Development Of Asymmetric Catalysis Research Articles

Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes.

Despite the enormous developments in asymmetric catalysis, the basis for asymmetric induction is largely limited to the spatial interaction between the substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between two aryl groups without a directing group or electronic manipulation. Here we address this challenge by using a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With versatile 2-indole imine methide as the platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π–π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.

Harnessing Noncovalent Interactions in Dual-Catalytic Enantioselective Heck-Matsuda Arylation.

The use of more than one catalyst in one-pot reaction conditions has become a rapidly evolving protocol in the development of asymmetric catalysis. The lack of molecular insights on the mechanism and enantioselectivity in dual-catalytic reactions motivated the present study focusing on an important catalytic asymmetric Heck-Matsuda cross-coupling. A comprehensive density functional theory (M06 and B3LYP-D3) investigation of the coupling between a spirocyclic cyclopentene and 4-fluorophenyl diazonium species under a dual-catalytic condition involving Pd2(dba)3 (dba = trans, trans-dibenzylideneacetone) and chiral 2,2'-binaphthyl diamine (BINAM)-derived phosphoric acids (BDPA, 2,2'-binaphthyl diamine-derived phosphoric acids) is presented. Among various mechanistic possibilities examined, the pathway with explicit inclusion of the base (in situ generated sodium bicarbonate/sodium biphosphate) is found to be energetically more preferred over the analogous base-free routes. The chiral phosphate generated by the action of sodium carbonate on BDPA is found to remain associated with the reaction site as a counterion. The initial oxidative addition of Pd(0) to the aryl diazonium bond gives rise to a Pd-aryl intermediate, which then goes through the enantiocontrolling migratory insertion to the cyclic alkene, leading to an arylated cycloalkene intermediate. Insights on how a series of noncovalent interactions, such as C-H···O, C-H···N, C-H···F, C-H···π, lp···π, O-H···π, and C-F···π, in the enantiocontrolling transition state (TS) render the migration of the Pd-aryl to the si prochiral face of the cyclic alkene more preferred over that to the re face are utilized for modulating the enantioselectivity. Aided by molecular insights on the enantiocontrolling transition states, we predicted improved enantioselectivity from 37% to 89% by changes in the N-aryl substituents of the catalyst. Subsequent experiments in our laboratory offered very good agreement with the predicted enantioselectivities.

Creation of chiral materials: Yesterday, today and tomorrow

Chirality is a fundamental characteristic of nature and pervades the world. The chiral materials closely related to our life, especially our health. The thalidomide tragedy, lessons for drug safety and regulation from the late 1950s and the early 1960s, indicated the importance of creating chiral materials in optically pure form. Pasteur was the first to conduct chiral resolution for the preparation of optically active molecules before 1860. Since then, scientists including chemists started to search methods for creating chiral materials like enzyme. After more than one hundred years of efforts, chemists find that the synthetic chiral catalysts (also known as artificial enzymes) catalyzed asymmetric reactions is the door to creating chiral materials. From 1970 to 2001, many efficient and selective catalytic asymmetric reactions and methods have been developed for creating chiral materials. In particular, the successes of catalytic asymmetric hydrogenations and catalytic asymmetric epoxidations and their applications in industrial preparation of chiral drugs enable this research field to won the Nobel Prize for chemistry in 2001. To date, tremendous amount of chiral materials such as chiral pharmaceuticals, chiral agrochemicals, chiral liquid crystals were created in a high selective and efficient manner. We now can create chiral materials like enzymes by using asymmetric catalysis with artificial enzymes as catalysts. The Chinese chemists also made great contributions for creating chiral materials, especially in the past two decades. They developed a series of highly efficient chiral ligands and catalysts including the magical chiral spiro ligands and catalysts, the privileged chiral N , N ￠-dioxides, as well as many original organocatalysts. These catalysts are highly efficient for a wide range of reactions involving asymmetric hydrogenation, asymmetric carbon-carbon bond formations, and asymmetric carbon-heteroatom bond formations, providing chiral alcohols, chiral amines, chiral acids, etc. Many new asymmetric catalytic reactions, new concepts, new strategies were also developed by Chinese chemists, which afforded new methodologies for creating chiral materials. From this century, in order to meet the new demand of mankind on the chiral materials, scientists begin to develop green and sustainable methods for the accurate, powerful and environment-friendly creation of chiral materials. In addition, the creation of chiral materials has been in depth combined with life sciences, environmental sciences, materials science and information sciences, etc. This review focus on the main line of the discovery and development of asymmetric catalysis, in combination with the development in China, to give a brief overview for the journey of creation of chiral materials.

