Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

A straightforward and transition metal-free one-pot protocol to synthesize halobenzo[b]furans has been developed employing simple and easily available starting materials such as O-aryl carbamates and alkynylsulfones. The fine-tuning of the different steps involved was key to achieving a successful one-pot procedure. Initially, a directed ortho-lithiation process, which uses the carbamate as the directed metalation group, was crucial in providing access to O-2-alkynylaryl N,N-diethyl carbamates by a direct alkynylation of the o-lithiated carbamate, with arylsulfonylalkynes as electrophilic reagents. Cyclization of the generated o-alkynylaryl carbamates was successfully accomplished through a strategy involving in situ carbamate alkaline hydrolysis under conventional heating or microwave irradiation, coupled with a subsequent heterocyclization step delivering the desired benzo[b]furans. A wide variety of new halobenzo[b]furans has been synthesized and their utility has been demonstrated by their further transformation.

Shelf-stable electrophilic reagents for the direct incorporation of SCF2CF2H and SCF2CF3 motifs

The introduction of fluoroalkylthioether groups has attracted the attention of the drug discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds. Synthetic advances in the field have been capitalized by methods to incorporate SCF3 and SCF2H motifs, however, longer and synthetically more challenging polyfluoroethyl chains are still underdeveloped. Here, two saccharin-based electrophilic reagents have been disclosed for the efficient incorporation of SCF2CF2H and SCF2CF3 motifs. Their reactivity performance has been thoroughly investigated with a variety of nucleophiles such as thiols, alcohols, amines, alkenes, (hetero)aromatics, and organometallic species, including natural products and pharmaceuticals. Finally, multigram-scale preparation and divergent derivatization has been explored from SCF2CF2H derivatives.

SYNTHESIS AND PROPERTIES OF ORGANOSILICON EPISULFIDES

A study was made of the interaction of thiourea with saturated and unsaturated organosilicon oxiranes in absolute methyl alcohol in a medium of potassium hydroxide, and methods were developed for the synthesis of unsaturated and unsaturated organosilicon silicides with a yield of 65–75%.The studies carried out revealed that the synthesized organosilicon episulfides are very reactive compounds and can react with nucleophilic and electrophilic reagents, while forming the corresponding silicon derivatives. The IR- spectra of the products were studied. It should be noted that, when comparing the IR- spectra of oxiranes and episulfides, it was revealed that the stretching vibrations of the CH2 group of the episulfide ring are underestimated by 50–70 cm-1 in comparison with the oxirane ring

A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

Photoredox catalysis has provided many approaches to C(sp3)–H functionalization that enable selective oxidation and C(sp3)–C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp3)–H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp3)–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles—including halides, water, alcohols, thiols, an electron-rich arene, and an azide—to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical—a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis—enabling new site-selectivity for late-stage C(sp3)–H functionalization.

Reversal of Regioselectivity in Reactions of Donor-Acceptor Cyclopropanes with Eelectrophilic Olefins

Cyclopropanes bearing donor and acceptor groups at the opposite ends of the C-C bond should react with both nucleophiles and electrophiles. Their reactivity towards nucleophiles is well explored while only few specific electrophilic reagents give desired products.These methods are limited by the specific philicity of the carbon atoms resulting from the strong polarization of the central C-C bond. Herein, we report that vitamin B12 catalysis enables the transformation of initially electrophilic center into a nucleophilic radical that as such reacts with SOMOphiles. This radical-based strategy reverses the standard regioselectivity and thus complements the classical approaches.

A Review on Recent Advances in the Synthesis of Aziridines and their Applications in Organic Synthesis

: Aziridines are the saturated three-membered cyclic amines that constitute an important group of synthetic intermediates. These could act as a precursor for diverse organic compounds owing to the reactivity due to the ring strain associated with them. The outstanding property of aziridines is their high reactivity towards various nucleophilic and electrophilic reagents to acquire more stable ring-opened or ring-expanded amines that could be obtained from the release of strain energy intrinsic in a small ring. As such, aziridines could be used in the synthesis of 4-7 membered heterocycles of biological and industrial significance, such as azetidines, imidazoles, thiazoles, pyrazines, pyrimidines, benzothiazines, benzodiazepines, etc. Earlier synthesis of aziridines was considered a laborious task due to their instability. However, various synthetic approaches leading to the formation of aziridines are now available in the literature. Recently, green, cost-effective and approaches based on simpler work-up for these reactions have attracted researcher's attention. This review article deals with synthetic routes of aziridines and aziridine applications in organic synthesis.

