Palladium(II)-catalyzed asymmetric synthesis of (Z)-alpha-alkylidene-gamma-butyrolactams from (Z)-N-allylic 2-Alkynamides. Total synthesis of (-)-isocynometrine

Pd(OAc)2 combined with nitrogen-containing ligands catalyzed the cyclization of (Z)-N-allylic 2-alkynamides in acetic acid to afford the alpha-(Z)-acetoxyalkylidene-gamma-butyrolactams in high yield and high stereoselectivity. When chiral nitrogen-containing ligands were used, the catalytic asymmetric protocol was achieved with moderate enantioselectivity (up to 80 degrees C). The utility of this new methodology was exemplified by the total synthesis of (-)-isocynometrine.     

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…     

Lewis Base/Brønsted Acid Co‐catalyzed Enantioselective Sulfenylation/Semipinacol Rearrangement of Di‐ and Trisubstituted Allylic Alcohols

An enantioselective sulfenylation/semipinacol rearrangement of 1,1‐disubstituted and trisubstituted allylic alcohols was accomplished with a chiral Lewis base and a chiral Brønsted acid as cocatalysts, generating various β‐arylthio ketones bearing an all‐carbon quaternary center in moderate to excellent yields and excellent enantioselectivities. These chiral arylthio ketone products are common intermediates with many applications, for example, in the design of new chiral catalysts/ligands and the total synthesis of natural products. Computational studies (DFT calculations) were carried out to explain the enantioselectivity and the role of the chiral Brønsted acid. Additionally, the synthetic utility of this method was exemplified by an enantioselective total synthesis of (?)‐herbertene and a one‐pot synthesis of a chiral sulfoxide and sulfone.     

Novel nitrogen ligands based on imidazole derivatives and their application in asymmetric catalysis

Recently prepared chiral amines have been used in the preparation of novel tridentate ligands based on an imidazole ring with an additional (hetero)ring. The synthesis was carried out by the reaction of chiral amines with suitable aldehydes (2-phenylimidazole-4-carbaldehyde, 2-hydroxybenzaldehyde or pyridine-2-carbaldehyde) under reductive conditions (H₂/Pd or NaBH₄). All ligands prepared showed strong hydrogen bonds in d₆-DMSO solution, which resulted in hindered imidazole tautomerism. The observed hindered tautomerism was studied by ¹H NMR spectroscopy. The structures of the prepared ligands were also confirmed by APCI mass spectroscopy. Both chiral amines and tridentate compounds have been applied as ligands in copper (II)-catalyzed nitroaldol reactions (Henry reaction). Various reaction conditions for the Henry reaction have been studied (influence of temperature, molar ratio, solvent or copper (II) precursors). The compounds prepared with the two imidazole rings showed fast reaction times and a reversal in enantioselectivity compared to other chiral amines.     

Enantiocatalytic activity of substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-one ligands

Currently, asymmetric synthesis represents one of the main streams of organic synthesis. Although an extensive research has been carried out in this area, the synthesis of chiral compounds with the required enantiomeric purity is still a challenging issue. Herein, we focus on the preparation of new enantioselective catalysts based on pyridine-imidazolidinones. The substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-ones 5–8 were prepared by condensation of chiral amino acid amides (α-methylDOPA and α-methylphenylalanine) with 2-acetylpyridine and pyridine-2-carbaldehyde. The individual isomers of the described ligands 5–8 were separated chromatographically. The copper(II) complexes of these chiral ligands were studied as enantioselective catalysts for the asymmetric Henry reaction of substituted aldehydes with nitromethane or nitroethane. The ligands containing a methyl group at the 2-position of the imidazolidinone ring 6a and 8a exhibit a high degree of enantioselectivity (up to 91% ee). The nitroaldols derived from nitroethane (2-nitropropan-1-ols) were obtained with a comparable enantiomeric purity to derivatives of 2-nitroethanol. This group of ligands represents a new and promising class of enantioselective catalysts, which deserve further attention.     

Synthesis of 7,7’-Disubstituted BINAP and Their Application in Asymmetric Catalytic Reaction

The design of new chiral ligands plays a very important role 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 reported, BINAP was found to have been the widest application in the transition metal catalyzed reaction. Recently we have developed a novel oxovanadium (Ⅳ) complex catalyst for the oxidative …     

手性配体在钯催化不对称碳氢键活化反应中的应用

目前,手性配体辅助钯催化的区域和对映选择性碳氢键活化是过渡金属催化的前沿领域.在过去的十年中,它作为一种越来越重要的合成工具,用于合成含有各种不对称元素(中心手性、轴手性和平面手性)的手性分子,也是快速构建各种碳碳键和碳杂原子键的最有效方法之一.本文介绍了一些典型手性配体在钯催化不对称sp2和sp3碳氢键活化/官能团化...     

