Design and synthesis of novel chiral spiro ionic liquids

[reaction: see text] Novel chiral imidazolium salts have been synthesized as examples of chiral ionic liquids with a spiro skeleton. Effects of N-substituents and counteranions on the melting point of spiro imidazolium salts and their chiral discrimination abilities are described.     

Synthesis of novel spiro imidazolium salts as chiral ionic liquids

A library of 13 novel chiral spiro imidazolium salts has been synthesized. The effects of N-substituents and counteranions on the melting point of spiro bis(imidazolium) salts are studied in efforts toward the development of room temperature chiral ionic liquids.     

Design and synthesis of spiro bis(1,2,3-triazolium) salts as chiral ionic liquids

Room temperature chiral spiro ionic liquids 1 and 2 based on 1,2,3-triazolium salts, were synthesized via an intramolecular double Huisgen reaction. The preparation of the enantiomerically pure spiro triazolium salts was achieved by resolution by HPLC using a chiral stationary phase column and subsequent N-dialkylations of spiro triazoles 6 and 10.     

Recent developments on chiral ionic liquids: design, synthesis, and applications

The recent progress in chiral ionic liquids with respect to their syntheses and applications in enantioselective reactions and chiral recognition is described. In addition to the conventional chiral ionic liquids derived from chiral natural products, a library of novel chiral spiro compounds, including spiro bis(pyridinium) and spiro bis(imidazolium) salt, is also described.     

Highly enantioselective 1,3-dipolar cycloaddition of imino esters with benzofuranone derivatives catalyzed by thiourea−quaternary ammonium salt

Highly enantioselective 1, 3-dipolar cycloaddition of 2-arylidene-benzofuran- 3(2H)-ones with imino esters catalyzed by thiourea?quaternary ammonium salts has been developed. This reaction provides efficient construction of a range of chiral spiro[benzofuran-2,3′-pyrrolidine] in high yields (up to 99%) and with good enantioselectivities (up to 99% ee) under mild conditions.     

Making Spiroketal‐based Diphosphine (SKP) Ligands via a Catalytic Asymmetric Approach

The spiro concept for chiral ligand design represents an important contribution to the area of asymmetric catalysis. Due to the considerable difficulties in the construction of enantiopure all‐carbon spiro backbones, the development of catalytic asymmetric synthesis of chiral spiro structures via short steps is highly valuable. Herein we present our studies on the catalytic asymmetric synthesis of aromatic spiroketals and the corresponding diphosphine (SKP) ligands.     

Enantioselective Synthesis of Spiro Heterocyclic Compounds Using a Combination of Organocatalysis and Transition-Metal Catalysis

Over the last ten years, the combination of organocatalysis with transition metal (TM) catalysis has become one of the most important toolboxes used for synthesizing optically pure compounds containing chiral quaternary centers, including spiro heterocyclic molecules. The dominant method in the enantioselective synthesis of spiro heterocyclic compounds based on synergistic catalysis includes chiral aminocatalysis and NHC catalysis, as already established covalent organocatalytic strategies. Another area of organocatalysis widely combined with TM catalysis producing enantiomerically enriched spiro heterocyclic compounds is non-covalent catalysis, dominated by chiral phosphoric acids, thiourea, and squaramide derivatives. This review article aims to summarize enantioselective methods used for constructing spirocyclic heterocycles based on a combination of organocatalysis and transition metal catalysis.     

手性螺环配体及催化剂在不对称催化反应中的应用研究进展

金属参与的不对称催化反应是制备光学活性化合物的重要途径之一,其中新型手性配体的设计合成一直是不对称催化领域中十分关键且富有挑战性的课题.从20世纪90年代末开始,化学家们尝试在手性配体中引入螺环结构,创造性地发展了螺[4.4]壬烷骨架、螺双二氢茚骨架、螺[4.4]壬二烯骨架和螺二色满骨架等手性螺环单齿配体,多齿配体及其催化剂,并成功应用于不对称催化氢化、不对称碳碳键形成或碳杂键形成等不对称转化反应中,合成了众多富有价值的手性产品,有力地推动了不对称催化反应的工业应用化进程.本文综合评述了手性螺环配体的早期发现、发展历程以及近期的研究成果,介绍了螺环配体在药物及天然产物中的应用研究进展,并对手性螺环结构的小分子催化剂的研究进展进行叙述和说明.     

