LongLarf

Abstract

Synlett
DOI: 10.1055/s-0037-1610486

In this account, our group’s efforts towards exploring new substrates as precursors for the Wittig reaction have been discussed. Several new strategies developed by our group for the generation of requisite ylides for the Wittig reaction are highlighted. The idea behind the development of some chemoselective and diversity-oriented strategies are discussed in detail in a progressive manner. These strategies encompass a wide range of substrates that are employed for the synthesis of an array of heterocycles and multifunctional olefins and present a huge scope for their application on an industrial level.1 Introduction2 Development of New Methods to Effect Intramolecular Wittig Reaction3 Development of a Catalytic Wittig Reaction4 New Synthesis of Bis-Heteroarenes5 Direct β-Acylation of 2-Arylidene-1,3-indandiones6 Doubly Chemoselective Protocol for the Diversity-Oriented Synthesis of Coumarin Derivatives7 Conclusion
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© Georg Thieme Verlag Stuttgart · New York

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Remote access: Metal‐free, visible‐light‐induced site‐selective heteroarylation of remote C(sp³)−H bonds has been accomplished through the design of a class of N‐alkoxyheteroarenium salts serving as both alkoxy radical precursors and heteroaryl sources. This strategy features a photoredox radical cascade process involving the sequential fragmentation of an N‐alkoxyheteroarenium substrate, 1,5‐HAT reaction, and pyridylation, and is well suited for late‐stage functionalization of complex bioactive molecules.

Abstract

Metal‐free, visible‐light‐induced site‐selective heteroarylation of remote C(sp³)−H bonds has been accomplished through the design of N‐alkoxyheteroarenium salts serving as both alkoxy radical precursors and heteroaryl sources. The transient alkoxy radical can be generated by the single‐electron reduction of an N‐alkoxypyridinium substrate by a photoexcited quinolinone catalyst. Subsequent radical translocation of the alkoxy radical forms a nucleophilic alkyl radical intermediate, which undergoes addition to the substrate to achieve remote C(sp³)−H heteroarylation. This cascade strategy provides a powerful platform for remote C(sp³)−H heteroarylation in a controllable and selective manner and is well suited for late‐stage functionalization of complex bioactive molecules.

Something’s fishy

Something’s fishy, Published online: 19 October 2018; doi:10.1038/s41557-018-0162-0

Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins

Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins, Published online: 18 October 2018; doi:10.1038/s41586-018-0669-y

The development of highly reactive and stereoselective catalytic systems is required not only to improve existing synthetic methods but also to invent distinct chemical reactions. Herein, a homogenized combination of nickel-based Lewis acid–surfactant-combined catalysts and single-walled carbon nanotubes is shown to exhibit substantial activity in water. In addition to the enhanced reactivity, stereoselective performance and long-term stability were demonstrated in asymmetric conjugate addition reactions of aldoximes to furnish chiral nitrones in high yields with excellent selectivities. The practical and straightforward application of the designed catalysts in water provides an expedient, environmentally benign, and highly efficient pathway to access optically active compounds.

Methylation mine: In this work, 22 different methylation reagents are reviewed, 12 of which are shown in the graphic. MeI, Me₃OBF₄, and methyl sulfonates are red because of their toxicity or too high electrophilicity. HCHO is blue owing to its over‐methylation in reductive aminations when a primary amine is the substrate, and a secondary amine product is desired. The rest are colored green because of low toxicity (dimethyl carbonate, DMC), low cost (MeOH, CO₂, HOAc, FA), or popular application in high‐through‐put screenings (methyl boronic acid, MBA, MeBF₃K, trimethylboroxine, TMB).

Abstract

Methylation is a well‐known structural modification in organic and medicinal chemistry. This review summarizes recent advances in methylation by categorizing specific methylation reagents. The challenges of mono N‐methylation of aliphatic amines and N‐methylation of peptides are discussed. This review will be useful for chemists wanting to select the appropriate reagents for methylation chemistry. Based on the large diversity of methylation reagents and their wide scope, this review also broadens perspectives on which strategies to select for utilizing a particular methylation, resulting in an increased flexibility in synthetic route planning.

All in one: An electrostatically enhanced phenol as a simple and competent bifunctional organocatalyst for the conversion of epoxides to cyclic carbonates under environmentally benign conditions is described. Incorporating a positively charged center into phenols results in a bifunctional system with enhanced acidity and reactivity, capable of epoxide activation, a halide nucleophilic ring‐opening process, and CO₂ incorporation.

