Enantioselective Multicatalysed Tandem Reactions: Volume 20 (Catalysis Series) - Hardcover

Hélène Pellissier

Hardcover

ISBN 10: 1849739889 ISBN 13: 9781849739887

Publisher: Royal Society of Chemistry, 2014

Synopsis

A comprehensive overview of enantioselective multicatalysed tandem reactions involving organocatalysts, transition metals as well as enzymes in all possible combinations.

About this title

About the Author

Hélène Pellissier is a Researcher at the Centre National de la Recherche Scientifique (CNRS), where she focuses in organic synthesis.

From the Back Cover

Chiral molecules are needed for the production of many pharmaceuticals and materials, and catalytic asymmetric synthesis provides a method for the preparation of such chiral products. For the synthesis of complex molecules, such as natural products and biologically active compounds, more than one catalytic reaction may be necessary and tandem catalysis refers to the combination of catalytic reactions into one synthesis. By combing catalysts it enables a more efficient, economical and selective one pot approach for complex molecule synthesis which could not be achieved through single specific catalytic systems. The challenge is finding the right catalyst which is compatible with other catalysts but also tolerates reagents, solvent and intermediates generated during the course of the reaction.

Enantioselective Multicatalysed Tandem Reactions provides an overview of recent developments in the area. The first part of the book covers asymmetric tandem reactions catalysed by multiple catalysts from the same discipline (organocatalysts, two metal and multienzyme-catalysed reactions). The second part looks at tandem reactions catalysed by multiple catalysts from different disciplines including reactions catalysed by a combination of metals and organocatalysts, reactions catalysed by a combination of metals and enzymes, and finally reactions catalysed by a combination of organocatalysts and enzymes.

The book will appeal to researchers and professionals in academic and industrial laboratories interested in catalysis, biocatalysis and organic synthesis of chiral compounds.

Excerpt. © Reprinted by permission. All rights reserved.

Enantioselective Multicatalysed Tandem Reactions

By Hélène Pellissier

The Royal Society of Chemistry

Copyright © 2014 Hélène Pellissier
All rights reserved.

ISBN: 978-1-84973-988-7

Contents

Abbreviations, xvii, 
Section I Asymmetric Tandem Reactions Catalysed by Multiple Catalysts from the Same Discipline, 
Chapter 1 Introduction, 3, 
Chapter 2 Reactions Catalysed by Multiple Organocatalysts, 5, 
Chapter 3 Reactions Catalysed by Two Metals, 46, 
Chapter 4 Multienzyme-Catalysed Reactions, 60, 
Chapter 5 Conclusions, 85, 
Section II Asymmetric Tandem Reactions Catalysed by Multiple Catalysts from Different Disciplines, 
Chapter 6 Introduction, 89, 
Chapter 7 Reactions Catalysed by a Combination of Metals and Organocatalysts, 91, 
Chapter 8 Reactions Catalysed by a Combination of Metals and Enzymes, 162, 
Chapter 9 Reactions Catalysed by a Combination of Organocatalysts and Enzymes, 217, 
Chapter 10 Conclusions, 223, 
General Conclusion, 224, 
Subject Index, 226, 

