An Indium(III)‐Catalyzed Synthesis of 4,4‐Dichloro‐1‐aryl‐N‐alkyl‐1‐yn‐3‐amines via an Intermolecular C(sp2)?C(sp) Bond Formation

This paper demonstrates an indium(III) triflate‐catalyzed reaction of electron‐deficient α,α‐dichloroaldimines with terminal alkynes leading to a rapid and selective access to highly functionalized propargylic amines in good to excellent yields. The dichloromethylene moiety of the aldimine acts as an activating group to accomplish this transformation under very mild conditions.     

Copper‐Catalyzed C?NH2 Arylation of 2‐Aminobenzimidazoles and Related C‐Amino‐NH‐azoles

A copper(II)‐catalyzed selective C NH₂ arylation of 2‐aminobenzimidazoles and related C‐amino‐NH‐azoles was achieved in presence of 2,2′‐bipyridine and cesium carbonate at 60 °C under open air conditions and this is first method for the copper‐catalyzed selective C NH₂ arylation in the presence of other reactive nucleophilic sites. Previously unexplored heteroaromatics possessing multiple nucleophilic sites that are selectively arylated at the C NH₂ position are obtained, providing an exceptional tool for rapid delivery of a diverse array of medicinally important C NH(aryl) derivatives of aminoazoles without any protection/deprotection of ring N H bonds. It is first example for the selective C NH₂ arylation of 5‐aminoindazole, 4‐aminopyrazole, 5‐aminopyrazole, 9H‐purine‐6‐amine, and 1H‐pyrazolo[3,4‐d]pyrimidin‐4‐amine derivatives.

     

In‐situ‐EPR‐Spektroskopie in der heterogenen Katalyse: Stiefkind oder Lichtblick?

This review evaluates the potential of electron paramagnetic resonance (EPR, also known as electron spin resonance, ESR) as an in situ technique for analyzing structure‐reactivity relationships in heterogeneous catalysis under reaction condition. It starts with a general overview on the state of the art, followed by a short introduction of its theory. In due course the use of the method is illustrated by three selected application examples. At the end a critical evaluation of opportunities and limitations of in situ EPR in heterogeneous catalysis is given.     

The Nitrile‐Forming Enzyme 7‐Cyano‐7‐Deazaguanine Synthase from Geobacillus kaustophilus: A Reverse Nitrilase?

7‐Cyano‐7‐deazaguanine synthase (E.C. 6.3.4.20) is an enzyme that catalyzes the formation of a nitrile from a carboxylic acid and ammonia at the expense of ATP. The protein from G. kaustophilus was heterologously expressed, and its biochemical characteristics were explored by using a newly developed HPLC‐MS based assay, ³¹P NMR, and a fluorescence‐based thermal‐shift assay. The protein showed the expected high thermostability, had a pH optimum at pH 9.5, and an apparent temperature optimum at 60 °C. We observed strict substrate specificity of QueC for the natural substrate 7‐carboxy‐7‐deazaguanine, and determined AMP and pyrophosphate as co‐products of preQ₀.     

Are 1,4‐ and 1,5‐Disubstituted 1,2,3‐Triazoles Good Pharmacophoric Groups?

Over the last decade, 1,2,3‐triazoles have received increasing attention in medicinal chemistry thanks to the discovery of the highly useful and widely applicable 1,3‐dipolar cycloaddition reaction between azides and alkynes (click chemistry) catalyzed by copper salts and ruthenium complexes. After a decade of medicinal chemistry research on 1,2,3‐triazoles, we feel that the time is ripe to demonstrate the real ability of this heterocycle to participate in important and pivotal binding interactions with biological targets while maintaining a good pharmacokinetic profile. In this study, we retrieved and analyzed X‐ray crystal structures of complexes between 1,2,3‐triazoles and either proteins or DNA to understand the pharmacophoric role of the triazole. Furthermore, the metabolic stability, the capacity to inhibit cytochromes, and the contribution of 1,2,3‐triazoles to the overall aqueous solubility of compounds containing them have been analyzed. This information should furnish fresh insight for medicinal chemists in the design of novel bioactive molecules that contain the triazole nucleus.     

Iridium(III)‐Catalyzed Direct C?H Sulfonamidation of 2‐Aryl‐1,2,3‐triazole N‐Oxides with Sulfonyl Azides

We have developed a method for the direct sulfonamidation of 2‐aryl‐1,2,3‐triazole N‐oxides using sulfonyl azides as the amino source to release molecular nitrogen as the sole by‐product. This protocol exhibits excellent functional group tolerance and proceeds efficiently under external oxidant‐free conditions. Various 2‐(2‐sulfonamidoaryl)‐1,2,3‐triazoles were prepared in up to 97% yields for 25 examples with excellent regioselectivity.

