Catalytic Asymmetric Reactions of Conjugated Nitroalkenes

Irishi N.N. Namboothiri, Meeta Bhati, Madhu Ganesh, Basavaprabhu Hosamani, Thekke V. Baiju, Shimi Manchery, Kalisankar Bera

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781000165234
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Chemistry
• Index: Chemistry

Nitroalkenes have often been referred to as "synthetic chameleons" owing to their reactivity, synthetic utility and biological significance. In the last two decades, the reactivity of nitroalkenes as substrates in diverse catalytic asymmetric transformations has been of tremendous interest on account of the powerful abilities of the nitro group to coordinate and withdraw electrons, as well as its amenability to undergo a wide variety of synthetic transformations. Although numerous original articles and reviews have appeared in the literature, a monograph providing a comprehensive coverage of this topic was conspicuous by its absence.

This book features:

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• A systematic, up-to-date, in-depth and well-organized compilation, spread over 12 chapters, of various catalytic asymmetric reactions of nitroalkenes with diverse substrates reported to date

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• A wide coverage of reactions such as Michael additions, Friedel–Crafts reactions, cycloadditions, asymmetric reductions, multicomponent and cascade reactions, as well as other miscellaneous reactions

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• Various chiral organo, metal and even biocatalysts involved in the stereoselective synthesis of multifunctional adducts via catalytic asymmetric reactions of nitroalkenes

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• Schemes and figures detailing all the reagents, reaction conditions and product profiles

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• Mechanistic details, including transition state models, which will be useful for effective catalytic design

This book will be an invaluable resource for those who are working in the area of asymmetric catalysis and synthetic methodologies.

1 Catalytic Asymmetric Michael Addition of 1,3-Dicarbonyls to Nitroalkenes

1.1 Introduction

1,3-Dicarbonyls possessing an active methylene group serve as good nucleophilic partners that easily generate stable carbanions. The stability of the resulting enolate is due to the formation of an extremely stable cyclic structure with pseudoaromatic character, making it a good nucleophile. Chiral organocatalysts bearing functional groups such as thiourea, squaramide, guanidine, etc. were the catalysts of choice for the asymmetric Michael addition of various 1,3-dicarbonyls such as 1,3-diketones, malonates, β-ketoesters, Meldrum’s acid and 1,3-dicarbonyl surrogates such as 2-hydroxynaphthoquinones and hydroxycoumarins. There are sporadic reports of chiral 1,2-diamine-based ligand-metal complex catalyzed Michael additions as well.

1.2 Addition of 1,3-Diketones

Shao and co-workers reported a bifunctional amine-thiourea C1 catalyzed asymmetric Michael addition of 1,3-dicarbonyl compound 2 to nitroalkenes 1 to afford corresponding products 3 with good enantioselectivity (Scheme 1.1).¹ The catalyst bears central and axial chiral elements that play a pivotal role in enhancing the stereochemical control of the reaction. The reaction involves an initial activation of the nitroalkene 1 by H-bonding interactions of the catalyst with the nitro group and the deprotonation of the 1,3-dicarbonyl compound 2 to form an anion which adds to the activated nitroalkene 1 to form a ternary complex (TS-1, Scheme 1.1). This on protonation and followed by hydrolysis yields the product 3. In 2009, Shao and co-workers described a matched-mismatched effect of two different chiral units in an organocatalyst C2 for an asymmetric Michael addition of acetylacetone 2 (R¹ = H, R² = R³ = Me) to different nitroalkenes 1 under mild conditions to give products 3 in high yields and enantioselectivities (Scheme 1.1).² Both the enantiomers of the product were isolated with nearly the same enantiomeric excess in the presence of “matched” and “mismatched” organocatalysts C2 by switching the solvent from THF to toluene.

SCHEME 1.1 Michael addition of 1,3-dicarbonyl compounds to nitroalkenes using bifunctional thiourea catalysts.

