Chirality from Dynamic Kinetic Resolution: Rsc - Hardcover

Pellissier, Helene (CNRS, France)

Hardcover

ISBN 10: 1849731977 ISBN 13: 9781849731973

Verlag: Royal Society of Chemistry, 2011

Inhaltsangabe

The last 15 years have witnessed significant developments in the efficiency and scope of the application of DKR. These now offer a serious alternative to conventional methods for asymmetric synthesis. Indeed, impressive examples using new enzymes and major progress in the DKR of racemates have taken place over the past few years. The powerful combination of enzymes and metals has also been the subject of spectacular development. In addition, a new type of DKR, involving organocatalysts, has recently appeared. Although asymmetric catalysis has undergone development during the last two decades, the most common industrial process used to obtain enantiomerically pure compounds is still via resolution of racemic mixtures. This is despite the major disadvantage that only a maximum of 50% product yield can be obtained. It is not surprising that DKR, which solves the problem of the limitation in yield, has attracted an increasing amount of interest from both the industrial and the academic perspective. This book provides an up-date on the principle methods employed to obtain dynamic kinetic resolution (DKR) by either enzymatic or non-enzymatic methods. It also illustrates the diversity of useful chiral products that can be obtained through this powerful concept. Divided into three sections, the book deals successively with non-enzymatic methods, enzymatic methods, and the use of transition metals and enzymes in tandem.

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Über die Autorinnen und Autoren

Hélène Pellissier was born in Gap, France. She carried out her PhD under the supervision of Dr G. Gil in Marseille and then entered the Centre National de la Recherche Scientifique in 1988. After a postdoctoral position in Professor K. P. C. Vollhardt's group at Berkeley, she joined the group of Professor M. Santelli in Marseille in 1992. Here she focused on the chemistry of BISTRO and its large application in organic synthesis.

Hélène Pellissier was born in Gap, France. She carried out her PhD under the supervision of Dr G. Gil in Marseille and then entered the Centre National de la Recherche Scientifique in 1988. After a postdoctoral position in Professor K. P. C. Vollhardt's group at Berkeley, she joined the group of Professor M. Santelli in Marseille in 1992. Here she focused on the chemistry of BISTRO and its large application in organic synthesis.

Von der hinteren Coverseite

The last 15 years have witnessed significant developments in the efficiency and scope of the application of DKR. These now offer a serious alternative to conventional methods for asymmetric synthesis. Indeed, impressive examples using new enzymes and major progress in the DKR of racemates have taken place over the past few years. The powerful combination of enzymes and metals has also been the subject of spectacular development. In addition, a new type of DKR, involving organocatalysts, has recently appeared. Although asymmetric catalysis has undergone development during the last two decades, the most common industrial process used to obtain enantiomerically pure compounds is still via resolution of racemic mixtures. This is despite the major disadvantage that only a maximum of 50% product yield can be obtained. It is not surprising that DKR, which solves the problem of the limitation in yield, has attracted an increasing amount of interest from both the industrial and the academic perspective. This book provides an up-date on the principle methods employed to obtain dynamic kinetic resolution (DKR) by either enzymatic or non-enzymatic methods. It also illustrates the diversity of useful chiral products that can be obtained through this powerful concept. Divided into three sections, the book deals successively with non-enzymatic methods, enzymatic methods, and the use of transition metals and enzymes in tandem.

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Chirality from Dynamic Kinetic Resolution

By Hélène Pellissier

The Royal Society of Chemistry

Copyright © 2011 Hélène Pellissier
All rights reserved.

ISBN: 978-1-84973-197-3

Contents

General Introduction, xv, 
Chapter 1 Chiral Auxiliaries, 1, 
Chapter 2 Chiral Catalysts, 49, 
Chapter 3 Enzymatic Methods, 145, 
Chapter 4 Use of Transition Metals and Enzymes in Tandem, 191, 
Chapter 5 Atroposelective Reactions, 243, 
General Conclusions, 283, 
Abbreviations, 285, 
Subject Index, 289, 

CHAPTER 1

Chiral Auxiliaries

1.1 Introduction

There are numerous ways of obtaining resolutions of chiral compounds by chemical means. The combination of these chemical kinetic resolutions with racemisation is, however, less obvious. Nevertheless, DKR processes can be exploited just as successfully for non-enzymatic reactions. Typically, chiral auxiliaries or chiral organometallic complexes are employed to achieve the desired resolution. Hence, besides metal complexes bearing chiral ligands, such as ruthenium catalysts together with a chiral ligand such as 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl (BINAP), there is also the possibility of using chiral auxiliaries for the asymmetric induction through a dynamic kinetic process. One of the first clear examples of DKR was reported by Weygand et al. (1966), dealing with the reaction of azlactones with chiral auxiliaries such as chiral amino esters to form dipeptides.

1.2 Configurationally Labile Alkyl Halides

Nucleophilic substitution on configurationally labile halides has been involved in compounds with a bromo or iodo atom in the α-position with respect to a carboxylic acid derivative, in which the SN2 reaction is governed by a chiral auxiliary placed in the carboxylic moiety. Racemisation takes place by consecutive inversions at the labile centre induced by additives such as polar solvents, bases or halide salts (Scheme 1.1).

