Chiral iridium(I) bis(NHC) complexes as catalysts for asymmetric transfer hydrogenation

The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L ‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley & Sons, Ltd.     

Efficient Enantioselective Syntheses of Chiral Natural Products Facilitated by Ligand Design

The employment of enantioselective transition‐metal‐catalyzed transformations as key steps in asymmetric natural product syntheses have attracted considerable attention in recent years owing to their versatile synthetic utilities, mild conditions and high efficiency in chirality generation. The chiral catalysts or supporting ligands are believed to be crucial for the requisite reactivity and enantioselectivity. Therefore, the rational design of chiral ligands is at the heart of developing new asymmetric transition‐metal catalyzed reactions and provides an avenue to the asymmetric synthesis of natural products. Our group has been engaged in the development of transition‐metal‐catalyzed enantioselective cross‐coupling, cyclization and other related reactions and the application of these methodologies to natural product syntheses. In this account, we summarized our recent synthetic efforts towards the efficient total syntheses of several different types of natural products including terpenes, alkaloids and polyketides facilitated by the design of a series of versatile P‐chiral phosphorous ligands.     

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.     

New chiral Schiff bases derived from (+)- and (−)-α-pinenes in the metal complex catalyzed asymmetric oxidation of sulfides

New chiral Schiff bases were derived from (+)- and (−)-α-pinenes for the first time. Coordinated to vanadium ions, they can be used as ligands in catalytic oxidation of sulfides into chiral sulfoxides. Conditions for the asymmetric oxidation of thioanisole to methyl phenyl sulfoxide in optical purity up to 32% were found. Variation of substituents in the ligand has a significant effect not only on enantioselectivity of the reaction, but also on absolute configuration of the sulfoxide formed. Dedicated to Academician G. A. Tolstikov in honor of his 75th anniversary. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 105–113, January, 2008.     

Chiral sulfoxide ligands bearing nitrogen atoms as stereocontrollable coordinating elements in palladium-catalyzed asymmetric allylic alkylations

Palladium-catalyzed asymmetric allylic alkylations were studied by using chiral sulfoxide ligands bearing nitrogen atoms as coordinating elements, such as chiral α-sulfinylacetamides, β or γ-amino sulfoxides, and β-sulfinyl sulfonamides. The effects of the chiral sulfinyl functions on the asymmetric induction were demonstrated. Use of (S)-2-pyrrolidinophenyl p-tolyl sulfoxide or (S)-2-(N-butyl-N-methylaminomethyl)phenyl p-tolyl sulfoxide as chiral ligands in the palladium-catalyzed asymmetric allylic alkylations provided the highest enantioselectivity (50 or 58% e.e., respectively) among chiral sulfoxide ligands examined by us. The participation of the sulfinyl groups in these catalytic asymmetric reactions is rationalized, and the mechanism for the asymmetric induction is proposed on the basis of the stereochemical outcome obtained.     

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.     

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

The ProPhenol ligand is a member of the chiral aza‐crown family that spontaneously forms a bimetallic complex upon treatment with alkyl metal reagents, such as Et₂Zn and Bu₂Mg. The resulting complex features Lewis acidic and Brønsted basic sites, enabling simultaneous activation of both nucleophile and electrophile in the same chiral environment. Since the initial report in 2000, metal‐ProPhenol catalysts have been used to facilitate a broad range of asymmetric transformations, including aldol, Mannich, and Henry reactions, as well as alkynylations and conjugation additions. By promoting such a diverse array of reactions, these complexes provide rapid and atom‐economical access to valuable complex building blocks. In this Review, we describe in detail the development and synthetic applications of these versatile catalysts with a special focus on recent efforts to improve reactivity and selectivity through ligand design and structural modification.     

