Asymmetric Total Synthesis of Vincadifformine Enabled by a Thiourea-Phosphonium Salt Catalyzed Mannich-Type Reaction

An asymmetric total synthesis of vincadifformine is described. The limited tactics with chiral cation-directed catalysis in total synthesis inspired the development of our strategy for accessing this alkaloid in enantionrich form. The route features a thiourea–phosphonium salt catalyzed Mannich-type reaction, a phosphine-promoted aza-Morita–Baylis–Hillman reaction and a trifluoroacetic acid promoted deprotection/amidation cascade process.     

从碳中心到硅中心:手性螺环双膦配体研究的发展

手性螺环配体和催化剂已被公认是一类优势手性配体和催化剂。手性螺环配体的相关研究，促进了不对称催化领域的发展。根据螺环骨架类型进行分类，分别讨论具有螺[4.4]壬烷骨架、螺二氢茚骨架、螺[4.4]壬二烯骨架以及螺二色烷骨架的手性螺环双膦配体的合成及在不对称催化反应中的应用，为今后发展新的不对称催化体系提供了重要参考。     

Chiral Frustrated Lewis Pair@Metal-Organic Framework as a New Platform for Heterogeneous Asymmetric Hydrogenation

Asymmetric hydrogenation, a seminal strategy for the synthesis of chiral molecules, remains largely unmet in terms of activation by non-metal sites of heterogeneous catalysts. Herein, as demonstrated by combined computational and experimental studies, we present a general strategy for integrating rationally designed molecular chiral frustrated Lewis pair (CFLP) with porous metal–organic framework (MOF) to construct the catalyst CFLP@MOF that can efficiently promote the asymmetric hydrogenation in a heterogeneous manner, which for the first time extends the concept of chiral frustrated Lewis pair from homogeneous system to heterogeneous catalysis. Significantly, the developed CFLP@MOF, inherits the merits of both homogeneous and heterogeneous catalysts, with high activity/enantio-selectivity and excellent recyclability/regenerability. Our work not only advances CFLP@MOF as a new platform for heterogeneous asymmetric hydrogenation, but also opens a new avenue for the design and preparation of advanced catalysts for asymmetric catalysis.     

Synthesis of a chiral phosphonium salt for the preparation of α-substituted alaninol derivatives

We herein report the synthesis of a chiral phosphonium salt, {[(4S)-4-methyl-2-oxo-1,3-oxazolidin-4-yl]methyl}(triphenyl)phosphonium iodide 13 to provide a new Wittig reagent for the general method of synthesizing α-substituted alaninol derivatives. Our method described here is widely applicable to reactions with various types of aldehyde to afford olefin products with high E-selectivity, enabling us to provide a new approach to the synthesis of chiral S1P₁ agonists including our key intermediates, and of the trace amine-associated receptor 1 (TAAR1) agonist.     

Chiral quaternary phosphonium salts: a new class of organocatalysts

Phase-transfer catalysis has widely been used as a prime synthetic tool for both laboratory and industrial processes. During the last twenty years, asymmetric phase-transfer catalysis using chiral organocatalysts has attracted widespread interest. However, the scope of chiral phase-transfer catalysis has been limited mostly to the quaternary ammonium salts. As an emerging area, the recent developments in the application of quaternary phosphonium salts as chiral phase-transfer catalysts are discussed in this article.     

The versatile roles of ammonium salt catalysts in enantioselective reduction and alkylation of α,β-unsaturated aldehydes: iminium catalysis, enamine catalysis and acid catalysis

A novel strategy for highly efficient utilization of chiral ammonium salt catalysts has been described in this paper. Three kinds of catalytic functions including iminium catalysis, enamine catalysis, and acid catalysis of chiral ammonium salt catalysts, have been achieved in the enantioselective reduction and alkylation reaction of α,β-unsaturated aldehydes with alcohols.     

Bifunctional Ion Pair Catalysts from Chiral α‐Amino Acids

Asymmetric ion pair catalysis presents a powerful strategy for the construction of chiral molecules. However, the ion‐pair interactions are weakly directional and result in difficultly controlling the conformational constraint for high stereo‐ inductions. Based on the hydrogen bonding interactions, we have successfully designed and synthesized a new family of bifunctional ion pair catalysts derived from chiral amino acids via simple operations. With these chiral ammonium salts and phosphonium salts in hand, the enantioselective construction of C—C and C—X bonds was realized in our lab.     

Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities

In the field of chiral Brønsted base catalysis, a new generation of chiral catalysts has been highly anticipated to overcome the intrinsic limitation of pronucleophiles that are applicable to the enantioselective reactions. Herein, we reveal conceptually new chiral Brønsted base catalysts consisting of two different organobase functionalities, one of which functions as an organosuperbase and the other as the substrate recognition site. Their prominent activity, which stems from the distinctive cooperative function by the two organobases in a single catalyst molecule, was demonstrated in the unprecedented enantioselective direct Mannich‐type reaction of α‐phenylthioacetate as a less acidic pronucleophile. The present achievement would provide a new guiding principle for the design and development of chiral Brønsted base catalysts and significantly broaden the utility of Brønsted base catalysis in asymmetric organic synthesis.     

Recent Advances in Asymmetric Catalysis Using p-Block Elements

The development of new methods for enantioselective reactions that generate stereogenic centres within molecules are a cornerstone of organic synthesis. Typically, metal catalysts bearing chiral ligands as well as chiral organocatalysts have been employed for the enantioselective synthesis of organic compounds. In this review, we highlight the recent advances in main group catalysis for enantioselective reactions using the p-block elements (boron, aluminium, phosphorus, bismuth) as a complementary and sustainable approach to generate chiral molecules. Several of these catalysts benefit in terms of high abundance, low toxicity, high selectivity, and excellent reactivity. This minireview summarises the utilisation of chiral p-block element catalysts for asymmetric reactions to generate value-added compounds.     

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.     

Synergistic Pd/Cu Catalysis in Organic Synthesis

Synergistic Pd/Cu catalysis has been utilized in the Sonogashira reaction since 1975. However, this strategy has not received much attention from the organic chemist community until recently. Synergistic Pd/Cu catalysis is becoming a proficient method for the development of catalytic reactions, including several new and efficient cross-coupling reactions. Additionally, several challenging asymmetric reactions, including stereodivergent synthesis, have been discovered by the combined use of a chiral metal catalyst and a second achiral metal catalyst or two chiral metal catalysts. This review provides an overview of this field, with the aims of highlighting both the development of synergistic Pd/Cu catalysis in organic synthesis and the reaction mechanisms involved in this research area.     

Phosphonium ion tagged chiral phosphoric acids and their application in Friedel-Crafts reactions of indoles

The attachment of phosphonium ion phase tags to chiral binapthyl-based phosphoric acid catalysts, and the use of these materials in a range of organocatalytic asymmetric Friedel-Crafts reactions of indoles has been studied. Placement of the tags at the 3 and 3′ positions of the phosphoric acid, so that they could serve as steric blocking groups, failed to produce an active catalyst. However, moving the phosphonium ion groups to the 6 and 6′ positions produced an efficient and enantioselective catalyst. Aided by the presence of the phase tags, the chiral catalyst was easily removed at the end of the reactions, and could be reused several times, albeit with somewhat decreased efficiency and enantioselectivity.     

Enantioselective direct Mannich reaction of functionalized acetonitrile to N-Boc imines catalyzed by quaternary phosphonium catalysis

Quaternary phosphonium ion-pair or a salt derived from amino acid has been developed to catalyze the Mannich-type reaction of α-substituted ethyl cyanoacetates and 2-(2-nitrophenyl) acetonitrile to N-Boc imines. Experiments shown that more active cyanoacetates could be catalyzed by the gentle phosphonium ion-pair catalysis, while 2-(2-nitrophenyl) acetonitrile as the substrate has to be activated by quaternary phosphonium salts and strong base. All the reactions gave the corresponding highly functionalized chiral β-amino nitriles products with good yields, high diastereo- and enantioselectivities in mild conditions.     