Extensive studies have been carried out on nucleophilic substitution of α-halocarboxylic acid derivatives containing a chiral auxiliary in the carboxylic moiety. Racemisation of the labile chiral centre in the α-position to the carbonyl — induced by additives such as polar solvents, bases or halide salts — allows a high asymmetric induction through a DKR process to be obtained. This methodology has been recently recognised as a powerful synthetic method for asymmetric syntheses of α-heteroatom-substituted carboxylic acid derivatives. As an example, tert-butyl (4S)-1-methyl-2-oxoimidazolidine-4-carboxylate was used by Nunami and colleagues as a chiral auxiliary for DKR of α-bromo-carboxylic acids. In this case, the nucleophile was a malonic ester enolate and the role of the polarity of the solvent (hexamethylphosphoramide, HMPA) was demonstrated (Scheme 1.2).3 The alkylated products were further easily converted to chiral α-alkylsuccinic acid derivatives and chiral β-amino acid derivatives. Moreover, these authors showed that this methodology could be extended to other nucleophiles such as amines. Therefore, the reaction of a diastereomeric mixture of tert-butyl (4S)-1-methyl-2-oxoimidazolidine-4carb-oxylate with potassium phthalimide predominantly afforded tert-butyl (4S)-1methyl-3-((2S)-2-(phthaloylamino)propionyl)-2 -oxoimidazolidine-4-carboxylate in 90% yield and 94% diastereomeric excess (de). The successive removal of the chiral auxiliary afforded N-phthaloyl-L-alanine.

Durst and colleagues applied the same methodology to benzylamine as the nucleophile and obtained the expected aminoimides in good yields and excellent enantiomeric purities (R1 = Et: 92%, de = 98%). They also described in same paper the successful condensation of dibenzylamine on racemic α-bromoesters of (R)-pantolactone (Scheme 1.3).

In 2004, Ben and colleagues reported the first example of a DKR using immobilised amine nucleophiles. This novel approach involved a nucleophilic amine attached to a solid phase resin via an organic spacer, providing optical purities of the N-substituted α-amino ester products superior to the solution phase DKR process with diastereoselectivities ranging from 84 to 90% and yields between 66% and 95% (Scheme 1.4).

In the course of preparing α-amino acids and their N,N-dibenzyl derivatives, Camps et al. involved (R)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as the chiral auxiliary (Scheme 1.5).8 In this way, the corresponding α-dibenzylamino acids were obtained through a DKR process followed by a non-epimerisable hydrolysis.

The use of alkoxides as nucleophiles is not common in the area of DKR. In 1997, Camps et al. reported, however, the asymmetric synthesis of ahydroxyacids based on the DKR of a diastereomeric mixture of abromoesters derived from (R)- or (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone with p-methoxyphenoxide in the presence of tetra-n-hexylammonium iodide (Scheme 1.6).

The synthesis of (R)-α-aryloxypropanoic acid herbicides was achieved by involving the same chiral auxiliary with the corresponding trisubstituted phenoxides. The DKR, which gave in this case moderate diastereoselectivities, was followed by mild acid hydrolysis, as shown in Scheme 1.7.

In 1999, Bettoni and colleagues developed a DKR in order to prepare 2-aryloxyacid analogues of clofibrate, which show markedly different biological activities depending on the nature of the enantiomer. The key step of the synthesis was the condensation of sodium 4-chlorophenoxide on diastereomeric 2-bromoimides. (4S)-4-Isopropyl-1,3-oxazolidin-2-one was used as the chiral auxiliary, as shown in Scheme 1.8.

Chiral imidazolidinones have been widely employed as chiral auxiliaries for more than 20 years due to their low flexibility. In this context, Caddick and colleagues studied the DKR of α-haloacylimidazolidinones with a large variety of nitrogen, sulfur and carbon nucleophiles. An unusual dichotomy of diastereoselection has been observed whereby the metallated nucleophiles preferentially reacted via the (5S, 2'R) diastereomer (Scheme 1.9) while the amine nucleophiles reacted via the (5S, 2'S) diastereomer (Scheme 1.10).

In order to explain the stereochemical outcome of their DKR processes, extensive molecular modelling experiments were carried out by Caddick and colleages. It seems that a non-bifurcated H-bond model which minimises the bromine–phenyl interaction is probably the most accurate. The stereoselectivity of the reaction therefore arises from the interaction between the leaving group and the stereo-differentiating substituent of the chiral auxiliary (Figure 1.1).

As the amine undergoes substitution, a twisting of the C1–C2 bond is required which potentiates these interactions in the 2'R isomer but not in the 2'S isomer, thereby explaining its greater reactivity with H-bonding nucleophiles. For the DKRs with metallated nucleophiles, a different result was observed. In fact, considering that the counterion of these nucleophiles can only be weakly complexed to the carbonyl group of the chiral auxiliary, direct attack of the anion should be more relevant and should take place preferentially from the less hindered side of the substrates in the anti-parallel carbonyls conformation. Therefore, the most reactive diastereomer was the 2'R and the selectivity depends mainly on the...

Details zur Ausgabe

• Verlag: Royal Society of Chemistry
• Erscheinungsdatum: 2011
• Sprache: Englisch
• ISBN 10: 1849731977
• ISBN 13: 9781849731973
• Einband: Gebundene Ausgabe
• Anzahl der Seiten: 318
• Kontakt zum Hersteller: Nicht verfügbar
• Verantwortliche Person: Nicht verfügbar