手性亚砜的合成及其在不对称合成中的应用

本文综述了手性亚砜的合成。由于亚砜结构上的特征以及与金属离子的络合能力,使手性亚砜在不对称合成中具有强烈的诱导作用,使它成为进行不对称合成的一个手段。本文列举了它在不对称合成中的应用情况。     

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。     

A new chiral sulfinyl-NH-pyridine ligand for Ir-catalyzed asymmetric transfer hydrogenation reaction

A new flexible C₁-symmetric tridentate ligand (S)-N-(2-(tert-butylsulfinyl)benzyl)-1-(pyridin-2-yl)methanamine sulfoxide (L1) was successfully prepared and utilized as a chiral ligand for Ir(I)-catalyzed ATH (asymmetric transfer hydrogenation) reactions. Without any cooperation of other chiral center, encouraging ee and conversion values have been achieved, which provide us a better understanding on these types of ligands and a new strategy to develop new high-efficiency chiral catalysts for asymmetric reaction.     

手性二胺的合成及其在催化不对称反应中的应用

手性二胺作为具有良好催化活性和对映选择性的手性配体或手性辅助剂, 在多种催化不对称反应中已经得到广泛应用, 并取到了很好的研究成果. 目前, 手性二胺化学的研究已成为催化不对称化学领域中一个十分活跃和引人注目的研究热点. 综述了手性二胺化学近几年的研究进展.     

Synthesis of Enantioenriched Sulfoxides by an Oxidation-Reduction Enzymatic Cascade

Chiral sulfoxides are versatile synthons and have gained a particular interest in asymmetric synthesis of active pharmaceutical and agrochemical ingredients. Herein, a linear oxidation–reduction bienzymatic cascade to synthesize chiral sulfoxides is reported. The extraordinarily stable and active vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) was used to oxidize sulfides into racemic sulfoxides, which were then converted to chiral sulfoxides by highly enantioselective methionine sulfoxide reductase A (MsrA) and B (MsrB) by kinetic resolution, respectively. The combinatorial cascade gave a broad range of structurally diverse sulfoxides with excellent optical purity (>99 % ee) with complementary chirality. The enzymatic cascade requires no NAD(P)H recycling, representing a facile method for chiral sulfoxide synthesis. Particularly, the envisioned enzymatic cascade not only allows CiVCPO to gain relevance in chiral sulfoxide synthesis, but also provides a powerful approach for (S)-sulfoxide synthesis; the latter case is significantly unexplored for heme-dependent peroxidases and peroxygenases.     

手性pybox-金属络合物及其在不对称催化反应中的应用

具有C2对称性的双噁唑啉型吡啶(pybox)是一类有效的手性配体,能与许多金属离子配位,其手性催化性能已得到越来越多的关注。本文综述了手性配体pybox和pybox-金属络合物的合成方法,特别是近年来pybox-金属络合物在不对称催化反应如不对称环丙烷化反应、不对称Diels-Alder反应、1,3-偶极环加成反应、不对称aldol反应等中应用的最新进展。     

Chiral Ditopic Cyclophosphazane (CycloP) Ligands: Synthesis,Coordination Chemistry,and Application in Asymmetric Catalysis

A series of dichlorocyclophosphazanes [{ClP(μ‐NR)}₂] containing chiral and achiral R groups was obtained from simple commercially available amines and PCl₃. Their condensation reactions with axially chiral biaryl diols yielded ansa‐bridged chiral cyclophosphazane (CycloP) ligands. This highly modular methodology allows extensive elaboration of the ligand set, in which the chirality can be introduced at the diol bridge and/or the amido R group. This provides the possibility to observe match and mismatch effects in catalysis. A series of twenty CycloP ligands was synthesized and characterized by multinuclear NMR spectroscopy, HRMS, elemental analysis, and in selected cases, single‐crystal X‐ray diffraction. These studies show that all of the ditopic CycloP ligands are C₂ symmetric, rendering their metal coordination sites symmetry equivalent. Two well‐established enantioselective reactions were explored by using late‐transition metal CycloP complexes as catalysts; the gold‐catalyzed hydroamination of γ‐allenyl sulfonamides and the asymmetric nickel‐catalyzed three‐component coupling of a diene and an aldehyde. The steric demands of the CycloP ligands have a subtle influence on the reactivity and selectivity observed in both reactions. Good enantiomeric ratios (e.r.) as high as 89:11 in the gold‐catalyzed reaction and 92:8 in the nickel‐catalyzed bis‐homoallylation reaction were observed.     

