Influence of sulfur groups on carboxylic acid strengths

The relative acid strength for a series of monocarboxylic acids of the general formula RX(CH₂)_nCOOH and related dicarboxylic acids of the general formula HOOC(CH₂)_nX(CH₂)_nCOOH, where R?=?Ph or Me, X?=?CH₂, S, SO, or SO₂; and n?=?1 or 2 as appropriate; have been studied as a function of X. It is found that sulfur containing acids have lower pKa values than the corresponding carbon analogues, that the pK_a is highest for the thioacids and lowest for the sulfonyl acids, that the pK_as increase as n increases, and that for the dicarboxylic acid systems only the thio members show a significant reduction in pK_a (2) – pK_a (1) differences upon changing n from 1 to 2.     

Phosphinate selective hosts and importance of CH hydrogen bonding for affinity modulation toward anion guests

Even though phosphinate and its analogs are very important guests in nature, the artificial receptors which are capable of selective recognition of phosphinate are rare. Here, we report a series of acetate and phosphinate selective hosts (1, 2 and 3) which utilize amide NH and aliphatic CH groups as hydrogen bonding donors. In this series of receptors, even though the amide NH hydrogen bonding element was found to be the most significant, by varying the polarity of CH group, the magnitude of recognition could be modulated considerably. The affinities of host 3 against all the tested anion guests showed significantly higher affinities compared with those of hosts 1 and 2, and this could be attributed to the difference of CH group polarities among the receptors 1, 2 and 3. C_α-H hydrogen in host 3 is the most highly polarized by the charged pyridinium group. Therefore, it is the strongest host in this series of hosts. From the experiments shown here, we demonstrated the importance of CH hydrogen bonding element as a decisive modulating moiety for anionic recognition.     

Rhodium-catalyzed NH-indole-directed ortho CH coupling of 2-arylindoles with diazo compounds via metal carbene migratory insertion

A high regioselective rhodium-catalyzed ortho CH coupling of 2-arylindoles with diazo compounds via NH-indole-directed CH bond activation has been developed. The catalytic reaction features mild reaction conditions, broad substrate scope and good functional group tolerability.     

Visible-light-mediated cascade difunctionalization/cyclization of alkynoates with acyl chlorides for synthesis of 3-acylcoumarins

A new visible-light-mediated radical cyclization of alkynoates with acyl chlorides is described for the one-pot construction of diverse 3-acylcoumarins with high efficiency and selectivity. This method is successful by sequential difunctionalization of an alkynes CC triple bond with the CCl bonds of acyl chloride and aromatic C(sp²)H bonds. The cyclization is proposed to simultaneously form two new carbon–carbon bonds, and involves radical acylation, 5-exo-trig cyclization, and ester migration.     

Concept of Ir-catalyzed CH bond activation/borylation by noncovalent interaction

Noncovalent interactions play a fundamental role in molecular biology, crystal engineering, supramolecular chemistry, drug design, sensing applications, and many other research fields in the chemical sciences. Because of this importance, thorough research efforts have been focused on the interpreting and quantifying these interactions, which include H-bonding, electrostatic effects, ππ interaction, cation-π interaction, hydrophobic-hydrophobic interaction, van der Waals forces, and other such type of interactions. However, on the synthetic standpoint, use of these noncovalent interactions are rare, although might be beneficial for the site-selective CH bond activation and functionalization by transition metal catalysis. In this context, iridium-catalyzed CH borylation has gained immense popularity due to the versatility conferred to the CB bonds. Very recently, researchers have started employing these interactions as a governing factor for attaining regioselectivity in arene CH borylation. In this perspective, we will focus on the advancements made so far by the use of various noncovalent interactions in Ir-catalyzed borylations.     

Morita-Baylis-Hillman enal-based triple cascade strategy for anti-selective synthesis of highly functionalized tetrahydropyridines using iminium-enamine catalysis

A novel and efficient three-component coupling strategy for stereoselective synthesis of highly substituted tetrahydropyridines (THP) is reported in high yield (83–94%) with excellent diastereoselectivity (95–99%) in favor of anti-isomer. The reaction proceeds via sequential iminium-iminium-enamine mediated formation of three consecutive CC, CC and CN bonds in one-pot through reaction of [E]-α-cyano/nitro unsaturated aldehyde, activated methylene and aldimine/phenyl-N-tosyl-methanimine and opens up a new aspect for the utility of Morita-Baylis-Hillman (MBH) adducts in THP synthesis.     