Abstract

An electrostatically enhanced phenol as a simple and competent bifunctional organocatalyst for the atom‐economical conversion of epoxides to cyclic carbonates under environmentally benign conditions is described. Incorporating a positively charged center into phenols through a modular one‐step synthesis results in a bifunctional system with enhanced acidity and reactivity, capable of epoxide activation, a halide nucleophilic ring‐opening process, and CO₂ incorporation in a synergistic fashion. A rational survey of the efficiency of different positively charged phenols and the influence of different parameters, such as temperature, catalyst loading, and the nature of the nucleophile, on catalytic activity was conducted. In addition, the time‐dependent conversion of epoxide into the corresponding cyclic carbonate was further explored by FTIR‐ATR and ¹H NMR spectroscopy. This bifunctional catalytic platform is among one of the mildest and most efficient metal‐free systems that is capable of converting a variety of epoxides into cyclic carbonates under virtually ambient conditions. The ¹H NMR titration experiment validated the bifunctional catalytic mechanism wherein both the epoxide activation and the nucleophilic ring‐opening process occur in concert en route to carbon dioxide fixation.

Chiral resolution: A bis‐cyclometalated chiral‐at‐iridium complex catalyzes the kinetic resolution of monosubstituted epoxides with carbon dioxide to provide non‐racemic cyclic carbonates at room temperature with selectivity factors up to 16.6.

Abstract

Chiral‐at‐metal bis‐cyclometalated iridium(III) complexes are introduced as a new class of chiral catalysts for the reaction of epoxides with CO₂ to form cyclic carbonates under conditions of kinetic resolution. Reactions are typically performed at room temperature in the presence of 1 mol % of iridium catalyst and 1.5 mol % of tetraethylammonium bromide as the nucleophilic cocatalyst to provide selectivity factors of up to 16.6. A variety of monosubstituted epoxides, including styrene epoxide, epoxides with aliphatic side chains, glycidyl ethers, and a glycidyl ester, are found to be suitable substrates. No polymerization side reaction is observed for any of the investigated substrates.

Abstract

A new [OSSO]‐Fe(III) metallate complex was prepared and characterized. We demonstrated that such metallate is the real catalytic active species for the cycloaddition of CO₂ to the epoxides, formed from the in situ reaction of the related [OSSO]‐Fe(III) neutral complexes and tetrabutylammonium bromide. The metallate complex was used as a single component catalyst for the formation of cyclic organic carbonates from ten epoxides and CO₂ at 1 bar pressure with good activity.

Catalytic dehydrogenative decarboxyolefination of carboxylic acids

Catalytic dehydrogenative decarboxyolefination of carboxylic acids, Published online: 08 October 2018; doi:10.1038/s41557-018-0142-4

Various unprotected carboxylic acids undergo enantioselective aldol reactions in the presence of a chiral phosphine oxide as a Lewis base catalyst. The carboxylic acids were activated with silicon tetrachloride to form the bis(trichlorosilyl)enediolates in situ, which subsequently underwent an aldol reaction with an aldehyde or a ketone to produce β‐hydroxycarboxylic acids in high enantioselectivities of up to 92 % ee.

Abstract

The first catalytic enantioselective aldol reaction of various unprotected carboxylic acids is described. In the presence of a chiral bis(phosphine oxide) as a Lewis base catalyst, carboxylic acids were activated with silicon tetrachloride to form the corresponding bis(trichlorosilyl)enediolates in situ, which subsequently underwent an aldol reaction with an aldehyde or a ketone to produce β‐hydroxycarboxylic acids in high enantioselectivities of up to 92 % ee.

Reactions that form a product with the same reactive functionality as that of one of the starting compounds frequently end in oligomerization. As a salient example, selective aldol coupling of the smallest, though arguably most useful, enolizable aldehyde, acetaldehyde, with just one partner substrate has proven to be extremely challenging. Here, we report a highly enantioselective Mukaiyama aldol reaction with the simple triethylsilyl (TES) and tert-butyldimethylsilyl (TBS) enolates of acetaldehyde and various aliphatic and aromatic acceptor aldehydes. The reaction is catalyzed by recently developed, strongly acidic imidodiphosphorimidates (IDPi), which, like enzymes, display a confined active site but, like small-molecule catalysts, have a broad substrate scope. The process is scalable, fast, efficient (0.5 to 1.5 mole % catalyst loading), and greatly simplifies access to highly valuable silylated acetaldehyde aldols.

With a certain lag time, metal‐catalyzed carboxylation reactions of organic matter with CO₂ as C₁ feedstock have entered a new era of exponential growth. These C−C bond formations are characterized by their mild conditions and excellent chemo‐ and site selectivity for a wide range of coupling partners, holding promise to streamline synthetic sequences en route to carboxylic acids.

Abstract

Driven by the inherent synthetic potential of CO₂ as an abundant, inexpensive and renewable C₁ chemical feedstock, the recent years have witnessed renewed interest in devising catalytic CO₂ fixations into organic matter. Although the formation of C−C bonds via catalytic CO₂ fixation remained rather limited for a long period of time, a close look into the recent literature data indicates that catalytic carboxylation reactions have entered a new era of exponential growth, evolving into a mature discipline that allows for streamlining the synthesis of carboxylic acids, building blocks of utmost relevance in industrial endeavors. These strategies have generally proven broadly applicability and convenient to perform. However, substantial challenges still need to be addressed reinforcing the need to cover metal‐catalyzed carboxylation area in a conceptual and concise manner, delineating the underlying new principles that are slowly emerging in this vibrant area of expertise.