One-pot synthesis of 5-sulfonamidopyrazole from terminal alkynes, sulfonyl azides and hydrozones

5-Sulfonamidopyrazoles were efficiently synthesized from terminal alkynes, sulfonyl azides and hydrozones. The sequential reaction involves a copper-catalyzed three-component reaction, a Lewis acid-catalyzed electrocyclic reaction and a dehydrogenation.     

Potassium 2,2,5,7,8-pentamethylchroman-6-oxide: a rationally designed base for Pd-catalysed amination

This base is just right! A new base, potassium 2,2,5,7,8-pentamethylchroman-6-oxide, for Pd-catalysed amination has been rationally designed that has sufficient basicity to efficiently deprotonate the intermediate aryl palladium ammonium complex, leading to far better rates than obtained with carbonate, which is known to be very mild. At the same time, this new base possesses minimal nucleophilicity to mitigate the degradation of base-sensitive functional groups in the starting materials and products, such as is commonly seen with potassium or sodium tert-butoxide.     

Programming Organic Molecules: Design and Management of Organic Syntheses through Free‐Radical Cascade Processes

Cascade, domino, or tandem processes, that link together two or more transformations in one pot, are increasing in popularity because they lead to improvements in synthetic efficiency and decreases in environmental impact. Not only do these cascades contain choice mechanistic gems but they also deliver compact and elegant syntheses of complex natural products. Longer cascades require more functional groups precisely configured within carefully designed initial molecular architectures. Such “purposeful” molecules can be thought of as chemical algorithms.This article surveys the phenomenal range of unimolecular free‐radical cascades. A convenient system for classifying free‐radical cascades is described that is useful for evaluating and comparing cascades and aids the design of synthetic routes to polycyclic structures.Double cyclization cascades lead to cyclopentylcyclopentane or bicyclo[3.3.0]octane derivatives. Precursors that contain a ring as a template have been used to control stereochemistry in syntheses of triquinanes and many related compounds. Of the cascades containing ring‐cleavage steps, the most useful are the ring expansions which have opened up new synthetic routes to medium ring polycycles.The key design features of three‐stage unimolecular free‐radical cascades that yielded steroid structures, are linear arrays of radical acceptor units associated with methyl groups distributed every fifth C‐atom in the precursor polyenes. Ring cleavage is the reverse of cyclization. In special, symmetrical structures, therefore, this led to sequences that were reversible, thus launching endlessly repeating cascades supported by delightfully fluxional structures. The science of “programming” organic molecules to achieve particular target structures is maturing rapidly. Coordination and classification of the welter of information in this area is intended to facilitate design and hence to extend the range and complexity of attainable structures.     

A practical oxidative method for the cleavage of hydrazide N[bond]N bonds

The selective N-oxidation of the most nucleophilic amino nitrogen atom in hydrazides is central to the development of an unprecedented methodology for the cleavage of their N[bond]N bonds under oxidative conditions. Treatment of a series of hydrazides 1-9 with peracids such as magnesium monoperoxyphtalate hexahydrate (MMPP.6 H(2)O) or meta-chloroperbenzoic acid (m-CPBA) afforded the corresponding amides 10-16 in good-to-excellent yields (80-92 %). The extension of the methodology to carbamate-like substrates such as 17 and 18 was also investigated, but in this case the process is synthetically useless in view of the low yields observed of carbamates 19 and 20 (approximately 15 %). Experiments carried out with equivalent amounts of oxidant produced nitrones, such as 26, proceeding from the dialkylamino moiety, and (1)H NMR experiments indicated that this product is formed by fast conversion of the parent hydrazide, without detection of the expected hydrazide N-oxides. In addition, the over oxidation of 26 into nitronate 25 proceeds through an unknown intermediate. This oxidative N[bond]N bond cleavage by peracids is an alternative method for the deamination of hydrazides, and constitutes the only solution compatible with substrates carrying functionalities sensitive to reducing conditions.     

A novel approach for the formation of carbon-nitrogen bonds: azidation of alkyl radicals with sulfonyl azides.

Two preparatively attractive methods for the azidation of alkyl radicals are described. Secondary and tertiary alkyl iodides and dithiocarbonates are easily converted into the corresponding azides, either by reaction with ethanesulfonyl azide in the presence of dilauroyl peroxide, or by treatment with benzenesulfonyl azide and hexabutylditin in the presence of a radical initiator. Interestingly, intramolecular tandem radical cyclization-azidation processes can be performed in high yields.     