Synthesis of cyclic olefins via Mitsunobu C-alkylation followed by Ramberg-Bäcklund ring contraction

Cyclic olefins were prepared via a novel synthetic approach that involves the formation of two CC bonds in a potentially stereoselective fashion. The first bond is formed by employing a Mitsunobu dehydrative C-alkylation; the second CC bond involves a ring contraction via Ramberg-Bäcklund rearrangement.     

Experimental and theoretical studies on rhodium-catalyzed direct CH benzoxylation reaction

An efficient Rh(III)-catalyzed, chelation assisted CH benzoxylation reaction has been developed, releasing H₂O as the single byproduct. The reaction proceeded under mild conditions, with controllable mono- and dioxygenation selectivity, thus providing a good complement to previous CH oxygenation reactions. DFT calculations support that a nucleophilic addition pathway is most likely involved in the current reaction system.     

Four-component synthesis of alkyl [2-[(cyclohexylamino)carbonyl]-4-oxo-2H-chromen-3(4H)-ylidene]methyl 3,4,5,6-tetrahalophthalates via a domino O-acylation/α-addition cyclization/alcoholysis sequence

A novel protocol was developed for the synthesis of alkyl [2-[(cyclohexylamino)carbonyl]-4-oxo-2H-chromen-3(4H)-ylidene]methyl 3,4,5,6-tetrahalophthalate derivatives via the one-pot, four-component domino O-acylation/α-addition cyclization/alcoholysis reaction of tetrahalophthalic anhydrides, 3-formylchromones, cyclohexyl isocyanide and various alcohols. The highlights of this novel cascade reaction include mild reaction conditions, easy workup, and high bond efficiency resulting in the formation of four new bonds (two CO, one CO and one CC) in a single operation.     

Recent advances in carbon-difluoroalkylation and -difluoroolefination with difluorocarbene

In the past few years, organic chemists have made significant contributions to the development of difluoromethylation and difluoromethylenation of carbon nucleophiles via difluorocabene intermediate. This article summarizes the recent progress of CCF₂ and CCF₂ functionalization with difluorocarbene.     

Palladium-catalyzed [5+2] oxidative annulation of N-Arylhydrazones with alkynes through CH activation to synthesize Benzo[d][1,2]diazepines

An efficient and novel method using palladium catalyst for the synthesis of benzo[d][1,2]diazepines by [5 + 2] annulation of N-arylhydrazones with alkynes has been developed. This methodology undergoes through eight membered palladacycle serving as a backbone for the formation of CC/CN bond to provide benzodiazepine derivatives in moderate to good yield.     

Silver(II) oxide-mediated synthesis of 2,4-diarylquinazolines

A single-pot procedure for the synthesis of 2,4-diarylquinazolines is described which involves a silver oxide-mediated CH activation/CN bond formation process. The generality of this method with respect to substituent effects is presented along with studies leading to process optimization. Mechanistic investigations provide support for the involvement of radical intermediates in the reaction process.     

Visible-light-induced halogenation of aliphatic CH bonds

Alkyl halides are of particular interests in the areas of pharmaceutical, agrochemical, and material sciences. Direct CH halogenation has been recognized as the most efficient method for the introduction of halogen atoms into organic molecules. This Digest paper highlighted some of the most recent and significant developments in the visible light-promoted halogenation of aliphatic CH bonds.     

Highly efficient and stereoselective cycloaddition of nitrones to indolyl- and pyrrolylacrylates

The reactions of various nitrones with indolyl- and pyrrolylacrylates proceeds regioselectively with high diastereoselectivity in the case of aldonitrones, and represents an effective method for obtaining new indolyl- and pyrrolyl-substituted isoxazolidine carboxylates stabilized by weak (CH?O) and moderate (NH?N) strength intramolecular hydrogen bonding. The resulting cycloadducts exhibit promising in vitro anti-influenza activities.     

Recent advances in C(sp3)H bond carbonylation by first row transition metals

Carbonylation is one of the most valuable processes both in academia and industry. Direct functionalization of inert C(sp²)H bond into C(sp²)-carbonyl derivatives was actively pursued over decades using noble metals. But the corresponding C(sp³)H bond carbonylation is a challenging area and only few examples were known till now. Utilization of first row transition metals as an alternative to their noble partners is more sustainable. In this context, use of first row transition metals for direct C(sp³)H bond functionalization is burgeoning as an exciting area. This digest review covers some of the recent achievements in this regard especially using Ni, Co and Cu as first row transition metals. The reported approaches are categorized in two types: directed and non-directed activation/functionalization of C(sp³)H bonds using carbon monoxide gas or its surrogates as a C1 source.     