Chiral Cooperativity: The Effect of Distant Chiral Centers in Ferrocenylamine Ligands upon Enantioselectivity in the Gold(I)-Catalyzed Aldol Reaction

Long-range chiral cooperativity in enantiomerically pure ferrocenylamine ligands containing both planar and multiple centers of chirality (multiple stereogenic C-atoms) was demonstrated in the Au^I-catalyzed reaction of aldehydes and isocyanoesters. Synthetic methodology was developed for the synthesis of ferrocenylamine ligands with two and three chiral centers of known absolute configuration in the C-side chain in addition to the planar chirality of the molecule. The diastereo- and enantioselectivity of the Au^I-catalyzed formation of the trans- and cis-dihydrooxazoles 5 and 6 , respectively, from benzaldehyde ( 1 ) and methyl isocyanoacetate ( 2 ) depend upon the sequence of chirality (absolute configuration of the chiral centers) in the side chain of the ferrocenylamine ligands. Particularly significant effects were observed upon the enantioselectivity for the minor cis-dihydrooxazole 6 , for which, in certain cases, resulted in a change in the enantiomeric dihydrooxazole 6 produced in excess with a change in the absolute configuration of a distant chiral center. Significant effects upon diastereo- and enantioselectivity were observed when chiral ferrocenylamine ligands containing free OH groups were utilized. Using ligands containing a free OH group gave 6 with an absolute configuration opposite to that produced by the corresponding ester and carbamate derivatives. The possible mechanisms for the transmission of chiral information in the proposed stereoselective transition state (TS) was discussed, including both the formation of a stereogenic N-atom and steric effects based upon Newman's rule of six.     

Optimization of catalyst enantioselectivity and activity using achiral and meso ligands

The optimization of asymmetric catalysts for enantioselective synthesis has conventionally revolved around the synthesis and screening of enantiopure ligands. In contrast, we have optimized an asymmetric reaction by modification of a series of achiral ligands. Thus, employing (S)-3,3'-diphenyl BINOL [(S)-Ph(2)-BINOL] and a series of achiral diimine and diamine activators in the asymmetric addition of alkyl groups to benzaldehyde, we have observed enantiomeric excesses between 96% (R) and 75% (S) of 1-phenyl-1-propanol. Some of the ligands examined have low-energy chiral conformations that can contribute to the chiral environment of the catalyst. These include achiral diimine ligands with meso backbones that adopt chiral conformations, achiral diimine ligands with backbones that become axially chiral on coordination to metal centers, achiral diamine ligands that form stereocenters on coordination to metal centers, and achiral diamine ligands with pendant groups that have axially chiral conformations. Additionally, we have structurally characterized (Ph(2)-BINOLate)Zn(diimine) and (Ph(2)-BINOLate)Zn(diamine) complexes and studied their solution behavior.     

New synthetic routes toward enantiopure nitrogen donor ligands

New polypyridylic chiral ligands, having either C3 or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kr?hnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-alpha-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br2], (-)-20, and [RuCl((-)-10)(bpy)](BF4), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.     

Synthesis and characterization of highly conjugated, chiral bridging ligands

This paper describes the synthesis of four chiral derivatives of the electronically highly conjugated tetra-2-pyridylpyrazine (TPPZ) bridging ligand, which are denoted (R)- and (S)-4,5- and 5,6-pineno-tetra-2-pyridylpyrazine (PTPPZ). Preparation of these ligands was undertaken through the use of commercially available, enantiomerically pure (1R)- and (1S)-alpha-pinene, which was functionalized and subsequently employed in a Krohnke pyridine synthesis involving a furan-substituted pyridinium salt to yield a chiral, furan-substituted pyridyl intermediate. Oxidative degradation and subsequent reduction of this furan led to a chiral, substituted 2-pyridylaldehyde, which underwent a pyridoin condensation followed by cyclization to produce the final PTPPZ ligands.     

Optically active transition metal complexes. Part 119:New rhodium(I) complexes containing two different types of optically active ligands

The synthesis of novel rhodium(I) complexes containing two different chiral ligands is described. These ligands are on the one hand (−)-diop and on the other hand various optically active pyrroleimines, which derive from 1-phenylethylamine or 1-cyclohexylethylamine with an (R)- or (S)-configuration. The resulting (−)-diop–pyrrolylimine–rhodium(I) complexes are diastereomers and are expected to give different stereoselectivities in enantioselective catalysis (double stereoselection). In addition, the synthesis of novel rhodium(I) complexes containing 1,5-cyclooctadiene and various chiral pyrroleoxazoline ligands is described. All the complexes are used in the enantioselective hydrogenation of ketopantolactone (see following paper).     

