New Frontiers in Asymmetric Catalysis - Hardcover

Hardcover

ISBN 10: 0471680265 ISBN 13: 9780471680260

Verlag: Wiley-Interscience, 2007

Inhaltsangabe

A compilation of recent advances and applications in asymmetric catalysis

The field of asymmetric catalysis has grown rapidly and plays a key role in drug discovery and pharmaceuticals. New Frontiers in Asymmetric Catalysis gives readers a fundamental understanding of the concepts and applications of asymmetric catalysis reactions and discusses the latest developments and findings. With contributions from preeminent scientists in their respective fields, it covers:

* "Rational" ligand design, which is critically dependent on the reaction type (reduction, oxidation, and C-C bond formation)
* Recent findings on activation of C-H bonds, C-C bonds, and small molecules (C=O, HCN, RN=C, and CO2) and the latest developments on C-C bond reorganization, such as metathesis
* Advances in "chirally economical" non-linear phenomena, racemic catalysis, and autocatalysis
* Some of the recent discoveries that have led to a renaissance in the field of organocatalysis, including the development of chiral Brönstead acids and Lewis acidic metals bearing the conjugate base of the Brönstead acids as the ligands and the chiral bi-functional acid/base catalysts

The book ends with a thought-provoking perspective on the future of asymmetric catalysis that addresses both the challenges and the unlimited potential in this burgeoning field. This is an authoritative, up-to-date reference for organic chemists in academia, government, and industries, including pharmaceuticals, biotech, fine chemicals, polymers, and agriculture. It is also an excellent textbook for graduate students studying advanced organic chemistry or chemical synthesis.

Über diesen Titel

Über die Autorin bzw. den Autor

Koichi Mikami is Professor in the Department of Applied Chemistry at the Tokyo Institute of Technology.

Mark Lautens is AstraZeneca Professor of Organic Synthesis and Merck Frosst/NSERC Industrial Research Chair in the Davenport Laboratories at the University of Toronto.

Von der hinteren Coverseite

A compilation of recent advances and applications in asymmetric catalysis

The field of asymmetric catalysis has grown rapidly and plays a key role in drug discovery and pharmaceuticals. New Frontiers in Asymmetric Catalysis gives readers a fundamental understanding of the concepts and applications of asymmetric catalysis reactions and discusses the latest developments and findings. With contributions from preeminent scientists in their respective fields, it covers:

• "Rational" ligand design, which is critically dependent on the reaction type (reduction, oxidation, and C-C bond formation)

• Recent findings on activation of C-H bonds, C-C bonds, and small molecules (C=O, HCN, RN=C, and CO2) and the latest developments on C-C bond reorganization, such as metathesis

• Advances in "chirally economical" non-linear phenomena, racemic catalysis, and autocatalysis

• Some of the recent discoveries that have led to a renaissance in the field of organocatalysis, including the development of chiral Brönstead acids and Lewis acidic metals bearing the conjugate base of the Brönstead acids as the ligands and the chiral bi-functional acid/base catalysts

The book ends with a thought-provoking perspective on the future of asymmetric catalysis that addresses both the challenges and the unlimited potential in this burgeoning field. This is an authoritative, up-to-date reference for organic chemists in academia, government, and industries, including pharmaceuticals, biotech, fine chemicals, polymers, and agriculture. It is also an excellent textbook for graduate students studying advanced organic chemistry or chemical synthesis.

The field of asymmetric catalysis has grown rapidly and plays a key role in drug discovery and pharmaceuticals. New Frontiers in Asymmetric Catalysis gives readers a fundamental understanding of the concepts and applications of asymmetric catalysis reactions and discusses the latest developments and findings. With contributions from preeminent scientists in their respective fields, it covers:

• Rational ligand design, which is critically dependent on the reaction type (reduction, oxidation, and C-C bond formation)

• Recent findings on activation of C-H bonds, C-C bonds, and small molecules (C=O, HCN, RN=C, and CO2) and the latest developments on C-C bond reorganization, such as metathesis

• Advances in chirally economical non-linear phenomena, racemic catalysis, and autocatalysis

