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The area of catalysis of radical reactions has recently flourished. Various reaction conditions have been discovered and explained in terms of catalytic cycles. These cycles rarely stand alone as unique paths from substrates to products. Instead, most radical reactions have innate chains which form products without any catalyst. How do we know if a species added in "catalytic amounts" is a catalyst, an initiator, or something else? Herein we critically address both catalyst-free and catalytic radical reactions through the lens of radical chemistry. Basic principles of kinetics and thermodynamics are used to address problems of initiation, propagation, and inhibition of radical chains. The catalysis of radical reactions differs from other areas of catalysis. Whereas efficient innate chain reactions are difficult to catalyze because individual steps are fast, both inefficient chain processes and non-chain processes afford diverse opportunities for catalysis, as illustrated with selected examples.

Readily available NHC-arylboranes (NHC-BH2Ar) are converted in high yield to stable NHC-difluoro(aryl)boranes (NHC-BF2Ar) by treatment with 2 equiv of 1-chloromethyl-4-fluoro-1,4-diazonia-bicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor). In turn, the NHC-difluoro(aryl)boranes participate directly in Suzuki reactions under conditions previously used for anionic trifluoroborate salts. Accordingly, NHC-difluoroboranes are a new class of stable precursors for Suzuki reactions.

1,1-Divinyl-2-phenylcyclopropanes are a class of substrates showing a rich array of both thermal and photochemical rearrangement reactions.

Addition of NHC-boranes to intermediate arynes proceeds with remarkable regioisomeric outcomes, especially, the formation of ortho products from arynes bearing electron-withdrawing groups.

This Review draws an analogy between acid–base catalysis and redox catalysis. The 'electron is a catalyst' paradigm unifies mechanistically an assortment of synthetic transformations that otherwise have little or no apparent relationship. Various radical cascades catalysed by the electron are discussed.

Boryl sulfide (I) and N-borylthioamide (IV) are employed as neutral sources of sulfur nucleophiles in substitution reactions with alkyl- and acyl halogenides.

Long-thriving movements often have a habit of continually reinventing themselves in a process called renaissance. The word itself is an English reinvention (some would say theft) of the French word for “rebirth”. Renaissances often occur in waves with each new wave typically building on the prior one. The European Renaissance is a perfect example, occurring in waves over about three centuries. Quoting from Yogi Berra, after a few of these waves that bear certain resemblances, it starts to feel like “deja vu all over again” [1]. The discipline of organic radical chemistry dates back over 110 years, and it has been thriving for decades because it continuously reinvents itself. Often this happens when groups of researchers with different interests and expertise immigrate to the field. About 30 years ago there began a flourishing period in the field of organic radical chemistry that delivered groundbreaking results, especially in organic synthesis. By the 1990’s, radical reactions (especially cyclizations) were broadly recognized as powerful tools to make molecules. This Renaissance I in organic radical chemistry was built on prior renaissances in polymer and physical (especially physical organic) chemistry of radicals. In turn, the knowledge gained during Renaissance I was diverted to spark new waves of developments in neighboring disciplines such as biology and materials science. A comprehensive overview of the various aspects of modern radical chemistry addressing all these major fields can be found in the recently published four-volume “Encyclopedia of Radicals in Chemistry, Biology and Materials” [2]. Over the past few years, the process has again come full circle as research in organic radical chemistry, especially synthetic radical chemistry, has been reignited. This renaissance, Renaissance II if you will, is documented by the many exciting contributions recently published in high impact journals. This Thematic Series on radical chemistry in the Beilstein Journal of Organic Chemistry brings together papers from top research groups and representing many of the most significant themes in the current field of radical chemistry. A partial list of topics that have seen new developments in the past few years follows. Many of these themes are represented once or multiple times in papers of the Thematic Series: a) Base mediated homolytic aromatic substitution (BHAS) [3], b) photoredox catalysis [4–8], c) redox chemistry using Bu4NI in combination with t-BuOOH [9], d) transition metal catalyzed processes where radicals are suggested to interact directly with copper, nickel, zinc, palladium, gold and so on [10–16], e) radical trifluoromethylation [17] and radical fluorination [18–20], f) natural product synthesis [21], g) new main group radical chemistry involving elements like boron [22], phosphorous [23] and selenium [24], tellurium [25], among others, h) synthesis or functionalization of all sorts of heterocyclic ring systems, especially heteroaromatic systems [26–27], i) radical chemistry with water or in water [28], k) sequential transformations with both reductants and oxidants, l) radical chemistry in materials science [29–30], and m) high level computations of radicals and their reactions [31]. Just as in Renaissance I, the field of radical chemistry is currently being joined by all sorts of researchers whose primary interests have until recently been elsewhere. In the 1980’s there were immigrants from natural products chemistry and synthetic methodology. Today, many of the new immigrants again come from a background of synthesis, often with a focus on catalysis. They bring along new ideas and different perspectives. As both new and established researchers have dared to try radical reactions in challenging new areas, their results have lit up the field. Successful explorers of all ages have always taken the best existing maps on their voyages of discovery. These maps were invaluable, even though they inevitably were incomplete and even inconsistent. Little by little, the inconsistencies got fixed and the empty spaces got filled in. The reviews in the Encyclopedia of Radical Chemistry and other sources serve as maps to drive organic radical research in new directions. Like old maps of the earth, these maps are also inevitably incomplete and at times inconsistent. But they are powerful aids to help you understand both where you are and where you are going. Or, you can forget the maps and wander out on your own. But to again quote Yogi, “if you don’t understand where you are going, you might end up someplace else [1].” To all those new folks joining the field, we welcome you to the world of organic radical chemistry. Get yourself a good set of maps and start exploring. There is one final parallel to draw between Renaissance I and Renaissance II in organic radical chemistry. In 1985, a thematic special issue on organic radical chemistry in Tetrahedron organized by Bernd Giese [32] brought many of the advances of radical chemistry to a wider audience. Similarly, this Thematic Series edited by Corey Stephenson advances the same goal. Take some time to read a few of the papers in this Thematic Series. Think of the papers as evolving maps of regions of radical chemistry under exploration. Allow yourself to be drawn into the exciting world that is modern organic radical chemistry.

