Regioselective iodination of flavonoids by N-iodosuccinimide under neutral conditions

Regioselective synthesis of C-6 and C-8 monoiodo flavonoids, which are important intermediates for the synthesis of flavonoid natural products and drug molecules, was achieved by iodination of suitably alkylated flavonoids with N-iodosuccinimide (NIS) in DMF. The iodination gives either a C-6 or C-8 iodo flavonoid in high yield, depending on the protection pattern of the C-5 and C-7 OH groups. The mild and neutral conditions render this novel protocol particularly useful for the regioselective iodination of acid-sensitive substrates.     

Facile p-toluenesulfonic acid-promoted para-selective monobromination and chlorination of phenol and analogues

para-Regioselective bromination of phenol and analogues, promoted by p-toluenesulfonic acid, is achieved in high to excellent yields at room temperature with N-bromosuccinimide. Chlorination with N-chlorosuccinimide and catalysed by p-toluenesulfonic acid also gives para-chlorinated phenol analogues in good yields at room temperature.     

An efficient and selective tosylation of alcohols with p-toluenesulfonic acid

Silica chloride has been found to be an efficient catalyst for facile tosylation of alcohols directly with p-toluenesulfonic acid in methylene chloride under reflux. The process is associated with selective tosylation of secondary alcohols over primary alcohols.     

Cobalt(II) catalyzed tosylation of alcohols with p-toluenesulfonic acid

Cobalt(II) chloride hexahydrate (CoCl₂·6H₂O) has been found to catalyze the tosylation of both aliphatic and aromatic alcohols with p-toluenesulfonic acid (p-TsOH) in high yields in 1,2-dichloroethane under reflux (ca. 80 °C). In the case of aliphatic alcohols, secondary alcohols undergo tosylation chemoselectively in the presence of primary hydroxy groups.     

Intramolecular diamination and alkoxyamination of alkenes with N-sulfonyl ureas employing N-iodosuccinimide

Reaction of N-δ-alkenyl-N′-sulfonyl urea 1 with N-iodosuccinimde (NIS; 2 equiv) and a catalytic amount of AgOTf (20 mol %) at room temperature led to intramolecular alkoxyamination to form bicyclic isourea 2a in 95% isolated yield. In comparison, reaction of 1 with NIS and sodium bicarbonate (1 equiv) at room temperature led to isolation of bicyclic imidazolidin-2-one 2b in 91% yield. These NIS-mediated alkoxyamination and diamination protocols were effective for a range of N-δ-alkenyl-N′-sulfonyl ureas to form the corresponding heterobicyclic compounds in good yield with high chemoselectivity and good to excellent diastereoselectivity.     

Mild and regioselective iodination of aromatic compounds with N,N′-diiodo-N,N′-1,2-ethanediylbis(p-toluenesulphonamide)

N,N′-Diiodo-N,N′-1,2-ethanediylbis(p-tolouenesulphonamide) [NIBTS] and catalytic trifluoroacetic acid can be used for the regioselective iodination of aromatic compounds in acetonitrile under mild conditions in excellent yields.     

Aromatic iodination using N-iodosaccharin in room temperature ionic liquids

More reactive iodination conditions have been developed that combine the use of room temperature ionic liquids with N-iodosaccharin. Using these reaction conditions, even very modestly activated arenes such as toluene can be iodinated in good yield under very mild conditions.     

PhI- and polymer-supported PhI-catalyzed oxidative conversion of ketones and alcohols to α-tosyloxyketones with m-chloroperbenzoic acid and p-toluenesulfonic acid

Various ketones were converted to the corresponding α-tosyloxyketones with mCPBA and p-toluenesulfonic acid in the presence of a catalytic amount of iodobenzene. Moreover, secondary alcohols were directly converted to the corresponding α-tosyloxyketones using mCPBA and catalytic amounts of iodobenzene and potassium bromide, followed by treatment with p-toluenesulfonic acid in a one-pot manner. Poly(4-iodostyrene) could be also used as a recyclable catalyst for the same α-tosyloxylation of ketone     

Regioselective, photochemical bromination of aromatic compounds using N-bromosuccinimide

Regioselective nuclear bromination of aromatic compounds is investigated with N-bromosuccinimide as the brominating agent under UV irradiation to afford the corresponding brominated compounds. The reaction proceeds at ambient temperature (30 ± 2 °C) without any catalyst. In most of the reactions, regioselectively mono-brominated products are obtained in good to high yields. The conversion and selectivity for bromination depend on the nature of the substituent on the aromatic ring.     

