Copper-Mediated Cyclization of Terminal Alkynes with CF3-Imidoyl Sulfoxonium Ylides To Construct 5-Trifluoromethylpyrroles.

A copper-mediated [3 + 2] cyclization of CF3-imidoyl sulfoxonium ylides and terminal alkynes has been demonstrated. This work provides a practical approach for assembling 5-trifluoromethylpyrroles with the merits of a broad substrate scope, good functional tolerance, and mild reaction conditions. Control experiments and DFT studies indicate that this reaction may involve the addition of π-bonds of terminal alkynes by copper-carbene radicals and hydrogen migration.

Nickel-Catalyzed 8-Aminoquinoline Directed Reductive Dialkylcyclization/Homodialkylation of Unactivated Alkenes.

Chemo and regioselective dialkylation of alkene is an efficient protocol for constructing useful chemicals, but challenges remain in the unrestricted application of alkylating reagents. Alkyl bromide belongs to the easy-to-access and operable alkyl electrophiles that can be used in reductive coupling with alkenes. Here, we reported convenient strategies for dialkylcyclization and homodialkylation of unactivated ß,γ- and γ,δ-unsaturated alkenyl amides with 1,3-dibromoalkanes or primary alkyl bromides under nickel-catalyzed reductive conditions that exhibited high regioselectivity and functional-group tolerance.

Photoredox catalysis in alkene and alkyne alkylsulfonylations: the construction of Markovnikov selective α-sulfones.

Photoredox alkene or alkyne alkylsulfonylation has been achieved with phthalimide esters and sulfinates providing unexpected α-sulfones. Mechanistic studies disclose that the preferential alkyl radical addition to the alkene or the Markovnikov hydrosulfonation of the alkyne should contribute to the formation of the ß-alkylated α-sulfones. Moreover, the reaction is easy to operate covering quite large substrate scales including primary, secondary and tertiary alkyl groups and all sorts of terminal aryl alkenes or alkynes. Besides, the reaction was also suitable for the sulfonylation of several drug molecules.

Synthesis of Benzoselenophenes via TMSCN-Enabled Radical-Mediated Tandem Reaction Involving Enamides and Elemental Selenium.

This study presents a TMSCN-enabled tandem reaction involving enamides and elemental selenium to access a diverse array of benzoselenophenes. Notably, this methodology involves the direct 2-fold C(sp2)-H bond activation without the need for preinstalled halides or boronic acids as reaction handles. The protocol offers several noteworthy features, including the absence of transition metals and strong oxidants, high reaction efficiency, broad substrate scopes, and the use of stable elemental selenium as a selenium source.

Transition-metal-free Synthesis of tetra-substituted Vinyl Iodides by Cascade Sequential Reaction of α-Keto Acids, 1-Iodoalkynes, and Alkyl Halides.

The cascade sequential reaction of α-keto acids, 1-iodoalkynes, and alkyl halides are reported herein to synthesize tetra-substituted vinyl iodides. It represents an efficient protocol to access a diverse range of tetra-substituted vinyl iodides starting from simple materials in a one-pot fashion, featuring mild reaction conditions, ease of operation, and broad substrate scope.

Recent Advances in the Electrochemical Functionalization of Isocyanides.

Isocyanides are well-known as efficient CO surrogates and C1 synthons in modern organic synthesis. Although tremendous efforts have been devoted to fully exploiting the reactivity of isocyanides, these transformations are primarily limited by their utilization of stoichiometric toxic chemical oxidants. With the recent resurgence of organic electrochemistry, which has considerably laid dormant over the past several decades, electrolysis has been identified as a green and powerful tool to enrich structural diversity by solely utilizing electric current as clean and inherently safe redox equivalents of stoichiometric chemical oxidants. In this regard, the unique reactivity of isocyanides has been studied in numerous electrochemical transformations. This review comprehensively highlights the most relevant progress in electrochemical strategies towards the functionalization of isocyanides up until June of 2022, with a focus on reaction outcomes and mechanisms.

One-pot synthesis of 3-trifluoromethylbenzo[b][1,4]oxazines from CF3-imidoyl sulfoxonium ylides with 2-bromophenols.

Herein, a method to access 3-trifluoromethyl-1,4-benzoxazines from CF3-imidoyl sulfoxonium ylides and 2-bromophenols has been demonstrated. This synthetic protocol proceeds via a one-pot two-step sequence that includes the lithium-bromide-promoted O-H insertion of sulfoxonium ylides and annulation, and has the merits of broad substrate scope, excellent functional tolerance and operational simplicity, which provides an alternative means of obtaining CF3-substituted heterocycles.

BF3·Et2O-Mediated annulation of α-keto acids with aliphatic ketones for the synthesis of γ-hydroxy-butenolides and γ-alkylidene-butenolides.

Annulation reaction of α-keto acids with cyclic or acyclic aliphatic ketones is reported herein to divergently access γ-hydroxy-butenolides and γ-alkylidene-butenolides depending on the amount of BF3·Et2O. This protocol features good functional tolerance and ease of operation, to open a route to access butenolides via an annulation and dehydration process.

Iodine pentoxide-mediated oxidative selenation and seleno/thiocyanation of electron-rich arenes.