The title reaction affords fused and spirocyclic imines with five-, six- and seven-membered rings.

It is demonstrated that phenylhydrazine is a cheap initiator for the direct arylation of unactivated arenes with diverse aryl iodides.

The hydroboration of alkenes of diverse structural types by assorted N-heterocyclic carbene boranes can be accomplished by addition of 5–10% diiodine. For example, reaction of 1,3-dimethylimidazol-2-ylidene borane (diMe-Imd-BH3) with 10% I2 followed by addition of 2,3-dimethyl-2-butene provided the corresponding thexyl NHC-borane (diMe-Imd-BH2thexyl) in 75% yield. This and related monohydroboration products are stable to chromatography and storage. The scope of the new reaction is described, and the mechanism is probed by 11B NMR experiments.

This method also works with substituted imidazole-borane adducts as well as 1,2,4-triazole-derived borane adducts.

While iodoarenes react smoothly, bromoarenes and chloroarenes do not couple under conditions used.

Visible light photoredox catalyzed inter- and intramolecular C–H functionalization reactions of tertiary amines have been developed. Oxygen was found to act as chemical switch to trigger two different reaction pathways and to obtain two different types of products from the same starting material. In the absence of oxygen, the intermolecular addition of N,N-dimethyl-anilines to electron-deficient alkenes provided γ-amino nitriles in good to high yields. In the presence of oxygen, a radical addition/cyclization reaction occurred which resulted in the formation of tetrahydroquinoline derivatives in good yields under mild reaction conditions. The intramolecular version of the radical addition led to the unexpected formation of indole-3-carboxaldehyde derivatives. Mechanistic investigations of this reaction cascade uncovered a new photoredox catalyzed C–C bond cleavage reaction.

This account documents our recent progress in exposing some of the potential of mucohalic acids in synthetic applications. Understanding their stability and reactivity in different reaction media allows the development of mild and regioselective methods to access various substituted butenolides, butenolactams, and 4,5-di­halopyridazin-3(2H)-ones and to create other novel, multifunctionalized building blocks. 1 Introduction 2 The Rationale for the Reinvestigation of Mucohalic Acid Chemistry 3 Understanding the Stability of Mucohalic Acids 4 One-Pot Synthesis of a 4,5-Dihalopyridazin-3(2H)-one and the Process Chemistry of ABT-963 5 Reductive Amination of Mucochloric Acid and Synthesis of Antiseizure Drug Levetiracetam (Keppra) 6 Reduction of Mucohalic Acids and Synthesis of Anti-­inflammatory Agent Rofecoxib (Vioxx) 7 Lewis Acid Catalyzed Knoevenagel Aldol Reaction 8 Lewis and Bronsted Acid Promoted Friedel–Crafts ­Hydroxyalkylation 9 Lewis Acid Facilitated Mukaiyama Aldol Reaction 10 Indium-Mediated Allylation in Water 11 Palladium-Free Regioselective Etherification and Amination 12 Novel Building Blocks Derived from Mucohalic Acids 13 Direct Vinylogous Aldol Addition Using α,β-Dihalo-­Substituted Butenolides and Butenolactams 14 Other Applications 15 Summary and Conclusion

One, two, or all three of the boron hydrides of carbene borane NHC and its dimethyl analogue can be transferred to the aldehydes and ketones to give primary and secondary alcohols under ambient conditions and in the presence of SiO2, which is crucial for the rapid reduction.

Compounds (I) decompose to (II) and (III) even when exposed to light of the laboratory and air.

Selenide ions are superior to previously reported thiolate analogues and promote the disproportionation of aldehydes with increased reaction rates and broader scope at lower loadings and temperature.

The reduction of ketones, esters and the imine (XXIV) under mild conditions is achieved with diphenylsilane in the presence of TAC.

