Neutral Reaction Conditions Research Articles

Hypervalent iodine reagents enable chemoselective deboronative/decarboxylative alkenylation by photoredox catalysis.

Chemoselective C(sp(3))-C(sp(2)) coupling reactions under mild reaction conditions are useful for synthesizing alkyl-substituted alkenes having sensitive functional groups. Reported here is a visible-light-induced chemoselective alkenylation through a deboronation/decarboxylation sequence under neutral aqueous reaction conditions at room temperature. This reaction represents the first hypervalent-iodine-enabled radical decarboxylative alkenylation reaction, and a novel benziodoxole-vinyl carboxylic acid reaction intermediate was isolated. This C(sp(3))-C(sp(2)) coupling reaction leads to aryl-and acyl-substituted alkenes containing various sensitive functional groups. The excellent chemoselectivity, stable reactants, and neutral aqueous reaction conditions of the reaction suggest future biomolecule applications.

Hypervalent Iodine Reagents Enable Chemoselective Deboronative/Decarboxylative Alkenylation by Photoredox Catalysis

AbstractChemoselective C(sp3)C(sp2) coupling reactions under mild reaction conditions are useful for synthesizing alkyl‐substituted alkenes having sensitive functional groups. Reported here is a visible‐light‐induced chemoselective alkenylation through a deboronation/decarboxylation sequence under neutral aqueous reaction conditions at room temperature. This reaction represents the first hypervalent‐iodine‐enabled radical decarboxylative alkenylation reaction, and a novel benziodoxole‐vinyl carboxylic acid reaction intermediate was isolated. This C(sp3)C(sp2) coupling reaction leads to aryl‐and acyl‐substituted alkenes containing various sensitive functional groups. The excellent chemoselectivity, stable reactants, and neutral aqueous reaction conditions of the reaction suggest future biomolecule applications.

Synthesis of Biphenyl-Based Ligand: Application in Copper-Mediated Chemoselective Michael Reaction

A biphenyl-based ligand attached was synthesized and screened in copper-mediated Michael reaction. The catalyst system works well with carbon or sulfur nucleophiles as Michael donors and cyclohexenone or chalcones as the acceptors under mild and neutral reaction conditions in a chemoselective manner.

ChemInform Abstract: Palladium‐Catalyzed C—S Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones.

The insertion of an aryne into a C-S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α-carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2-quinolinones in high yields under neutral reaction conditions by a C-S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio-substituted quinolinone products.

ChemInform Abstract: Highly Enantioselective S—H Bond Insertion Cooperatively Catalyzed by Dirhodium Complexes and Chiral Spiro Phosphoric Acids.

The first highly enantioselective S–H bond insertion reaction was developed by cooperative catalysis of dirhodium(II) carboxylates and chiral spiro phosphoric acids (SPAs) under mild and neutral reaction conditions with fast reaction rates, high yields (77–97% yields), and excellent enantioselectivities (up to 98% ee). The catalytic S–H bond insertion reaction provides a highly efficient method for the synthesis of chiral sulfur-containing compounds and advances the synthesis of a chiral sulfur-containing drug (S)-Eflucimibe. A systematic 31P NMR study revealed that no ligand exchange between dirhodium(II) carboxylates and SPAs occurred in the reaction. The distinct behaviors of cooperative catalysts Rh2(TPA)4/(R)-1a and the prepared complex Rh2(R-1a)4 observed by in situ FT-IR spectroscopy excluded the feasibility of Rh2(R-SPA)4 being the real catalyst. DFT calculations showed that the activation barrier in the proton shift step became remarkably low as promoted by SPAs. Based on the experimental results and the calculations, the SPA was proposed as a chiral proton shuttle for the proton shift in reaction. Additionally, the single crystal structures of several SPAs were measured and used to rationalize the configurations of the S–H insertion products obtained in the reactions. The rigid and crowded environment around the SPAs ensures the high enantioselectivity in the S–H bond insertion reaction.

Carboxylate switch between hydro- and carbopalladation pathways in regiodivergent dimerization of alkynes.