The Wang group reported binaphthyl-derived bifunctional amine-thiourea C3 catalyzed Michael addition of 1,3-diketone 2 to nitroalkenes 1a.³ As low as 1 mol% of catalyst C3 was sufficient to promote the reaction and provided the Michael adducts 3 in high yields and enantioselectivities (Scheme 1.2). The Michael adducts 3 were further utilized for the synthesis of substituted-α-amino acids. The Bolm group synthesized ephedrine- and pseudoephedrine-derived bifunctional tertiary amine-thiourea catalysts and investigated their catalytic properties for the Michael addition of 1,3-diketone 2 to nitroalkenes 1a (Scheme 1.2).⁴ Among those catalysts, C4 provided the products 3 in excellent yields and enantioselectivities up to 94% ee. Song and co-workers described an asymmetric Michael addition of acetylacetone 2 to nitroalkenes 1a by employing chiral bifunctional L-thiazoline-thiourea derivative C5 (Scheme 1.2).⁵ In the proposed mechanism, nitroalkene 1a gets activated by the thiourea moiety of catalyst C5 through H-bonding interactions, whereas the tertiary N-atom of catalyst C5 deprotonates the acidic proton of 1,3-diketone 2 forming a ternary complex. In addition, the synergistic steric effects of the chiral motif of the catalyst C5 increased the stereocontrol of this reaction, offering products 3 exclusively with (S)-configuration.

SCHEME 1.2 Various chiral thioureas as bifunctional organocatalysts in the Michael addition of 1,3-diketones to nitroalkenes.

In the realm of H-bonding catalysis, in 2008, the Rawal group introduced a new H-bonding catalyst based on the squaramide moiety. Squaramide exhibits better H-bonding ability than the corresponding thioureas.⁶ As little as 0.5 mol% of squaramide catalyst C6 catalyzed the reaction between acetylacetone 2 and nitroalkenes 1 to afford the Michael adducts 3 in excellent yields and enantioselectivities (Scheme 1.3). Under these reaction conditions, various aryl-substituted 1,3-diketones, acyclic and cyclic β-ketoesters also gave the addition products with nitrostyrene 1 in excellent yields and enantioselectivities, as well as with moderate-to-excellent diastereoselectivities. The Song group reported an asymmetric Michael addition of 1,3-diketones 2 to nitroalkenes 1 by employing the same squaramide-based organocatalyst C6 in brine to give the products 3 in excellent yields and enantioselectivities (Scheme 1.3).⁷ The reaction was performed with 0.5 mol% of the catalyst C6. Due to the hydrophobic hydration effect, the rate of reaction was observed to be faster when the reaction was performed in brine as solvent rather than in organic solvents.

SCHEME 1.3 Asymmetric Michael addition of 1,3-diketone to nitroalkenes using squaramide-based organocatalyst.

Zlotin’s group developed a bifunctional ionic liquid-supported recyclable organocatalyst C7 for the asymmetric Michael reaction of 1,3-diketones 2 with nitroalkenes 1a to give the corresponding Michael adducts 3 in excellent yields and enantioselectivities (Scheme 1.4).⁸ The catalyst C7 can be recycled and reused without any significant loss of activity and selectivity. The Miura group designed and synthesized cinchona–diaminomethylenemalononitrile (DMM) organocatalyst C8 and employed it successfully for the asymmetric Michael addition of acetylacetone 2 to nitroalkenes 1a under mild reaction conditions in diethyl ether to afford the respective Michael adducts 3 in high yields and enantioselectivitie...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Dedication
• Table of Contents
• List of Abbreviations
• Foreword
• Preface
• Authors
• Introduction
• 1 Catalytic Asymmetric Michael Addition of 1,3-Dicarbonyls to Nitroalkenes
• 2 Catalytic Asymmetric Michael Addition of Aldehydes to Nitroalkenes
• 3 Catalytic Asymmetric Michael Addition of Ketones to Nitroalkenes
• 4 Catalytic Asymmetric Michael Addition of Miscellaneous Carbonyl Compounds to Nitroalkenes
• 5 Catalytic Asymmetric Friedel–Crafts Reactions of Nitroalkenes
• 6 Catalytic Asymmetric Michael Addition of Miscellaneous Carbon-centered Nucleophiles to Nitroalkenes
• 7 Catalytic Asymmetric Michael Addition of Heteroatom-centered Nucleophiles to Nitroalkenes
• 8 Catalytic Asymmetric Cycloadditions of Nitroalkenes
• 9 Catalytic Asymmetric Reduction of Nitroalkenes
• 10 Catalytic Asymmetric Synthesis of Cycloalkanes via Cascade Reactions of Nitroalkenes
• 11 Catalytic Asymmetric Synthesis of Aryl-Fused Heterocycles via Cascade Reactions of Nitroalkenes
• 12 Catalytic Asymmetric Synthesis of Five- and Six-Membered Heterocycles via Cascade Reactions of Nitroalkenes
• Index