CHAPTER 1

Introduction

The first section of the book illustrates how much asymmetric multicatalysis based on the use of catalysts belonging to the same discipline has contributed to the development of various types of powerful enantioselective tandem reactions. It collects all the major progress in the field of enantioselective tandem reactions promoted by multiple (two or three) organocatalysts, two metal catalysts, or two or more biocatalysts. It demonstrates the power of these remarkable one-pot processes of two or more bond-forming reactions, occurring with minimum workup or change in conditions in which the subsequent transformation takes place at the functionalities obtained in the former transformation, following the same principles that are found in biosynthesis in nature. The first section of the book is subdivided into five chapters, dealing successively after this introduction (Chapter 1) with reactions catalysed by multiple organocatalysts (Chapter 2), reactions catalysed by two metals (Chapter 3), and multienzyme-catalysed reactions (Chapter 4) followed by conclusions (Chapter 5). The two catalysts can interact in a cooperative, relay or sequential manner; these three types of catalysis will be treated successively in chapters 2 and 3. In cooperative catalysis, both the two catalysts are present at the onset of the reaction, and share the same catalytic cycle, activating two different functional groups cooperatively to achieve the bond-formation steps. On the other hand, in relay or sequential catalysis, the substrate first reacts with one catalyst to give an intermediate through a first catalytic cycle. Then, this former intermediate reacts with the second catalyst to provide, through a second catalytic cycle, the final product or an intermediate for subsequent transformations. The difference between relay and sequential catalysis consists of the presence or not of the two catalysts at the onset of the reaction. Thus, relay as well as sequential catalysis involves a set of reactions independently catalysed by two catalysts in a consecutive manner but, while in relay catalysis the two compatible catalysts are both present from onset, in sequential catalysis the addition of the second catalyst during the course of the reaction is necessary to avoid compatibility issues. Chapter 4 dealing with multienzyme-catalysed reactions is divided into three sections concerning multienzymatic synthesis of chiral alcohols, multienzymatic synthesis of chiral amines and amino acids, and other multienzymatic reactions.

CHAPTER 2

Reactions Catalysed by Multiple Organocatalysts

2.1 Introduction

Organocatalysts are known to be the most robust catalysts, well tolerating impurities and traces of water. Additionally, they are usually readily available, easy to handle, and present a high compatibility which is a significant advantage. Furthermore, a wide variety of organocatalysts is able to induce different types of transformations through different activation models. These advantages allow the combination of different organocatalysts to be achieved to design novel enantioselective tandem reactions. The two (or three) organocatalysts can interact in a cooperative, relay or sequential manner; these three types of catalysis will be treated successively in the text. In cooperative catalysis, both the two catalysts are present at the onset of the reaction, and share the same catalytic cycle, activating two different functional groups cooperatively to achieve the bond-formation steps. On the other hand, in relay or sequential catalysis, the substrate first reacts with one catalyst to give an intermediate through a first catalytic cycle. Then, this former intermediate reacts with the second catalyst to provide, through a second catalytic cycle, the final product or an intermediate for subsequent transformations. The difference between relay and sequential catalysis consists of the presence or not of the two catalysts at the onset of the reaction. Thus, relay as well as sequential catalysis involves a set of reactions independently catalysed by two catalysts in a consecutive manner but, while in relay catalysis the two compatible catalysts are both present from onset, in sequential catalysis the addition of the second catalyst during the course of the reaction is necessary to avoid compatibility issues. Various types of organocatalysts, such as phosphoric acids, L-proline and its derivatives, cinchona alkaloids, ureas, thioureas, amino acids, N-heterocyclic carbenes, pyrrolidines, and various (di)amines, have already been combined to induce enantioselective domino and multicomponent domino reactions evolving through cooperative as well as relay catalysis, but also used sequentially to achieve enantioselective tandem reactions. In a number of examples, both the two organocatalysts employed are chiral which is possible when one does not interfere with the activity of the other. Their simultaneous use is particularly useful when a synergistic effect is present as in the case of cooperative catalysis which is the most developed.

2.2 Cooperative Catalysis

In 2007, a chiral tertiary amine, such as (-)-spartein, was used by Hong et al. to enhance the nucleophilic character of an enamine intermediate by deprotonation and effectively shield one of the enantiotopic faces of this intermediate, thus improving the stereoselectivity of a reaction. This enamine was the intermediate of an enantioselective Robinson condensation occurring between two α, β-unsaturated aldehydes, providing the corresponding chiral cyclohexadienes in good yields and enantioselectivities of up to 93% ee, as shown in Scheme 2.1.