Experimental and theoretical investigation of the regiodivergent palladium-catalyzed dimerization of terminal alkynes is presented. Employment of N-heterocyclic carbene-based palladium catalyst in the presence of phosphine ligand allows for highly regio- and stereoselective head-to-head dimerization reaction. Alternatively, addition of carboxylate anion to the reaction mixture triggers selective head-to-tail coupling. Computational studies suggest that reaction proceeds via the hydropalladation pathway favoring head-to-head dimerization under neutral reaction conditions. The origin of the regioselectivity switch can be explained by the dual role of carboxylate anion. Thus, the removal of hydrogen atom by the carboxylate directs reaction from the hydropalladation to the carbopalladation pathway. Additionally, in the presence of the carboxylate anion intermediate, palladium complexes involved in the head-to-tail dimerization display higher stability compared to their analogues for the head-to-head reaction.

Fluorescein-5-thiosemicarbazide (FTSC) labeling for fluorescent imaging of pectin-derived oligogalacturonic acid transported in living cells by confocal microscopy

Confocal microscopy is a powerful and effective tool for in vivo elucidation of the molecular basis of biological molecules. Chemical labeling of non-ultraviolet or non-fluorescent carbohydrate with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible. However, current labeling methods have proved unsuitable for functional pectin-derived oligogalacturonic acid due to the low fluorescence intensity and/or the formation of lactone byproducts. Here, fluorescein-5-thiosemicarbazide (FTSC) was employed for fluorescent labeling of pectin-derived oligogalacturonic acid under mild and neutral reaction conditions to avoid the generation of lactone byproducts. ESI–MS and LC–MS data displayed that pectin-derived pentagalacturonic acid, GalA5, could be quantitatively labeled with FTSC to afford thiosemicarbazones, without any lactone byproducts yielded. Moreover, GalA5-FTSC thiosemicarbazone showed good stability and desirable fluorescence characteristics and exhibited rather low levels of cytotoxicity against sensitive rat thymus cells. Additionally, we have achieved successful fluorescent imaging of GalA5-FTSC thiosemicarbazones transported in living SW-620 and HepG2 cells. The assay illustrates methodological significance in structure–activity elucidation study of functional carbohydrates especially acid oligo-/polysaccharides.

Selective oxidation of alcohols with hydrogen peroxide catalyzed by tungstate ions (WO4=) supported on periodic mesoporous organosilica with imidazolium frameworks (PMO-IL)

Tungstate ions supported on the periodic mesoporous organosilica with ionic liquid frameworks (WO4=@PMO-IL) were found to be a recoverable catalyst system for the highly selective oxidation of various primary or secondary alcohols to the corresponding aldehydes or ketones by 30% H2O2 as green oxidant under neutral aqueous reaction conditions. The catalyst can be also recovered and efficiently reused in seven subsequent reaction cycles without any remarkable decreasing in the catalyst activity and selectivity. Moreover, N2 sorption analysis, transmission electron microscopy (TEM) images, and thermal gravimetric analysis (TGA) showed that the structure regularity and functional groups loaded of the catalyst were not affected during the reaction process.

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

AbstractThe insertion of an aryne into a CS bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)2, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a CS activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C-S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α-carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2-quinolinones in high yields under neutral reaction conditions by a C-S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio-substituted quinolinone products.

Highly enantioselective S–H bond insertion cooperatively catalyzed by dirhodium complexes and chiral spiro phosphoric acids

The first highly enantioselective S–H bond insertion reaction was developed by cooperative catalysis of dirhodium(II) carboxylates and chiral spiro phosphoric acids (SPAs) under mild and neutral reaction conditions with fast reaction rates, high yields (77–97% yields), and excellent enantioselectivities (up to 98% ee). The catalytic S–H bond insertion reaction provides a highly efficient method for the synthesis of chiral sulfur-containing compounds and advances the synthesis of a chiral sulfur-containing drug (S)-Eflucimibe. A systematic 31P NMR study revealed that no ligand exchange between dirhodium(II) carboxylates and SPAs occurred in the reaction. The distinct behaviors of cooperative catalysts Rh2(TPA)4/(R)-1a and the prepared complex Rh2(R-1a)4 observed by in situ FT-IR spectroscopy excluded the feasibility of Rh2(R-SPA)4 being the real catalyst. DFT calculations showed that the activation barrier in the proton shift step became remarkably low as promoted by SPAs. Based on the experimental results and the calculations, the SPA was proposed as a chiral proton shuttle for the proton shift in reaction. Additionally, the single crystal structures of several SPAs were measured and used to rationalize the configurations of the S–H insertion products obtained in the reactions. The rigid and crowded environment around the SPAs ensures the high enantioselectivity in the S–H bond insertion reaction.