N,N′-Dialkyl and N,N′-diaryl imidazol-2-ylidene-boranes and trifluoroboranes are rapidly lithiated at C4 of the imidazole ring, and the resulting intermediates have been quenched with an assortment of electrophiles to provide ring-functionalized imidazol-2-ylidene-boranes. Further deprotonation and functionalization of C5 have been demonstrated. Deboronation of the products by treatment with triflic acid or iodine and then methanol opens a route to C4/C5 functionalized imidazolium salts and imidazol-2-ylidenes.

Boranes are widely used Lewis acids and N-heterocyclic carbenes (NHCs) are popular Lewis bases, so it is remarkable how little was known about their derived complexes until recently. NHC-boranes are typically readily accessible and many are so stable that they can be treated like organic compounds rather than complexes. They do not exhibit “borane chemistry”, but instead are proving to have a rich chemistry of their own as reactants, as reagents, as initiators, and as catalysts. They have significant potential for use in organic synthesis and in polymer chemistry. They can be used to easily make unusual complexes with a broad spectrum of functional groups not usually seen in organoboron chemistry. Many of their reactions occur through new classes of reactive intermediates including borenium cations, boryl radicals, and even boryl anions. This Review provides comprehensive coverage of the synthesis, characterization, and reactions of NHC-boranes.

The carbene derived from triazolium salt TRC catalyzes the title reactions to give the corresponding saturated alcohols or (E)-alkenols, correspondingly, after quenching of the resulting siloxanes with Bu4NF.

Cyclic urea derivatives are synthesized by carbonylation of primary and secondary diamines.

A radical outlook: Recently published "organocatalytic C-H activation reactions" have now been interpreted as base-promoted homolytic substitutions. The addition of an aryl radical to an arene followed by deprotonation (see above) and electron transfer form part of the chain reaction. Although these new results are not conceptual breakthroughs, they could be experimental breakthroughs because they presage new transformations in radical (anion) chemistry. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fast and efficient homo and cross Tishchenko reaction is achieved under microwave irradiation to give esters (II), (V) and (VII) in moderate to high yields within 10 to 180 minutes.

Reduction of boryl iodide (I) with LDBB and subsequent trapping of the resulting N-heterocyclic carbene boryl anion with various electrophiles yields derivatives that would be difficult to access with existing methods.

Eight possible diastereomers of hydantoin-fused hexahydrochromenopyrrole (VI) are synthesized by FDMS.

Starting from pure (S)-2,2′-bis(bromomethyl)-1,1′-binaphthyl, the synthesis of a new chiral, enantiomerically pure dinaphthostannepin is described. Preliminary reactions of this hydride with a racemic organic halide under radical conditions gave the reduced product in up to 41 % enantiomeric excess, depending on the experimental conditions.

Mono- and dialkylated malononitriles (geminal dinitriles) are reductively decyanated to mononitriles (10 examples) on treatment with tributyltin hydride and a catalytic amount of 2,2′-azobisisobutyronitrile in refluxing benzene. A mechanism for this reaction is also proposed.

We describe a new tandem radical cyclization strategy for the construction of the congested angular triquinane portion of the naturally occurring tetraquinane crinipellin A. The preparation and cyclization of three 5,5-disubstituted-1,4-dimethyl-1,3-cyclopentadienes are detailed. This cyclization strategy results in a 1,4-functionalization of the cyclopentadiene nucleus, mediated by an allylic radical cyclization. Each tandem cyclization produces two diastereomeric triquinanes in a rationof 5:1. The minor diastereomer possesses the correct relative stereochemistry for the D-ring isopropyl group of crinipellin A. A tandem cationic cyclization, paralleling the radical cyclizations, is also described

Sunlamp irradiation of 1-substituted 5-iodo-1-pentynes, 5 equiv of phenyl isocyanide, and 1.5 equiv of hexamethylditin in tert-butylbenzene (0.01-0.025 M) at 150 o C produces 9-substituted 2,3-dihydro-1H-cyclopenta [b] quinolines in 36-70% yields. A mechanistic proposal for this first example of a 4+1 radical annulation includes the following: (1) radical addition to an isonitrile, (2) cyclization of the resulting imidoyl radical to the alkyne, (3) addition of the so-formed vinyl radical to the aromatic ring, and (4) rearomatization. When substituted isonitriles (p-F p-OMe, m-F) are employed, the major unrearranged products are accompanied by 7-30% or rearranged products. Independent generation of a proposed intermediate suggests that the rearranged products arise by initial closure of the vinyl radical to form a five-membered ring, followed by C-N bond cleavage and recyclization

Syntheses of the three title natural products are used to illustrate that optically pure isoxazolines can be transformed into a wide variety of functional groups including β,γ-dihydroxy ketones, alcohols, 1,2- and 1,3-diols, 1,3,4-triols, 1,3-amino alcohols, and 1,3,4-amino diols. It is suggested that this cycloadditive strategy complements existing asymmetric aldol routes to such functionality

A Stereoselective aldol reaction between bis(tert-butyldimethylsilyloxy) acetone and an isoxazoline-derived azaenolate is a key step in the construction of a C-ring model of sesbanimide A.