Spiro Skeletons: A Class of Privileged Structure for Chiral Ligand Design

This Focus Review highlights the exciting results obtained in the area of asymmetric catalysis using spirobiindane‐ or spirobifluorene‐based chiral ligands. The spiro, mono, and bidentate ligands have been successfully applied in a wide range of transition‐metal‐catalyzed asymmetric reactions, including hydrogenations, carbon–carbon and carbon–heteroatom coupling reactions, with superior or comparable enantioselectivities to those obtained by using the related ligands bearing other backbones, thus proving that the spiro skeleton is a type of privileged structure for chiral ligand design. It is expected that the spiro concept for chiral ligand design will stimulate the future efforts to understand the features that account for their broad applicability and to apply this understanding to seek new privileged chiral ligands and catalysts.     

Asymmetric synthesis of spiro 2-pyrrolidin-5-ones, 2-piperidin-6-ones and 1-isoindolin-3-ones. Part 1: N-Acyliminium ion cyclisations with an internal arene nucleophile

A series of chiral non-racemic 5,5- and 5,6-bicyclic lactams is prepared from (R)-phenylglycinol. These are isomerised on treatment with aluminium trichloride in 1,2-dichloroethane to give spiro lactams in high yield and >3:1 diastereoselectivity. From four structures determined by X-ray crystallography, it follows that spiro indenes are formed preferentially with retention of configuration at the spiro carbon atom and spiro naphthalenes with inversion.     

Asymmetric synthesis of chiral spiro bis(isoxazoline) and spiro (isoxazole–isoxazoline) ligands

Asymmetric synthesis of novel chiral ligands, bis(isoxazoline) on a spiro[4.4]nonane scaffold and isoxazole–isoxazoline on a spiro[4.5]decane scaffold, has been achieved by utilizing an enantiomerically pure alcohol as the starting material.     

Stereocontrolled spirocyclization of exo-glucal derivatives for stereodivergent synthesis of spiro[5.5]ketals

This Letter describes a stereoselective synthetic approach to spiro[5.5]ketals from the exo-glucals, constructed from 1-(4-hydroxyalkylidene)-1,5-anhydro-d-glucitol, by spirocyclization based on intramolecular α- and β-selective glycosylation. Stereodivergent synthesis of both α- and β-glucoside of spiro[5.5]ketals was attained by combination of chiral d-glucopyranose environment and C-4′ chiral center on the side chain.     

手性螺环配体的合成及其在不对称催化反应中的应用研究进展

手性螺环配体的合成及其在不对称催化反应中的应用是不对称合成和催化研究中重要的研究领域之一, 一些手性螺环配体被合成出来并成功地应用于不对称催化反应中. 综述了近十年来手性螺环配体的合成及在不对称催化反应中的应用研究进展.     

手性螺环单磷配体在不对称氢甲酰化反应中的应用

为了进一步拓展具有螺二氢茚骨架的亚磷酸酰胺酯、亚磷酸酯、亚膦酸酯等手性螺环单磷配体在不对称反应中的应用范围, 研究了手性螺环单磷配体在铑催化苯乙烯衍生物的氢甲酰化反应中的选择性.     

Formal (4+1) Cycloaddition and Enantioselective Michael–Henry Cascade Reactions To Synthesize Spiro[4,5]decanes and Spirooxindole Polycycles

Spiro[4,5]decanes and polycyclic compounds bearing spiro[4,5]decane systems are important biofunctional molecules. Described are diastereoselective formal (4+1) cycloaddition reactions to afford oxindole-functionalized spiro[4,5]decanes and organocatalytic enantioselective Michael–Henry cascade reactions of the (4+1) cycloaddition products to generate spirooxindole polycyclic derivatives bearing the spiro[4,5]decane system. Spiro[4,5]decanes bearing oxindoles containing three stereogenic centers and spirooxindole polycycles having seven stereogenic centers, including two all-carbon chiral quaternary centers and one tetrasubstituted chiral carbon center, were obtained with high diastereo- and enantioselectivities.     