     

Nickel‐Catalyzed Cross‐Coupling of Arene‐ or Heteroarenecarbonitriles with Aryl‐ or Heteroarylmanganese Reagents through C?CN Bond Activation

The nickel‐catalyzed cross‐coupling reaction of arene‐ or heteroarenecarbonitriles with aryl‐ or heteroarylmanganese reagents via C CN bond activation has been developed. Both electron‐rich and electron‐deficient nitriles can be employed as the electrophilic substrates. The reaction tolerates a range of functional groups and aromatic heterocycles.     

Palladium‐Catalyzed C?N Cross‐Coupling of N′‐Monosubstituted Sulfondiimines with Aryl Bromides

A general method for the N‐arylation of sulfondiimines with aryl bromides using tris(dibenzylideneacetone)dipalladium(0) [Pd₂(dba)₃] and 2‐dicyclohexylphosphino‐2′,6′‐diisopropoxybiphenyl (RuPhos) as catalyst system was developed. A new benzothiazine was obtained, and a protocol for the cleavage of para‐methoxyphenyl (PMP) groups in PMP‐protected sulfondiimines has been found, which provides access to synthetically useful NH‐derivatives, that are difficult to prepare by other means.     

Nano‐Iron Oxide as a Recyclable Catalyst for Intramolecular C?N Cross‐Coupling Reactions under Ligand‐Free Conditions: One‐Pot Synthesis of 1,4‐Dihydroquinoline Derivatives

The ligand‐free nanoparticle ferroferric oxide catalytic system has been developed to promote the intramolecular C N cross‐coupling reaction. With this protocol, various 1,4‐dihydroquinoline derivatives were synthesized from o‐halobenzaldehydes and β‐enaminones in moderate to good yields.     

Copper‐Catalyzed Direct C?H Arylation of Thieno[3,4‐c]pyrrole‐4,6‐dione (TPD): Toward Efficient and Low‐Cost Synthesis of π‐Functional Small Molecules

A series of thieno[3,4‐c]pyrrole‐4,6‐dione (TPD)‐based functional small molecules were efficiently synthesized through direct C H arylations using inexpensive copper salts. In this study, we examined all required reaction parameters including various copper complexes, ligands, bases, and (co)solvents. Under the optimum reaction conditions, the C H arylation proceeded smoothly and a variety of functional groups such as ester, nitrile, fluoride, chloride, triazene, and amine were tolerated. This method provides a step‐economical and relatively low‐cost synthetic alternative to presently used coupling reactions for the preparation of TPD‐containing π‐functional materials.

     

Synthesis of 3‐Aryl‐1‐trifluoromethyltetrahydroisoquinolines by Brønsted Acid‐Catalyzed C(sp3)?H Bond Functionalization

A concise route to 3‐aryl‐1‐trifluoromethyltetrahydroisoquinolines by a benzylic [1,5]‐hydride shift‐mediated C H bond functionalization was developed. The [1,5]‐hydride shift of the benzylic C(sp³) H bond to the trifluoromethylketimine derived from para‐anisidine occurred smoothly to produce cis‐1‐trifluoromethyl‐3‐aryltetrahydroisoquinolines in good to excellent chemical yields with good diastereoselectivities. In contrast, use of the N H ketimine furnished N‐unprotected tetrahydroisoquinolines in good yields in favor of the trans‐isomer.

     

Enantioselective Fluorination of β‐Ketoamides Catalyzed by Ar‐BINMOL‐derived Salan?Copper Complex

A facile and powerful enantioselective construction of C F containing molecules was successfully developed through asymmetric fluorination of β‐ketoamides catalyzed by Ar‐BINMOL‐derived salan–Cu^II system (Ar‐BINMOL=1,1′‐Binaphthalene‐2‐α‐arylmethanol‐2′‐ol, Cu = copper). The present catalytic system exhibited excellent enantioselectivity and a broad substrate scope for indanone‐derived β‐ketoamides under mild conditions (up to 99 % ee and 99 % yields). Notably, the biomimetic salan‐copper complex was demonstrated for the first time to be a highly efficient catalyst in the fluorination of β‐ketoamides. Experimental results and mechanistic studies indicated that both excess amount of copper salt and electrophilic attack of cationic fluorine to activated methylene assisted by amide group on the β‐ketoamides were key factors for high yield and excellent enantioselectivity, respectively, in this enantioselective fluorination, which was controlled by the two‐point binding between the salan–copper complex with cyclic β‐ketoamides and hydrogen‐bonding activation of the electrophilic fluorinating reagent.

