Triflic Anhydride-Mediated Unprecedented Reactivities of Diacetonide Endoglucofuranose and Ribose Tetracetate: Direct Access to γ-Butenolides and Oxazoles.

Herein, we present two unprecedented reactions for the synthesis of γ-butenolides and oxazoles, leveraging Tf2O's promoted reactivity of nitriles with diacetonide endoglucofuranose and 1,2,3,5-tetra-O-acetyl-ß-d-ribofuranose. This method is highly efficient and straightforward and employs a one-step, metal-free protocol. It is effective with both aromatic and aliphatic nitriles and demonstrates a broad substrate scope. Our approach provides a versatile and practical pathway for the synthesis of structurally diverse compounds, significantly expanding the utility of Tf2O in synthetic chemistry.

Triflic Anhydride-Mediated Approach to Furo[3,2-b]furans from Diacetonide Protected Furanoses.

Trifluoromethanesulfonic anhydride (Tf2O) exhibits excellent reactivity as an electrophile, serving as a highly versatile reagent in diverse chemical transformations. Herein, we report an operationally simple, efficient, unique, and practical one-step strategy for synthesizing diverse valuable structures bearing furo[3,2-b]furans core leveraging Tf2O's promoted reactivity of nitriles with diacetonide protected furanose. Furthermore, we demonstrate the potential of furo[3,2-b]furan as a precursor for complex structures through 1,3-dipolar cycloaddition.

Correction to 1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

[This corrects the article DOI: 10.1021/acsomega.2c03325.].

Synthesis of unsymmetric phosphorotrithioates by sequential coupling of 1,1-dichloro-N,N-diethylphosphanamine with thiols and sulfenyl chloride.

Herein, we present the first, one-step, direct synthesis of unsymmetric phosphorotrithioates through a process involving sequential coupling of 1,1-dichloro-N,N-diethylphosphanamine with thiols and sulfenyl chloride. This method showcases excellent functional group tolerance, substrate compatibility, and mild reaction conditions, offering a streamlined approach for the challenging phosphorotrithioate synthesis. Additionally, the applicability of this method can be extended to the synthesis of mixed phosphoroselenodithioates.

Synthesis of mixed phosphorotrithioates via thiol coupling with bis(diisopropylamino)chlorophosphine and sulphenyl chloride.

In this study, we report a novel and efficient one-pot synthesis of mixed phosphorotrithioates under mild conditions at ambient temperature, obviating the requirement for supplementary additives. The method's versatility stems from its utilization of diverse thiols as nucleophilic reactants, 1-chloro-N,N,N',N'-tetraisopropylphosphanediamine [bis(diisopropylamino)chlorophosphine] as the phosphorus precursor, and various sulphenyl chlorides as sources of electrophilic sulfur. Notably, our investigation extends beyond mixed phosphorotrithioates to encompass the synthesis of phosphoroselenodithioates, underscoring the broad applicability of this synthetic protocol.

DMSO-KOH mediated stereoselective synthesis of Z-enamides: an expeditious route to Z-enamide bearing natural products.

An efficient strategy towards stereoselective amidation of alkynes is reported. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope and fast kinetics to furnish Z-enamides. Moreover, the method was successfully applied for the facile synthesis of the natural products lansiumamide A, lansiumamide B and Z-alatamide. Notably, DMSO plays two vital roles: hydrogen source and solvent.

Tf2O-Promoted Regioselective Heteronucleophilic Ring-Opening Approaches of Tetrahydrofuran.

The ring-opening functionalization strategy in tetrahydrofuran (THF) represents an ideal approach to access different valuable structures. Herein, we report different operationally simple, efficient, unique, and practical regioselective heteronucleophilic ring-opening strategies for the THF system. Tf2O, which is a strong electrophilic activator, was found to generate a THF triflate intermediate that triggers the nucleophilicity of nitriles (Nu1) and led to regioselective ring opening in the presence of different nucleophiles (Nu2). Furthermore, the synthesis of different heteronucleophilic ring-opening dimerization products was attributed to the nucleophilicity of Nu2. We also demonstrated that use of borane-tetrahydrofuran (BTHF) can achieve challenging hydride addition in a similar manner.