Synthesis of New Chiral Phosphine Ligands and Their Application in Asymmetric Hydrogenation of Ketones

The design of new chiral ligands is the key in the development of transition metal catalyzed asymmetric synthesis. Many chiral diphosphine ligands have been prepared and applied in asymmetric catalytic reactions with excellent enantioselectivities. Among the chiral diphosphine ligands that have been reported, the atropisomeric C2-symmetric phosphines with a biaryl scaffold initiated by Noyori and co-workers with BINAP were found to have the widest application in the transition metal catalyze…     

Well-defined binuclear chiral spiro copper catalysts for enantioselective N-H insertion

An asymmetric N-H insertion of α-diazoesters with anilines catalyzed by well-defined copper complexes of chiral spiro bisoxazoline ligands was studied in detail. The copper-catalyzed asymmetric N-H insertion of a wide range of α-alkyl-α-diazoacetates with anilines was accomplished with excellent enantioselectivity (up to 98% ee) and provided an efficient method for the preparation of optically active α-amino acid derivatives. A correlation study of the electronic properties of the substrates with the enantioselectivity of the N-H insertion reaction supports a stepwise insertion mechanism, and the significant first-order kinetic isotope effect proves that the proton transfer is most likely the rate-limiting step. A binuclear chiral spiro copper catalyst having 14-electron copper centers, a trans coordination model, a perfect C(2)-symmetric chiral pocket, and significant Cu-Cu interaction was isolated and extensively studied. The novel structure of the binuclear chiral spiro copper catalyst leads to unique reactivity as well as enantioselectivity in the N-H insertion reaction.     

Highly efficient Rh(I)-catalyzed asymmetric hydrogenation of enamines using monodente spiro phosphonite ligands

A highly enantioselective hydrogenation of nonfunctionalized enamines has been developed by using rhodium complexes of chiral spiro phosphonite ligands, providing chiral tertiary amines in excellent enantioselectivities.     

金属催化的不对称氢化反应研究进展与展望

手性过渡金属络合物催化的不对称氢化反应是合成光学活性化合物的重要方法. 本文从手性配体及手性催化剂、不对称催化新反应、新方法和新策略三个方面简要评述新世纪以来过渡金属催化的不对称氢化反应研究领域的新进展. 从新世纪初至今, 手性单磷配体得到了复兴, 出现了如MonoPhos、SiPhos、DpenPhos等高效单齿亚磷酰胺酯配体; 磷原子手性(P-手性)配体也得到了快速发展, 如BenzP*、ZhanPhos、TriFer等已成为新的高效手性双膦配体; 螺环骨架手性配体成为新世纪手性配体设计合成的亮点, 除了SiPhos、SIPHOX、SpinPHOX等高效手性螺环配体外, 手性螺环吡啶胺基磷配体SpiroPAP的铱催化剂成为目前最高效的分子催化剂. 不对称催化氢化新反应研究也取得了突破, 如非保护烯胺、杂芳环化合物及N-H亚胺的氢化等反应都实现了高对映选择性. 自组装手性催化剂、树枝状手性催化剂、铁磁性纳米负载的可回收手性催化剂, 以及“混合”配体手性催化剂等新方法和新策略也在不对称催化氢化反应中得到了应用. 然而, 手性过渡金属络合物催化的不对称氢化研究仍然充满挑战, 也期待新的突破.     

Highly enantioselective hydrovinylation of alpha-alkyl vinylarenes. an approach to the construction of all-carbon quaternary stereocenters

The highly enantioselective hydrovinylation of alpha-alkyl vinylarenes was realized by using nickel complexes of chiral spiro phosphoramidite ligands. The method provided a new approach to the construction of chiral all-carbon quaternary centers.