Intramolecular photocycloaddition of cyclic thioimides as a method for heterocyclic synthesis

Cyclic thioimides undergo photocycloaddition with tethered pi-bonds in a regiospecific manner to afford spirocyclic amidothietanes. These highly strained multicycles undergo a subsequent ring opening reaction to furnish novel fused pyrrolizinones.     

Decarboxylative cyclizations and cycloadditions of palladium-polarized aza-ortho-xylylenes

Vinyl benzoxazinones undergo decarboxylation in the presence of palladium catalysts to form palladium-polarized aza-ortho-xylylenes, which are versatile reaction intermediates. These palladium-polarized aza-ortho-xylylenes are generated under exceptionally mild conditions and undergo a plethora of different reactions depending on the reaction conditions. Specifically, they undergo dimerization reactions to produce macrocycles, cyclizations to form dihydroquinolines, cycloadditions with electrophilic p-bonds, and nucleophilic attack by amines. Thus, a wide array of structurally unique aniline derivatives can be accessed from these unique intermediates.     

A convenient scalable one-pot conversion of esters and Weinreb amides to terminal alkynes

Esters and amides undergo reduction to the corresponding aldehydes using DIBAL-H followed by same pot conversion to terminal alkynes utilizing the Bestmann-Ohira reagent in good to excellent yields. Additionally chiral nonracemic substrates undergo this transformation with complete preservation of stereochemical integrity.     

Synthesis and reactivity of azapalladacyclobutanes

N-Sulfonyl aziridines undergo oxidative addition to palladium(0) complexes generated in situ from mixtures of Pd2(dba)3 and 1,10-phenanthroline. The resulting azapalladacyclobutane complexes undergo intramolecular carbopalladation in the presence of copper(I) iodide to afford azapalladabicyclo[3.2.1]octanes. A deuterium-labeling experiment indicates that the oxidative addition proceeds via SN2-type attack of palladium(0) on the less-hindered carbon of the aziridine ring and that alkene insertion occurs in a syn fashion. The azapalladabicyclo[3.2.1]octane complexes undergo oxidative palladium-carbon bond functionalization in the presence of copper(II) bromide.     

The diastereoselective synthesis of functionalised isoxazolidines using a Cope elimination/intramolecular nitrone cycloaddition strategy

Functionalised hydroxylamine derivatives of (S)-prolinol prepared by a Cope elimination have been found to undergo oxidation to the nitrone either in the presence of air or a catalytic quantity of TPAP. These undergo intramolecular cycloaddition to give tricyclic isoxazolidines with high diastereoselectivity.     

Dynamic,Bioresponsive Hydrogels via Changes in DNA Aptamer Conformation

DNA aptamers are integrated into synthetic hydrogel networks with the aim of creating hydrogels that undergo volume changes when exposed to target molecules. Specifically, single‐stranded DNA aptamers in cDNA‐bound, extended state are incorporated into hydrogel networks as cross‐links, so that the nanoscale conformational change of DNA aptamers upon binding to target molecules will induce macroscopic volume decreases of hydrogels. Hydrogels incorporating adenosine triphosphate (ATP)–binding aptamers undergo controllable volume decreases of up to 40.3 ± 4.6% when exposed to ATP, depending on the concentration of DNA aptamers incorporated in the hydrogel network, temperature, and target molecule concentration. Importantly, this approach can be generalized to aptamer sequences with distinct binding targets, as demonstrated here that hydrogels incorporating an insulin‐binding aptamer undergo volume changes in response to soluble insulin. This work provides an example of bioinspired hydrogels that undergo macroscopic volume changes that stem from conformational shifts in resident DNA‐based cross‐links.     

Evidence for metal surface catalysed reduction of unsaturated carboxylic acids under negative ion chemical ionization

Unsaturated carboxylic acids have been found to undergo hydrogenation in the presence of methanol prior to ionization. Z-Isomers are found to undergo more facile reduction than the E-isomers in the case of two pairs of dicarboxylic acids studied.     

Recent advances in metal carbenoid mediated nitrogen-containing zwitterionic intermediate trapping process

Zwitterionic intermediates generated from metal carbenoids and compounds containing enamine units belong to a class of highly active synthetic intermediates that undergo different types of transformations. They can undergo rapid proton transfer to afford C–H functionalization products, or undergo intramolecular trapping process to give [3+2] annulation products. Recently, by taking advantage of its unique electronic feature, novel transformations have been developed by applying suitable electrophiles to trap such type of zwitterionic intermediates. The successful trapping process offers a powerful strategy for the effective construction of diversified nitrogen-containing molecules.     

Transformations of unsymmetrical N-hetarylformazans in acidic media

1-Aryl-3-phenyl-5-hetarylformazans undergo acid cleavage to give benzaldehyde hetarylhydrazones, whereas 1-hetaryl-3-phenyl-5-(4-nitrophenyl)formazans undergo acid cleavage to give benzaldehyde 4-nitrophenylhydrazones. 1-Aryl-3-phenyl-5-(6-oxo-4-methyl-2-pyrimidinyl)-formazans undergo cyclization to 1,2,4-triazolo[4,3-a]pyrimidine derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1268–1270, September, 1977.     

Copper-catalyzed silylation of cyclopropenes using (trifluoromethyl)trimethylsilane

A variety of cyclopropenes undergo direct silylation using (trifluoromethyl)trimethylsilane in the presence of a copper-bisphosphine catalyst; under these conditions, cyclopropenes that might otherwise undergo ring-opening are silylated efficiently.     