In the same year, Zhou and List reported a novel one-pot tandem reaction which, for the first time, combined chiral Brønsted acid catalysis with enamine and iminium catalysis. Later, on the basis of control experiments and ESI-MS/MS analysis, a reasonable mechanism was proposed (Scheme 2.2). The initial step of this tandem reaction was mediated by achiral p-ethoxyaniline (PEP-NH2) and chiral phosphoric acid (R)-TRIP; either reagent alone was inefficient in promoting this aldol condensation to afford the first iminium intermediate. The following step was a conjugate reduction which was also Brønsted acid and amine co-catalysed, and no further conversion took place in the absence of either catalyst. The final step was an acid-catalysed reductive amination. This novel sequence allowed the highly enantioselective synthesis of pharmaceutically active chiral cis-3-substituted cyclohexyl or heterocyclohexyl amines in high diastereo- and enantioselectivities of up to 98% de and 92% ee, as shown in Scheme 2.2. It should be noted that the stereocontrol of the conjugate reduction and reductive amination step was accomplished by the chiral phosphoric acid TRIP, as demonstrated by the control experiments.

In 2009, Xie et al. developed an enantioselective synthesis of highly functionalised chiral 2-amino-2-chromene derivatives based on a domino reaction occurring between α, β-unsaturated enones, such as 2-hydro-xybenzalacetones, and malononitrile. This novel process was catalysed by a cinchona alkaloid-derived primary amine, such as 9-amino-9-deox-yepiquinine, in combination with (R)-1,1'-binaphth-2,2'-diyl hydrogen phosphate ((R)-BDHP). As shown in Scheme 2.3, excellent enantioselectivities of up to 96% ee were obtained in combination with high yields of up to 84% for a range of β-substituted 2-hydroxybenzalacetones. The scope of the reaction could be extended to other 2-hydroxychalcones, providing the corresponding 2-amino-2-chromene derivatives in good yields and enantioselectivities (75–95% ee), as shown in Scheme 2.3. A hypothetical mechanism is depicted in Scheme 2.3 in which the chiral primary amine was an effective catalyst for the formation of the iminium from the enone. This iminium could be stabilised through hydrogen-bonding with the chiral phosphoric acid. Then, the higher reactivity of this iminium was used to facilitate the Michael reaction between the enone and malononitrile to produce the corresponding enamine intermediate, and the final products were obtained from the following Knoevenagel condensation (R2 = Me) and the nucleophilic addition of the phenolic OH group on the cyano moiety and proton transfer. On the other hand, when the iminium intermediate bore a bulkier imine moiety (R2 = Et, Ar), ketones were obtained instead of the alkylidene malononitriles arising from Knoevenagel condensation under the same reaction conditions.

In 2009, Bella et al. reported a formal [4 + 2] cycloaddition of substituted arylacetaldehydes and 2-cyclohexen-1-one which was promoted by a chiral thiazolidine catalyst and chiral quinine via enamine formation and spontaneous intramolecular aldol reaction (Scheme 2.4). The stereoselection depended upon the secondary amine catalyst, whereas the secondary catalyst was involved in the enhancement of the nucleophilicity of the derived enamine, probably through deprotonation of the carboxylic group. There was a synergistic effect in the contemporary use of the two catalysts because neither of them was able to efficiently promote the reaction alone. As shown in Scheme 2.4, the domino products were reached in low to moderate yields and good to high enantioselectivities of up to 90% ee.

In 2010, Kotsuki et al. used another combination of organocatalysts to achieve a new powerful strategy for the asymmetric construction of a quaternary carbon stereogenic centre at the 4-position of cyclohexenone derivatives. Indeed, the simultaneous employment of (1S, 2S)-1,2-cyclohex-anediamine and (1S, 2S)-1,2-cyclohexanedicarboxylic acid as organocatalysts in the Robinson-type annulation of methyl vinyl ketone or ethyl vinyl ketone with β-aryl-substituted aldehydes allowed the corresponding chiral cyclo-hexenones bearing a quaternary carbon centre to be achieved in moderate yields and good to excellent enantioselectivities of up to 97% ee, as shown in Scheme 2.5. The authors have proposed the mechanism depicted in Scheme 2.5 to explain the results. First, condensation of (1S, 2S)-1,2-cyclo-hexanediamine catalyst with both a-aryl-substituted aldehyde and enone in the presence of (1S, 2S)-1,2-cyclohexanedicarboxylic acid proceeded through the formation of an enamine-iminium double activation intermediate 1, which then underwent an intramolecular Michael addition to afford the corresponding cyclic enamine-iminium ion intermediate 2. This intermediate collapsed spontaneously via hydrolysis to give the corresponding keto-aldehyde precursor 3 and regenerated the catalytic system. In this sequence, the vicinal trans-diamine arrangement in (1S, 2S)-1,2-cyclohex-anediamine was essential not only to activate both the Michael donor and acceptor components but also to bring them together in close proximity to achieve carbon–carbon bond formation with the observed enantiocontrol. The synthetic utility of this novel method was demonstrated by its application to a short synthesis of (+)-sporochnol A which is a natural chemical fish deterrent.