BF3-Et2O promoted bifunctionalization of aldehydes for the synthesis of arylmethyl substituted organophosphorus compounds.

A simple and efficient protocol for the synthesis of arylmethyl substituted organophosphorus compounds is presented. This method involves the reaction of diphenyl phosphite with aldehydes in the presence of BF3-Et2O. In this method, BF3-Et2O plays a dual role, as it facilitates the generation of both hydrophosphonylated intermediate and phenol from diphenyl phosphite. A significant feature of this approach is its tolerance to the presence of external nucleophiles, such as phenol, aliphatic thiols, indole and 3-methylanisole. The simplicity of the reaction conditions and the high yields achieved make this method promising for applications in areas where phosphonate compounds are of interest.

BF3-Et2O Promoted Heteronucleophilic Addition Reactions for the Synthesis of Unsymmetrical gem-Diarylmethyl Thioethers.

Herein, we present the BF3/BF4- mediated activation of diphenyl phosphite for the formation of thionium ions from aldehydes and thiophenols. These reactive species subsequently undergo reaction with in situ generated phenol, resulting in the synthesis of diarylmethyl thioethers. It was demonstrated that the addition of external phenol in the reaction produced unsymmetrical gem-diarylmethyl thioethers in good yields.

I2-DMSO Promoted Deaminative Coupling Reactions of Glycine Esters: Access to 5-(Methylthio)pyridazin-3(2H)-ones.

An unprecedented, one-step strategy for the synthesis of 5-(methylthio)pyridazin-3(2H)-one derivatives has been developed through iodine triggered deaminative coupling of glycine esters with methyl ketones and hydrazine hydrate in DMSO. These transformations in the absence of hydrazine helped to generate different 3-methylthio-4-oxo-enoates in good yields. Notably, DMSO played multiple roles such as oxidant, methylthiolating reagent, and solvent.

Iodine and ammonium persulfate mediated activation of DMSO: an approach to N-formylation of amides and synthesis of isatins.

An efficient strategy towards N-formylation of amides and oxidation of indolines to isatins is described. This method employs readily available (NH4)2S2O8, I2, and DMSO. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope, and fast kinetics. Moreover, the method was applied to the synthesis of the natural product alatamide. Notably, DMSO plays three vital roles: a formyl group source, an oxidant, and a solvent.

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 µM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin (10) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC50 values of 6.65 and 5.55 µM, respectively, while compounds 18b, 18c, 18f, and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC50 values ranging between 2.9 and 10.5 µM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC50 value of 2.91 µM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds.

Tf2O- and Cu(OTf)2-Assisted Acylamination Reaction of Unactivated Alcohols with Nitriles: A One-Pot P(IV) Activation, Stereoretention in Cycloalkanols and Deprotection Approach.

Described herein is a simple, novel, one-pot acylamination reaction of unactivated alcohols. This reaction employs the combination of PCl3 and triflic anhydride (Tf2O) or copper triflate Cu(OTf)2, which serves as a source of P(IV)-activated complex for nitriles to react under the Ritter-type mechanism. The synthetic utility of Tf2O-promoted reactions was demonstrated by its effectiveness to generate different acylaminated products. By employing Cu(OTf)2, this method represents a rare example of α-selective acylamination reaction. With chiral cycloalkanols, using the Cu(OTf)2-promoted procedure, acylaminated products are formed with complete retention of configuration. The synthetic utility of the copper-assisted reaction in acetonitrile was readily demonstrated as a mild deprotection strategy.

Coupling of 1-Chloro-N,N-diisopropylphosphanamine-Based Reagents with Alcohols and Thiosulfonates: A Precise Construction of O-P(O)-S Bonds.