• Some of the recent discoveries that have led to a renaissance in the field of organocatalysis, including the development of chiral Brönstead acids and Lewis acidic metals bearing the conjugate base of the Brönstead acids as the ligands and the chiral bi-functional acid/base catalysts

The book ends with a thought-provoking perspective on the future of asymmetric catalysis that addresses both the challenges and the unlimited potential in this burgeoning field. This is an authoritative, up-to-date reference for organic chemists in academia, government, and industries, including pharmaceuticals, biotech, fine chemicals, polymers, and agriculture. It is also an excellent textbook for graduate students studying advanced organic chemistry or chemical synthesis.

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New Frontiers in Asymmetric Catalysis

John Wiley & Sons

Copyright © 2007 John Wiley & Sons, Inc.
All right reserved.
ISBN: 978-0-471-68026-0

Chapter One

LIGAND DESIGN FOR CATALYTIC ASYMMETRIC REDUCTION

Takeshi Ohkuma Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University, Sapporo, Japan

Masato Kitamura and Ryoji Noyori Department of Chemistry and Research Center for Materials Science, Nagoya University, Chikusa, Nagoya, Japan

1.1 INTRODUCTION

Molecular catalysts consisting of a metal or metal ion and a chiral organic ligand are widely used for asymmetric synthesis. Figure 1.1 illustrates a typical (but not general) scheme of asymmetric catalytic reaction. The initially used chiral precatalyst 1A is converted to the real catalyst 1B through an induction process. An achiral reactant A and substrate B are activated by 1B to form reversibly an intermediate 1C. The chiral environment of 1C induces asymmetric transformation of A and B to the chiral product A-B (R or S) through an intermediate 1D with reproduction of catalyst 1B. The absolute configuration of A-B is kinetically determined at the first irreversible step, 1C->1D. The efficiency of catalysis depends on several kinetic and thermodynamic parameters, because most catalytic reactions proceed through such multistep transformation.

Catalytic asymmetric reduction of unsaturated compounds is one of the most reliable methods used to synthsize the corresponding chiral saturated products. Chiral transition metal complexes repeatedly activate an organic or inorganic hydride source, and transfer the hydride to olefins, ketones, or imines from one of two enantiofaces selectively, resulting in the enantio-enriches alkanes, alcohols, or amines, respectively. The three-dimensional (3D) structure and functionality of the chiral ligand, among other factors, are the obvious key for efficient asymmetric reduction. Rational design of chiral ligand can be done on the basis of full understanding of the corresponding catalytic reaction. This chapter presents successful examples of catalytic asymmetric reduction and the concepts of the ligand design. The description is brought to focus on the BINAP-transition metal chemistry.

1.2 HYDROGENATION OF OLEFINS

1.2.1 Enamide Hydrogenation with Rhodium Catalysts

The discovery of Wilkinson complex, RhCl[[P[([C.sub.6][H.sub.5]).sub.3]].sub.3], acting as an effective catalyst for hydrogenation of olefins opened the door for developing asymmetric reaction catalyzed by rhodium complexes with a chiral phosphine ligand. The enantioselective ability of chiral ligands has often been evaluated by hydrogenation of [alpha]-hydroxycarbonyl- or [alpha]-alkoxycarbonyl-substituted enamides. Figure 1.2 illustrates typical examples of phosphorus-based chiral ligands, with which Rh(I) catalyst selectively afforded (S)-amino acid derivatives in hydrogenation of (Z)-2-(acylamido) cinnamic acids and the methyl esters. Key factors for designing of these ligands are: (1) monodentate or bidentate, (2) steric effects (bulkiness, conformational flexibility, space coordinate, etc.), (3) electronic effects (alkylphosphine, arylphosphine, phosphite, phosphoramidite, etc.), (4) bite angle for bidentate ligands, (5) [ITLITL.sub.1] or [ITLITL.sub.2] symmetry for bidentate ligands, and (6) chirality on the backbone or on phosphorus atoms. A DIPAMP-Rh-catalyzed hydrogenation of an enamide substrate is industrially used in the synthesis of L-dopa, a drug for the parkinsonian disease.