Lactones. Part 16: Lactonization of γ,δ-epoxy esters with p-toluenesulfonic acid monohydrate

The reaction of cyclic γ,δ-epoxy esters with p-toluenesulfonic acid monohydrate is described. The reaction carried out in benzene or methylene chloride gave tosyloxy lactones as product. The ethoxy or methoxy lactones were obtained when ethanol or methanol were used as solvent. A mechanism of this lactonization is proposed.     

A first synthesis of sulfonic acid analogues of N-acetylneuraminic acid

Sulfonic acid analogues of N-acetylneuraminic are synthesized from 1-thio-l-fucoside derivatives with the introduction of an azido group at C-4 of the fucose moiety and carbanionic addition onto fully protected lactones. The analogues in the form of methyl glycosides are subjected to a neuraminidase inhibition assay.     

Regioselective nitration of N,N-dialkylanilines using cerium(IV) ammonium nitrate in acetonitrile

A highly regioselective and inexpensive nitration of N,N-dialkylanilines by cerium(IV) ammonium nitrate (CAN) in acetonitrile under room temperature to yield p-nitryl-N,N-dialkylanilines in good yields was reported.     

An efficient and regioselective iodination of electron-rich aromatic compounds using N-chlorosuccinimide and sodium iodide

An efficient and regioselective method for iodination of electron-rich aromatic compounds was found using N-chlorosuccinimide and sodium iodide in AcOH with short reaction times. This method is also applicable to non-benzenoid aromatic or heteroaromatic compounds.     

Selective N-debenzylation of amides with p-TsOH

N-Benzylamides were debenzylated efficiently with 4 equiv. of p-TsOH in refluxing toluene. Good to quantitative yields of the desired primary amides were obtained within 2-4 h from a wide variety of N-2,4-dimethoxybenzylamides. N-4-Methoxylbenzyl amides and N-benzylamides were also debenzylated cleanly. In the case of N-2,4-dimethoxylbenzylamides, selective N-debenzylation was possible in the presence of N-Fmoc, N-t-BOC or N-trityl-protection. Protected amino acid amides survived these conditions without any detectable epimerization.     

Regioselective ortho-nitration of N-phenyl carboxamides and primary anilines using bismuth nitrate/acetic anhydride

An efficient and one-pot synthetic method for the regioselective ortho-nitration of the N-phenyl carboxamides and primary anilines has been developed by using bismuth nitrate and acetic anhydride as the nitrating reagents. Reaction proceeds at room temperature and results in corresponding ortho-nitrated products in moderate to excellent yields. This method provides an operationally simple, regioselective, and efficient access to synthesize o-nitro anilines under the mild conditions.     

N-Arylation of α-aminoesters with p-tolylboronic acid promoted by copper(II) acetate

Copper-promoted N-arylation of α-amino esters with p-tolylboronic acid at room temperature was accomplished with little or no racemization.     

Glycosylation reactions with ‘disarmed’ thioglycoside donors promoted by N-iodosuccinimide and HClO4-silica

Glycosylation of ‘disarmed’ thioglycosides promoted by NIS in the presence of HClO₄ immobilized on silica compares very favourably with the accepted NIS-TfOH procedure.     

Oxidation of nitrotoluenes with air using N-hydroxyphthalimide analogues as key catalysts

Nitrotoluenes are efficiently oxidized with air to the corresponding nitrobenzoic acids by the use of N-acetoxyphthalimide (NAPI) as a key catalyst. Thus, p- and m-nitrotoluenes under 10 atm of air in the presence of NAPI combined with Co(OAc)₂ (0.5 mol%) and Mn(OAc)₂ (0.05 mol%) at 130°C afforded p- and m-nitrobenzoic acids in 81 and 92% yields, respectively. o-Nitrotoluene was oxidized to o-nitrobenzoic acid in 51% yield by the aid of NO₂.     

Regioselective synthesis of 1-arylnaphthalenes from N-tosylaziridine derivatives

Regioselective synthesis of 1-arylnaphthalene derivatives was carried out from N-tosylaziridines, which was made from the reaction of N-tosylimines and cinnamyl bromides by using the sulfur ylide chemistry.     

Synthesis of p-amino-N,N′-dihydroxybenzamidine using a TBDMS protecting group protocol

A synthetic route to p-amino-N,N′-dihydroxybenzamidine is established using a TBDMS protecting group strategy starting with p-nitrobenzhydroxamic acid chloride, which is transformed to O,O′-bis(tert-butyldimethylsilyl)-N,N′-dihydroxybenzamidine. Reduction with sodium dithionite occurs without degradation of the dihydroxyamidine functional group. Deprotection with ammonium fluoride is fast and efficient. This is important because no other possibility to synthesize this derivative has been found up to now. Furthermore, TBDMS protecting group strategy is proved to be adaptable to other substituted N,N′-dihydroxybenzamidines.