     

Rhodium‐Catalyzed N‐tert‐Butoxycarbonyl (Boc) Amination by Directed C?H Bond Activation

N‐tert‐Butoxycarbonyl azide (BocN₃) was shown to be an efficient and economic source for the directed introduction of N‐Boc protected amino groups into the thiophene and benzene nucleus. Yields for the amination of 2‐pyridin‐2‐ylthiophenes (10 examples) were 52–88%. For the amination of the respective benzenes (10 examples) yields between 54% and 99% were recorded with an improved reactivity observed for substrates that bear an electron‐withdrawing group. The reaction was applied to short total syntheses of the indoloquinoline alkaloids quindoline and cryptolepine. The facile removal of the Boc protecting group was the key to the success of the syntheses. The scope of the reaction was extended to a C(sp³) H bond amination and to the amination of 2‐phenyloxazoline. For the amination of 2‐pyridin‐2‐ylbenzene a kinetic deuterium isotope effect of 2.0 was determined.

     

One‐Pot Tandem Palladium‐Catalyzed Decarboxylative Cross‐Coupling and C?H Activation Route to Thienoisoquinolines

Two experimental approaches to the synthesis of a scarcely reported biologically active thienoisoquinoline system are demonstrated. A 5‐step linear synthesis employing a palladium‐catalyzed decarboxylative cross‐coupling and functionalization sequence allowed for the preparation of a diverse range of substituted thienoisoquinoline systems. Alternatively the palladium‐catalyzed decarboxylative cross‐coupling and C H activation steps can be telescoped to produce a one‐pot reaction sequence that provides efficient access to aryl‐substituted thienoisoquinolines.

     

One‐Step Synthesis of Substituted Benzofurans from ortho‐ Alkenylphenols via Palladium‐Catalyzed C?H Functionalization

A dehydrogenative oxygenation of C(sp²) H bonds with intramolecular phenolic hydroxy groups has been developed, which provides a straightforward and concise access to structurally diversely benzofurans from ortho‐alkenylphenols. The reaction is catalyzed by palladium on carbon (Pd/C) without any oxidants and sacrificing hydrogen acceptors.

     

Rhodium(II)‐Catalyzed Carbenoid Insertion of N‐Tosylhydrazones into Amide N?H Bonds: An Efficient Approach to N3‐Benzyl/Alkyl‐2‐arylquinazolinones

Dirhodium(II) acetate‐catalyzed reactions of N‐tosylhydrazones with dihydroquinazolinones bearing different types of N H bonds that give N³‐benzyl/alkyl‐2‐arylquinazolin‐4(3H)‐ones through Csp³ N bond formation by oxidative dehydrogenation and insertion of rhodium‐carbenoid into amide N H bond are reported for the first time. This method features good to excellent yields, good functional group tolerance, high regioselectivity and readily available starting materials.

     

iso‐OPDA: An Early Precursor of cis‐Jasmone in Plants?

Cis-jasmone is a highly appreciated fragrance and plant-derived signal molecule that controls pollination, attracts parasitoids of attacking herbivores, and serves as an intra- and interspecific signal that controls gene expression. cis-Jasmone is produced from linolenic acid along the jasmonic acid cascade. In addition to the conversion of jasmonic acid into cis-jasmone, a novel pathway might exist that converts cis-oxophytodienoic acid (OPDA), an early precursor of jasmonic acid, into iso-OPDA. The planar iso-OPDA is degraded by beta-oxidation to 3,7-didehydrojasmonic acid, which yields cis-jasmone by spontaneous decarboxylation. The degradation of iso-OPDA to cis-jasmone is demonstrated for many plant species and the yeast Saccharomyces cerevisiae.     

“On Water” Direct and Site‐Selective Pd‐Catalysed C?H Arylation of (NH)‐Indoles

This communication describes the development of a versatile catalytic system based on palladium(II) acetate/bis(diphenylphosphino)methane [Pd(OAc)₂/dppm] that works “on water” giving site‐selective C H arylation of (NH)‐indoles without protecting or directing groups. Remarkably, the control of regioselectivity was achieved by small changes in the “extra‐catalytic” base/halide partners. These innovative methodologies allow a high‐yielding access to both C2 and C3‐arylindoles, as well as 2,3‐diarylindoles, and display high chemo/regioselectivities and structural versatility with regard to either indole or aryl moieties.     

DDQ‐mediated Direct C(sp3)?H Cyanation of Benzyl Ethers and 1,3‐Diarylpropenes under Solvent‐ and Metal‐free Conditions

A direct cyanation of benzyl ethers and 1,3‐diarylpropenes with TMSCN was performed under solvent‐ and metal‐free conditions. This oxidative cross dehydrative coupling (CDC) reaction was promoted by 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) and provided rapid access to a broad range of nitriles in good to excellent yields.