The mechanism of hydrogenation of methyl (Z)-2-(acetamido)cinnamate catalyzed by a CHIRAPHOS- or DIPAMP-Rh complex have been exhaustively studied by Halpern and Brown. They proposed the "unsaturate/dihydride mechanism" as illustrated in Figure 1.3. The Rh complex with the R,R ligand [(R)-3A] (solvate) and an enamide reversibly form the substrate complex 3B, which undergoes irreversible oxidative addition of molecular [H.sub.2] to the Rh center, affording Rh(III) dihydride species 3C. Both hydrides on Rh migrate onto the C-C double bond of the coordinated substrate. The first hydride migration to the C3 position forms a five-membered alkyl-hydride complex 3D, and then reductive elimination of the hydrogenation product (second hydride migration) completes the cycle with regeneration of 3A. The stereochemistry of product is determined at the first irreversible step, 3B -> 3C, although a detailed theoretical investigation suggests the possibility that the process 3B -> 3C is reversible and the step 3C -> 3D constitutes the turnover-limiting step. The BINAP-Rh-catalyzed hydrogenation of enamides is proposed to proceed with the same Halpern-Brown mechanism.

CHIRAPHOS, DIPAMP, and BINAP are all chiral diphosphines with a [ITLITL.sub.2] symmetry (Figure 1.2) forming chelate complexes with transition metallic elements. DIOP developed by Kagan is the origin of this type of chiral ligand. Figure 1.4 illustrates the chiral template created by an (R)-BINAP-transition metal complex. The naphthalene rings are omitted in the side view for clarity. In this template, the chiral information of binaphthyl backbone is transmitted through the P-phenyl rings to the four coordination sites shown by [??] and [??]. The in-plane coordination sites, [??], are sterically affected by the "equatorial" phenyl rings, whereas the out-of-plane coordination sites, [??], are influenced by the "axial" phenyl groups. Consequently, the two kinds of quadrant of the chiral template (first and third vs. second and fourth) are clearly differentiated spatially, where the second and fourth quadrants are sterically congested, while the first and third ones are relatively uncrowded. (R,R)-CHIRAPHOS and (R,R)-DIPAMP form a similar chiral environment with metals.

As shown in Figure 1.3, the Rh catalyst (R)-3A and a bidentate enamide substrate reversively form the substrate complex 3B. Figure 1.5 illustrates two possible diastereomeric structures of 3B, depending on the Si/Re-face selection at C2, which leads to the R or S hydrogenation product. Therefore, the enantioselectivity is determined by the relative equilibrium ratio and reactivity of Si-3B and Re-3B. A [sup.31]P NMR spectrum of the Rh complex and an enamide substrate in C[H.sub.3]OH showed a single signal for thermodynamically more favored Si-3B. Most importantly, the Re-3B which is less favored because of the nonbonded repulsion between an equatorial phenyl ring of the (R)-BINAP ligand and a carboxylate function of substrate reacts with [H.sub.2] much faster than the more stable Si-3B, leading to the S isomer as a major product. The observed enantioselectivity is a result of the delicate balance of the stability and reactivity of the diastereomeric 3B. This inherent mechanistic problem requires careful choice of reaction parameters. For instance, the hydrogenation should be conducted under a low substrate concentration and low [H.sub.2] pressure to minimize reaction via the major diastereomeric intermediate Si-3B. Therefore, the hydrogenation of enamides catalyzed by BINAP-, CHIRAPHOS-, or DIPAMP-Rh complex, though giving amino acids in high enantiomeric excess (ee), is not ideal from the mechanistic standpoint. A Rh complex bearing Et-DuPHOS, a [ITLITL.sub.2]-chiral diphosphines (see Figure 1.2), catalyzes the hydrogenation basically with the same mechanism.