Phosphoramidites: Privileged Ligands in Asymmetric Catalysis

Asymmetric catalysis with transition‐metal complexes is the basis for a vast array of stereoselective transformations and has changed the face of modern synthetic chemistry. Key to this success has been the design of chiral ligands to control the regio‐, diastereo‐, and enantioselectivity. Phosphoramidites have emerged as a highly versatile and readily accessible class of chiral ligands. Their modular structure enables the formation of ligand libraries and easy fine‐tuning for a specific catalytic reaction. Phosphoramidites frequently show exceptional levels of stereocontrol, and their monodentate nature is essential in combinatorial catalysis, where a ligand‐mixture approach is used. In this Review, recent developments in asymmetric catalysis with phosphoramidites used as ligands are discussed, with a focus on the formation of carbon–carbon and carbon–heteroatom bonds.     

Nanosheet‐Enhanced Asymmetric Induction of Chiral α‐Amino Acids in Catalytic Aldol Reaction

An efficient ligand design strategy towards boosting asymmetric induction was proposed, which simply employed inorganic nanosheets to modify α‐amino acids and has been demonstrated to be effective in vanadium‐catalyzed epoxidation of allylic alcohols. Here, the strategy was first extended to zinc‐catalyzed asymmetric aldol reaction, a versatile bottom‐up route to make complex functional compounds. Zinc, the second‐most abundant transition metal in humans, is an environment‐friendly catalytic center. The strategy was then further proved valid for organocatalyzed metal‐free asymmetric catalysis, that is, α‐amino acid catalyzed asymmetric aldol reaction. Visible improvement of enantioselectivity was experimentally achieved irrespective of whether the nanosheet‐attached α‐amino acids were applied as chiral ligands together with catalytic Zn^II centers or as chiral catalysts alone. The layered double hydroxide nanosheet was clearly found by theoretical calculations to boost ee through both steric and H‐bonding effects; this resembles the role of a huge and rigid substituent.     

金属催化硫醚的不对称氧化研究进展

手性金属络合物催化硫醚的不对称氧化是合成手性亚砜最有效的方法. 理性设计各种手性金属络合物催化剂应用于催化对映选择性氧化潜手性硫醚反应中, 近年来引起了化学家们较大的关注. 综述了各类手性金属络合物催化剂在硫醚不对称氧化中的应用.     

Asymmetric Henry Reaction of α-Keto Ester Catalyzed by Tridentate Bis( oxazoline ) and B is( thiazoline )

Bidentate and tetradentate ligands containing the oxazoline unit have been successful in a range of asymmetric transformations.[1～3] Chiral tridentate ligands may form a deeper chiral concave pocket around the metal center, and have been less extensively used in asymmetric catalysis than their bidentate or tetradentate analogues. Nishiyama's tridentate "pybox"ligand, in which a pyridine ring links two chiral oxazoline moieties, has been successfully used in various asymmetric reactions.     

Asymmetric Borohydride Reduction of Acetophenone Catalyzed by Chiral Salen-Co(Ⅱ) Complex Using Sodium Borohydride

Development of efficient catalytic asymmetric reactions is the most challenging task in current synthetic chemistry; much effort has been devoted to create the chiral metal complexes of asymmetric catalysis. In the last two decades' many brand-new ligands had been synthesized and their combination with various metal ions has been applied in asymmetric catalysis. However, most ligands have only narrow applications and their use is limited to some reactions. Exceptionally, a few ligands and their metal complexes such as binaphthol, semicollin,and binap show wide applicability. Chiral salen ligand is one of such ligands and their metal complexes are now used as the catalysts for a variety of asymmetric reactions such as epoxidation^[1], aziridination^[2], cyclopropanation^[3], Diels-Alder reaction^[4], asymmetric transfer hydrogenation of aromatic ketones^[5] and kinetic resolution of racemic epoxides^[6] and so on.