In the same year, Xu et al. developed an efficient example of asymmetric cooperative catalysis applied to a domino oxa-Michael–Mannich reaction of salicylaldehydes with cyclohexenones. The process was catalysed by a combination of two chiral catalysts, such as a chiral pyrrolidine and amino acid D-tert-leucine. The authors assumed that there was protonation of the aromatic nitrogen atom of the pyrrolidine catalyst by D-tert-leucine, which spontaneously led to the corresponding ion-pair assembly (Scheme 2.6). This self-assembled catalyst possessed dual activation centres, enabling the catalysis of the electrophilic and nucleophilic substrates simultaneously. The domino oxa-Michael–Mannich reaction provided a range of versatile chiral tetrahydroxanthenones in high yields and high to excellent enantioselectivities of up to 98% ee, as shown in Scheme 2.6.

In 2011, Wang et al. disclosed a highly enantioselective domino double Michael reaction of dienones with 3-nonsubstituted oxindoles to access chiral spirocyclic oxindoles in high yields of up to 98% and excellent dia-stereo- and enantioselectivities of up to 490% de and 98% ee, respectively. This novel reaction was performed in the presence of a cinchona-based primary amine in combination with a chiral phosphoric acid, as shown in Scheme 2.7. This reactivity pattern was also applied to other pronucleophiles such as pyrazolones.

The Povarov reaction, an inverse electron-demand aza-Diels–Alder reaction of 2-azadienes with electron-rich olefins, allows a rapid construction of polysubstituted tetrahydroquinolines. It must be noted that enantioselective versions of the Povarov reaction remain rare. Actually, the first highly enantioselective example of this type of reaction was developed by Zhu et al., in 2009. Later, Jacobsen et al. reported another enantioselective Povarov reaction catalysed by a combination of a strong Brønsted acid, such as o-nitrobenzene sulfonic acid, with a chiral urea. As shown in Scheme 2.8, the reaction of electron-rich alkenes with imines provided the corresponding tricyclic products in good yields, moderate diastereoselectivities of up to 62% de, and generally high enantioselectivities ranging from 90 to 98% ee.

In 2010, Melchiorre et al. demonstrated the compatibility of a chiral quinidine derivative with a chiral BINOL-derived phosphoric acid as catalysts (Scheme 2.9) to induce the reaction of α, β-unsaturated aldehydes with an aromatic secondary alcohol.14 The reaction evolved through the formation of an enamine from the corresponding enal and the chiral quinidine catalyst, which further added to the carbocation arising from the aromatic alcohol to give the corresponding γ-alkylated α, β-unsaturated aldehyde. As shown in Scheme 2.9, a range of functionalised chiral α, β-unsaturated aldehydes could be achieved in good to excellent yields and moderate to high enantioselectivities of up to 94% ee.