This mechanistic problem can be solved when the more stable diastereomer of 3B gives the major enantiomeric product. A Rh complex with a [ITLITL.sub.1]-chiral P/S mixed ligand, (R,R)-L1 (see Figure 1.2), catalyzes hydrogenation of methyl (Z)-2-(acetamido)cinnamate to afford the S product in excellent ee. The enamide substrate is reduced along with the catalytic cycle illustrated in Figure 1.3. However, unlike traditional catalyst systems, the stereochemistry of hydrogenation product suggests that the major S product is obtained via the most stable diastereomer of 3B. A substrate complex, Re-3B-L1, is the only visible species among four possible diastereomers. Figure 1.6 illustrates the structure of an (R,R)-L1-metal complex. The bulky t-butyl group on sulfur plays a crucial role in achieving high enantioface selectivity. This group is placed at the axial position to avoid steric hindrance with the ligand backbone. The two phenyl groups on phosphorus atom occupy the axial and equatorial positions. The high enantiodiscriminatory ability of the catalyst is rationalized by means of the quadrant model of Re-3B-L1. The electron-donating olefin function of the enamide substrate preferably binds to Rh at the trans position to the less electron-donating sulfur atom instead of phosphorus, that is, the first and fourth quadrants are unfavorable for the olefinic function for electronic reasons. The third and fourth quadrants are blocked by equatorial P-phenyl and bulky S-t-butyl group, respectively. Therefore, only the second quadrant is available for approach of methoxycarbonyl group (Z).

The unsaturate/dihydride is not a sole mechanism for enamide hydrogenation. Its mechanistic problem can be resolved by a total change in catalytic cycle. t-Bu-BisP* is a [ITLITL.sub.2]-symmetric, fully alkylated diphosphine with chiral centers at phosphorus (see Figure 1.2). Hydrogenation of enamides catalyzed by an (R,R)-t-Bu-BisP*-Rh complex gives the S product in excellent ee. The hydrogenation is revealed to proceed through the "dihydride/unsaturate mechanism" as shown in Figure 1.7. The major difference of this cycle from the unsaturate/ dihydride cycle in Figure 1.3 is the order of reaction of the substrate and [H.sub.2]. Now the catalyst (R,R)-7A first reversibly reacts with [H.sub.2], giving 7B, followed by interaction with an enamide substrate to form a substrate-Rh[H.sub.2] complex 7C. The stereochemistry of product is determined at the first irreversible step, 7C -> 7D. Because of the [ITLITL.sub.2]-symmetric structure of (R,R)-t-Bu-BisP*, the quadrants of the chiral template are spatially differentiated into two kinds. The first and third quadrants are crowded by the location of bulky P-t-butyl groups, whereas the second and fourth ones are open for substrate approach owing to the presence of only small methyl groups. Therefore, two diastereomers of bidentate substrate-Rh(III)[H.sub.2] complex, Re-7C and Si-7C, are possible (Figure 1.8). Formation of Si-7C is unfavored because it suffers from serious steric repulsion between bulky P-t-butyl group and substrate amide function. On the other hand, only small methyl/amide repulsive interaction exists in Re-7C. The major S enantiomeric product is derived from the more stable diastereomeric species, Re-7C. The hydrogenation catalyzed by a [2.2] PHANEPHOS-Rh complex (see Figure 1.2) is also suggested to proceed through the dihydride/unsaturate mechanism.

Chiral monodentate phosphites and phosphoramidites are also effective ligands for Rh-catalyzed asymmetric hydrogenation of enamide substrates. As seen in the structure of MonoPhos illustrated in Figure 1.2, combination of the modified BINOL backbone and the amine part gives a structural variety to this type of ligand. Combinatorial methods are effective for optimization of the chiral structures. Elucidation of the hydrogenation mechanism catalyzed by the MonoPhos-Rh complex is in progress.

1.2.2 Hydrogenation of Functionalized Olefins with Ruthenium Catalysts

The BINAP-Rh catalyzed hydrogenation of functionalized olefins has a mechanistic drawback as described in Section 1.2.1. This problem was solved by the exploitation of BINAP-Ru(II) complexes. Ru[(OCOC[H.sub.3]).sub.2](binap) catalyzes highly enantioselective hydrogenation of a variety of olefinic substrates such as enamides, [alpha],- and ,[gamma]-unsaturated carboxylic acids, and allylic and homoallylic alcohols (Figure 1.9). Chiral citronellol is produced in 300 ton quantity in year by this reaction.