Herein, we present the first mild, one-step direct synthesis of mixed phosphorothioates through selective generation of O-P(O)-S bonds at rt under additive-free condition. Further, reactions of different model natural products with 1,1-dichloro-N,N-diisopropylphosphanamine helped to present an alternative dimerization strategy. The synthetic utility of the methodology was extended for the synthesis of mixed phosphoroselenoates as well. The potential of the reaction was further demonstrated for the synthesis of mixed phosphorothioate bearing two different alcohols.

Correction: Conversion of N-acyl amidines to amidoximes: a convenient synthetic approach to molnupiravir (EIDD-2801) from ribose.

[This corrects the article DOI: 10.1039/D1RA06912H.].

Sulfonyl-Promoted Michaelis-Arbuzov-Type Reaction: An Approach to S/Se-P Bonds.

By facilitating the chemical conversion of thiols to thiosulfonates, phosphoramidite/phosphite bearing sp3-hybridized carbon serves as an ideal coupling material to forge new connections at room temperature. In this work, a functional group-induced, additive-free, novel, S-P bond-forming approach is presented. This protocol exhibits good functional group tolerance with wide applications that include phosphorylation of cysteine derivatives, development of a one-pot approach to mixed unsymmetrical thiophosphonates, and extension of the concept to different Se-P bonds. Meticulously, our reaction also generated a S-P bond against cyclic 1,2-dithiane-1-dioxide in a byproduct-free manner. These Michaelis-Arbuzov-type reactions are easy to conduct, work efficiently in a reduced reaction time, and are applicable to gram-scale preparation as well.

Conversion of N-acyl amidines to amidoximes: a convenient synthetic approach to molnupiravir (EIDD-2801) from ribose.

An efficient method is described for the preparation of molnupiravir (EIDD-2801) an antiviral agent via regioselective conversion of an N-acyl-nucleoside intermediate, generated through stereo and regioselective glycosylation of protected ribose and N 4-acetyl cytosine, to an amidoxime. This method avoids use of expensive starting materials, enzymes, complex reagents, and cumbersome purification procedures.

Triethylamine-methanol mediated selective removal of oxophenylacetyl ester in saccharides.

A highly selective, mild, and efficient method for the cleavage of oxophenylacetyl ester protected saccharides was developed using triethylamine in methanol at room temperature. The reagent proved successful against different labile groups like acetal, ketal, and PMB and also generated good yields of the desired saccharides bearing lipid esters. Further, we also observed DBU in methanol as an alternative reagent for the deprotection of acetyl, benzoyl, and oxophenylacetyl ester groups.

BCl3-Mediated C-N, C-S, and C-O Bond Formation of Imidazo[1,2-a]pyridine Benzylic Ethers.

An efficient BCl3-mediated reaction of imidazo[1,2-a]pyridines has been developed for the C-N, C-S, and C-O bond formation. The salient features of this method correspond to the substitution of different nucleophiles via in situ unconventional debenzylation. The developed process is applicable for the synthesis of a wide variety of ((3-amino/thio/alkoxy)-methyl)-imidazo[1,2-a]pyridines.

Introducing Oxo-Phenylacetyl (OPAc) as a Protecting Group for Carbohydrates.

A series of oxo-phenylacetyl (OPAc)-protected saccharides, with divergent base sensitivity profiles against benzoyl (Bz) and acetyl (Ac) were synthesized, and KHSO5/AcCl in methanol was identified as an easy, mild, selective, and efficient deprotecting reagent for their removal in the perspective of carbohydrate synthesis. Timely monitoring of AcCl reagent was supportive in both sequential and simultaneous deprotecting of OPAc, Bz, and Ac. The salient feature of our method is the orthogonal stability against different groups, its ease to generate different valuable acceptors using designed monosaccharides, and use of OPAc as a glycosyl donar.