ChemInform Abstract: Reduction of Secondary and Tertiary Phosphine Oxides to Phosphines

AbstractReview: [77 refs.

ChemInform Abstract: Asymmetric Catalysis with Short‐Chain Peptides

AbstractReview: 43 refs.

Axial coordination dichotomy in dirhodium carbenoid catalysis: a curious case of cooperative asymmetric dual-catalytic approach toward amino esters.

One of the most recent developments in asymmetric catalysis is to employ two or more catalysts under one-pot reaction conditions. This article presents some interesting mechanistic insights on a cooperative dual-catalytic protocol relying on the catalytic ability of dirhodium carbenoid (derived from rhodium(II) tetracarboxylate and a diazo compound) and a chiral spirophosphoric acid ((R)-SPA) in an asymmetric N-H insertion reaction. We have employed DFT(M06 and B3LYP) computational methods to identify the stereocontrolling transition states wherein a chiral (R)-SPA protonates a dirhodium-bound enol intermediate. A true cooperative action elicited by both catalysts has been noted in the enantioselective protonation. More importantly, whether the second axial ligand on the remote rhodium atom could influence the energetic features of the reaction has been probed for the first time. In all steps (such as nitrogen extrusion, addition of amine to the dirhodium carbenoid, and the enol formation), except that in the stereocontrolling event, no major effect of axial ligation has been noticed. However, the presence of the axial ligand helps in stabilizing the protonation transition state and reduces the activation barrier for protonation, suggesting a vital role in stereoselectivity. The predicted sense of stereoselectivities is in good agreement with the experimental results.

Editorial

This themed issue guest edited by Alfons Baiker (ETH-Zurich) provides inspiring insight into new developments in asymmetric catalysis on chiral surfaces covering various catalyst design strategies, mechanistic aspects, and catalytic performances.

Chiral N,N′-dioxide ligands: synthesis, coordination chemistry and asymmetric catalysis

A class of conformationally flexible ligands composed of a tertiary amino oxide–amide backbone and a straight-chain alkyl spacer was developed. These C2-symmetric chiral N,N′-dioxide ligands could be straightforwardly synthesized from readily available amino acids and amines. They act as neutral tetradentate ligands to bind a wide variety of metal ions. Non-planar cis-α M(N,N′-dioxide) complexes enable an intriguing and easily fine-tuned chiral platform for a number of asymmetric reactions. Privileged N,N′-dioxide ligands frequently show wide substrate generality and exceptional levels of stereocontrol for a specific catalytic reaction. We describe approaches to the ligand design and synthesis, structure and bonding in coordination complexes, and the recent developments in asymmetric catalysis.

Facts are the Enemy of Truth—Reflections on Serendipitous Discovery and Unforeseen Developments in Asymmetric Catalysis

As Louis Pasteur said, "Chance favors only a prepared mind." Serendipitous events reorienting the pathway of science often occur through the actions of dedicated individuals with unique cultural and educational backgrounds, an original sense of values, and firm principles. Science is the fountainhead of human knowledge and possesses an indispensable cultural value. Science-based technologies and the innovations derived from them are the foundation of the civilized society in which we live today. All scientific endeavors begin with observations, or facts. However, the real goal of research activity is to convert accumulated knowledge to something with new technological, economic, or social value. Innovation is an essential aspect to assure the continued survival of humanity. And often, as my half-century of research reflects, the act of turning facts into values is facilitated by dialogue. Thus, to acquire the necessary combined wisdom, scientists must have ongoing conversations with the societies they serve, as well as with their counterparts in other nations.

ChemInform Abstract: Recent Developments in Asymmetric Catalysis in the Presence of Chiral Gold Complexes

AbstractReview: ca. 80 refs.

Recent Developments in Asymmetric Catalysis in the Presence of Chiral Gold Complexes

Catalytic asymmetric gold-catalyzed reactions provide versatile routes to enantiomerically enriched carbo- and heterocycles. This review summarizes the recent work on the development of novel catalytic systems combining gold and a chiral ligand.

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.

Tandem reactions for streamlining synthesis: enantio- and diastereoselective one-pot generation of functionalized epoxy alcohols.