It is worth noting that an opposite sense of enantioface selection is observed in going from the BINAP-Rh complex to the Ru catalyst. Hydrogenation of methyl (Z)-2-(acetamido)cinnamate with the (R)-BINAP-Ru catalyst in C[H.sub.3]OH gives the R (not S) product selectively (Figure 1.9). Figure 1.10 illustrates the "monohydride/unsaturate mechanism," in which the RuH(AcO) species 10B, formed by the heterolytic cleavage of [H.sub.2] by the precatalyst 10A, acts as a real catalyst. Thus, the Ru hydride species is generated before the substrate coordination forming 10C. The migratory insertion giving 10D, in which the Ru-C bond is cleaved mainly by [H.sub.2], but also by C[H.sub.3]OH solvent to some extent. The irreversible step determines the absolute configuration of the product. Because the diastereomers of 10D would have a similar reactivity, the enantioselectivity well corresponds to the relative stability of the diastereomeric substrate-RuH(AcO) complexes, Re-10C and Si-10C (Figure 1.11). In order for 10C to undergo migratory insertion, the Ru-H and C2-C3 double bond must have a syn-parallel alignment. As discussed above, the intermediate Re-10C is unfavored relative to Si-10C because of existence of P-Ph/COOC[H.sub.3] repulsion. Therefore, the major Si-10C is converted to the R hydrogenation product through 10D. The two hydrogen atoms incorporated in the product are from two different [H.sub.2] molecules, or [H.sub.2] and protic C[H.sub.3]OH.

1.2.3 Hydrogenation of Simple Olefins with Iridium Catalysts

Phosphinodihydroxazole (PHOX) compounds, L2-4, act as P/N bidentate ligands showing excellent enantioselectivity in Ir-catalyzed hydrogenation of simple [alpha],[alpha]-disubstituted and trisubstituted olefins (Figure 1.12). The use of tetrakis[3,5-bis(trifluoromethyl)phenyl]borate ([Bar.sub.F]) as a counter anion achieves high catalytic efficiency due to avoidance of an inert Ir trimer formation. A chiral carbene-oxazoline ligand L5 is also useful for this purpose. The mechanism of this reaction is to be elucidated by experimental and Theoretical studies. Chiral titanocene catalysts also show high enantioselectivity for hydrogenation of simple olefins. This subject is discussed in Section 1.4.

1.3 REDUCTION OF KETONES

1.3.1 Hydrogenation of Functionalized Ketones

Although Ru[(OCOC[H.sub.3]).sub.2](binap) exhibits excellent catalytic performance on asymmetric hydrogenation of functionalized olefins, it is feebly active for reaction of ketones. This failure is due to the property of the anionic ligands. Simple replacement of the carboxylate ligand by halides achieves high catalytic activity for reaction of functionalized ketones. Thus, chiral precatalysts including Ru[Cl.sub.2][(R)-binap] (polymeric form), Ru[Cl.sub.2][(R)-binap][(dmf).sub.n] (oligomeric form), [RuCl{(R)-binap}(arene)]Cl, [N[H.sub.2][([C.sub.2][H.sub.5]).sub.2]] [[{RuCl[(R)-binap]}.sub.2]-[(-Cl).sub.3]], and other in situ formed (R)-BINAP-Ru complexes are successfully used for hydrogenation of -keto esters, resulting in the R -hydroxy esters in >99% ee (Figure 1.13). An intermediate for the synthesis of carbapenem antibiotics is produced industrially by this method.

(Continues...)

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Details zur Ausgabe

• Verlag: Wiley-Interscience
• Erscheinungsdatum: 2007
• Sprache: Englisch
• ISBN 10: 0471680265
• ISBN 13: 9780471680260
• Einband: Tapa dura
• Anzahl der Seiten: 448
• Herausgeber: Mikami Koichi, Lautens Mark
• Kontakt zum Hersteller: Nicht verfügbar