Photocatalytic anion oxidation achieves direct aerobic difunctionalization of alkenes leading to β-thiocyanato alcohols

A novel visible light-driven oxidative cascade reaction for the synthesis of β-thiocyanato alcohols via difunctionalization of alkenes is described for the first time. In this protocol inorganic ion thiocyanate was successfully converted into radical through photocatalysis by employing Rose Bengal as a photocatalyst to mediate the single-electron transfer. This hydroxylation process did not need extra reducing agent and the new CS and CO bonds could be constructed in one pot. Molecular oxygen not only was used as an excellent terminal oxidant, but also served as a green oxygen source, which is one of the most ideal processes to realize CH bond oxidation functionalization. Moreover, the reaction also proceeded very well under irradiation of sunlight.     

Rh(III)-catalyzed, 1,2,3-triazole-assisted directed CH coupling with diazo diphosphonates

A mild and efficient procedure was developed for the [Cp1Rh(III)]-catalyzed, 1,2,3-triazole directed CH coupling with diazomethylene-diphosphonates. This protocol provided a step- and atom-economical protocol for CC bond formation and led to structurally diverse 2-(1,2,3-triazol-2-yl)benzyl diphosphonates in good to excellent yields.     

N-(acridin-9-yl)arenesulfonamides: Synthesis,quantum chemical studies and crystal structure analysis to establish the tautomeric preferences

The potentiality of the N-(acridin-9-yl)arenesulfonamide moiety as a hybrid pharmacophore due to the distinct pharmacological activities of acridines and aryl/heteroaryl sulfonamides prompts to synthesise N-(acridin-9-yl)arenesulfonamides and study their structural properties. Various N-(acridin-9-yl)arene/heteroarenesulfonamides were obtained through the development of a new methodology adopting the Pd₂(dba)₃-catalyzed CN bond formation strategy for the reaction of 9-chloloroacridine with arene/heteroarenesulfonamides. The 1H and ¹³C NMR spectra suggest these N-(acridin-9-yl)arene/heteroarenesulfonamides to exist solely as the sulfonimide tautomer rather than anticipated sulfonamide form and was confirmed by the single crystal XRD analysis of one of the newly synthesized compounds. The quantum chemical studies rationalized this tautomeric preference revealing that the sulfonimide tautomers are more stable than the sulfonamide tautomers by ?0.67 to ?5.12?kcal/mol in the gas phase. In the solid state, the sulfonimide tautomer is stabilized by intermolecular hydrogen bond between NH?OS and π? π stacking between the acridine rings.     

Efficient acid catalytic synthesis of pyrazolopyrimidines from 1H-pyrazol-5-yl-N,N-dimethylformamidines with cyanamide

The efficient acid catalytic synthesis of pyrazolo [3,4-d]pyrimidine was developed by treating 1H-pyrazol-5-yl-N,N-dimethylformamidine with various aminating agents including N,O-bis(trimethylsilyl)hydroxylamine (NHSiMe₃(OSiMe₃)), cyanamide (NH₂CN), hydroxylamine (NH₂OH), methoxyamine (NH₂OMe), hydrazine (NH₂NH₂), and urea (NH₂C(O)NH₂) in acidic solution at reflux. Based on the experimental result, cyanamide (NH₂CN) and methanesulfonic acid were indicated the best aminating agent and acid mediated solvent. On the other hands, the reactivity tendency was involved the activity of original leaving species grafting on the aminating agents, such as –OH, –OMe, –OSiMe₃, –NH₂, –OSiMe₃, –C(O)NH₂, and –CN, in acid catalytic heterocyclic reaction.     

Recent advance in radical fluoroalkylation with sulfinate salts

In the last few years, the incorporation of a fluoroalkyl moiety into an organic molecule has been extensively studied. Especially, radical fluoroalkylation, involving the formation of CC and Cheteroatom bonds, presents its valuable synthetic potential to achieve fluoroalkylated compounds. This digest paper highlights recent progress on fluoroalkylation with sulfinate salts, and focuses on radical tri-/di-/monofluoromethylation during the last five years.