A simple and efficient method for the regioselective selenation of electron-rich arenes by employing non-metal inorganic iodine pentoxide (I2O5) as a reaction promoter under ambient conditions has been developed. The present protocol showed broad functional group tolerance and easy-to-operate and time-economical features. Additionally, this protocol also allows access to 3-seleno and 3-thiocyanoindoles by the use of readily available selenocyanate and thiocyanate salts. A mechanistic study indicated that the transformation operated through selenenyl iodide-induced electrophilic substitution processes.

Ruthenium-catalyzed acceptorless dehydrogenative coupling of amino alcohols and ynones to access 3-acylpyrroles.

Herein, a new strategy for the direct synthesis of functionalized pyrroles from ß-amino alcohols and ynones via ruthenium-catalyzed acceptorless dehydrogenative coupling has been demonstrated. This developed methodology proceeds in an atom- and step-economic fashion together with the merits of broad substrate scope, operational simplicity, and water and hydrogen gas as the sole by-products, which provides an alternative and sustainable way to access functionalized pyrroles. Further, this method was applied to the rapid synthesis of the COX-1/COX-2 inhibitor and boron dipyrromethene derivative successfully.

Electrochemical sulfonylation of enamides with sodium sulfinates to access ß-amidovinyl sulfones.

The electrochemical sulfonylation of enamides with sodium sulfinates was developed in an undivided cell in constant current mode, leading to the formation of ß-amidovinyl sulfones in moderate to good yields. The catalyst-, electrolyte- and oxidant-free protocol features good functional group tolerance and employs electric current as a green oxidant. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.

K2S2O8-mediated regio- and stereo-selective thiocyanation of enamides with NH4SCN.

A direct and straightforward thiocyanation of enamides with NH4SCN under metal-free conditions has been accomplished. A variety of (E)-ß-thiocyanoenamides are readily produced in a regio- and stereo-selective manner. The protocol features mild reaction conditions, good functional group tolerance and operational simplicity. The potential utility of this strategy was further demonstrated by transformation of thiocyanate into thiotetrazole-containing compounds and a Pd-catalyzed cross-coupling reaction to afford six- or seven-membered sulfur-containing heterocycles. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.

General Synthesis of α-Alkyl Ynones from Morpholine Amides and 1-Copper(I) Alkynes Promoted by Triflic Anhydride.

The first general method for the synthesis of α-alkyl ynones was developed based on the strategy of electrophilic activation of amides. Its distinctive advantages are attributed to the use of air-stable "bare" 1-copper(I) alkyne as a mild nucleophile without any exogeneous ligand.

A silver-catalyzed radical ring-opening reaction of cyclopropanols with sulfonyl oxime ethers.

A silver-catalyzed ring-opening reaction of cyclopropanols with sulfonyl oxime ethers has been developed. The protocol was conducted under mild reaction conditions to provide a series of γ-keto oxime ethers with moderate to good yields. The reaction proceeded in a stereoselective manner for CF3-containing oxime ethers to provide a single stereoisomer, while an inseparable E and Z mixture was obtained for CN-containing oxime ethers. Mechanistic studies indicate that the reaction proceeded via a radical mechanism.

Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial-Mesenchymal Transition.

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial-mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence.

Metal-Free Method for Direct Synthesis of Functionalized ß-Ketoenamines.

A new method for direct synthesis of ß-ketoenamines was developed by a BF3·OEt2-catalyzed cyclization of 1-iodoalkyne and α-keto acid followed by an amine-mediated ring-opening in one pot. Its metal-free conditions allowed the easy synthesis of those products bearing the transition metal-sensitive functional groups. Its three-component process achieved wide range of functionalized products.

A general two-step one-pot synthesis process of ynones from α-keto acids and 1-iodoalkynes.

A general two-step one-pot synthesis process of ynones was developed by cycloaddition of α-keto acids and 1-iodoalkynes followed by a ring-opening reaction. Its easy conditions and novel mechanism endowed it with two distinctive advantages: iodine-atom bonded to C(sp2) remained intact and α-keto acids became a part of the triple bonds in ynones.

N-Sulfonyl acetylketenimine as a highly reactive intermediate for the synthesis of N-sulfonyl amidines.

A highly reactive intermediate N-sulfonyl acetylketenimine was generated from a 3-butyn-2-one participating CuAAC/ring-opening method. Its high reactivity due to bearing two EWGs allowed us to offer the first example of a reaction between ketenimine and amide to synthesize N-sulfonyl amidines efficiently.

Silver-catalyzed decarboxylative acylation of quinoxalin-2(1H)-ones with α-oxo-carboxylic acids.

A novel silver-catalyzed decarboxylative acylation of α-oxo-carboxylic acids was developed, by which various 3-acyl quinoxalin-2(1H)-ones were synthesized by direct C-H bond acylation of quinoxalin-2(1H)-ones. In this method, α-oxo-carboxylic acids served as efficient acylating reagents to in situ generate the required active acyl radical. Its excellent chemoselectivity allowed the molecular diversity of 3-acyl quinoxalin-2(1H)-ones to be achieved by convenient functionalizations of both N1- and C3-positions.

Tandem Synthesis of α-Diazoketones from 1,3-Diketones.

A highly efficient synthesis of α-diazoketone was achieved by simply stirring the mixture of 1,3-diketone, TsN3, and MeNH2 in EtOH. It was a tandem reaction including a novel primary amine-catalyzed Regitz diazo transfer of 1,3-diketone and a novel primary amine-mediated C-C bond cleavage of 2-diazo-1,3-diketone.