The utility of N-heterocyclic carbenes as organocatalysts in domino reactions has received growing attention in the past few years. In this context, Rovis et al. developed in 2011 a novel efficient synthesis of chiral trans-γ-lactams by using a combination of a chiral catalyst of this type with a Brønsted acid, such as o-chlorobenzoic acid. Under this cooperative catalysis, strongly electrophilic ethyl trans-4-oxo-2-butenoate reacted with unactivated imines to provide the corresponding chiral trans-γ-lactams in good to high yields, high diastereoselectivities of up to 490% de, combined with good to high enantioselectivities of up to 93% ee, as shown in Scheme 2.10. A plausible mechanism for this process could involve the generation of a Breslow intermediate arising from the reaction of ethyl trans-4-oxo-2-butenoate with the carbene. This intermediate attacked the acid-activated imine via hydrogen-bonding intermediate 4. Steric hindrance led to an anti-orientation of the CO2Et group and the alkenyl group. Proton transfer then resulted in the formation of acyl carboxylate 5. The nitrogen species replaced the carbene to afford the final product and the free carbene (Scheme 2.10). The scope of the reaction could be extended to a variety of imines and enals other than ethyl trans-4-oxo-2-butenoate. Indeed, several less nucleophilic p-nitrocinnamaldehydes provided the corresponding lactams in yields ranging from 48 to 99%, diastereoselectivities of 86 to 90% de, and high enantioselectivities of 90 to 93% ee. On the other hand, using a ketone as a substituent on the enal (Et instead of OEt) gave the corresponding lactam in lower enantioselectivity (66% ee).

Even though the history of multicomponent reactions dates back to the second half of the 19th century with the reactions of Strecker, Hantzsch, and Biginelli, it was only in the last few decades with the work of Ugi et al. that the concept of the multicomponent reaction emerged as a powerful tool in synthetic chemistry. In this context, Feng et al. investigated in 2008 the Biginelli reaction of aromatic aldehydes, urea, and b-ketoesters catalysed by a combination of a chiral trans-4-hydroxyproline-derived secondary amine and a Bronsted acid, such as 2-chloro-4-nitrobenzoic acid, as catalyst system. The dual-catalysed process was performed at 25 1C with 5 mol% of catalyst loading of each of the two catalysts in 1,4-dioxane and in the presence of an additive such as t-BuNH2 TFA. Under these conditions, the Biginelli products were obtained in moderate to good yields (34–73%) and good to excellent enantioselectivities (70–98% ee). Later, another example of cooperative catalysis was developed by Cordova et al. in a dynamic one-pot three-component asymmetric transformation between aldehydes, protected α-cyanoglycine esters, and α, β-unsaturated aldehydes. The domino reaction afforded the corresponding chiral cyano-, formyl-, and ester-functionalised α-quaternary proline derivatives bearing four contiguous stereocentres. When it was induced by a combination of a chiral amine catalyst, such as chiral diphenylprolinol triethylsilyl ether, and an hydrogen-bond-donating catalyst, such as the oxime derived from methyl cyanoacetate, the products were obtained in good to high yields, good to high endo/ exo ratios of up to 419 : 1, good diastereoselectivities of up to 490% de, and generally excellent enantioselectivities of 93 to 98% ee, as shown in Scheme 2.11. The authors have demonstrated that the hydrogen-bond-donating catalyst was crucial for the formation of the imine and thus pushed the equilibrium of the reaction towards the imine formation. Most likely this occurred by activation of the carbonyl group of the aldehyde. Next, the intramolecular hydrogen-bonding network, which can be created by the oxime catalyst, activated the imine and locked its conformation to 6 (Scheme 2.11). The imine then underwent proton shifts to form intermediates 7–9, which were stabilised by the hydrogen-bonding network. In parallel, the chiral amine catalyst formed the iminium intermediate 10, which was efficiently shielded at the Si face by the bulky aryl groups. Next, the activated species 7–9, for which the conformation was locked by hydrogen-bonding with the oxime catalyst, approached the opposite face, and stereoselective C–C bond formation occurred from the Re face of intermediate 11 either by a concerted endo-selective mechanism (cycloaddition) or a stepwise (Michael–Mannich) mechanism to give iminium intermediate 12. Subsequent hydrolysis regenerated the amine catalyst and gave the poly-substituted proline product.

(Continues...)

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Edition details

• Publisher: Royal Society of Chemistry
• Publication date: 2014
• Language: English
• ISBN 10: 1849739889
• ISBN 13: 9781849739887
• Binding: Hardcover
• Edition number: 1
• Number of pages: 253