[Reaction: see text] In 1980, Sharpless and Katsuki introduced the asymmetric epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki asymmetric epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy alcohols. This reaction was a milestone in the development of asymmetric catalysis because it was the first highly enantioselective oxidation reaction. Furthermore, it provided access to enantioenriched allylic alcohols that are now standard starting materials in natural product synthesis. In 1981, Sharpless and co-workers made another seminal contribution by describing the kinetic resolution (KR) of racemic allylic alcohols. This work demonstrated that small-molecule catalysts could compete with enzymatic catalysts in KRs. For these pioneering works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori. Despite these achievements, the Sharpless KR is not an efficient method to prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol must be stopped at low conversion, because the ee of the product epoxy alcohol decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols containing stereogenic carbinol carbons are needed. This Account summarizes our efforts to develop one-pot methods for the synthesis of various epoxy alcohols and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity. Our laboratory developed titanium-based catalysts for use in the synthesis of epoxy alcohols with tertiary carbinols. The catalysts are involved in the first step, which is an asymmetric alkyl or allyl addition to enones. The resulting intermediates are then subjected to a titanium-directed diastereoselective epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent epoxidation. The methods described here enable the synthesis of skeletally diverse epoxy alcohols.

ChemInform Abstract: Developments in Asymmetric Catalysis by Metal Complexes of Chiral Chelating Nitrogen‐Donor Ligands

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Developments in asymmetric catalysis by metal complexes of chiral chelating nitrogen-donor ligands

In part because of their straightforward and modular syntheses from readily available enantiopure starting materials, and their capacity to bind a wide variety of transition metals, chiral, chelating nitrogen-donor ligands have played a prominent role in asymmetric catalysis. A large number of highly enantioselective transformations rely upon these ligands whose reported classes are built around amine, imine, pyrrole, pyrrolidine, oxazoline and oxazolidine donor groups, among others. In this Perspective, we examine a selection of transformative developments in asymmetric catalysis by metal complexes of bi- and polydentate members of this ligand family. We describe approaches to ligand design and synthesis, structure and bonding in coordination complexes, and limitations and future challenges.

The 2005 Bower Award in science presented to Henri B. Kagan

The scientific theme for the 2005 Bower Award was Chemistry, specifically the field of Catalysis. The Franklin Institute, Philadelphia, Pennsylvania, awarded the 2005 Bower Award and Prize for achievement in Science to Henri B. Kagan for his seminal discovery of fundamental chemical principles that explain the impact of catalyst shape on its effectiveness in controlling chemical reactions, thus greatly simplifying the manufacture of pharmaceutically important compounds. Henri Kagan is widely recognized as a pioneer in the field of asymmetric catalysis. Starting in the early 1970s, his reports of the synthesis of the chiral bidentate diphosphine ligand and the demonstration of its use with soluble rhodium compounds to catalyze the efficient production of large enantiomeric excesses of chiral molecules in asymmetric hydrogenations has had far reaching effects on research in the field asymmetric catalysis. The concept of using chiral bidentate ligands of C2 symmetry has led the way for numerous developments in asymmetric catalysis. Later in 1986 his introduction of the concept and investigations into “nonlinear effects in asymmetric synthesis” using catalysts with chiral ligands that were not optically pure challenged the widely accepted assumption that the enantiomeric excess which is possible correlates linearly with the optical purity of the chiral ligands. He reported the first example in asymmetric catalysis where the optical purity of the product significantly exceeded the optical purity of the chiral ligand.

ChemInform Abstract: Recent Developments in Asymmetric Catalysis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Recent Developments in Asymmetric Catalysis

Asymmetric catalysis has long been dominated by C2-symmetric bidentate ligands. More recently, sterically and electronically unsymmetrical ligands have found increasing attention. An important family of these are the phosphinooxazoline (PHOX) ligands incorporating one P-coordinating and one N-coordinating unit. Important applications of PHOX ligands include Pd-catalyzed allylic substitution and Ir-catalyzed hydrogenation.

ChemInform Abstract: Recent Developments in Asymmetric Catalysis Using Synthetic Polymers with Main Chain Chirality

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Recent developments in asymmetric catalysis using synthetic polymers with main chain chirality

Some recent developments in the use of main chain chiral polymer catalysts are summarized. These polymers are different from the traditional polymer catalysts that are prepared by anchoring monomeric chiral catalysts to an achiral polymer backbone. Three classes of synthetic main chain chiral polymers are discussed including: (1) helical polymers represented by polypeptides; (2) polymers with flexible chiral chains such as polyesters and polyamides; and (3) polymers of rigid and sterically regular chiral chains represented by chiral conjugated polybinaphthyls. Some of these polymer catalysts have shown high enantioselectivity in asymmetric organic transformations.