Synthesis of novel diastereomeric diphosphine ligands and their applications in asymmetric hydrogenation reactions

[structure: see text] Diastereomeric biaryl diphosphine ligands 10 and 11 with added chiral centers on the backbone were synthesized. Substrate-directed asymmetric synthesis occurred in the coupling step of the preparation of the diastereomeric diphosphine oxides. The diastereomeric diphosphine oxides were easily separated by column chromatography with silica gel. Ruthenium catalysts containing these ligands were highly effective in the hydrogenation of 2-(6'-methoxy-2'-naphthyl)propenoic acid and beta-ketoesters. The additional chiral centers had a significant influence on the enantioselectivity and activity of the catalysts.     

Preparation of new axially chiral bridged 2,2'-bipyridines and pyridyl monooxazolines (pymox). Evaluation in copper(I)-catalyzed enantioselective cyclopropanation

This work reports the synthesis of new axially chiral bridged 2,2'-bipyridines 1 and pyridylmonooxazolines (pymox) 2. The potential of these new axially chiral N,N-ligands was evaluated in asymmetric catalytic cyclopropanation of styrene derivatives 22a-c with diazoesters 21a,b. While 2,2'-bipyridines 1a-c afforded the corresponding cyclopropanes 23a-f in up to 65% ee, pymoxs 2a-e gave somewhat lower enantioselectivities (up to 53% ee). Both classes of ligands produced trans-cyclopropanes 23a-f as the major isomer, although with modest diasteroselectivities (56 : 44 to 78 : 22). A structure-stereoselectivity relationship study of ligands 1 and 2 identified the chiral biaryl axis as being mostly responsible for the enantioselective performances of these ligands.     

天然酒石酸在合成手性含膦配体中的应用

本文综述了以天然酒石酸为光活性原料的手性含膦配体合成, 对三十三种手性含膦配体进行归类,同时也简要地介绍了部分配体的Rh(I)配合物催化剂对(Z)-α-乙酰氨基肉桂的催化氢反应结果。     

手性配位聚合物的构筑及其应用

手性配位聚合物因其结构多样性、可调控性以及潜在的多功能性,已经成为当前化学和材料学的研究热点。在合成中,可以通过选择特定的非手性配体、手性配体、手性溶剂或手性模板剂等来构筑手性配位聚合物。此外,还可以选择特定的金属离子赋予目标手性配位聚合物光、电、磁、催化和非线性光学等性能。本文详细综述了近年来纯手性配位聚合物的合成方法,以及在手性分离、手性催化、非线性光学、铁电和多铁等领域的应用研究进展。最后,对手性配位聚合物的合成方法及应用前景进行了展望。     

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.     

Synthesis and Crystal Structure of rac-N,N-Dimethyl-1- ferrocenylethylamine Hydrochloride

Ferrocene with planar chirality are of increasing importance in the synthesis of chiral ligands used in asymmetric catalysis and asymmetric synthesis.[1～3] To prepare Ugi type of chiral base, the most common method is the resolution of rac-N,N-dimethyl- 1-ferrocenylethylamine (1).     

二类手性铜催化剂的合成及其在光学活性菊酸合成中的应用研究

报道了双恶唑啉和Ｓｃｈｉｆｆ碱二类手性配合物的合成及其在光学活性菊酸的不对称合成中的应用，以合成氯霉素中间体的无效体（１Ｓ，２Ｓ）－２－氨基－１－对硝基苯基－１，３－丙二醇为原料，分别制得了二取代双恶唑啉和Ｓｃｈｉｆｆ碱二类配体，并将其分别与醋酸铜配合后得到手性铜催化剂来诱导烯烃（２，５－二甲基－２，４－己二烯和１，１－二苯乙烯）与重氮乙酸酯的不对称环丙烷化反应，最高获得４５．２％ｅ．ｅ。     

手性双噁唑啉配体在不对称合成中的应用

双噁唑啉手性配体已广泛用于不对称Henry反应、环丙烷化反应、Aldol反应、烷基化反应、环加成反应中,并表现出很高的对映选择性和催化活性,成为最有用的手性配体之一。文章综述了近10年来双噁唑啉手性配体及高分子受载手性双噁唑啉在不对称合成中的研究进展。