymmetric catalysts, but also a model to gain a better understanding for the fundamental principles of enzymatic catalysis in a chiral environment. The focus here is on recent progress of supramolecular coordination cages for asymmetric catalysis, and based on how supramolecular coordination cages function as reaction vessels, three approaches have been demonstrated. The aim of this review is to offer researchers general guidance and insight into the rational design of sophisticated cage containers for asymmetric catalysis.     

Inner Workings of a Cinchona Alkaloid Catalyzed Oxa‐Michael Cyclization: Evidence for a Concerted Hydrogen‐Bond‐Network Mechanism

Cinchona alkaloids catalyze the oxa‐Michael cyclization of 4‐(2‐hydroxyphenyl)‐2‐butenoates to benzo‐2,3‐dihydrofuran‐2‐yl acetates and related substrates in up to 99 % yield and 91 % ee (ee=enantiomeric excess). Catalyst and substrate variation studies reveal an important role of the alkaloid hydroxy group in the reaction mechanism, but not in the sense of a hydrogen‐bonding activation of the carbonyl group of the substrate as assumed by the Hiemstra–Wynberg mechanism of bifunctional catalysis. Deuterium labeling at C‐2 of the substrate shows that addition of RO? H to the alkenoate occurs with syn diastereoselectivity of ≥99:1, suggesting a mechanism‐based specificity. A concerted hydrogen‐bond network mechanism is proposed, in which the alkaloid hydroxy group acts as a general acid in the protonation of the α‐carbanionic center of the product enolate. The importance of concerted hydrogen‐bond network mechanisms in organocatalytic reactions is discussed. The relative stereochemistry of protonation is proposed as analytical tool for detecting concerted addition mechanisms, as opposed to ionic 1,4‐additions.     

Two Reaction Mechanisms via Iminium Ion Intermediates: The Different Reactivities of Diphenylprolinol Silyl Ether and Trifluoromethyl‐Substituted Diarylprolinol Silyl Ether

The reactions of α,β‐unsaturated aldehydes with cyclopentadiene in the presence of diarylprolinol silyl ethers as catalyst proceed via iminium cations as intermediates, and can be divided into two types; one involving a Michael‐type reaction (type A) and one involving a cycloaddition (type B). Diphenylprolinol silyl ethers and trifluoromethyl‐substituted diarylprolinol silyl ethers, which are widely used proline‐type organocatalysts, have been investigated in this study. As the LUMO of the iminium ion derived from trifluoromethyl‐substituted diarylprolinol silyl ether is lower in energy than that derived from diphenylprolinol silyl ether, as supported by ab initio calculations, the trifluoromethyl‐substituted catalyst is more reactive in a type B reaction. The iminium ion from an α,β‐unsaturated aldehyde is generated more quickly with diphenylprolinol silyl ether than with the trifluoromethyl‐substituted diarylprolinol silyl ether. When the generation of the iminium ion is the rate‐determining step, the diphenylprolinol silyl ether catalyst is the more reactive. Because acid accelerates the generation of iminium ions and reduces the generation of anionic nucleophiles in the Michael‐type reaction (type A), it is necessary to select the appropriate acid for specific reactions. In general, diphenylprolinol silyl ether is a superior catalyst for type A reactions, whereas the trifluoromethyl‐substituted diarylprolinol silyl ether catalyst is preferred for type B reactions.     

Insight into the Folding and Cooperative Multi-Recognition Mechanism in Supramolecular Anion-Binding Catalysis

H-bond donor catalysts able to modulate the reactivity of ionic substrates for asymmetric reactions have gained great attention in the past years, leading to the development of cooperative multidentate H-bonding supramolecular structures. However, there is still a lack of understanding of the forces driving the ion recognition and catalytic performance of these systems. Herein, insight into the cooperativity nature, anion binding strength, and folding mechanism of a model chiral triazole catalyst is presented. Our combined experimental and computational study revealed that multi-interaction catalysts exhibiting weak binding energies (≈3–4 kcal mol⁻¹) can effectively recognize ionic substrates and induce chirality, while strong dependencies on the temperature and solvent were quantified. These results are key for the future design of catalysts with optimal anion binding strength and catalytic activity in target reactions.     

Hydrogen‐Bonding Catalysis of Alkyl‐Onium Salts

The synthetic utility of alkyl‐onium salt compounds is widely recognized in the field of organic chemistry. Among the wide variety of onium salts, quaternary ammonium, phosphonium, and tertiary sulfonium salts have been the most useful compounds in organic syntheses. These compounds have been very useful reagents in the construction of organic building blocks. In addition, onium salts are known as reliable catalysts, which are used to promote important organic transformations by serving as phase‐transfer and ion‐pair catalysts through the activation of nucleophiles. Although phase‐transfer catalysis is a major direction for onium salt catalysis, hydrogen‐bonding catalysis of alkyl‐onium salts, which is promoted via the activation of electrophiles, has recently become a relevant topic in the field of onium salt chemistry. This Minireview introduces new possibilities and future directions for alkyl‐onium salt chemistry based on its use in hydrogen‐bonding catalysis and on its overall utility.     

Unifying Metal‐ and Organocatalysis for Asymmetric Oxidative Iminium Activation: A Relay Catalytic System Enabling the Combined Allylic Oxidation of Alcohols and Prolinol Ether Catalyzed Iminium Reactions

A multicatalytic system consisting of tetrapropylammonium perruthenate/N‐methylmorpholine N‐oxide (TPAP/NMO) as oxidant, and diarylprolinol TMS‐ether as chiral amine catalyst, has been developed and applied in the efficient construction of valuable chiral molecules. The one‐pot domino reactions elaborated in the present study are based on the in situ generation of α,β‐unsaturated aldehydes from allylic alcohols and their subsequent use in various asymmetric transformations (e.g., cyclopropanation, Michael addition, Michael addition/acetalization). TPAP as a substrate‐selective redox catalyst is well tolerated by the amine catalyst and the domino reactions proceed in good yields and high enantioselectivities. The compatibility of metal and organocatalysis presented herein widens the scope of asymmetric iminium catalysis.     

基于大环主体化合物的不对称超分子催化

超分子化学与催化的不断渗透融合催生了超分子催化这一挑战性的前沿研究热点。作为超分子化学的主要研究对象,大环化合物因具有可以和不同客体分子通过非共价相互作用可逆结合的识别位点,模拟酶催化中对底物分子的预组织过程,在超分子催化发展之初就备受关注,并在近二十年来取得了可喜的发展。本综述主要介绍了近十年来发展的基于冠醚、环糊精和杯芳烃等大环主体分子的代表性手性超分子催化剂,以及它们在不对称催化反应中的应用,重点阐述了主-客体等弱相互作用对催化剂活性和对映选择性的超分子调控作用,同时对这一研究领域目前存在的局限性和不足进行了总结,并展望了不对称超分子催化的发展前景。