Silver Acetate Mediated Acetoxylations of Alkyl Halides

Silver acetate promotes the acetoxylation of alkyl halides under neutral reaction conditions. The reaction is applicable to primary and activated secondary alkyl halides, and 2,2-dibromoacetophenones for preparing the corresponding acetates in good yields. The presence of ester, amide, nitrile, hydroxy, and OTBDMS functions on the substrate is tolerated.

ChemInform Abstract: Efficient and Regioselective Ring‐Opening of Epoxides with Alcohols and Sodium Azide by Using Catalytic Amounts of GaCl3/Polyvinylpyrrolidone.

/PVP). This catalyst was employed for efficient and regioselective ring-opening reaction of epoxides by variousalcohols under solvent-free conditions at room temperature. In our procedure, this heterogeneous catalyst wasused at neutral and mild reaction conditions to afford high yields of β-alkoxy alcohols. Also, regioselectiveconversion of epoxides to β-azidohydrines was accomplished by sodium azide in MeOH in the presence ofGaCl

ChemInform Abstract: Three‐Component and One‐Pot Reaction Between Phenacyl Bromide and Primary Amines in the Presence of Carbon Disulfide.

AbstractThe main features of the reported methodology are neutral reaction conditions and starting materials which need not to be mixed with any activation nor modification.

ChemInform Abstract: Catalyst‐Free, Direct, High Regio‐ and Chemoselective Conversion of Epoxides to Vicinal Haloesters under Mild, Neutral and Solvent‐Free Conditions.

AbstractTitle reaction providing haloesters [(III) and (VIII)] is proved to be suitable for preparation of vic‐haloesters even in the presence of many functional groups with high regio‐ and chemoselectivity under mild and neutral reaction conditions.

Efficient and Regioselective Ring-Opening of Epoxides with Alcohols and Sodium Azide by using Catalytic Amounts of GaCl3/Polyvinylpyrrolidone

/PVP). This catalyst was employed for efficient and regioselective ring-opening reaction of epoxides by variousalcohols under solvent-free conditions at room temperature. In our procedure, this heterogeneous catalyst wasused at neutral and mild reaction conditions to afford high yields of β-alkoxy alcohols. Also, regioselectiveconversion of epoxides to β-azidohydrines was accomplished by sodium azide in MeOH in the presence ofGaCl

Synthesis of Furoxans from Styrenes under Basic or Neutral Conditions

Furoxans (1,2,5-oxadiazole 2-oxides) can be synthesized from the corresponding styrenes using NOBF4 under basic or even almost neutral reaction conditions. Acid-sensitive functional groups are tolerated under the developed basic conditions. For the substrates having poor reactivity, almost neutral conditions (using pyridine equimolar to NOBF4) are suitable for better yields.

ChemInform Abstract: Diastereoselective Ruthenium Porphyrin‐Catalyzed Tandem Nitrone Formation/1,3‐Dipolar Cycloaddition for Isoxazolidines. Synthesis, in silico Docking Study and in vitro Biological Activities.

AbstractThe described method features a broad scope of alkene compounds, excellent compatibility of various functionalities, neutral reaction conditions, and high regio‐, chemo‐ and diastereoselectivity.

ChemInform Abstract: A Facile and Expedient One‐Pot Three‐Component Reaction Leading to Multifunctionalized Stabilized Phosphorus Ylides.

AbstractPhosphorus ylides (IV) are obtained by a simple and effective one‐pot three‐component reaction of NH‐acids (I), triphenylphosphine (II), and acetylenic esters (III) under mild and neutral reaction conditions.

Mechanistic investigations and substrate scope evaluation of ruthenium-catalyzed direct sp3 arylation of benzylic positions directed by 3-substituted pyridines.

A highly efficient direct arylation process of benzylic amines with arylboronates was developed that employs Ru catalysis. The arylation takes place with greatest efficiency at the benzylic sp3 carbon. If the distance to the activating aryl ring is increased, arylation is still possible but the yield drops significantly. Efficiency of the CH activation was found to be significantly increased by use of 3-substituted pyridines as directing groups, which can be removed after the transformation in high yield. Calculation of the energy profile of different rotamers of the substrate revealed that presence of a substituent in the 3-position favors a conformation with the CH2 group adopting a position in closer proximity to the directing group and facilitating C–H insertion. This operationally simple reaction can be carried out in argon atmosphere as well as in air and under neutral reaction conditions, displaying a remarkable functional group tolerance. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.