Recent Advances in Minisci‐Type Reactions Proctor, Rupert S. J.; Phipps, Robert J.
Angewandte Chemie International Edition,
September 23, 2019, Letnik:
58, Številka:
39
Journal Article
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Reactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. First developed into ...a useful synthetic tool in the late 1960s by Minisci, this reaction type has been in constant use over the last half century by chemists seeking to functionalize heterocycles in a rapid and direct manner, avoiding the need for de novo heterocycle synthesis. Whilst the originally developed protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder and more benign conditions. The recent surge of interest in new transformations based on free radical reactivity has meant that numerous choices are now available to a synthetic chemist looking to utilize a Minisci‐type reaction. Radical‐generation methods based on photoredox catalysis and electrochemistry have joined approaches which utilize thermal cleavage or the in situ generation of reactive radical precursors. This review will cover the remarkably large body of literature that has appeared on this topic over the last decade in an attempt to provide guidance to the synthetic chemist, as well as a perspective on both the challenges that have been overcome and those that still remain. As well as the logical classification of advances based on the nature of the radical precursor, with which most advances have been concerned, recent advances in control of various selectivity aspects associated with Minisci‐type reactions will also be discussed.
Under control: Reactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. Whilst the original protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder conditions.
Asymmetric catalysis has been revolutionised by the realisation that attractive non-covalent interactions such as hydrogen bonds and ion pairs can act as powerful controllers of enantioselectivity ...when incorporated into appropriate small molecule chiral scaffolds. Given these tremendous advances it is surprising that there are still a relatively limited number of examples of non-covalent interactions being harnessed for control of regioselectivity or site-selectivity in catalysis, two other fundamental selectivity aspects facing the synthetic chemist. This perspective examines the progress that has been made in this area thus far using non-covalent interactions in conjunction with transition metal catalysis as well as in the context of purely organic catalysts. We hope this will highlight the great potential in this approach for designing selective catalytic reactions.
This perspective examines the progress that has been made in using non-covalent interactions to control regioselectivity and site-selectivity in catalysis.
Recent advances related to catalytic enantioselectice fluorination are examined. Catalytic enantioselective monofluoromethylation and catalytic enantioselective difluoromethylation are among the ...topics discussed.
Catalytic enantioselective Minisci-type addition to heteroarenes Proctor, Rupert S J; Davis, Holly J; Phipps, Robert J
Science (American Association for the Advancement of Science),
2018-Apr-27, 2018-04-27, 20180427, Letnik:
360, Številka:
6387
Journal Article
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Basic heteroarenes are a ubiquitous feature of pharmaceuticals and bioactive molecules, and Minisci-type additions of radical nucleophiles are a leading method for their elaboration. Despite many ...Minisci-type protocols that result in the formation of stereocenters, exerting control over the absolute stereochemistry at these centers remains an unmet challenge. We report a process for addition of prochiral radicals, generated from amino acid derivatives, to pyridines and quinolines. Our method offers excellent control of both enantioselectivity and regioselectivity. An enantiopure chiral Brønsted acid catalyst serves both to activate the substrate and induce asymmetry, while an iridium photocatalyst mediates the required electron transfer processes. We anticipate that this method will expedite access to enantioenriched small-molecule building blocks bearing versatile basic heterocycles.
The use of noncovalent interactions to direct transition-metal catalysis is a potentially powerful yet relatively underexplored strategy, with most investigations thus far focusing on using hydrogen ...bonds as the controlling element. We have developed an ion pair-directed approach to controlling regioselectivity in the iridium-catalyzed borylation of two classes of aromatic quaternary ammonium salts, leading to versatile meta-borylated products. By examining a range of substituted substrates, this provides complex, functionalized aromatic scaffolds amenable to rapid diversification and more broadly demonstrates the viability of ion-pairing for control of regiochemistry in transition-metal catalysis.
Enantioselective transition metal catalysis is an area very much at the forefront of contemporary synthetic research. The development of processes that enable the efficient synthesis of enantiopure ...compounds is of unquestionable importance to chemists working within the many diverse fields of the central science. Traditional approaches to solving this challenge have typically relied on leveraging repulsive steric interactions between chiral ligands and substrates in order to raise the energy of one of the diastereomeric transition states over the other. By contrast, this Review examines an alternative tactic in which a set of attractive noncovalent interactions operating between transition metal ligands and substrates are used to control enantioselectivity. Examples where this creative approach has been successfully applied to render fundamental synthetic processes enantioselective are presented and discussed. In many of the cases examined, the ligand scaffold has been carefully designed to accommodate these attractive interactions, while in others, the importance of the critical interactions was only elucidated in subsequent computational and mechanistic studies. Through an exploration and discussion of recent reports encompassing a wide range of reaction classes, we hope to inspire synthetic chemists to continue to develop asymmetric transformations based on this powerful concept.
For over a century, chemical transformations of benzene derivatives have been guided by the high selectivity for electrophilic attack at the ortho/para positions in electron-rich substrates and at ...the meta position in electron-deficient molecules. We have developed a copper-catalyzed arylation reaction that, in contrast, selectively substitutes phenyl electrophiles at the aromatic carbon-hydrogen sites meta to an amido substituent. This previously elusive class of transformation is applicable to a broad range of aromatic compounds.
The past decade has seen unprecedented growth in the development of new chemical methods that proceed by mechanisms involving radical intermediates. This new attention has served to highlight a ...long-standing challenge in the field of radical chemistry - that of controlling absolute stereochemistry. This Review will examine developments using a strategy that offers enormous potential, in which attractive non-covalent interactions between a chiral catalyst and the substrate are leveraged to exert enantiocontrol. In a simplistic sense, such an approach mimics the modes of activation and control in enzyme catalysis and the realization that this can be achieved in the context of small-molecule catalysts has had sizable impact on the field of asymmetric catalysis in recent years. This strategy is now starting to quickly gather pace as a powerful approach for control of enantioselectivity in radical reactions and we hope that this focused survey of progress so far will inspire future developments in the area.
Selective functionalization at the meta position of arenes remains a significant challenge. In this work, we demonstrate that a single anionic bipyridine ligand bearing a remote sulfonate group ...enables selective iridium‐catalyzed borylation of a range of common amine‐containing aromatic molecules at the arene meta position. We propose that this selectivity is the result of a key hydrogen bonding interaction between the substrate and catalyst. The scope of this meta‐selective borylation is demonstrated on amides derived from benzylamines, phenethylamines and phenylpropylamines; amine‐containing building blocks of great utility in many applications.
Clever positioning: A bipyridine ligand incorporating a remote anionic sulfonate group directs iridium‐catalyzed borylation to the meta‐position on a range of amide‐containing arenes. It is proposed that this selectivity is a result of a hydrogen bonding interaction to correctly position the iridium metal centre in the crucial C−H activation.
Despite the tremendous advances of the past four decades, chemists are far from being able to use chiral catalysts to control the stereoselectivity of any desired reaction. New concepts for the ...construction and mode of operation of chiral catalysts have the potential to open up previously inaccessible reaction space. The recognition and categorization of distinct approaches seems to play a role in triggering rapid exploration of new territory. This Review both reflects on the origins as well as details a selection of the latest examples of an area that has advanced considerably within the past five years or so: the use of chiral anions in asymmetric catalysis. Defining reactions as involving chiral anions is a difficult task owing to uncertainties over the exact catalytic mechanisms. Nevertheless, we attempt to provide an overview of the breadth of reactions that could reasonably fall under this umbrella.
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