手性配体催化二烷基锌—羰基不对称加成制光活性醇的反应

关于手性配体催化二烷基锌一羰基的不对称加成生成光活性醇的反应,从催化剂、不对称催化机理与自催化过程、手性放大等方面进行了概述,参考文献50篇。     

The development for the synthesis of chiral acyclic nucleosides and their phosphonates

Acyclic nucleosides and their phosphonates possess significantly antiviral and cytostatic activities. For acyclic nucleosides and their phosphonates, the introduction of a chiral group to their side chain or the absolute configuration of the chiral atom could affect their biological activities obviously. Thus, the asymmetric synthesis of chiral acyclic nucleosides and their phosphonates has received continuous attention. The previous reports mainly focus on employing the chiral pool and chiral auxiliary methods for the synthesis of chiral acyclic nucleosides and their phosphonates. In contrast, the asymmetric catalysis methods for the synthesis of acyclic nucleosides and their phosphonates are still in the beginning. This digest paper will serve to highlight the significant progress that has been made in these areas.     

Additive-Free Transfer Hydrogenative Direct Asymmetric Reductive Amination Using a Chiral Pyridine-Derived Half-Sandwich Catalyst

Chiral amines are broadly used compounds in pharmaceutical industry and organic synthesis, and reductive amination reactions have been the most appreciated methods for their syntheses. However, one-step transfer hydrogenative direct asymmetric reductive amination (THDARA) that could expand the scope, simplify the operation and eliminate the use of additives has been challenging. In this work, based on the Xiao's racemic transfer hydrogenative reductive amination in 2010 and our recent work in novel chiral pyridine ligands, chiral half-sandwich iridium catalysts were rationally designed and synthesized. Using the optimized catalyst and azeotropic mixture of formic acid and triethylamine as the hydrogen source, a broad range of α-chiral (hetero)aryl amines, including various polar functional groups and heterocycles, were prepared in generally high yield and enantioselectivity under mild and operationally simple conditions. Density functional theory (DFT) calculation of the catalytically active Ir−H species and the key hydride transfer step supported the chiral pyridine-induced stereospecific generation of the iridium center, and the enantioselection by taming the highly flexible key transition structure with multiple attractive non-covalent interactions. This work introduced a type of effective chiral catalysts for simplified approach to medicinally important chiral amines, as well as a rare example of robust enantioselective transition-metal catalysis.     

聚合物负载的手性联二萘酚的合成及其在不对称催化中的应用进展

作为一种有机配体, 手性1,1'-联二萘酚(BINOL)被广泛应用于过渡金属催化的均相不对称有机反应. 为克服均相催化剂不易回收重复使用等缺陷, 人们深入研究了聚合物负载手性BINOL催化剂的方法. 总结了近年来聚合物负载手性BINOL催化剂的合成及其在不对称有机催化中的应用, 并对负载型BINOL催化剂进行了展望.     

The even-handed approach: strategies for the deployment of racemic chiral catalysts

Asymmetric catalysis is predominantly associated with the use of enantiomerically pure chiral ligands and catalysts. Although racemic chiral catalysts have been employed quite extensively in polymerization, their utility in mainstream organic synthesis and catalyst development has arguably been rather overlooked. This Minireview collates various themes for the strategic application of racemic ligands and catalysts, ranging from the estimation of selectivity and determination of enantiomeric excess, through to control of regio- and stereochemical outcomes, and mechanistic studies. What emerges is a clear picture that, in isolation or in concert with enantiopure catalysts, the "even-handed" approach has much to offer.     

Chiral metal cluster and nanocluster complexes and their application in asymmetric catalysis

Asymmetric catalysis has always been the focus of attention for synthetic chemistry. In this review, we summarize recent advances in the synthesis and asymmetric catalysis application of chiral metal clusters, nanoclusters and nanoparticles.     

高分子支载手性催化剂在Michael反应中的研究进展

高分子手性催化剂用于不对称有机合成,它易与产物分离、可通过适当的处理后回收重复使用;具有毒性或气味的手性催化剂支载在高分子上后,使用更加安全和方便;而且,适当结构的高分子聚合物可以为不对称反应提供更有利的微环境,提高立体选择性.正是这些优点,高分子手性催化剂的研究越来越受到人们的关注.不对称Michael反应是形成手性碳-碳、碳-杂键的重要反应,在有机合成和药物合成中起着重要的作用.本文综述了近年来的高分子手性催化剂在Michael反应中的应用及最新进展.