Radical trans‐Hydroboration of Alkynes with N‐Heterocyclic Carbene Boranes

Hydroboration of internal alkynes with N‐heterocyclic carbene boranes (NHC‐boranes) occurs to provide stable NHC (E)‐alkenylboranes upon thermolysis in the presence of di‐tert‐butyl peroxide. The E isomer results from an unusual trans‐hydroboration, and the E/Z selectivity is typically high (90:10 or greater). Evidence suggests that this hydroboration occurs by a radical‐chain reaction involving addition of an NHC‐boryl radical to an alkyne to give a β‐NHC‐borylalkenyl radical. Ensuing hydrogen abstraction from the starting NHC‐borane provides the product and returns the starting NHC‐boryl radical. Experiments suggest that the observed trans‐selectivity results from kinetic control in the hydrogen‐transfer reaction.     

Synthesis of hindered anilines: copper-catalyzed electrophilic amination of aryl boronic esters

No longer a hindrance: copper-catalyzed electrophilic amination of aryl boronic esters is accomplished under mild reaction conditions using 2.5-5.0 mol % of a catalyst derived from copper tert-butoxide and Xantphos ligand. The reaction tolerates a wide range of functional groups and can be used to prepare some of the most hindered anilines made to date.     

Iron‐Induced Regio‐ and Stereoselective Addition of Sulfenyl Chlorides to Alkynes by a Radical Pathway

The radical addition of the Cl? S σ‐bond in sulfenyl chlorides to various C? C triple bonds has been achieved with excellent regio‐ and stereoselectivity in the presence of a catalytic amount of a common iron salt. The reaction is compatible with a variety of functional groups and can be scaled up to the gram‐scale with no loss in yield. As well as terminal alkynes, internal alkynes underwent stereodefined chlorothiolation to provide tetrasubstituted alkynes. Preliminary mechanistic investigations revealed a plausible radical process involving a sulfur‐centered radical intermediate via iron‐mediated homolysis of the Cl? S bond. The resulting chlorothiolation adducts can be readily transformed to the structurally complex alkenyl sulfides by cross‐coupling reactions. The present reaction can also be applied to the complementary synthesis of the potentially useful bis‐sulfoxide ligands for transition‐metal‐catalyzed reactions.     

O2‐mediated dehydrogenative amination of phenols

A method was developed for the direct dehydrogenative construction of C? N bonds between unprotected phenols and a series of cyclic anilines without resorting to any kind of metal activation of either substrate and without the use of halides. The resulting process relies on the exclusively organic activation of molecular oxygen and the subsequent oxidation of the aniline substrate. This allows the coupling of ubiquitous phenols, thus furnishing aminophenols through an atom‐economical and most sustainable dehydrogenative amination method. This new reactivity, which relies on the intrinsic organic reactivity of cumene in what can be seen as a modified Hock activation process of oxygen, is expected to have a large impact on the formation of C? N bonds in organic synthesis.     

A Facile Route to Ortho‐Hydroxyanilnes through an IrIII‐Catalyzed Direct C−H Amidation of 2‐Phenoxypyridines

A highly efficient and regioselective Ir^III‐catalyzed C−H amidation of 2‐phenoxypyridines has been developed by using sulfonyl azides as an amino source. The amidated products were provided in good‐to‐excellent yields with broad functional‐group tolerance. Furthermore, the 2‐pyridyl moiety in the amidated products could be readily removed, thus offering an efficient route to synthetically useful ortho ‐hydroxyanilnes, which are important building blocks in organic synthesis.     

Zinc-Mediated Intermolecular Reductive Radical Fluoroalkylsulfination of Unsaturated Carbon–Carbon Bonds with Fluoroalkyl Bromides and Sulfur Dioxide

A versatile and general zinc-mediated intermolecular reductive radical fluoroalkylsulfination of unsaturated C−C bonds has been developed using readily available fluoroalkyl bromides and 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct (DABSO) with wide substrate scope and excellent functional group tolerance. Sulfur dioxide anion radical generated in situ from the reduction of sulfur dioxide with zinc may be involved in the reaction mechanism.