Bicyclo[2.2.0]hexene derivatives as a proaromatic platform for group transfer and chemical sensing

Here we report the design, preparation, synthetic utility, and sensing application of a class of proaromatic structures, namely bicyclo[2.2.0]hexene (BCH) derivatives. Building on a valence isomerism concept, they feature modular and easy synthesis as well as high thermal stability, and can be oxidatively activated under mild conditions. New alkyl transfer reactions using BCHs as a radical donor have been developed to showcase the utility of their proaromaticity. Moreover, the redox-triggered valence isomerization of a quinoline-derived BCH led to colorimetric and fluorescent responses toward vapors of electrophilic reagents in solution and solid phase, respectively. This optical response was shown to involve a 1,3-cyclohexadiene structure that possesses an intramolecular charge transfer excited state with interesting aggregation induced emission (AIE) character. Thus, the potential of BCHs has been demonstrated as a versatile platform for the development of new reagents and functional materials.

Ruthenium Catalyzed β-Selective Alkylation of Vinylpyridines with Aldehydes/Ketones via N2H4 Mediated Deoxygenative Couplings

Umpolung (polarity reversal) tactics of aldehydes/ketones have greatly broadened the carbonyl chemistry by enabling transformations with electrophilic reagents and deoxygenative functionalizations. Herein, we reported the first ruthenium-catalyzed β-selective alkylation of...

Diaryliodonium Salts: Structures and Synthesis

Due to similar reactivity in comparison with aromatic organometallic reagents, diaryliodonium salts are currently in broad usage as less toxic, highly efficient, stable and mild electrophilic reagents in organic synthesis. The hypervalent iodine center of diaryliodonium salts can lead to unique reactivity, which thus is frequently presented in metal-free arylations or metal-involved elementary reactions such as oxidative addition, reduction elimination, ligand coupling and ligand exchange reaction. As such, diaryliodonium salts have experienced explosive growth by transferring aromatics to the target molecules. In contrast to the reviews on the synthetic utility or aryl transformations by using diaryliodonium salts, this review provides a summary of their structures and the synthetic strategies towards them during recent decades.

Synthesis of Some New 1, 3, 4-Oxadiazole, Pyrazole, and Pyrimidine Bearing Thienopyrazole Moieties

Aim and Objective: According to the literature survey, pyrazole is a unique template that is associated with several biological activities. This article highlighted the research work of many researchers reported in the literature for synthesis and different pharmacological activities of the pyrazole nucleus. In the present work, pyrazol- 3-one 1 was reacted with cyanoacetic acid hydrazide and elemental sulfur to afford the corresponding thieno[3,2-c]pyrazol-6-carbohydrazide 3 derivatives. The latter compound reacted with some electrophilic reagents such as DMF-DMA, triethylorthoformate, arylidenemalononitriles and chalcones under neat conditions to give substituted oxadiazole and pyrazole, respectively. The treatment of compound 3 with active methylene reagents such as acetylacetone, diethylmalonate, ethyl acetoacetate and ethyl cyanoacetate under suitable conditions afforded pyrazole derivatives 10, 11, 13, and 15, respectively. Novel pyrazolothienopyrimidine 27 and 30 were prepared from precursor 26 with carbon disulfide and triethylorthoformate, respectively. The chemical structures of the newly synthesized compounds were established by elemental and spectral analyses including IR, and 1HNMR in addition to 13C-NMR and mass spectra. Materials and Methods: A novel substituted pyrazole, pyrimidine and pyrazolothienopyrimidine were obtained via Gewald synthesis of thiophene and fused thiophene and Mannich reactions of 5-amino-3-phenyl-1Hthieno[ 3,2-c]pyrazole-6-carbohydrazide. Results and Discussion: A series of some newly azoles and azines were prepared via reaction of thieno[3,2- c]pyrazol-6-carbohydrazide derivative 3 as starting material with some electrophilic and nucleophilic reagents. The structures of target compounds were established by elemental analyses and spectral data. Conclusion: Pyrazole is a unique template that is associated with several biological activities. This article highlighted the research work of many researchers reported in the literature for synthesis and different pharmacological activities of the pyrazole nucleus. In the current investigation, we have developed new and efficient methods for the synthesis of thieno[3,2-c]pyrazol-6-carbohydrazide derivatives. In addition, we have explored the preparative potential of these substances as intermediates for the synthesis of substituted pyrazoles and fused pyrazoles 10-30, respectively.