Intramolecular [2 + 2] cycloaddition reactions of alkynyl ether derived ketenes. A convenient synthesis of donor-acceptor cyclobutanes

Mild thermolysis of tert-butyl alkynyl ethers furnishes aldoketenes, which undergo facile [2 + 2] cycloaddition reactions with pendant di- and trisubstituted alkenes. A wide variety of cis-fused cyclobutanones are produced in moderate to high diastereoselectivity and good to excellent yields by this method, and free hydroxyl groups are tolerated in the ene-ynol ether starting materials. Enol-ynol ethers also undergo efficient reaction to produce donor-acceptor cyclobutanes in high yields.     

Nickel hydrides supported by a non-innocent diphosphine arene pincer: mechanistic studies of nickel-arene H-migration and partial arene hydrogenation

Nickel hydrides supported by a terphenyl diphosphine were synthesized and found to undergo nickel-to-arene H-transfers. Some of the resulting complexes also undergo the reverse (C-to-Ni) H-migration, indicating the potential for storing H-equivalents in this type of pincer ligand. NMR spectroscopy, single crystal X-ray diffraction, and isotopic labeling studies investigating the mechanism of these processes are discussed.     

Acid-Catalyzed Reaction of (4,4-Diethoxybutyl)ureas with Phenols as a Novel Approach to the Synthesis of α-Arylpyrrolidines

1-(4,4-Diethoxybutyl)-3-alkylureas undergo intramolecular cyclization in the presence of trifluoroacetic acid and various phenols, leading to the new N-alkyl-2-arylpyrrolidine-1-carboxamides with moderate to excellent yields. It was found that these compounds undergo spontaneous solid-phase epimerization at room temperature. Advantages of the proposed approach are mild reaction conditions and no need for expensive reagents or catalysts.     

The acid-mediated ring opening/cyclisation reaction of N-benzyl-α-aryl-azetidinones

N-Benzyl-4-aryl-azetidinones undergo ring opening with triflic acid to form N-benzyl-cinnamamides, which either undergo cyclisation to give 5-aryl-benzazepin-3-ones or N-debenzylation to give cinnamamides.     

One‐pot Three‐component Synthesis of Furan‐based Heterocycles from Benzyl Halides

An efficient and a novel approach for the synthesis of furochromene and furopyran scaffolds are described. Benzyl halides undergo oxidation in Kornblum conditions to give the corresponding aldehydes, which in turn undergo [4 + 1] cycloaddition reaction with isocyanide to afford the corresponding furan derivatives. The significant attraction of this protocol is simple procedure, mild reaction condition, and good yield.     

Fe+ chemical ionization of peptides

Laser-desorbed peptide neutral molecules were allowed to react with Fe⁺ in a Fourier transform mass spectrometer, using the technique of laser desorption/chemical ionization. The Fe⁺ ions are formed by laser ablation of a steel target, as well as by dissociative charge-exchange ionization of ferrocene with Ne⁺. Prior to reaction with laser-desorbed peptide molecules, Fe⁺ ions undergo 20–100 thermalizin collisions with xenon to reduce the population of excited-state metal ion species. The Fe⁺ ions that have not experienced thermalizing collisions undergo charge exchange with peptide molecules. Iron ions that undergo thermalizing collisions before they are allowed to react with peptides are found to undergo charge exchange and to form adduct species [M + Fe⁺] and fragment ions that result from the loss of small, stable molecules, such as H₂O, CO, and CO₂, from the metal ion-peptide complex.     

The Ketene‐Surrogate Coupling: Catalytic Conversion of Aryl Iodides into Aryl Ketenes through Ynol Ethers

tert‐Butoxyacetylene is shown to undergo Sonogashira coupling with aryl iodides to yield aryl‐substituted tert‐butyl ynol ethers. These intermediates participate in a [1,5]‐hydride shift, which results in the extrusion of isobutylene and the generation of aryl ketenes. The ketenes are trapped in situ with multiple nucleophiles or undergo electrocyclic ring closure to yield hydroxynaphthalenes and quinolines.     

Hydrogen isotope effect in primary alkyl chlorides in the presence of aprotic acids

Summary Based on n-butyl, n-propyl, and ethyl chlorides as examples, it was established that these alkyl chlorides, in the absence of tertor sec-alkyl chlorides, do not undergo hydrogen exchange reaction with deuterium chloride in nitrobenzene solution in the presence of aprotic acids. Under these conditions, n-BuCl and n-PrCl are isomerized to secondary alkyl chlorides, which easily undergo the hydrogen exchange reaction.     

Dimerization and isomerization reactions of alpha-lithiated terminal aziridines

The scope of dimerization and isomerization reactions of alpha-lithiated terminal aziridines is detailed. Regio- and stereoselective deprotonation of simple terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide (LTMP) or lithium dicyclohexylamide (LiNCy2) generates trans-alpha-lithiated terminal aziridines. These latter species can then undergo dimerization or isomerization reactions depending on the nature of the N-protecting group. alpha-Lithiated terminal aziridines bearing N-alkoxycarbonyl (Boc) protection undergo N- to C-[1,2] migration to give N-H trans-aziridinylesters. In contrast, aziridines bearing N-organosulfonyl [tert-butylsulfonyl (Bus)] protection undergo rapid dimerization to give 2-ene-1,4-diamines or, if a pendant alkene is present, diastereoselective cyclopropanation to give 2-aminobicyclo[3.1.0]hexanes. All of these reactions were used as key steps in the preparation of synthetically and biologically important targets.     

Straightforward approach to iminoxazines and azetidinimines via 1,4-additions of chelated enolates toward nitroalkenes

[reaction: see text] Chelated amino acid ester enolates undergo 1,4-addition toward nitroalkenes in a highly stereoselective fashion. Trapping the nitronates formed in the addition step with chloroformates or acyl chlorides gives rise to highly reactive intermediates that directly undergo cyclization. Depending on the N-protecting group (PG) used, iminoxazines or azetidinimines are formed in a simple one-pot protocol.